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Cardiovascular Journal of Africa

AFRICA

ISSN 1995-1892 (print) ISSN 1680-0745 (online)

Vol 29, No 2, MARCH/APRIL 2018

CONTENTS

Cardiovascular Journal of Africa 67

www.cvja.co.za

From the Editor’s Desk P Commerford

CARDIOVASCULAR TOPICS 68 Stroke distribution patterns and characteristics in Kenya’s leading public health tertiary institutions: Kenyatta National Hospital and Moi Teaching and Referral Hospital L Kaduka • A Korir • CO Oduor • J Kwasa • J Mbui • S Wabwire • R Gakunga • N Okerosi • Y Opanga • I Kisiang’ani • MR Chepkurui • E Muniu • SC Remick 73

Prevalence, awareness, treatment and control of hypertension, diabetes and hypercholesterolaemia among adults in Dande municipality, Angola JM Pedro • M Brito • H Barros

Assessment of left atrial function in patients with type 2 diabetes mellitus with a disease duration of six months O Gulmez • H Parildar • O Cigerli • N Demirağ

Upper limb ischaemia: a South African single-centre experience T du Toit • K Manning • NG Naidoo

Comparison of carotid intima–media thickness and coronary artery calcium score for estimating subclinical atherosclerosis in patients with fatty liver disease H-J Kim • H-B Park • Y Suh • Y-H Cho • E-S Hwang • D-K Cho • T-Y Choi

Participation in research improves overall patient management: insights from the Global Rheumatic Heart Disease registry (REMEDY) EA Prendergast • S Perkins • ME Engel • B Cupido • V Francis • A Joachim • M Al Kebsi • F Bode-Thomas • A Damasceno • A Abul Fadl • A El Sayed • B Gitura • N Kennedy • A Ibrahim • J Mucumbitsi • AM Adeoye • J Musuku • E Okello • T Olunuga • S Sheta • B Mayosi • LJ Zühlke • for the REMEDY investigators

INDEXED AT SCISEARCH (SCI), PUBMED, PUBMED CENTRAL AND SABINET

Editors

SUBJECT Editors

Editorial Board

Editor-in-Chief (South Africa) Prof Pat Commerford

Nuclear Medicine and Imaging DR MM SATHEKGE

prof PA Brink Experimental & Laboratory Cardiology

PROF A LOCHNER Biochemistry/Laboratory Science

PROF R DELPORT Chemical Pathology

PROF BM MAYOSI Chronic Rheumatic Heart Disease

Assistant Editor Prof JAMES KER (JUN) Regional Editor DR A Dzudie Regional Editor (Kenya) Dr F Bukachi Regional Editor (South Africa) PROF R DELPORT

Heart Failure Dr g visagie Paediatric dr s brown Paediatric Surgery Dr Darshan Reddy Renal Hypertension dr brian rayner Surgical dr f aziz Adult Surgery dr j rossouw Epidemiology and Preventionist dr ap kengne Pregnancy-associated Heart Disease Prof K Sliwa-hahnle

PROF MR ESSOP Haemodynamics, Heart Failure DR MT MPE Cardiomyopathy & Valvular Heart Disease DR OB FAMILONI Clinical Cardiology DR V GRIGOROV Invasive Cardiology & Heart Failure

International Advisory Board PROF DAVID CELEMAJER Australia (Clinical Cardiology) PROF KEITH COPELIN FERDINAND USA (General Cardiology) DR SAMUEL KINGUE Cameroon (General Cardiology)

PROF DP NAIDOO Echocardiography

DR GEORGE A MENSAH USA (General Cardiology)

PROF B RAYNER Hypertension/Society

PROF WILLIAM NELSON USA (Electrocardiology)

PROF MM SATHEKGE Nuclear Medicine/Society PROF J KER (SEN) Hypertension, Cardiomyopathy, PROF YK SEEDAT Cardiovascular Physiology Diabetes & Hypertension

DR ULRICH VON OPPEL Wales (Cardiovascular Surgery)

DR J LAWRENSON Paediatric Heart Disease

PROF ERNST VON SCHWARZ USA (Interventional Cardiology)

PROF H DU T THERON Invasive Cardiology

PROF PETER SCHWARTZ Italy (Dysrhythmias)

106

Prevalence of cardiometabolic risk factors among professional male long-distance bus drivers in Lagos, south-west Nigeria: a cross-sectional study CE Amadi • TP Grove • AC Mbakwem • OB Ozoh • OA Kushimo • DA Wood • M Akinkunmi

115

Status of cardiac arrhythmia services in Africa in 2018: a PASCAR Sudden Cardiac Death Task Force report MA Talle • A Bonny • W Scholtz • A Chin • G Nel • KM Karaye • JB Anzouan-Kacou • A Damasceno • YR Lubenga • MU Sani • BM Mayosi

Vol 29, No 2, MARCH/APRIL 2018

CONTENTS

pascar report

REVIEW ARTICLE 122 The aetiology of cardiovascular disease: a role for mitochondrial DNA? M Venter • FH van der Westhuizen • JL Elson

PUBLISHED ONLINE (Available on www.cvja.co.za and in PubMed)

Absolute cardiovascular risk of women using hormonal contraception in Porto-Novo A Sonou • M Ogoudjobi • PM Adjagba • C Houehanou • R Aniglé • L Codjo • M Hounkponou • R Bognon • S Assani • D Amoussou-Guéno • M Houenassi

CARDIOVASCULAR TOPICS

CASE REPORTS e5

Partial anomalous pulmonary venous connection with accessory pulmonary veins V Arulselvam • NN Kalis • SR Al Amer

e8 Ischaemic heart disease and pregnancy: the tale of two stories MR Matshela

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GAUTENG CONTRIBUTOR PETER WAGENAAR Cell 082 413 9954 e-mail: skylark65@myconnection.co.za The Cardiovascular Journal of Africa, incorporating the Cardiovascular Journal of South Africa, is published 10 times a year, the publication date being the third week of the designated month. Copyright: Clinics Cardive Publishing (Pty) Ltd.

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

From the Editor’s Desk It is a great privilege to be able to edit this publication as it strives to record the development of research and services aimed at alleviating cardiovascular diseases prevalent on the continent. I am delighted that so many original research articles, reviews and case reports from Africa are being submitted for publication. In this regard, I do need to comment on the fact that there is another important aspect and responsibility of which all aspirant authors and researchers need to be cognisant. This is the need to be prepared to accept the responsibility of reviewing the work of peers and advising about suitability for publication. Authors often complain (legitimately) about delays in reviews and the publication of their work but are themselves reluctant to accept the invitation to review. My view is that it is essential that if we wish to continue to be an African journal, we need a core body of reviewers who understand Africa and the constraints of practice and research in Africa, and who are prepared to review submissions on the basis of their own local experience. I appeal to all of you, our readers, to accept requests for reviews when requested. If you are not already listed as a reviewer and are prepared to be a reviewer, please submit your name, qualifications and e-mail details to me, with your preferred specialities and area of review to patrick.commerford@uct.ac.za. In this issue, Amadi and colleagues (page 106) document, in a survey of long-distance male bus drivers from Lagos in Nigeria, the frequency of risk factors for cardiac disease. This information is not surprising, given information from other parts of the world, but hopefully may be helpful in guiding employers, unions and individuals in Africa towards guiding employees regarding adoption of healthier lifestyles. An issue that is often raised in discussions of clinical research is whether such research translates into clinical benefit for patients, and patients and researchers need an answer to that question. Prendergast and co-authors address that on page 98 of this issue. Their study demonstrates that participation in clinical research on rheumatic heart disease (RHD) can have a positive impact on patient management. Furthermore, REMEDY has led to increased patient awareness and improved healthcare workers’ knowledge and efficiency in caring for RHD patients. The researchers are to be commended for demonstrating that research has had immediate positive results for patients participating in the research. Little is known about the frequency and management of disturbances of cardiac rhythm in Africa and the report from Talle and colleagues (page 115), which highlights this dearth

Professor PJ Commerford

of information and lack of clinical services, is timely and useful. The information supplied by Kaduka and colleagues on stroke patterns in Kenya (page 68) is important and helpful. Unexpected observations include the preponderance of women affected by cerebrovascular disease and that cigarette smoking was the second most common risk factor. In contrast to the issues above, which reflect many of the unresolved clinical issues of medicine and cardiology in Africa, it is a pleasure to be able to publish the work of Venter and colleagues (page 122), which reviews the molecular and cellular basis of cardiac disease. P J Commerford Editor-in-Chief

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

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Cardiovascular Topics Stroke distribution patterns and characteristics in Kenya’s leading public health tertiary institutions: Kenyatta National Hospital and Moi Teaching and Referral Hospital Lydia Kaduka, Anne Korir, Chrispine Owuor Oduor, Judith Kwasa, Jane Mbui, Sylvanos Wabwire, Robai Gakunga, Nathan Okerosi, Yvonne Opanga, Isaac Kisiang’ani, Mercy Rotich Chepkurui, Erastus Muniu, Scot C Remick

Abstract Background: Cardiovascular diseases are the second leading cause of morbidity and mortality in Kenya. However, there is limited clinico-epidemiological data on stroke to inform decision making. This study sought to establish stroke distribution patterns and characteristics in patients seeking care at Kenyatta National Hospital (KNH) and Moi Teaching and Referral Hospital (MTRH), with the ultimate aim of establishing the first national stroke registry in Kenya.

Centre for Public Health Research, Kenya Medical Research Institute, Nairobi, Kenya Lydia Kaduka, PhD, lkaduka@kemri.org Erastus Muniu, MSc

Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya Anne Korir, MSc Jane Mbui, MD

Department of Medicine, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya Chrispine Owuor Oduor, MD

Department of Clinical Medicine and Therapeutics, Kenyatta National Hospital, Nairobi, Kenya Judith Kwasa, MD

Kenyatta National Hospital, Nairobi, Kenya Sylvanos Wabwire, MD

Methods: This was a prospective multicentre cohort study among stroke patients. The study used a modified World Health Organisation STEP-wise approach to stroke surveillance tool in collecting data on incidence, major risk factors and mortality rate. The Cochran’s Mantel–Haenszel chisquared test of conditional independence was used with p-value set at 0.05. Results: A total of 691 patients with confirmed stroke were recruited [KNH 406 (males: 40.9%; females: 59.1%); MTRH 285 (males: 44.6%; females: 55.4%)] and followed over a 12-month period. Overall, ischaemic stroke accounted for 55.6% of the stroke cases, with women being the most affected (57.5%). Mortality rate at day 10 was 18.0% at KNH and 15.5% at MTRH, and higher in the haemorrhagic cases (20.3%). The most common vascular risk factors were hypertension at 77.3% (males: 75.7%; females: 78.5%), smoking at 16.1% (males: 26.6%; females: 8.3%) and diabetes at 14.9% (males: 15.7%; females: 14.4%). Ischaemic stroke was conditionally independent of gender after adjusting for age. Conclusions: To our knowledge this is the first pilot demonstration establishing a stroke registry in sub-Saharan Africa and clearly establishes feasibility for this approach. It also has utility to both inform and potentially guide public policy and public health measures on stroke in Kenya. Important and unexpected observations included the preponderance of women affected by cerebrovascular disease and that cigarette smoking was the second most common risk factor. The latter, over time, will further impact on the clinico-epidemiological profile of cerebrovascular disease in Kenya.

Kenya Cancer Association, Nairobi, Kenya Robai Gakunga, MD Nathan Okerosi

Keywords: stroke, Kenya, sub-Saharan Africa, mortality, risk factors

School of Public Health, Moi University, Eldoret, Kenya Yvonne Opanga

Submitted 2/6/16, accepted 7/11/17

School of Public Health, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya

Cardiovasc J Afr 2018; 29: 68–72

Isaac Kisiang’ani, MSc Mercy Rotich Chepkurui

DOI: 10.5830/CVJA-2017-046

Maine Medical Center Research Institute, Portland, ME, USA Scot C Remick, MD, PhD

www.cvja.co.za

African countries are undergoing an epidemiological transition characterised by socio-demographic and lifestyle changes,

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

resulting in increased risk factors and burden of cerebrovascular disease (hereafter referred to as stroke). According to the World Health Organisation (WHO), low- and middle-income countries bear the heaviest (86%) global stroke burden,1 with 8% of all first-ever strokes occurring in Africa and 5% of the 30 million stroke survivors worldwide living in Africa.2 There are limited clinico-epidemiological data on stroke from sub-Saharan Africa to effectively inform policy and guide intervention efforts. Cardiovascular disease (CVD) is the second leading cause of morbidity and mortality in Kenya. The Kenya Health Sector Strategic Plan (KHSSP) estimates mortality rate due to CVD at 6.1%, while the WHO estimates it at 8%. Autopsy studies suggest that more than 13% of cause-specific deaths among adults could be due to CVD.2-4 Implementation of surveillance systems is necessary to monitor trends and inform prevention and management programmes.5,6 Although the WHO recommends establishment of an in-country system of surveillance and monitoring of non-communicable diseases, these systems have not been well executed in Africa, largely owing to resource constraints. This study sought to establish the nature of stroke cases (types) seen in Kenya’s two leading referral hospitals, Kenyatta National Hospital (KNH) and Moi Teaching and Referral Hospital (MTRH). It also sought to establish the prevalence of known cerebrovascular risk factors for the stroke subtypes, and ascertain the proportion of first-ever-in-a-lifetime stroke patients and recurrent cases in an effort to provide baseline data for the development of a stroke registry in Kenya. This article highlights the key findings and opportunities for advancing neuroscience in Kenya and sub-Saharan Africa.

Methods The study was carried out at KNH located in Nairobi, the capital city of Kenya, and MTRH located in Eldoret, western Kenya. KNH is the leading public tertiary hospital in Kenya with a bed capacity of 1 800, whose occupancy can go up by 300%. The hospital is frequented by patients from all over Kenya, but mostly from the urban areas (Nairobi and its surroundings). MTRH is the second largest public tertiary hospital with an 850-bed capacity that serves patients mainly from the western and Rift Valley regions in Kenya, which are predominantly rural. Permission to conduct this study was obtained from the Kenya Medical Research Institute (KEMRI) Scientific and Ethics Review Unit (SSC No. 2851), the MTRH institutional research and ethics committee (IREC/2014/213 approval number 0001279) and the Kenyatta National Hospital/University of Nairobi ethics review committee (study registration number MED/029/2015). Informed consent was obtained from each subject or guardian prior to participation in the study. Additional protection for vulnerable populations was put in place to ensure protection of patients’ rights and welfare. This was a prospective cohort study in which patients were recruited upon admission, and general information on demographics, stroke events and case management was collected using the WHO Stroke STEPS instrument.7 Follow up involved assessing clinical outcome at day 10 and 28, and month 3, 6 and 9 using the Modified Rankin Scale,8 and gathering information on patient management after discharge. The study population included all stroke patients diagnosed

and/or attended to in KNH and MTRH for the 12-month period between February 2015 and January 2016. The inclusion criteria were confirmed cases of stroke [based on computerised tomography (CT) scan and/or magnetic resonance imaging] treated in out-patient clinics or admitted in hospitals, and in-hospital patients who suffered stroke while on treatment for other illnesses. The sample size required for the study was based on an unknown proportion of most prevalent stroke type (therefore 50% assumed), a desired precision for the indicator of 5%, and 95% confidence level. Fisher’s formula9 for estimating the minimum sample size for descriptive studies was used, giving a minimum sample of 385. The current sample size comprised all recruited stroke patients from the two hospitals in the one-year period. The combination approach using hot (i.e. active, on-going recruitment) and cold (i.e. retrospective record review) casefinding methods was used to ensure complete identification of stroke cases. Patients were identified from the hospital registry, out-patient clinics, in-patient wards, emergency room and intensive care units. Referrals to specialist physicians or neurologists, physiotherapists, speech or occupational therapists were also monitored to avoid missing any cases. Discharge records and death certificates were scrutinised for stroke diagnosis. Care was taken to avoid duplicate reporting of cases by counterchecking with the hospital electronic database. The study utilised a modified WHO STEP-wise approach to stroke surveillance tool designed to collect in a standardised manner, basic epidemiological data on incidence, major risk factors, morbidity and mortality trends, and intervention strategies in recent (acute) stroke.10 The tool was administered through face-to-face interviews with patients and/or the contact person(s). Follow-up interviews were done where possible physically and/or by telephone. Data were collected on all aspects of stroke, including information on patient demographic details (gender, age and residence), date of stroke diagnosis, stroke subtype (ischaemic or haemorrhagic), single or multiple strokes, and history of cigarette smoking prior to the current stroke. Information related to care, such as whether or not a CT scan was done was also collected. Regular follow up visits were done every three months to ascertain the patient status after discharge.

Statistical analysis Data were analysed using SPSS version 20, with p < 0.05 considered statistically significant. Results are expressed as means ± SD or as proportions (%). For categorical variables, the chi-squared test and Fisher’s exact probability were used. Linear associations were calculated using the Spearman correlation coefficient.

Results A total of 691 patients with confirmed stroke [KNH 406 (males: 40.9%; females: 59.1%); MTRH 285 (males: 44.6%; females: 55.4%)] were recruited; 293 (42.4%) were males and 398 (57.6%) were females, giving a male:female ratio of 1:1.4. The median age was 60 years [interquartile range (IQR): 45–73 years], with a minimum of 18 and maximum of 115 years.

patients were 40 years and older. Cases of haemorrhagic stroke were highest in those aged 50–69 years, while ischaemic stroke peaked in the 60–69 age group. Fig. 1 shows the distribution of stroke type by age group. Among the 691 patients recruited, 106 (15.4%) had suffered a recurrent stroke, among whom 55.6% were women. A significant association was observed between increasing age and recurrent stroke (p = 0.05). Mortality rate at day 10 and 28 in KNH was 18 and 8.4%, respectively, whereas in MTRH it was 15.5 and 10.3%, respectively. Mortality rate at month 3, 6 and 9 was 10.6, 5.4 and 1.6% at KNH and 12, 8.2 and 8.8% at MTRH, respectively. Table 1 shows the distribution of mortality rate at day 10 and 28 and month 3, 6 and 9 of follow up by gender, health facility and stroke type. More deaths occurred among haemorrhagic stroke patients by day 10 (20.3%) and day 28 (9.9%) compared to the ischaemic cases (14.6 and 8.9%, respectively), although this was not statistically significant. Thereafter, mortality rate was significantly higher in ischaemic stroke at month 3 (p = 0.027) and month 6 (p = 0.006), and more so in MTRH at month 3 (p = 0.010) and month 6 (p = 0.011). The most common risk factors were hypertension [77.3% (males: 75.7%; females: 78.5%)], cigarette smoking [16.1% (males: 26.6%; females: 8.3%) p < 0.001], diabetes [14.9% (males: 15.7%; females: 14.4%)], and hypercholesterolaemia [2.8% (males: 4.1%; females: 1.8%) p < 0.05]. Other factors associated with stroke were history of previous migraine [32.8% (males: 28.3%; females: 36.0%) p < 0.05], HIV infection [8% (males: 7.2%; females: 8.6%)], use of oral contraceptives [3.9% (females: 6.8%)] and cocaine use [0.7% (males: 0.7%; females: 0.8%)]. Table 2 shows the distribution of risk factors for stroke by gender and age group.

Frequency (%)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

< 30

30–39

40–49 50–59 60–69 Age group (years)

Ischaemic stroke

70–79

≥ 80

Haemorrhagic stroke

Fig. 1. Distribution of stroke type by age.

Overall, ischaemic stroke accounted for 55.6% of the stroke cases. The occurrence of ischaemic stroke in MTRH was significantly higher (KNH, 50.9%; MTRH 62.1%) than haemorrhagic stroke (KNH 49.1%; MTRH 31.9%) (p = 0.002). There were more women diagnosed with stroke than men (57.5 vs 42.5%, respectively). Ischaemic stroke was more prevalent in females (males: 41.1%; females: 58.9%) compared to haemorrhagic stroke (males: 44.4%; females: 55.6%). The occurrence of stroke increased with increasing age. The distribution of stroke across the age groups ≤ 30, 30–39, 40–49, 50–59, 60–69, 70–79 and ≥ 80 years was 6.3, 10.8, 15.8, 16.2, 19.9, 16.1 and 14.9%, respectively. Up to 82.9% of all the stroke

Table 1. Distribution of stroke mortality rates at day 10 and 28, and month 3, 6 and 9 by gender, health facility and stroke type Day 10 Alive (%) Number Male

Day 28

Dead (%)

549

113

84.2

Alive (%) 475

14.7

Month 3

Dead (%)

Alive (%)

87.8

340

10.9

Month 6

Dead (%)

Alive (%)

85.6

206

11.4

89.1

Month 9

Dead (%)

Alive (%)

92.7

4.9

5.9

Dead (%)

Female

81.3

18.7

91.6

8.1

87.9

11.2

92.1

7.1

96.3

3.7

KNH

82.0

18.0

91.6

8.4

89.4

10.6

94.6

5.4

98.4

1.6

MTRH

83.4

15.5

87.9

10.3

84.0

12.0

85.7

8.2

88.2

8.8

Ischaemic stroke

84.6

14.6

90.1

8.9

83.3

14.0

85.5

9.9

89.8

8.2

Haemorrhagic stroke

79.7

20.3

89.6

9.9

92.5

6.9

97.9

2.1

100

Table 2. Distribution of risk factors by gender and age group Age groups < 30 years Risk factors

Men n (%)

Women n (%)

30–39 years Men n (%)

40–49 years

Women n (%)

Men n (%)

Women n (%)

Men n (%)

Women n (%)

60–69 years

70–79 years

Men n (%)

Women n (%)

Men n (%)

4 (5.6)

11 (20)

Current tobacco use+

1 (9.1)

0 (0)

6 (19.4)

2 (4.7)

12 (27.9)

17 (33.3)

2 (3.2)

18 (27.7)

Diabetes mellitus*

1 (9.1)

0 (0)

1 (3.2)

4 (9.3)

2 (4.7)

8 (11.9)

3 (5.9)

4 (6.6)

19 (29.2) 21 (29.2) 14 (25.5)

1 (3.1)

2 (6.5)

0 (0)

1 (2.3)

0 (0)

2 (3.9)

2 (3.2)

Hypercholesterolaemia† 0 (0) Hypertension‡

5 (45.5) 15 (46.9) 15 (48.4) 25 (59.5) 29 (69) 6 (18.8)

0 (0)

12 (27.9)

0 (0)

2 (3)

50–59 years

46 (69.7) 42 (82.4) 49 (79) 8 (11.9)

0 (0)

3 (4.6)

1 (1.4)

3 (5.5)

Women n (%)

≥ 80 years Men n (%)

Women n (%)

9 (16.4) 13 (35.1) 14 (21.2) 9 (16.4)

6 (16.2) 11 (16.7)

2 (3.6)

1 (2.7)

1 (1.5)

57 (87.7) 68 (94.4) 47 (85.5) 51 (92.7) 26 (70.3) 56 (84.8)

Oral contraceptives

0 (0)

Previous migraine

4 (36.4) 18 (56.3) 14 (45.2) 19 (44.2) 12 (27.9) 30 (44.8) 16 (31.4) 20 (32.3) 20 (30.8) 27 (37.5)

0 (0)

1 (1.4)

0 (0)

9 (16.4) 14 (25.5)

0 (0)

8 (21.6) 15 (22.7)

HIV infection

0 (0)

7 (21.9)

3 (9.7)

7 (16.3)

9 (20.9) 12 (17.9)

5 (9.8)

5 (8.1)

3 (4.6)

2 (2.8)

1 (1.8)

0 (0)

Cocaine use

0 (0)

1 (3.2)

1 (2.3)

0 (0)

1 (2)

0 (0)

1 (1.4)

0 (0)

1 (1.5)

+ Cigarette smoking within the last five years. *Elevated fasting glucose level > 5.6 mmol/l or treatment of previously diagnosed diabetes. †High-density lipoprotein cholesterol < 1.3 mmol/l; triglycerides > 2.2 mmol/l; total cholesterol > 6.2 mmol/l; low-density lipoprotein cholesterol > 4.1 mmol/l, or speciﬁc treatment for this abnormality. ‡Elevated blood pressure 140/90 mmHg or treatment of previously diagnosed hypertension.

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A test of conditional independence (Cochran’s Mantel– Haenszel chi-squared) gave χ21 = 0.314; p = 0.575, indicating that ischaemic stroke was conditionally independent of gender after adjusting for age. No significant association was observed therefore between ischaemic stroke and gender across the various age groups.

Discussion There is scanty information on the extent and nature of stroke in Kenyan public hospitals. This study was set to determine the clinico-epidemiological profile of stroke in Kenya’s leading public health tertiary institutions. Higher incidence of ischaemic stroke was observed, with hypertension, tobacco use and diabetes as the most common vascular risk factors. These findings agree with those previously reported from Nairobi and Aga Khan private hospitals, where ischaemic stroke was the most common stroke sub-type, and hypertension and diabetes were the leading risk factors.11,12 An important observation in this study was the distribution of stroke and the associated risk factors in both rural (MTRH) and urban (KNH) regions. This signifies a general shift in lifestyle and demographics, which often accompanies economies in transition, and it is perhaps best substantiated by cigarette smoking as the second most-common risk factor. Advancing age is the most important predictor of cardiovascular morbidity and mortality. The increased stroke cases observed with increasing age in this study attest to that.13 The stroke burden was higher in the 40–79-year age bracket, which represents middle-aged adults, whom as has been stated before, contribute to the 78% stroke burden in low- and middleincome countries.14 It has also been shown that high and increasing rates of stroke affect people at much younger ages in sub-Saharan Africa, resulting in greater numbers of years of potential life lost.15,16 Hence, aggressive efforts in improving cardiovascular health, promoting healthy aging, preventing cardiovascular risk factors and fast-tracking proven intervention strategies are necessary to halt and reverse the CVD burden.13,17 The post-stroke mortality rate in the current study was higher than the average national estimate of 12% for CVD deaths in hospitals, suggesting poor outcomes in post-stroke events. Similar high fatalities have been observed elsewhere in Africa, with high blood pressure predicting fatality in the short term, particularly with haemorrhagic stroke.18 In-patient stroke mortality rate of 19.3% has also been reported in the Congo, 33.3% in Tanzania, 43.2% in Ghana and 23.2% in Cameroon by day 30.18-21 Monthly stroke mortality rates in South Africa are similarly high, with 23% mortality rate reported at month 6.22,23 Therefore continuous monitoring of stroke incidence, outcomes and determinants should be enhanced to provide the much-needed information for guiding health service provision and allocation of resources. More work is required to assess the impact of actual care patterns on stroke prognosis over time, while prioritising the reduction of haemorrhagic stroke in Kenya and sub-Saharan Africa as a whole.24,25 Hypertension is the single most important risk factor and contributor to disability and premature death. In our study, the burden of hypertension was equally distributed across gender. This confirms previous findings from sub-Saharan Africa that show hypertension as the most powerful predictor

of stroke. The contribution of untreated hypertension to stroke burden has been demonstrated in Ethiopia and Tanzania,26,27 and reiterates the importance of understanding the primary drivers for effective prevention.15,28,29 Treatment of hypertension can reduce the risk of stroke by more than 40%. There is a need therefore to develop comprehensive risk-reduction strategies to mitigate the social and economic burden of stroke. Renewed emphasis on prevention and control of high blood pressure is necessary.16,30 Non-communicable diseases are beginning to feature on the public health agenda in developing countries.31,32 However, despite CVD being the second leading cause of morbidity and mortality in Kenya, its prevention and mitigation of risk factors are yet to receive the warranted attention necessary to protect and improve public health. There is a need to build scientific evidence that will assist in health planning, advocacy and policy making. The Kenyan county governments should deliberately invest in capacity building and harnessing of resources for CVD research and service provision. Supporting the development and sustenance of CVD surveillance systems will enhance knowledge generation and utilisation of evidence in fast-tracking prevention and control measures.

Conclusions Ischaemic stroke was the most prevalent stroke at 55.6%. Hypertension was the commonest risk factor, followed by smoking and diabetes, and the overall mortality rate was higher than that estimated by the WHO. Variation in stroke occurrence was observed based on gender and increasing age. There is a need to implement and/or scale up proven interventions geared towards preventing and controlling stroke and the associated risk factors, while being cognisant of the socio-demographic and cultural changes accompanying economies in transition. In addition, raising the population’s awareness of lifestyle factors likely to predispose them to stroke, and investing in care, management and surveillance systems may, with time, reduce the number of cases of stroke, initial stroke severity and improve public health. This research was supported by an NIH grant (D43 TW009333) from Fogarty International Centre for the ‘Cancer and Tobacco Control Training and Research across the Lifespan in Kenya’ project spearheaded by Prof Scot C Remick of Mary Babb Randolph Cancer Centre, West Virginia University. We thank the director of the Kenya Medical Research Institute, and the KNH and MTRH review boards for granting permission and providing an enabling environment to undertake this study. Many thanks to Doreen Njeri and Ayub Alembi of Nairobi, and Henry Mwangi and Meinard Shikhang’a of MTRH, and the KNH and MTRH medical fraternity for their continued support.

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10. Truelsen T, Heuschman PU, Bonita R, Ariundas G, Dalal P, Damasceno A, et al. Standard method for developing stroke registers in low-income

871–878. 21. Agyemang C1, Attah-Adjepong G, Owusu-Dabo E, De-Graft Aikins A, Addo J, Edusei AK, et al. Stroke in Ashanti region of Ghana. Ghana Med J 2012; 46(Suppl 2): 12–17. 22. De Villiers L, Badri M, Ferreira M, Bryer A. Stroke outcomes in a socio-economically disadvantaged urban community. S Afr Med J 2011; 101(5): 345–348. 23. Wasserman S, de Villiers L, Bryer A. Community-based care of stroke patients in a rural African setting. S Afr Med J 2009; 99(8): 579–583.

and middle-income countries: experiences from a feasibility study of a

24. Krishnamurthi RV, Moran AE, Forouzanfar MH, Bennett DA. Mensah

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11. Jowi JO, Mativo PM. Pathological sub-types, risk factors and outcome of stroke at the Nairobi Hospital, Kenya. East Afric Med J 2008; 85(12): 572–581. 12. Shavadia J, Yonga G, Mwanzi S, Jinah A, Moriasi A, Otieno H. Clinical characteristics and outcomes of atrial fibrillation and flutter at the Aga Khan University Hospital, Nairobi. Cardiovasc J Afr 2013; 24(2): 6. 13. Smith SM, Mensah GA. Population aging and implications for epidemic cardiovascular disease in sub-Saharan Africa. Ethn Dis 2003; 13(Suppl 2): S77–80. 14. Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor

9(Suppl 1): 101–106. 25. Collins TC, Petersen NJ, Menke TJ, Souchek J, Foster W, Ashton CM. Short-term, intermediate-term, and long-term mortality in patients hospitalized for stroke. J Clin Epidemiol 2003; 56(Suppl 1): 81–87. 26. Zenebe G, Alemayehu M, Asmera J. Characteristics and outcomes of stroke at Tikur Anbessa Teaching Hospital, Ethiopia. Ethiop Med J 2005; 43(4): 251–259. 27. Walker RW, Larty D, Kitange HM, Whiting D, Masuki G, Mtasiwa DM, et al. Stroke mortality in urban and rural Tanzania. Lancet 2000; 355(9216): 1684–1687.

M, Bennett DA, et al. Global Burden of Diseases, Injuries, and Risk

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Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet 2014; 383(9913): 245–254. 15. Kengne AP, Anderson CS. The neglected burden of stroke in subSaharan Africa. Int J Stroke 2006; 1(Suppl 4): 180–190. 16. Lemogoum D, Degaute JP, Bovet P. Stroke prevention, treatment and rehabilitation in sub-Saharan Africa. Am J Prev Med 2005; 29(Suppl 1): 95–101. 17. Sampson UK, Amuyunzu-Nyamongo M, Mensah GA. Health promotion and cardiovascular disease prevention in sub-Saharan Africa. Prog Cardiovasc Disc 2013; 56(Suppl 3): 344–355. 18. Nkoke C, Lekoubou A, Balti E, Kengne AP. Stroke mortality and its determinants in a resource-limited setting: A prospective cohort study in

Saharan Africa. Heart 2013; 99(Suppl 17): 1230–1235. 29. Dalal S, Beunza JJ, Volmink J, Adebamowo C, Bajunirwe F, Njelekea M, et al. Non-communicable diseases in sub-Saharan Africa: what we know now. Int J Epidemiol 2011; 40(Suppl 4): 885–901. 30. Mensah GA. Epidemiology of stroke and high blood pressure in Africa. Heart 2008; 94(Suppl 6): 697–705. 31. Mensah GA. A heart-healthy and “stroke-free” world through policy development, systems change, and environmental supports: a 2020 vision for sub-Saharan Africa. Ethn Dis 2003; 13(Suppl 2): S4–12. 32. Bennett DA, Krishnamurthi RV, Barker-Collo S, Forouzanfar MH, Naghavi M, Connor M, et al. The global burden of ischemic stroke: findings of the GBD 2010 study. Glob Heart 2014; 9(Suppl 1): 107–112.

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Prevalence, awareness, treatment and control of hypertension, diabetes and hypercholesterolaemia among adults in Dande municipality, Angola João M Pedro, Miguel Brito, Henrique Barros

Abstract Objectives: To estimate the prevalence, awareness, treatment and control of hypertension, diabetes and hypercholesterolaemia in an Angolan population aged 15 to 64 years and to determine relationships with sociodemographic, behavioural and anthropometric characteristics. Methods: A total of 2 354 individuals were assessed for behavioural, sociodemographic and physical characteristics in a cross-sectional, community-based survey. Post-stratification survey weights were applied to obtain prevalence levels. Adjusted odds ratios for each variable related to the conditions were calculated using logistic regression models. Results: Overall, the prevalence of hypertension was 18.0%, diabetes 9.2% and hypercholesterolaemia 4.0%. Among hypertensive individuals, the awareness rate was 48.5%; 15.8% were on treatment and 9.1% had their blood pressure controlled. Only 10.8% were aware they had diabetes, 4.5% were on treatment and 2.7% were controlled. The awareness level for hypercholesterolaemia was 4.2%, with 1.4% individuals on treatment and 1.4% controlled. Conclusions: The prevalence levels of hypertension and diabetes, which were higher than previous findings for the region, together with the observed low rates of awareness, treatment and control of all conditions studied, constitute an additional challenge to the regional health structures, which must rapidly adapt to the epidemiological shift occurring in this population. Keywords: epidemiology, hypertension, diabetes, hypercholesterolaemia, sub-Saharan Africa Submitted 25/11/16, accepted 7/11/17 Published online 14/12/17 Cardiovasc J Afr 2017; 29: 73–81

www.cvja.co.za

DOI: 10.5830/CVJA-2017-047

CISA, Centro de Investigação em Saúde de Angola, Caxito, Angola João M Pedro, BPharm, MEd, joao.almeidapedro@cisacaxito.org Miguel Brito, PhD

EPIUnit, Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal João M Pedro, BPharm, MEd Henrique Barros, MD, PhD

Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa, Lisboa, Portugal Miguel Brito, PhD

Faculdade de Medicina, Universidade do Porto, Porto, Portugal Henrique Barros, MD, PhD

Cardiovascular disease (CVD), a major cause of non-communicable diseases (NCDs), was responsible for 17.5 million deaths worldwide in 2012, most occurring in low- and middle-income countries (LMIC). In Africa, the frequency of NCDs is rising rapidly, reflecting the combined effect of population growth and ageing, as well as nutritional and epidemiological transitions.1 A large proportion of CVD is the result of exposure to modifiable risk factors (tobacco and alcohol consumption, unhealthy diet and physical inactivity), which influence metabolic pathways and ultimately result in obesity, hypertension, diabetes or hypercholesterolaemia.1,2 Together, these known adverse conditions explain approximately half of CVD cases, as demonstrated in the MONICA project and the INTERHEART study.3,4 Among the African population participating in the INTERHEART study, five risk factors (smoking, diabetes, hypertension, abdominal obesity and an elevated apolipoprotein B to apolipoprotein A-1 ratio) accounted for 89.2% of the population-attributable risk for the first myocardial infarction.5 The same study suggested that uncontrolled major risk factors have a larger impact on the burden of CVD in Africa than elsewhere in the world.5 If the current trends persist, the risk of dying from NCDs will increase in the African region. However, this rising risk could be reversed by reaching the proposed targets for six behavioural and physiological risk factors (tobacco and alcohol use, salt intake, obesity and increased blood pressure and glucose levels) out of the nine global targets proposed by the World Health Organisation (WHO) in the Global Action Plan for the Prevention and Control of NCD 2013–2020.6,7 To follow the achievement of those goals, there is a need for sound and updated epidemiological data from all regions of the world. The majority of published studies for the African region are conducted at hospital services, which does not allow one to detect risk factors, awareness rates and prevalence of such conditions in the general population.8-10 To provide core data on established risk factors for the major NCDs within the context of low-resource settings, WHO designed the STEPwise approach to Surveillance (STEPS).11 STEPS uses a modular structure with standardised questions and protocols, allowing adjustment of its application and appropriate comparisons across surveys.11 In Angola, infectious disease and maternal and child healthrelated problems remain the major causes of morbidity and mortality.12 However, an increased burden of NCDs has been observed, particularly CVD, which was responsible for 9% of adult deaths in 2013.13 Beyond general vital statistics, specific epidemiological information on CVD risk factors in Angola is based on only four local studies published after 2000: a survey of 667 adult students of Health Sciences in Lubango (prevalence of hypertension of 23.5%),14 a study conducted among 615 active employees of the University Agostinho Neto, Luanda

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(prevalence of hypertension 45.2% and hypercholesterolaemia 11.1%),15 1 464 participants surveyed in the Dande Health and Demographic Surveillance System (Dande-HDSS) catchment area (23% prevalence of hypertension),16 and a study of 421 subjects from a rural community of Angola (2.8% prevalence of diabetes).17 Building on the work carried out by Pires and colleagues,16 and based on the STEPS methodology,11 this study aimed to expand the sample population to the 15- to 24-year-old group, and to estimate the prevalence, awareness, treatment and control of hypertension, diabetes and hypercholesterolaemia, and its association with sociodemographic (gender, age, education and area of residence), behavioural (alcohol and tobacco consumption) and anthropometric [body mass index (BMI) and abdominal obesity] variables among 15- to 64-year-olds in the Dande-HDSS population.

Methods A cross-sectional, community-based survey was conducted from September 2013 to March 2014 in the catchment area of the Dande-HDSS, located in Dande municipality of Bengo Province, Angola.18 A representative gender- and age-stratified random sample list of 3 515 individuals, aged between 15 and 64 years, was drawn, as described previously.19 Of these, we were able to examine 2 484 (70.7%) individuals, 750 (21.3%) were unreachable and 281 (8.0%) refused to participate, thus approaching the predicted non-participation rate of 30%.19 For analysis, we excluded participants with missing anthropometric values (n = 14) and pregnant women (n =116) due to the fact that anthropometric parameters vary during pregnancy. Therefore 2 354 individuals (67.0%) were included in the final analysis. Information on age, completed years of school education, alcohol and tobacco consumption, and the previous measurement of any of the conditions under investigation, were collected through a structured interview conducted by trained interviewers, following a previously published protocol for data collection based on the WHO STEPS manual version 3.0.11,19 For this analysis, age was categorised into five 10-year age groups: 15 to 24, 25 to 34, 35 to 44, 45 to 54 and 55 to 64 years old. Education was categorised according to the number of completed years of schooling: none, one to four years, five to nine years, and 10 years or more. Area of residence was classified as rural or urban, as previously described.18 Alcohol consumption was defined as none if participants reported no alcohol consumption; occasional if participants reported drinking alcohol two or less days per week; and frequent if drinking any alcohol three or more days per week. Current tobacco smokers were defined as participants who reported smoking at least one cigarette per day. Previous measurements of blood pressure, and glucose or cholesterol levels in the last year were requested from all participants. In the case of a positive answer, participants were questioned about their awareness of a previous diagnosis of hypertension, diabetes or hypercholesterolaemia made by a healthcare worker. Any individual was considered under treatment if he/she indicated the use of a specific medication; a participant was considered controlled if they had a current normal value.

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Certified health professionals conducted all anthropometric and clinical measurements, as described previously.19 Anthropometric measurements were performed with individuals wearing light clothing and no footwear, and an overnight fast was requested of all participants. Body mass and height were measured using a digital scale SECA 803 (SECA United Kingdom, Birmingham, UK) and a portable stadiometer SECA 213 (SECA United Kingdom, Birmingham, UK). BMI was defined as the body mass (kg) divided by the square of the body height (m2), and further categorised according to WHO as underweight (< 18.5 kg/m2), normal (18.5 to 24.99 kg/m2), overweight (25.0 to 29.99 kg/m2) and obese (≥ 30 kg/m2).20 Waist and hip circumferences were measured using circumference tape SECA 203 (SECA United Kingdom, Birmingham, UK). The waist-to-hip ratio was calculated as the circumference of the waist (cm) to that of the hips (cm), and abdominal obesity was defined as waist-to-hip ratio ≥ 0.9 for men and ≥ 0.85 for women.21 Blood pressure was measured on the right arm with the automatic sphygmomanometer OMRON M6 Comfort (OMRON Healthcare Europe BV, Hoofddorp, The Netherlands), with the individual seated, and using an appropriate cuff size. Three readings were done at three-minute intervals. The mean value of the last two measurements was used to determine the blood pressure. Hypertension was defined as systolic blood pressure of ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/ or use of antihypertensive drugs during the previous two weeks.22 Blood sugar was measured using a blood glucose meter ACCU-CHEK Aviva (Roche Diagnostic, Indianapolis, IN, USA) with ACCU-CHEK Aviva glucose reactive strips (Roche Diagnostic, Indianapolis, IN, USA). The definition of diabetes followed WHO diagnostic criteria of 126 mg/dl (6.9 mmol/l) glucose in a fasting blood sample,23 and/or use of antidiabetic drugs during the previous two weeks. Total cholesterol in the blood was measured using a point-ofcare device ACCUTREND Plus (Roche Diagnostic, Indianapolis, IN, USA) with ACCUTREND cholesterol reactive strips (Roche Diagnostic, Indianapolis, IN, USA). Hypercholesterolaemia was defined according to WHO diagnostic criteria for STEPS, with cholesterol ≥ 240 mg/dl (6.2 mmol/l) in a fasting blood sample,2,11 and/or use of anticholesterol drugs during the previous two weeks. All procedures performed in this study were in accordance with the standards of the ethics committee of the Angolan Ministry of Health and with the 1964 Helsinki declaration and its later amendments. Written informed consent was obtained from all individual participants included in the study (in the case of those under 18 years old, from their parent or legal guardian). A copy of the signed consent form, as well as instructions regarding the fasting period and contact information, were delivered to each participant.

Statistical analysis Data were double entered into a PostgreSQL® database and SPSS® version 22 (IBM Corp, Armonk, NY, USA) was used for statistical analysis. Post-stratification survey weights were calculated using the known gender and categorical age distribution of the Dande-HDSS population,17 and these were used in all further calculations. Descriptive data are reported

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as absolute frequencies and percentages or means and standard deviations (SD), as appropriate. To facilitate comparisons with other studies, the prevalence of the three conditions under study was determined for three age groups: 15 to 64, 18 to 64 and 25 to 64 years. Logistic regression models were fitted to the categorical variable of age because of its known effect on hypertension, diabetes and hypercholesterolaemia. Gender-specific adjusted odds ratios (OR) were estimated for each variable (age, residence, education, BMI, abdominal obesity, tobacco and alcohol consumption) related to the conditions studied. A 95% confidence interval (95% CI) and a significance level of p < 0.05 were set for all applicable determinations.

Results The mean age of this population was 32.5 years (SD 13.6) with 63.0% (n = 1 482) women and the majority (81.0%) living in urban settings. Nearly 10% had never received any formal education, Table 1. Socio-demographic, anthropometric and behavioral characteristics of the population (Caxito, 2016) All participants (n = 2 354) % (95% CI)* 36.2 (34.3–38.1) 25.9 (24.2–27.7) 16.1 (14.7–17.6) 12.6 (11.3–14.0) 9.2 (8.1–10.4)

Age (years) (n = 2 354) 15–24 25–34 35–45 45–54 55–64 Residence (n = 2 354) Urban 81.0 (79.4–82.5) Rural 19.0 (17.5–20.6) Education (years completed) (n = 2 348) None 9.3 (8.2–10.5) 1–4 23.1 (21.5–24.9) 5–9 42.2 (40.2–44.2) > 10 25.4 (23.7–27.2) BMI class (kg/m2) (n = 2 354) 11.3 (10.1–12.6) Underweight (< 18.5) Normal (18.5–24.9) 66.1 (64.1–67.9) Overweight (25.0–29.9) 15.8 (14.4–17.3) 6.8 (5.9–7.9) Obese (≥ 30) Abdominal obesity (n = 2 354) No 75.1 (73.3–76.8) Yes 24.9 (23.2–26.7) Tobacco smoking (n = 2 342) Non-current 93.8 (92.7–94.7) Current 6.2 (5.3–7.3) Alcohol consumption (n = 2 335) No consumption 63.8 (61.8–65.7) Occasional (< 3 days per week) 18.8 (17.2–20.4) 17.5 (16.0–19.1) Frequent (≥ 3 days per week)

Female (n = 1 222) % (95% CI)* 30.1 (27.6–32.7) 25.4 (23.0–27.9) 18.7 (16.6–20.9) 15.3 (13.4–17.4) 10.6 (9.0–12.4)

Male (n = 1 132) % (95% CI)* 42.7 (39.9–45.6) 26.5 (24.0–29.1) 13.3 (11.5–15.4) 9.7 (8.1–11.6) 7.8 (6.3–9.5)

81.2 (78.9–83.3) 80.8 (78.4–83.0) 18.8 (16.7–21.1) 19.2 (17.0–21.6) 16.6 (14.6–18.8) 1.4 (0.9–2.3) 34.5 (31.9–37.2) 10.9 (9.2–12.8) 35.7 (33.1–38.5) 49.2 (46.3–52.1) 13.1 (11.4–15.2) 38.5 (35.7–41.4) 10.2 (8.7–12.1) 12.5 (10.7–14.5) 58.7 (55.9–61.4) 74.0 (71.4–76.5) 20.5 (18.4–22.9) 10.7 (9.0–12.6) 10.6 (9.0–12.4) 2.8 (2.0–4.0) 63.5 (60.8–66.2) 87.6 (85.6–89.4) 36.5 (33.8–39.2) 12.4 (10.6–14.4) 97.3 (96.2–98.1) 90.0 (88.1–91.6) 2.7 (1.9–3.8) 10.0 (8.4–11.9) 69.5 (66.9–72.0) 57.6 (54.7–60.4) 19.6 (17.5–21.9) 17.8 (15.7–20.2) 10.9 (9.2–12.7) 24.6 (22.2–27.2)

*Post-stratification weights used as described in the methods section.

with men having completed more school years. Overall, almost a quarter of participants had abdominal obesity (36.5% of women and 12.4% of men), 6.8% were obese (10.6% of women and 2.8% of men), 6.2% were smokers (2.7% of women and 10.0% of men) and approximately two-fifths consumed alcohol occasionally or frequently, with a higher proportion of frequent drinkers among men (24.6 vs 10.9%) (Table 1). The prevalence of hypertension in the general population was 18.0%, reaching 20.0% in those over 18 years of age, and 26.6% in those aged 25 to 64 years (Table 2). This prevalence was always higher among women than men, but with no statistically significant relationship (data not shown). The overall prevalence of diabetes among participants aged 15 to 64 years was 9.2%; the prevalence among those over 18 years old was 9.8%, and 11.9% in those aged over 25 years (Table 2). Men had a higher OR than women for diabetes of 1.4 (95% CI: 1.0–1.8, data not shown). Similar to that of hypertension and diabetes, the prevalence of hypercholesterolaemia was higher in the older age groups, with an estimated 5.5% in participants aged 25 to 64 years, and a lower prevalence of 4.0% in the overall population (Table 2). Women had an OR of 2.3 (95% CI: 1.3–4.0, data not show) for hypercholesterolaemia. Only five participants (0.2%; 95% CI: 0.1–0.4, data not shown) presented all three conditions, but 22.0% (95% CI: 18.4–26.2, data not shown) of hypertensive participants had an associated condition, as did 37.2% (95% CI: 31.1–43.7, data not shown) of participants with diabetes and 47.9% (95% CI: 36.7–59.3, data not shown) of those with hypercholesterolaemia. The most common associations were hypertension and diabetes, present in 71 individuals (3.0%; 95% CI: 2.4–3.7, data not shown). The prevalence of hypertension was higher in rural areas (26.9 vs 15.9% in urban areas) for both genders. Individuals with lower levels of education had a higher prevalence of hypertension, with women with no formal education presenting an OR for hypertension of 4.3 (Table 3). Hypertension was higher among the obese (34.9% of women and 48.5% of men) and individuals with abdominal obesity (32.5% of women and 45.7% of men), with a higher OR in men for both conditions (Table 3). Hypertension prevalence was also higher among current smokers (50.0% in women and 20.4% in men) and frequent alcohol drinkers (28.0% in women and 24.3% in men). Men presented a higher OR for hypertension than women, related to the consumption of alcohol (Table 3). Residents in urban areas presented a higher prevalence of diabetes, with a significantly higher OR for diabetes in men. Participants with lower education levels had a higher prevalence of diabetes, but without statistical significance (Table 4). With regard to anthropometric variables, there was a higher prevalence of diabetes among obese participants (17.1% in

Table 2. Prevalence of hypertension, diabetes and hypercholesterolaemia by gender and age (Caxito, 2016)

Hypertension, % (95% CI) Diabetes, % (95% CI) Hypercholesterolaemia, % (95% CI)

15–64 years (n = 2 354) 18.0 (16.5–19.6) 9.2 (8.1–10.4) 4.0 (3.2–5.0)

All Participants 18–64 years (n = 2 100) 20.0 (18.4–21.8) 9.8 (8.6–11.2) 4.4 (3.5–5.5)

25–64 years (n = 1 503) 26.6 (24.4–28.9) 11.9 (10.3–13.6) 5.5 (4.4–6.9)

15–64 years (n = 1 222) 20.0 (17.8–22.3) 8.9 (7.4–10.6) 5.6 (4.3–7.2)

Female 18–64 years (n = 1 116) 21.8 (19.5–24.3) 9.3 (7.8–11.2) 6.0 (4.7–7.8)

25–64 years (n = 854) 27.8 (24.9–30.8) 10.8 (8.9–13.0) 7.4 (5.7–9.5)

15–64 years (n = 1 132) 15.9 (13.9–18.1) 9.6 (8.0–11.4) 2.0 (1.2–3.2)

Male 18–64 years (n = 984) 18.1 (15.8–20.6) 10.4 (8.7–12.5) 2.4 (1.5–3.8)

25–64 years (n = 649) 25.1 (21.9–28.6) 13.5 (11.0–16.3) 2.9 (1.8–4.8)

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Table 3. Prevalence of hypertension and relation with other factors by gender (Caxito, 2016) All Participants(n = 2 354) Prevalence % (95% CI)* 18.0 (16.5–19.6)

Female (n = 1 222) Prevalence Adjusted ORa, b (95% CI)* % (95% CI)* 20.0 (17.8–22.3) –

Male (n = 1 132) Prevalence Adjusted ORa, b % (95% CI)* (95% CI)* 15.9 (13.9–18.1) –

Associated factor Total Age (years) 15–24 2.8 (1.9–4.2) 1.9 (0.9–3.9) 1 3.5 (2.2–5.6) 1 25–34 12.3 (9.9–15.2) 10.6 (7.7–14.6) 6.6 (2.8–15.4) 14.3 (10.8–18.8) 4.6 (2.6–8.2) 35–44 25.6 (21.5–72.0) 26.8 (21.4–32.9) 20.3 (8.9–46.5) 23.8 (17.7-31.2) 8.7 (4.7-16.0) 45–54 38.7 (33.4–44.4) 39.6 (32.8–39.6) 36.6 (16.0–83.8) 37.3 (28.8–46.6) 16.2 (8.7–30.0) 55–64 51.6 (45.0–58.2) 53.5 (44.9–61.9) 63.4 (27.1–147.9) 48.9 (38.7–59.1) 26.4 (13.9–50.0) Residence Urban 15.9 (14.3–17.6) 17.6 (15.3–20.1) – 14.0 (11.9–16.4) – Rural 26.9 (23.0–31.2) 30.0 (24.4–36.2) – 23.5 (18.4–29.6) – Education (years completed) None 45.4 (38.9–52.0) 45.5 (38.8–52.4) 4.3 (1.8–10.2) 46.7 (24.8–69.9) 2.0 (0.6–6.5) 1–4 24.9 (21.4–28.7) 23.3 (19.5–27.6) 2.4 (1.0–5.4) 29.8 (22.5–38.4) 0.8 (0.5–1.5) 5–9 12.7 (10.8–14.9) 10.3 (7.8–13.6) 2.2 (0.9–5.1) 14.5 (11.8–17.7) 0.9 (0.6–1.4) > 10 10.4 (8.2–13.1) 4.4 (2.1–8.8) 1 12.6 (9.8–16.1) 1 BMI class (kg/m2) 11.0 (7.8-15.3) 12.9 (8.1-19.0) 1 9.3 (5.5-15.2) 1 Underweight (< 18.5) Normal (18.5–24.9) 15.2 (13.5–17.1) 17.0 (14.4–19.9) 1.1 (0.6–2.1) 13.7 (11.5–16.2) 1.3 (0.7–2.5) Overweight (25.0–29.9) 25.8 (21.6–30.5) 23.9 (19.0–29.5) 1.2 (0.6–2.3) 29.2 (21.8–37.8) 2.2 (1.1–4.7) 37.3 (30.2–45.0) 34.9 (27.2–43.4) 2.0 (1.0–4.1) 48.5 (32.5–64.8) 5.1 (1.9–13.4) Obese (≥ 30) Abdominal obesity No 12.1 (10.6–13.7) 12.6 (10.5–15.2) 1 11.6 (9.7–13.7) 1 Yes 35.7 (31.9–39.6) 32.5 (28.3–37.0) 1.6 (1.2-2.3) 45.7 (37.7–54.0) 2.8 (1.8–4.3) Tobacco smoking Non-current 17.3 (15.8–18.9) 18.9 (16.7–21.2) – 15.5 (13.4–17.8) – Current 26.7 (20.2–34.4) 50.0 (34.1–65.9) – 20.4 (14.0–28.7) – Alcohol consumption No consumpion 14.2 (12.6–16.1) 18.1 (15.7–20.9) 1 9.1 (7.2–11.6) 1 23.5 (19.8–23.5) 21.4 (16.7–27.1) 0.9 (0.6–1.4) 26.0 (20.4–32.5) 2.5 (1.6–4.0) Occasional (< 3 days per week) 25.5 (21.5–25.5) 28.0 (21.1–36.2) 1.7 (1.1–2.7) 24.3 (19.6–29.7) 2.5 (1.7–3.9) Frequent (≥ 3 days per week) *Post-stratification weights used as described in the methods section; aAdjusted for age (categorical: 15–23, 25–34, 35–44, 45–54, and 55–64); bOnly variables with relations with statistical significance shown.

women and 24.2% in men) and those with abdominal obesity (8.8% in women and 24.3% in men). Men with obesity (2.4 vs underweight) and abdominal obesity (2.3 vs no abdominal obesity) presented higher ORs for diabetes than women (2.1 for obese vs underweight and 1.5 for abdominal obesity) (Table 4). For current smokers and occasional consumers of alcohol the prevalence of diabetes was higher, but with no significant relationship (Table 4). No significant relationships were found with education, residence, BMI, abdominal obesity, tobacco smoking and alcohol consumption; however, the prevalence of hypercholesterolaemia was higher among less educated individuals, the obese, smokers and frequent alcohol drinkers (Table 5). The majority of the population (61.5%; n = 1 460) reported previous measures of blood pressure, and nearly half (48.5%) of the hypertensive participants were aware of their condition. Only 32.5% of the aware hypertensive participants were on treatment and 57.7% of them had their blood pressure controlled. This represented only 9.1% of all hypertensive participants (Fig. 1). Only 7.3% (n = 172) of the population reported previous measurement of glycaemia, with a low awareness rate of 10.8% among participants with diabetes in this study. Of the aware participants, 41.7% were receiving treatment (4.5% of all hyperglycaemic participants) and 60.0% had a controlled blood sugar level (Fig. 1). Only 2.9% (n = 68) of participants reported previous measures of cholesterolaemia and only 4.2% of individuals with hypercholesterolaemia were aware of their condition (Fig. 1).

The hypertension awareness rate was higher among women (62.7%; 95% CI: 55.9–69.0) and older participants, without a difference regarding education level (Table 6). The diabetes awareness rate was higher among men (58.3%; 95% CI: 38.8– 75.5), older participants and those with higher education levels (Table 7). The hypercholesterolaemia awareness rate was higher among women (66.7%; 95% CI: 20.8–93.9), older age groups and higher education levels (Table 8). The treatment rate of all conditions was more prevalent in the older age groups and higher education levels, but the control rate was more frequent in younger participants. Among the individuals who were aware of any of the three conditions, the advice most often given by healthcare professionals to follow non-pharmacological approaches for the management of cardiovascular risk factors was a change in dietary habits, with a decrease in salt and fat intake, and increased fruit and vegetable intake (Table 9).

Discussion The prevalence of hypertension among participants in the range of 15 to 64 years old was 18.0%. This value rose to 26.6% among participants aged 25 to 64 years, which is slightly higher than those previously described for Angola over the last eight years,1415 particularly a study conducted in the same region in 2010,16 and the WHO age-standardised (25 to 64 years old) estimated hypertension prevalence for 2014 in Angola of 23.9% (95% CI:

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Table 4. Prevalence of diabetes and relation with other factors by gender (Caxito, 2016) All participants (n = 2 348) Prevalence % (95% CI)* 9.2 (8.1–10.4)

Female (n = 1 220) Prevalence Adjusted ORa,b (95% CI)* % (95% CI)* 8.9 (7.4–10.6) 1

Male (n = 1 128) Prevalence Adjusted ORa,b % (95% CI)* (95% CI)* 9.6 (8.0–11.4) 1.4 (1.0–1.8)

Associated factor Total Age (years) 15–24 4.4 (3.2–6.0) 4.4 (2.7–7.0) 1 4.4 (2.9–6.6) 1 25–34 5.6 (4.0–7.7) 3.2 (1.8–5.9) 0.8 (0.3–1.7) 8.0 (5.4–11.6) 1.9 (1.0–3.5) 35–44 13.2 (10.2–17.0) 12.7 (9.0–17.7) 3.3 (1.7–6.2) 13.9 (9.3–20.3) 3.4 (1.8–6.5) 45–54 19.3 (15.2–24.2) 17.6 (12.9–23.7) 4.8 (2.6–9.0) 22.2 (15.4–30.9) 6.2 (3.3–11.6) 55–64 17.2 (12.8–22.8) 15.5 (10.3–22.7) 4.0 (2.0–8.0) 20.7 (13.5–30.4) 5.6 (2.8–11.0) Residence Urban 9.8 (8.5–11.2) 9.2 (7.5–11.1) 1.6 (0.9–2.8) 10.4 (8.6–12.6) 2.6 (1.4–4.9) Rural 6.8 (4.8–9.5) 7.4 (4.7–11.6) 1 6.0 (3.6–10.1) 1 Education (years completed) None 11.5 (7.9–16.5) 11.9 (8.1-17.1) – 6.7 (1.2-29.8) – 1–4 11.7 (9.2–14.6) 10.0 (7.5-13.3) – 17.2 (11.5-24.9) – 5–9 8.3 (6.7–10.1) 7.1 (5.1–9.9) – 9.0 (6.9–11.6) – > 10 7.7 (5.9–10.2) 6.2 (3.4–11.1) – 8.3 (6.1–11.3) – BMI class (kg/m2) 7.5 (4.9–11.4) 4.0 (1.7–9.0) 1 10.7 (6.6–16.9) 1 Underweight (< 18.5) Normal (18.5–24.9) 7.8 (6.6–9.2) 7.7 (5.9–9.9) 2.0 (0.7–5.1) 7.9 (6.3–9.9) 0.7 (0.4–1.2) Overweight (25.0–29.9) 12.4 (9.4–16.1) 10.4 (7.2–14.7) 2.4 (0.9–6.5) 16.5 (11.0–24.2) 1.1 (0.5–2.3) 18.6 (13.4–25.4) 17.1 (11.5–24.5) 3.9 (1.4–11.1) 24.2 (12.8–41.0) 1.7 (0.6–4.5) Obese (≥ 30) Abdominal obesity No 7.0 (5.9–8.3) 3.5 (2.3–5.2) 1 7.5 (6.0–9.3) 1 Yes 15.9 (13.1–19.0) 8.8 (6.4–12.2) 1.5 (1.0–2.3) 24.3 (17.9–32.0) 2.3 (1.4–3.8) Tobacco smoking Non-current 8.8 (7.6–10.0) 8.6 (7.2–10.4) – 8.9 (7.3–10.8) – Current 14.4 (9.6–21.0) 17.6 (8.3–33.5) – 13.3 (8.2–20.8) – Alcohol consumption No consumption 8.9 (7.6–10.5) 8.7 (6.9–10.8) – 9.2 (7.2–11.7) – 10.5 (8.0–13.7) 10.1 (6.9–14.6) – 11.0 (7.4–16.1) – Occasional (< 3 days per week) 8.8 (6.4–12.0) 8.3 (4.7–14.3) – 9.1 (6.2–13.0) – Frequent (≥ 3 days per week) *Post-stratification weights used as described in the methods section; aAdjusted for age (categorical: 15–23, 25–34, 35–44, 45–54, and 55–64); bOnly variables with relations with statistical significance shown.

16.3–31.1).1 More recently, a cross-sectional study conducted in Uganda, South Africa, Tanzania and Nigeria encountered an overall age-standardised prevalence of hypertension of 25.9%.24 The estimated 9.2% prevalence of diabetes (9.8% in urban and 6.8% in rural areas) was higher than previous reports from Angola of 5.7% among an urban population (aged 20 to 72 years)

in 2010,15 and 2.8% for a rural community (aged 30 to 69 years) in 2009.17 The value of 9.8% estimated in individuals older than 18 years is in the middle range of prevalence levels encountered in STEPS surveys, with values from 3.0% in Benin to 22.5% in Niger.25,26 This value also falls within the confidence intervals of the WHO estimate of 12.1% (95% CI: 5.6–18.9) for increased

Hypertensive (n = 431)

Diabetic (n = 223)

Hypercholesterolaemic (n = 71)

Aware (n = 209) 48.5% (95% CI 43.8–53.2)

Aware (n = 24) 10.8% (95% CI 7.3–15.5)

Aware (n = 3) 4.2% (95% CI 1.5–11.7)

Treated (n = 68) 32.5% (95% CI 26.6–39.2) among the aware 15.8% (95% CI12.6–19.5) among the hypertensive

Treated (n = 10) 41.7% (95% CI 24.5–61.2) among the aware 4.5% (95% CI 2.5–8.1) among the diabetic

Treated (n = 1) 33.3% (95% CI 6.1–7.9) among the aware 1.4% (95% CI 0.3–7.6) among the hypercholesterolaemic

Controlled (n = 39) 57.7% (95% CI 46.2–68.6) among the treated 9.1% (95% CI 6.7–12.1) among the hypertensive

Controlled (n = 6) 60.0% (95% CI 31.3–83.2) among the treated 2.7% (95% CI 1.2–5.7) among the diabetic

Controlled (n = 1) 100% (95% CI 20.7–100) among the treated 1.4% (95% CI 0.3–7.6) among the hypercholesterolaemic

Post-stratification weights used as described in the methods section.

Fig. 1. F requencies, awareness, treatment and control of hypertension, diabetes and hypercholesterolaemia.

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

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Table 5. Prevalence of hypercholesterolaemia and relation with other factors by gender (Caxito, 2016) All participants (n = 1 781) Prevalence % (95% CI)* 4.0 (3.2–5.0)

Female (n = 978) Prevalence Adjusted ORa,b (95% CI)* % (95% CI)* 5.6 (4.3–7.2) 2.3 (1.3–4.0)

Male (n = 803) Prevalence Adjusted ORa,b % (95% CI)* (95% CI)* 2.0 (1.2–3.2) 1

Associated factor Total Age (years) 15–24 0.7 (0.3–1.8) 1.1 (0.4–3.2) 1 0.3 (0.1–1.9) 1 25–34 2.5 (1.4–4.3) 2.8 (1.4–5.7) 2.6 (0.6–10.8) 2.5 (1.1–5.3) 5.0 (0.8–31.6) 35–44 3.6 (2.0–6.4) 5.4 (2.9–9.6) 5.2 (1.4–20.0) 0.9 (0.2–4.7) 2.1 (0.2–24.4) 45–54 9.4 (6.3–13.7) 10.8 (6.9–16.7) 11.9 (3.30–42.7) 5.7 (2.5–12.8) 13.7 (2.1–88.1) 55–64 11.4 (7.6–16.8) 15.4 (10.0–23.0) 17.2 (4.8–61.9) 4.5 (1.6–12.5) 9.0 (1.2–69.5) Residence Urban 3.9 (3.0–5.0) 5.6 (4.2–7.4) – 1.8 (1.0–3.2) – Rural 4.2 (2.5–7.0) 5.3 (2.8–9.8) – 3.5 (1.5–7.9) – Education (years completed) None 10.8 (7.0–16.2) 10.7 (6.9–16.3) – 11.1 (2.0–43.5) – 1–4 5.7 (3.9–8.3) 6.4 (4.3–9.5) – 2.5 (0.7–8.8) – 5–9 2.6 (1.7–4.1) 3.3 (1.9–5.9) – 2.0 (1.0–3.9) – >10 2.0 (1.0–3.7) 2.3 (0.8–6.5) – 1.9 (0.9–4.0) – BMI class (kg/m2) 2.3 (0.9–5.7) 3.2 (1.1–9.1) – 1.2 (0.2–6.5) – Underweight (<18.5) Normal (18.5–24.9) 3.5 (2.6–4.7) 5.1 (3.6–7.3) – 1.9 (1.1–3.3) – Overweight (25.0–29.9) 5.3 (3.3–8.3) 6.0 (3.6–10.1) – 3.8 (1.5–9.3) – 6.7 (3.5–12.2) 8.6 (4.6–15.5) – –a – Obese (≥ 30) Abdominal obesity No 2.4 (1.7–3.4) 3.5 (2.3–5.2) – 1.5 (0.8–2.7) – Yes 8.1 (6.0–10.9) 8.8 (6.4–12.2) – 5.9 (2.9–11.6) – Tobacco smoking Non-current 3.7 (2.9–4.8) 5.1 (3.9–6.7) – 2.0 (1.2–3.3) – Current 6.4 (3.1–12.6) 17.9 (7.9–35.6) – 2.5 (0.7–8.6) – Alcohol consumption No consumption 4.3 (3.2–5.6) 5.7 (4.2–7.7) – 2.2 (1.2–4.1) – 2.7 (1.4–5.0) 4.6 (2.5–8.6) – –c – Occasional (< 3 days per week) 3.9 (2.2–6.7) 5.6 (2.6–11.6) – 2.5 (1.1–5.7) – Frequent (≥ 3 days per week) *Post-stratification weights used as described in the methods section; aAdjusted for age (categorical: 15–23, 25–34, 35–44, 45–54, and 55–64); bOnly variables with relations with statistical significance shown; cNo cases in this category.

blood glucose levels in those over 18 years in Angola for 2014.1 This rise in diabetes is aligned with the global tendency for this disease, which has increased faster in LMIC than in highincome countries since 1980.27 Since the end of the Angolan

civil war in 2002, the population has been increasing and ageing. This, together with changes in food habits and the urbanisation process, may have led to the increased prevalence of diabetes in this region.

Table 6. Awareness, treatment and control rates of hypertension by gender (Caxito, 2016) Awareness

Treatment

Control

All (n = 209) Female (n = 131) Male (n = 78)

All (n = 68) Female (n = 41) Male (n = 27)

All (n = 39) Female (n = 25) Male (n = 14)

% (95% CI)

none

21.5 (16.5–27.6)

34.4 (26.8–42.8)

17.6 (10.4–28.4)

26.8 (15.7–41.9)

3.7 (0.7–18.3)

10.3 (4.1–23.6)

16.0 (6.4–34.7)

1–4

31.1 (25.2–37.7)

40.5 (32.4–49.0)

15.4 (9.0–25.0)

27.9 (18.7–39.6)

39.0 (25.7–54.3)

11.1 (3.9–28.1)

25.6 (14.6–41.1)

40.0 (23.4–59.3)

5–9

28.2 (22.6–34.7)

22.1 (15.9–30.0)

38.5 (28.4–49.6)

29.4 (19.9–41.1)

26.8 (15.7–41.9)

33.3 (18.6–52.2)

33.3 (20.6–49.0)

36.0 (20.2–55.5)

28.6 (11.7–54.6)

> 10

19.1 (14.4–25.0)

3.1 (1.2–7.6)

46.2 (35.5–57.1)

25.0 (16.2–36.4)

7.3 (2.5–19.4)

51.9 (34.0–69.3)

30.8 (18.6–46.4)

8.0 (2.2–25.0)

71.4 (45.4–88.3)

15–24

2.9 (1.3–6.1)

0.8 (0.1–4.2)

6.4 (2.8–14.1)

1.5 (0.3–7.9)

2.4 (0.4–12.6)

2.6 (0.5–13.2)

4.0 (0.7–19.5)

25–34

16.7 (12.3–22.4)

12.2 (7.7–18.9)

24.4 (16.2–34.9)

26.5 (17.4–38.0)

24.4 (13.8–39.3)

29.6 (15.9–48.5)

33.3 (20.6–49.0)

32.0 (17.2–51.6)

35.7 (16.3–61.2)

35–44

19.6 (14.8–25.5)

19.1 (13.3–26.7)

20.5 (13.0–30.8)

20.6 (12.7–31.6)

19.5 (10.2–34.0)

22.2 ( 10.6–40.8)

25.6 (14.6–41.1)

24.0 (11.5–43.4)

28.6 (11.7–54.6)

45–54

31.1 (25.2–37.7)

37.4 (29.6–45.9)

20.5 (13.0–30.8)

23.5 (15.0–34.9)

26.8 (15.7–41.9)

18.5 (8.2–36.7)

17.9 (9.0–32.7)

20.0 (8.9–39.1)

14.3 (4.0–39.9)

55–64

29.7 (23.9–36.2)

30.5 (23.3–38.9)

19.4 (19.4–39.0)

27.9 (18.7–39.6)

26.8 (15.7–41.9)

29.6 (15.9–48.5)

20.5 (10.8–35.5)

20.0 (8.9–39.1)

21.4 (7.6–47.6)

Education (years completed)

Age (years)

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Table 7. Awareness, treatment and control rates of diabetes by gender (Caxito, 2016) Awareness

Treatment

Table 8. Awareness, treatment and control rates of hypercholesterolemia by gender (Caxito, 2016)

Control

Awareness

All Female Male All Female Male All Female Male (n = 24)(n = 10)(n = 14)(n = 10) (n = 6) (n = 4) (n = 6) (n = 5) (n = 1) % % % % % % % % % Education (years completed)

Treatment

Control

All Female Male All Female Male All Female Male (n = 3) (n = 2) (n = 1) (n = 1) (n = 1) (n = 0) (n = 1) (n = 1) (n = 0) % % % % % % % % % Education (years completed)

None

12.5

30.0

0.0

20.0

33.3

16.7

20.0

None

1–4

4.2

10.0

0.0

10.0

16.7

20.0

1–4

33.3

50.0

5–9

33.3

30.0

35.7

50.0

33.3

75.0

50.0

40.0

100.0

5–9

> 10

50.0

30.0

64.3

20.0

16.7

25.5

16.7

20.0

> 10

66.6

50.0

100.0

Age (years)

15–24

8.3

20.0

0.0

20.0

33.3

40.0

15–24

25–34

12.5

10.0

14.3

10.0

16.7

20.0

25–34

35–44

20.8

10.0

28.6

20.0

16.7

25.5

16.7

20.0

35–44

33.3

50.0

100.0

45–54

25.0

20.0

28.6

10.0

16.7

45–54

66.6

50.0

100.0

55–64

33.3

40.0

28.6

40.0

16.7

75.0

33.3

20.0

100.0

55–64

The prevalence of hypercholesterolaemia (5.3% among participants 25 and 64 years old) in this study was lower than that found in a previous study in Luanda among an older urban population.15 However, this value falls within a wide range of values from several STEPS surveys measuring the prevalence of total cholesterol, from 2.1% in Mozambique to 26.0% in Tanzania.25,26 This prevalence may also be tied to the ageing population and changes in dietary habits that most African countries are currently facing.28 There is a lack of solid knowledge regarding the prevalence levels of hypercholesterolaemia in Africa, mainly owing to the difficulties in determining values of blood cholesterol in African communities because of the high cost of laboratory tests. This situation presents a challenge when comparing research results. As described in other studies worldwide, the clustering of risk factors helps to explain the known impacts of age, education and obesity on the occurrence of hypertension, diabetes and hypercholesterolaemia. The prevalence of these three conditions was higher among individuals with less education, and increased with age and BMI. Obesity represents a major concern as a risk factor for CVD and NCDs in general, and is connected with the current nutritional transition in Africa, with a shift in the composition and structure of diets traditionally low in fat and high in unrefined carbohydrates toward higher intakes of refined carbohydrates, added sugars, fats and animal-source foods.28 This shift may have had an impact on the rise in incidence of diabetes over the past decades, revealed in recent literature reviews,29-31 as well as a WHO estimation of the rise in median prevalence of elevated total cholesterol for this region.2 Similar to this nutritional transition, the process of urbanisation underway in the region must be taken into consideration for future interventions. Living in an urban area has been associated with a two-fold increase in the prevalence of diabetes among this population, as described in other studies.1,29-31 Information regarding the awareness, treatment and control rates for the three conditions investigated is scarce for the African continent, except for hypertension; there are also some available data with regard to diabetes. Our findings for awareness of hypertension were higher than those calculated in 2010 for Africa, with an estimated 33.7% pooled awareness rate.32 Current values for awareness, treatment and control of hypertension are

higher than in 2011 in the same population; results for awareness were 21.6% (95% CI: 17.0–26.9) in 2011 and 48.5% in the present study. Values for participants who were aware of their condition and on pharmacological treatment (13.9%, 95% CI: 5.9–29.1) increased to 32.5%; approximately one-third of participants were controlled in 2011 and more than half were controlled in our study. This may have resulted from the positive effect of identification of hypertensive individuals and medical follow up after the first survey in 2011. Nonetheless, the levels of awareness about hypertensive status are still low, a situation common in Africa,33 with levels much lower than those in North America and Europe.34 A similar framework exists for diabetes awareness in Africa, with fewer than 50% of participants in one study aware of their condition.29 No data were found for awareness of total cholesterol levels. The lack of primary healthcare facilities in this region, especially in rural areas, makes the low levels of previous measurements plausible. Furthermore, the current training of Angolan health professionals and the availability of clinical equipment are still focused on infectious diseases, not considering CVD a priority. Therefore initiatives promoting the awareness of CVD are lacking in the region, and proper monitoring of patients’ conditions does not occur. Moreover, the information available to the population is not enough to convince patients to take lifelong medication in order to treat a condition, which is usually asymptomatic. Only

Table 9. Non-pharmacological advice by health professionals to aware participants (Caxito, 2016) Hypertension (n = 209) Advice

% (95% CI)

Diabetes (n = 24)

Hypercholesterolaemia (n = 3)

% (95% CI)* % (95% CI)*

Reduce salt in your diet

78.5 (72.4–83.5)

100.0

Reduce fat in your diet

61.7 (55.0–68.0)

91.7

66.7

Eat at least five servings of fruit and/ or vegetables each day

58.4 (51.6–64.8)

70.8

66.7

Reduce or stop alchool consumption

51.2 (44.5–57.9)

83.3

33.3

Start or do more physical activity

34.4 (28.3–41.1)

75.0

66.7

Quit using tobacco or don’t start

31.1 (25.2–37.7)

45.8

Maintain a healthy body weight or lose weight

30.1 (24.3-36.7)

75.0

66.7

*Due to the small sample size, the 95% CI was not determined.

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one-third of participants with any of these conditions had access to treatment, which demonstrates the inadequacy of the region’s health system to help patients manage risk factors. Economic difficulties and the lack of drugs to address CVD may also help explain the low levels of treatment and control found. Nevertheless, a positive note should be made as to the number of patients who had controlled levels of blood pressure, blood sugar and cholesterolaemia in this specific population. Considering that they were younger and better educated, they could have had easier access to drugs and health facilities. Also noteworthy, in the absence of access to drugs, physicians’ advice in most cases is to adopt non-pharmacological approaches to reducing modifiable risk factors, mainly associated with diet.

Strengths and limitations of the study Our study findings should be interpreted cautiously because the Dande-HDSS was developed as a district-level surveillance system in an urban and rural setting and is therefore not representative of the demographic structure of the country. In addition, age groups over 65 years old (known for higher rates of the conditions studied) were not considered owing to their low representation in the general structure of the population (3.6% of the Dande-HDSS population),18 which is a common practice for surveys conducted in sub-Saharan Africa. Internal migration and the geographical isolation of some hamlets within the Dande-HDSS, together with the fact that working individuals were unavailable during the daytime,17 were reflected in the sampling definition, with a 30% non-participation rate. The distribution of non-respondents was uneven, with a higher proportion of younger people and men (data not shown). This may have caused instability in the estimates in some strata. Participants were requested not to eat anything eight hours before participating in the study; however, it was difficult to measure adherence to this request, which adds uncertainty to the measures of blood glucose and cholesterol. We used dry chemistry devices to measure glycaemia and cholesterolaemia, but owing to high temperatures and humidity during field surveys, data collection was not possible in some cases, causing a higher number of missing data than expected. Due to the many variables covered in the survey and to avoid drop-out of participants in future rounds, additional questions relating to awareness, pharmacological treatments and non-pharmacological approaches were conducted in a more detailed form in individual follow-up visitations. These are not dealt with extensively in this article. Also the low number of aware individuals and consequently under-treatment limited the statistical analysis of data regarding these aspects. It is therefore not possible to extrapolate our findings to a larger population at country level. However, this study reveals new data about the prevalence, awareness, treatment and control of diabetes and hypercholesterolaemia, and it is the most comprehensive community-based study conducted to date in Angola.

for future interventions should be aimed at younger populations in which the prevalence of major risk factors is still low, so as to make a difference in the long term. In all LMIC, NCDs are the leading cause of death and disability, killing nearly eight million people under 60 years old in 2013.25 Over the past decade, the focus of assistance in these countries has primarily addressed maternal and child health and infectious diseases. Without setting these aside, there is an opportunity to use structures that are already in place, to maximise resources. The international community should consider expanding the mandate of current programmes to include outcome-orientated measures for improving general health and lifestyles. Many of the methods of NCD prevention, management and treatment, which are responsible for the decline in some of these diseases in high-income countries, are inexpensive but are not widely used in LMIC. These methods could be implemented through established global health strategies, such as increased use of low-cost drugs,35 and improved access to NCD services for young adults and people with low educational attainment.36

Conclusions This report reinforces the available data for the main CVD risk factors in Angola and helps to build the basis for further prospective studies, especially among the younger group in this region. We provide the first evidence that hypertension prevalence is rising, together with diabetes, when compared with previous studies in the region. Despite being a growing economy, Angola’s primary health system may not be currently able to provide an adequate answer to the changing health needs of this population. A gradual shift from infectious diseases to NCDs is underway and this puts additional stress on the reinforcement of primary care intervention in the region. The authors thank the clinical staff of Bengo General Hospital for establishing and supporting the follow-up consultation. We thank all Dande-HDSS staff for their continuing support during fieldwork, namely Joana Paz and Ana Oliveira for their field supervision roles, Eduardo Saraiva for data entry supervision and database management, Edite Rosário for the training of field workers and assistance in data-collection procedures. Most importantly, we thank the local administration and all of the individuals who agreed to take part in the study. This study was funded by the promoters of the CISA as follows: Camões, Institute of Cooperation and Language, Portugal; Calouste Gulbenkian Foundation, Portugal; Government of Bengo Province, Angola; and the Angolan Ministry of Health. Also, the Eduardo dos Santos Foundation, Angola and the Institute of Public Health of the University of Porto, Portugal (ref UID/DTP/04750/2013) funded this study. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Assessment of left atrial function in patients with type 2 diabetes mellitus with a disease duration of six months Oyku Gulmez, Hulya Parildar, Ozlem Cigerli, Nilgun Demirağ

Abstract Introduction: Changes in left atrial (LA) size and function are associated with adverse clinical events. Recently, duration of diabetes mellitus (DM2) has been found to be positively associated with increased LA volume and impaired LA function. This study was performed, using two-dimensional echocardiograpy, to evaluate the changes in LA volume and function in patients with DM2 with a disease duration of six months, and to assess the parameters that affect LA volume and function. Methods: Fifty-six patients (28 male, age: 52.6 ± 6.5 years) with DM2 and 56 controls (24 male; age: 50.1 ± 7.0 years) were enrolled in the study. Each subject underwent conventional twodimensional echocardiography to assess LA volume (indexed maximal LA volume: Vmax, pre-atrial contraction volume: Volp, minimal LA volume: Vmin) and LA function [passive emptying volume – passive emptying fraction (PEV – PEF), active emptying volume – active emptying fraction (AEV – AEF), total emptying volume – total emptying fraction (TEV – TEF)]. Results: LA diameter, indexed Vmax, Volp, Vmin, AEV and TEV were found to be significantly higher in the DM2 group compared with the controls (p < 0.05). Indexed Vmax, Volp and Vmin were significantly correlated with HbA1c level, body mass index (BMI), high-sensitivity C-reactive protein and uric acid levels, mitral A wave, E/E′ ratio and A′ wave. According to multivariate analysis, age and BMI had a statistically significant effect on LA volume. Conclusion: Impaired LA function may be present in patients with newly diagnosed DM2. BMI and increasing age caused LA enlargement and LA volumes that were independent of the effects of hypertension and DM2. Keywords: left atrial volume, left atrial function, diabetes mellitus, transthoracic echocardiography Submitted 25/5/17, accepted 7/11/17 Published online 30/11/17 Cardiovasc J Afr 2017; 29: 82–87

www.cvja.co.za

DOI: 10.5830/CVJA-2017-048

Department of Cardiology, Baskent University, Istanbul Medical and Research Centre, Istanbul, Turkey Oyku Gulmez, MD, gulmezoyku@yahoo.com

Department of Family Medicine, Baskent University, Istanbul Medical and Research Centre, Istanbul, Turkey Hulya Parildar, MD Ozlem Cigerli, MD

Department of Endocrinoloy and Metabolism, Baskent University, Istanbul Medical and Research Centre, Istanbul, Turkey Nilgun Demirağ, MD

The prevalence of type 2 diabetes mellitus (DM2) increases over a person’s lifetime due to aging, the epidemic of obesity and sedentary lifestyles. Moreover, the incidence of cardiovascular disease (CVD), and morbidity and mortality due to CVD increase in patients with DM2.1,2 Early changes in left ventricular (LV) function in patients with DM2 have been extensively investigated, however, assessment of left atrial (LA) function is of growing interest.2-8 The left atrium serves as a reservoir during ventricular systole, as a conduit during early diastole, and as an active contractile chamber that augments LV filling in late diastole. Total emptying volume (TEV) describes LA reservoir function, passive emptying volume (PEV) describes LA conduit function, and active emptying volume (AEV) describes LA booster pump function.7,9 Two-dimentional (2D) echocardiography is a non-invasive, easy-to-use and accessible method to evaluate LA volume and function. Several studies have shown that changes in LA size and function were associated with adverse clinical events such as atrial fibrillation, stroke, diastolic dysfunction and LV failure.10-13 Moreover, studies that evaluated LA volume and function in patients with DM2 showed that LA volume and function were independent predictors of cardiovascular events.4-8 Recently, the duration of DM2 disease has been found to be strongly and positively associated with larger LA volume and impaired LA function measured by echocardiography.14 The aims of our study were to evaluate the change in LA volume and function, and assess the parameters that affect LA volume and function in patients with DM2 with a disease duration of six months, using 2D echocardiograpy.

Methods Fifty-six patients (28 male, mean age 52.6 ± 6.5 years) with DM2, according to the American Diabetes Association (ADA) 2013 criteria, with a disease duration of a maximum of six months (recruited from the endocrinology and metabolism departments) and 56 age-matched healthy volunteers (24 male, mean age 50.1 ± 7.0 years) (recruited from the cardiology department) were included in the study.15 A detailed medical history, physical examination and 12-lead electrocardiography were obtained from the study population. All subjects underwent a treadmill exercise test according to the Bruce protocol, or myocardial perfusion scintigrapyh to rule out latent ischaemia. Patients with evidence of ischaemia, arrhythmia on an electrocardiogram (ECG), LV dysfunction with an ejection fraction (EF) of < 50%, significant valvular disease, history of coronary artery disease, suspicion of secondary hypertension, uncontrolled hypertension, thyroid disorder, pulmonary disease and renal failure (defined as decreased glomerular filtration rate of < 60 ml/min/1.73 m2 for at least three months), type 1 DM, electrolyte imbalance, and technically

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insufficient echocardiographic and electrocardiographic data were excluded. The local ethics committee approved the study. All participants provided written, informed consent prior to participation in the study. Transthoracic echocardiographic examinations were performed using a commercially available cardiac ultrasound scanner (Acuson Sequoia 512 system with 2.5–4.0 MHz transducer, Siemens Mountain View, California, USA) in the left lateral position, according to the criteria of the American Society of Echocardiography.16 During echocardiography a continuous one-lead ECG recording was done. Left ventricular end-diastolic and end-systolic volumes were determined in the apical view, and stroke volume and EF were measured using the modified Simpson’s equation.16 LV mass (LVM) was calculated with the Devereux formula as: LVM (g) = 1.04 [(LVID + PWT + IVST)³ – LVID³] – 14 Where LVID = LV internal dimension; PWT = posterior wall thickness; IVST = interventricular septum thickness. LVM was indexed to body surface area (BSA) by dividing LVM by BSA. Peak early diastolic (E) velocity, atrial contraction (A) velocity and E-wave deceleration time (DT) were measured from the transmitral pulsed-wave Doppler spectra, and the E/A ratio was calculated. Pulsed-wave tissue Doppler imaging (TDI) was performed in an apical four-chamber window with a sample volume of 5 mm and the monitor sweep speed was set at 100 mm/s to optimise the spectral display of myocardial velocities. All Doppler spectral velocities were averaged over three consecutive beats. The average pulsed-wave TDI-derived early (E′) diastolic myocardial velocity was obtained from the lateral and septal sides of the mitral annulus. Then the E/E′ ratio was calculated to provide an estimation of LV filling pressures.17 The TDI-derived late-diastolic wave (A′) was obtained from the mitral lateral annulus. LA diameter was measured from the parasternal long axis with M-mode echocardiography. LA volumes were traced and calculated by means of the modified Simpson’s method from apical four- and two-chamber views, according to the guidelines of the American Society of Echocardiography and European Association of Cardiovascular Imaging.16 LA volumes were measured as: (1) just before the mitral valve opening, at end-systole (maximal LA volume or Vmax); (2) at the onset of the P wave on electrocardiography (pre-atrial contraction volume or Volp); and (3) at mitral valve closure, at end-diastole (minimal LA volume or Vmin). From these, the following measurements were calculated: • LA passive emptying volume (PEV) = Vmax – Volp • LA passive emptying fraction (PEF) = PEV/Vmax × 100 • LA active emptying volume (AEV) = Volp – Vmin • LA active emptying fraction (AEF) = AEV/Volp × 100 • LA total emptying volume (TEV) = Vmax – Vmin • LA total emptying fraction (TEF) = TEV/Vmax × 100. Left atrial volumes were indexed to BSA in all patients.18

Statistical analysis Statistical analyses were performed with the MedCalc Statistical Software version 12.7.7 (MedCal Software bvbv, Ostend, Belgium; 2013). All continuous variables are expressed as mean

± standard deviation and median (minimum–maximum). All categorical variables are defined as frequency and percentage. All continuous variables were checked with the Kolmogorov– Smirnov normality test to show their distributions. Continuous variables with normal distributions were compared using the unpaired Student’s t-test, while continuous variables with abnormal distributions were compared using the Mann–Whitney U-test. For categorical variables, the chi-squared test was used. Pearson or Spearman’s correlation analyses were used to determine the associations between LA volume and function, and various laboratory parameters and 2D echocardiographic diastolic parameters. Multivariate evaluations were performed using linear regression analysis. The confounders that were found to have a statistically significant impact on the dependent variable on univariate analysis were described as the independent variables in a multivariate linear regression analysis model. The p-values less than 0.05 were considered significant. Sample size justification: according to the article ‘Effects of diabetes mellitus on left atrial volume and functions in normotensive patients without symptomatic cardiovascular disease’,8 the Vmax value for DM2 patients was 40.9 ± 11.9 ml, and for the control group, 34.6 ± 9.3 ml. The mean difference was assumed as 6.3 ml; the standard deviation of the DM2 group was 11.9 ml and of the control group, 9.3 ml. With the assumption of 5% of type 1 error (a) and 80% power (1b), the sample size was calculated at 46 patients for each group. With a 20% drop-out rate, a minimum of 56 patients (112 in total) would have to be enrolled in the study.

Results The study population consisted of 112 subjects (52 male, mean age 51.7 ± 7.0 years). Patient characteristics, analysed according to the two groups, are shown in Table 1. The groups were similar regarding age and gender. In the DM2 group, 44 (78.6%) patients were hypertensive and 33 (58.9%) were receiving insulin and oral antidiabetic agents. Patients in the DM2 group were also taking more medications, such as acetylsalicylic acid, angiotensin converting enzyme inhibitors, beta-blockers and statins than the control group. Body mass index (BMI) and levels of triglycerides (TG), highsensitivity C-reactive protein (hsCRP), uric acid, fasting glucose and HbA1c were significantly higher in the DM2 group compared with the control group (p < 0.05). There were no significant differences regarding total cholesterol and low- (LDL) and highdensity lipoprotein (HDL) cholesterol levels between the groups (p > 0.05) (Table 1). Table 2 reports the results of 2D echocardiographic parameters reflecting diastolic function with preserved systolic function. Twelve (21.4%) subjects in the control group and 29 (51.8%) patients in the DM2 group had some degree of diastolic dysfunction. Mitral A wave, E/E′ ratio and mitral A′ wave were significantly higher, and mitral E′ wave was significantly lower in the DM2 group compared with the controls (p < 0.05). There were no significant differences between the groups regarding EF, mitral E wave and E/A ratio (p > 0.05). LA diameter, and indexed Vmax, Volp, Vmin, AEV and TEV were found to be significantly higher in the DM2 group compared with the controls (p < 0.05). PEF was significantly lower in the DM2 group compared with the controls (p < 0.05). Between the two

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Table 1. Demographic characteristics and laboratory parameters of the groups Characteristics Age, year Male, n (%) BMI (kg/m2) Tobacco use, n (%)

Table 3. The echocardiographic parameters for the LA function of the study groups

Control group (n = 56)

DM2 group (n = 56)

50.1 ± 7.0

52.6 ± 6.5

0.06

LA diameter (mm)

28 (50)

0.55

28.0 ± 4.9

24 (42.9) 22.5 ± 2.0

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p-value

Parameters

Control group (n = 56)

DM2 group (n = 56)

p-value

33.3 (26–46)

37.5 (27–56)

< 0.001

Indexed Vmax (ml/m²)

19.8 ± 4.6

24.8 ± 6.6

< 0.001

Indexed Volp (ml/m²)

11.8 (4.6–23.6)

16.1 (9.5–30)

< 0.001

9 (16.1)

8 (14.3)

1.00

Indexed Vmin (ml/m²)

7.2 (2.8–14.0)

9.5 (3.8–24.5)

< 0.001

6 (10.7)

44 (78.6)

< 0.001

Indexed PEV (ml/m²)

11 (19.6)

47 (83.9)

< 0.001

Indexed AEV (ml/m²) Indexed TEV (ml/m²)

12.5 ± 3.7

14.6 ± 4.1

0.004

ACE inhibitors

5 (8.9)

40 (71.4)

LA passive emptying fraction (%)

35.5 ± 14.4

30.0 ± 11.1

0.003

Beta-blockers

1 (1.8)

16 (28.6)

LA active emptying fraction (%)

39.9 ± 13.5

42.0 ± 11.8

0.386

Statins

5 (8.9)

36 (64.3)

LA total emptying fraction (%)

60 (33.8–76.1)

63.9 (29.0–81.8)

0.05

37 (66.1)

3 (5.4)

Hypertension, n (%) Hyperlipidaemia, n (%) Medication, n (%)

ASA Insulin and OAD

33 (58.9) 153.0 ± 67.0

(5.21 ± 0.36)

(8.49 ± 3.72)

4.8 ± 0.6

8.1 ± 1.9

< 0.001

Total cholesterol (mg/dl)

211.4 ± 39.7

225.3 ± 50.6

0.11

(mmol/l)

(5.48 ± 1.03)

(5.84 ± 1.31)

(mmol/l) HbA1c (%)

48.2 ± 12.5

45.4 ± 8.5

(1.25 ± 0.32)

(1.18 ± 0.22)

LDL-C (mg/dl)

132.9 ± 38.2

140.1 ± 40.7

(mmol/l)

(3.44 ± 0.99)

(3.63 ± 1.05)

TG (mg/dl)

141.0 ± 84.7

190.4 ± 105.0

(mmol/l)

(1.59 ± 0.96)

(2.15 ± 1.19)

hsCRP (mg/l)

1.9 ± 1.2

5.3 ± 2.9

< 0.001

Uric acid (mg/dl)

4.6 ± 1.0

6.2 ± 1.6

< 0.001

0.16 0.34 0.01

DM: diabetes mellitus, BMI: body mass index, ACE: angiotensin converting enzyme, ASA: acetylsalisilic asid, OAD: oral antidiabetics, HbA1c: glycosylated haemoglobin, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density lipoprotein cholesterol, TG: triglycerides, hsCRP: high-sensitivity C-reactive protein.

groups, there were no significant differences in indexed PEV, AEF and TEF (p > 0.05) (Table 3). Patients in the DM2 group were divided according to presence of diastolic dysfunction. There were no significant differences within the DM2 group regarding LA volume and function (p > 0.05) (Table 4). To determine the influential factors for LA volume, we examined the potential variables that we thought to be echocardiographically and clinically relevant: mitral A wave, E′ wave, A′ wave, E/E′ ratio, BMI, and fasting glucose, HbA1c, hsCRP and uric acid levels. There were weak positive correlations between all indexed LA volumetric parameters and all the variables except for indexed PEV and BMI, fasting glucose,

HbA1c, hsCRP and uric acid levels, mitral A wave, E/E′ ratio and mitral A′ wave. There was a weak negative correlation between all indexed LA volumetric parameters and all the variables except indexed PEV and mitral E′ wave (Table 5). Univariate analysis showed that DM2, hypertension, age, BMI, and hsCRP and uric acid levels had a statistically significant impact on LA diameter, and indexed Vmax, Volp, Vmin, AEV and TEV. According to multivariate analysis when adjusted with other confounders, hypertension, age and BMI had a statistically significant effect on LA diameter; age and BMI had a statistically significant effect on indexed Vmax; age, BMI and uric acid level had a statistically significant effect on indexed Volp; uric acid level had a statistically significant effect on indexed Vmin; age had a statistically significant effect on indexed AEV; and age and BMI had a statistically significant effect on indexed TEV (Table 6).

Discussion Diabetes mellitus can lead to changes in LA volume and function. In most studies, LA function is determined by performing realtime three-dimensional (3D) echocardiography, cardiac magnetic resonance imaging (CMRI), and strain and strain rate tests. However, in general practice, LA function can be easily and non-invasively determined by performing 2D echocardiography. In our study, we showed that even if LA size and volume were within normal limits, LA dysfunction may be present in patients Table 4. Comparison of echocardiographic parameters regarding diastolic dysfunction for the LA function in the DM2 group Diastolic dysfunction (+) (n = 29)

Diastolic dysfunction (–) (n = 27)

LA diameter (mm)

37.4 ± 5.1

36.5 ± 5.8

0.548

Indexed Vmax (ml/m²)

25.8 ± 6.9

23.5 ± 6.2

0.196

Indexed Volp (ml/m²)

18.1 ± 5.8

16.1 ± 4.7

0.168

Indexed Vmin (ml/m²)

10.8 ± 4.6

9.2 ± 3.7

0.168

Table 2. Echocardiographic parameters of the study groups Parameters

Control group (n = 56)

DM2 group (n = 56)

EF (%)

61.9 ± 5.0

60.6 ± 4.4

0.14

102.3 ± 8.0

< 0.001

Parameters

0.66 < 0.001

< 0.001

(mmol/l)

HDL-C (mg/dl)

7.5 ± 3.2 6.6 (2.4–15.1)

DM: diabetes mellitus, LA: left atrium, PEV: passive emptying volume, AEV: active emptying volume, TEV: total emptying volume.

93.9 ± 6.4

Fasting glucose (mg/dl)

7.4 ± 3.4 5.0 (0.7–16.4)

p-value

Left ventricular mass (g/m2)

93.2 ± 8.4

Mitral E (cm/s)

79.1 ± 14.1

81.2 ± 16.7

0.47

Mitral A (cm/s)

66.4 ± 13.2

80.8 ± 18.8

< 0.001

1.2 ± 0.9

0.68

7.6 ± 3.2

7.3 ± 3.4

0.735

E/A ratio (cm/s)

1.2 ± 0.3

Indexed PEV (ml/m²)

199.0 ± 17.9

222.8 ± 19.7

< 0.001

Indexed AEV (ml/m²)

7.3 ± 2.8

6.8 ± 2.6

0.555

15.3 ± 3.3

< 0.001

14.9 ± 4.1

14.2 ± 4.0

0.505

Mitral E′ (cm/s)

18.5 ± 4.3

Indexed TEV (ml/m²)

16.1 ± 5.0

0.011

29.5 ± 10.9

30.5 ± 11.5

0.751

Mitral A′ (cm/s)

14.0 ± 3.2

LA passive emptying fraction (%)

5.5 ± 1.7

< 0.001

41.1 ± 11.1

43.0 ± 12.7

0.541

E/E′ ratio (cm/s)

4.4 ± 1.0

LA active emptying fraction (%) LA total emptying fraction (%)

12 (21.4)

29 (51.8)

60.9 ± 9.4

0.402

Diastolic dysfunction, n (%)

58.7 ± 9.8

Deceleration time (s)

DM: diabetes mellitus; EF: ejection fraction.

0.002

DM: diabetes mellitus, LA: left atrium, PEV: passive emptying volume, AEV: active emptying volume, TEV: total emptying volume.

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Table 5. Correlation analysis of LA volume and function with 2D echocardiographic parameters and laboratory findings Indexed Indexed Indexed Indexed Indexed Indexed Vmax Volp Vmin PEV AEV TEV (ml/m²) (ml/m²) (ml/m²) (ml/m²) (ml/m²) (ml/m²) Glucose (mg/dl) HbA1c (%) BMI (kg/m2) TG (mg/dl) hsCRP (mg/l)

0.153

0.252

0.182

–0.034

0.204

0.075

0.108

0.007

0.055

0.725

0.031

0.429

0.288

0.367

0.294

0.006

0.301

0.192

0.002

< 0.001

0.002

0.954

0.001

0.043

0.430

0.441

0.368

0.135

0.340

0.325

P < 0.001

< 0.001

0.154

< 0.001

0.152

0.248

0.136

–0.047

0.239

0.089

0.110

0.008

0.153

0.625

0.011

0.350

0.412

0.420

0.320

0.103

0.371

0.308

< 0.001

0.001

0.281

< 0.001

0.001

Uric acid

0.362

0.378

0.297

0.125

0.283

0.253

(mg/dl)

< 0.001

0.001

0.190

0.002

0.007

Mitral A (cm/s)

0.328

0.380

0.292

–0.002

0.321

0.232

< 0.001

0.002

0.981

0.001

0.014 –0.226

–0.274

–0.258

–0.211

–0.094

–0.202

0.003

0.006

0.026

0.323

0.033

0.017

Mitral A′ (cm/s)

0.278

0.281

0.310

0.064

0.117

0.138

0.003

0.001

0.504

0.220

0.147

E/E′ ratio (cm/s)

0.279

0.286

0.255

0.059

0.197

0.192

0.003

0.002

0.007

0.539

0.037

0.028

E/A ratio (cm/s)

0.085

0.129

0.288

–0.050

–0.135

–0.140

0.374

0.177

0.002

0.604

0.154

0.142

Mitral E′ (cm/s)

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LA: left atrium, BMI: body mass index, TG: triglycerides, hsCRP: high-sensitivity C-reactive protein, PEV: passive emptying volume, AEV: active emptying volume, TEV: total emptying volume.

with DM2 who was diagnosed in the preceding six months, and this finding was mainly due to BMI and age. Recent studies have shown that LA enlargement, obtained from 2D echocardiography, is a good predictor of cardiovascular outcomes.7 However, there are several limitations to estimating LA size because of the irregular geometry of the left atrium. Additionally, the left atrium often enlarges asymmetrically, which causes underestimation of its size. Therefore, it has been suggested that LA volume may be a superior measure of LA size.7 Moreover, changes in LA volume are increasingly becoming a parameter of interest as a marker of overall cardiac function. Several studies have shown that changes in LA size and mechanical function may be associated with adverse clinical

events such as atrial fibrillation, stroke, diastolic dysfunction and LV failure, both in the general and the diabetic population.6,8,10-14,19,20 Moreover, it has been reported that indexed Vmax ≥ 32 ml/m2 predicts cardiovascular mortality and morbidity independently of myocardial perfusion sintigraphy-detected myocardial ischaemia with a six-year follow-up period.21 Cardiovascular imaging modalities for the determination of LA function, such as computed tomography (CT), CMRI, 2D and 3D echocardiography, are evolving. Although the main advantage of CMRI and CT over echocardiography is the determination of all parts of the left atrium, including the LA appendage, the use of iodine and radiation during CT and the usefulness of CMRI in patients with pacemakers limit their usage.7 Therefore, we preferred to use 2D echocardiography, which is a non-invasive, easy-to-use and accessible method to evaluate LA volume and function. Moreover, similar to our findings, the mean indexed Vmax value was 23.6 ± 5.8 ml/m2 in a newly diagnosed diabetes group in the study population of Zoppini.14 The incidence of diastolic dysfunction in patients with DM2 is reported to be 43 to 75%.4 Recent evidence suggests that LA dilatation and dysfunction may be a co-existing marker of diastolic dysfunction in patients with DM2.4 However, Kadappu et al. demonstrated LA dilatation may be present in patients with DM2 independent of diastolic dysfunction and associated hypertension.4 Recently, another study by Zoppini et al. reported that diabetes itself might cause LA enlargement.14 These findings suggest that co-existing diabetic atrial cardiomyopathy may independently alter the LA size and function.4,14 In our study, 51.8% of the diabetic patients had some degree of diastolic dysfunction with no difference regarding LA volume and function, compared with the diabetic patients without diastolic dysfunction. This finding and a weak correlation between 2D echocardiographic diastolic parameters and LA volume in our study may have been due to the duration of DM2, normal LV filling pressures determined by E/E′ ratio, and normal LV mass. We demonstrated that increasing age and BMI had a significant effect on LA volume. The main difference of our study from previous ones was the duration of DM2, which was strongy and positively associated with larger LA diameter and impaired LA function. CARDIA investigators showed a 20-year follow-up period of diabetes was associated with indexed LA

Table 6. Univariate and multivariate analysis for predictors of LA volume and function of the study population Univariate analysis Parameters

Multivariate analysis

DM2

Age

BMI

hsCRP

Uric acid

Age

BMI

hsCRP

LA diameter (mm)

< 0.001

0.0281

< 0.001

0.003

0.001

0.227

0.001

0.005

0.002

< 0.001

0.879

Uric acid 0.194

Indexed Vmax (ml/m²)

< 0.001

0.003

< 0.001

0.438

0.056

0.100

0.001

0.004

0.191

0.064

Indexed Volp (ml/m²)

< 0.001

0.991

0.181

0.244

0.003

0.016

0.226

0.042

Indexed Vmin (ml/m²)

< 0.001

0.007

< 0.001

0.001

0.869

0.171

0.334

0.069

0.099

0.371

0.034

Indexed PEV (ml/m²)

0.66

0.268

0.971

0.171

0.164

0.281

0.190

Indexed AEV (ml/m²)

< 0.001

0.001

< 0.001

0.002

0.822

0.623

Indexed TEV (ml/m²)

0.004

0.001

0.051

< 0.001

0.001

0.007

0.189

0.259

LA passive emptying fraction (%)

0.003

0.052

0.011

0.169

0.044

0.065

0.338

0.150

LA active emptying fraction (%)

0.386

0.769

0.499

0.393

0.718

0.430

0.968

–

LA total emptying fraction (%)

0.05

0.117

0.162

0.293

0.148

0.395

0.363

–

– 0.476 – 0.438

– 0.010 0.003 –

–

0.064

0.383

0.486

0.020

0.443

0.418

0.897

–

DM: diabetes mellitus, HT: hypertension, HL: hyperlipidaemia, BMI: body mass index, hsCRP: high-sensitivity C-reactive protein, LA: left atrium, PEV: passive emptying volume, AEV: active emptying volume, TEV: total emptying volume.

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

diameters.19 On the other hand, Zoppini et al. showed a possible 65% LA enlargement (defined as indexed Vmax ≥ 34 ml/m2) for each 10 years’ duration of diabetes.14 On the basis of these findings, we speculate that although diabetes was an independent predictor of LA volume in univariate analysis, in multivariate analysis, age and BMI were the independent predictors of LA volume in the early stages of diabetes. LA function is evaluated and indexed to BSA by calculating PEV, AEV, TEV and PEF, AEF and TEF from Vmax, Vmin and Volp. TEV describes the reservoir, PEV describes the conduit, and AEV describes the pump function of the left atrium. Contrary to current knowledge, Vmin increases, even in mild LV diastolic dysfunction, whereas Vmax increases in the later stages, suggesting that Vmin may be a more sensitive marker of LV diastolic dysfunction. Moreover, this finding underlines the importance of evaluation of LA function.22 Based on current knowledge, LA reservoir function is associated with worsening LV diastolic function.7 Graca et al. showed that LA reservoir and conduit function were reduced in asymptomatic DM2 patients.23 The same study also demonstrated that DM2 was independently associated with LA reservoir function, but not with conduit function.23 Mondillo et al. investigated only diabetic patients with normal LA size and did not find any difference in conduit and pump function. However, they showed LA deformation was impaired in diabetics even if LA volumes were similar between the groups.24 Murakana et al. showed decreased LA reservoir and conduit functions in patients with DM2 even in the absence of LA dilatation.5 Huang et al. demonstrated, with 2D echocardiographic evaluation, increased reservoir and pump function and reduced conduit function in patients with DM2.6 Recently, Atas et al. reported depressed reservoir and pump function with similar conduit function in patients with DM2 compared to the control group.8 In our study, in accordance with the study of Huang et al., we found reduced conduit, and increased pump and reservoir function in diabetic patients compared with the controls. The possibly inconsistent results with previous studies may have been due to different cardiovascular imaging techiques used for the determination of LA function, small sample sizes, different baseline characteristics, and different diabetes durations of the study populations. There are some limitations to our study. As this was a crosssectional study, follow up of the patients for clinical endpoints such as AF and heart failure could not be done. Therefore, our study results cannot be used to direct standard clinical care. Moreover, as the population size was relatively small, our study does not permit any causal inferences and analysis on the effect of medications on LA volume and function. For this reason, long‑term follow up and large‑scale prospective studies are needed to determine the clinical predictive value of early LA functional impairment in this population. Evaluation of LA volume and function with 2D echocardiography was an additional limitation of our study.

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LA enlargement and LA volumes that were independent of the effects of hypertension and DM2. Further studies with larger sample sizes are needed to better define the underlying mechanisms. The authors thank Arzu Baygul from MedStats Consulting and Prof Sule Oktay, MD, PhD from Kappa Consulting, Traning and Limited Research Ltd for statistical analysis and interpretation of the results.

References 1.

Ryde’n L, Standl E, Bartnik M, et al. Guidelines on diabetes, prediabetes, and cardiovascular diseases: executive summary, the task force on diabetes and cardiovascular diseases of the European Society of Cardiology (ESC) and of the European Association for the study of Diabetes (EASD). Eur Heart J 2007; 28: 88–136.

Freire CM, Moura AL, Barbosa Mde M, et al. Left ventricule diastolic dysfunction in diabetes: an update. Arq Bras Endocrinol Metab 2007; 51(2): 168–175.

Poulsen MK, Henriksen JE, Dahl J, et al. Left ventricular diastolic function in type 2 diabetes mellitus. Prevalence and association with myocardial and vascular disease. Circ Cardiovasc Imag 2010; 3: 24–31.

Kadappu KK, Boyd A, Eshoo S, et al. Changes in left atrial volume in diabetes mellitus: more than diastolic dysfunction. Eur Heart J 2010; 13: 1016–1023.

Muranaka A, Yuda S, Tsuchihashi K, et al. Quantative assessment of left ventricular and left atrial functions by strain rate imaging in diabetic patients with and without hypertension. Echocardiography 2009; 26: 262–271.

Huang G, Zhang L, Xie M, Fu M, Huang J, Lv Q. Assessment of left atrial function in diabetes mellitus by left atrial volume tracking method. J Huazhong Univ Sci Technol 2010; 30: 819–823.

Tadic M, Cuspidi C. The influence of type 2 diabetes on left atrial remodeling. Clin Cardiol 2015; 38: 48–55.

Atas H, Kepez A, Atas DB, et al. Effects of diabetes mellitus on left atrial volume and functions in normotensive patients without sypmtomatic cardiovascular disease. J Diabetes Complicat 2014; 28: 858–862.

To ACY, Flamm SD, Marwick TH, Klein AL. Clinical utility of multimodality LA imaging: assessment of size, function, and structure. J Am Coll Cardiol Cardiovasc Imag 2011; 4: 788–798.

10. Vaziri SM, Larson MG, Benjamin EJ, Levy D. Echocardiographic predictors of nonrheumatic atrial fibrillation: the Framingham Heart Study. Circulation 1994; 89: 724–730. 11. Benjamin EJ, D’Agostino RB, Belanger AJ, Wolf PA, Levy D. Left atrial size and the risk of stroke and death: the Framingham Heart Study. Circulation 1995; 92: 835–841. 12. Modena MG, Muia N, Sgura FA, Molinari R, Castella A, Pessi R. Left atrial size is the major predictor of cardiac death and overall clinical outcome in patients with dilated cardiomyopathy: a long-term follow up study. Clin Cardiol 1997; 20: 553–560. 13. Simek CL, Feldman MD, Haber HL, Wu CC, Jayaweera AR, Kaul S. Relationship between left ventricular wall thickness and left atrial size: comparison with other measures of diastolic function. J Am Soc Echocardiogr 1995; 8: 37–47. 14. Zoppini G, Bonapace S, Bergamini C, et al. Evidence of left atrial

Conclusion The results of our study showed impaired LA function may be present in patients with DM2 with a disease duration of a maximum of six months. BMI and increased age caused

remodelling and left ventricular diastolic dysfunction in type 2 diabetes mellitus with preserved systolic function. Nutr Met CV Dis 2016; 26: 1026–1032. 15. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2013; 36(Suppl 1): S67–74.

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16. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande

right ventricular structure and function to cardiovascular risk factors

L, et al. Recommendations for cardiac chamber quantification by

in adolescent with type 2 diabetes participating in the TODAY clini-

echocardiography in adults: An update from the American Society

cal trial. (published online ahead of print January 22, 2014). Pediatr

of Echocardiography and European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28: 1–39. 17. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of

Diabetes 2014. Doi:10.1111/pedi.12119. 21. Poulsen MK, Dahl JS, Henriksen JE, et al. Left atrial volume index. J Am Coll Cardiol 2013; 62: 2416–2421.

Doppler echocardiography and tissue Doppler imaging in the estima-

22. Russo C, Jin Z, Homma S, et al. Left atrial minimum volume and reser-

tion of left ventricular filling pressures: a comparative simultaneous

voir function as correlates of left ventricular diastolic function: impact

Doppler-catheterization study. Circulation 2000; 102: 1788–1794.

of left ventricular systolic function. Heart 2012; 98: 813–820.

18. Anwar AM, Soliman OII, Geleijnse ML, Nemes A, Vletter WB, ten

23. Graca B, Ferreira MJ, Donato P, et al. Left atrial dysfunction in type 2

Cate FJ. Assessment of left atrial volume and function by real-time

diabetes mellitus: insights from cardiac MRI (published online ahead

three-dimensional echocardiography. Int J Cardiol 2008; 123: 155–161.

of print July 17,2014). Eur Radiol 2014; 24: 2669–2676. Doi:10.1007/

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24. Mondillo S, Cameli M, Caputo ML, et al. Early detection of left atrial

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898–908.

Smartphone apps launched for atrial fibrillation patients and their healthcare providers Novel smartphone and tablet applications (apps) for atrial fibrillation patients and healthcare professionals have been launched by heart experts. The objectives and design of the apps are outlined in an article published online recently in EP Europace, with a summary published in the European Heart Journal. Atrial fibrillation is the most common heart rhythm disorder and significantly increases the risk of stroke and death. One in four middle-aged adults in Europe and the US will develop atrial fibrillation, and the incidence and prevalence are rising. ‘Around two-thirds of people in Europe and the US have a mobile device and use it as their main way of accessing online information,’ said lead author Dr Dipak Kotecha, a clinician scientist in cardiovascular medicine at the Institute of Cardiovascular Sciences, University of Birmingham, UK. ‘This presents a big opportunity to improve self-management and shared decision making in atrial fibrillation.’ The My AF app and AF Manager app were designed by the European Society of Cardiology (ESC) Guidelines Task Force on Atrial Fibrillation and the CATCH ME consortium, of which the ESC is a partner. The apps were developed over the last two years in tandem with the writing of the 2016 ESC guidelines on atrial fibrillation. Both apps are freely available for Android and iOS devices through the Google Play, and Apple stores. My AF is for patients with atrial fibrillation. It provides information about the condition, the risk of stroke, atrial fibrillation treatments, and tips on improving lifestyle. Patients can record symptoms and quality of life in a diary which can be shared with a nominated health professional before each consultation to maximise face-to-face time. Developed in collaboration with patients and patient support groups, My AF provides high-quality information in a simple format that is suitable for adults of all ages. Work is underway to translate the app into several languages. Dr Kotecha said: ‘The app aims to encourage active patient involvement in the management of their condition.

There is evidence that patient education can improve selfcare, adherence to therapy, and long-term outcomes.’ AF Manager is for doctors, nurses and other healthcare professionals. It is the first app of its kind to be submitted for CE certification and is in the final stages of approval. AF Manager imports information shared by the patient and allows the healthcare professional to amend details and enter other medical information, such as electrocardiogram or echocardiography data. The Treatment Manager tool within the app then suggests individualised treatment options based on ESC guidelines. After a consultation, the notes, treatment decisions and medication dosages can be entered and then shared with the patient. ‘Many studies have shown that when clinicians follow guideline recommendations, patients have better outcomes,’” said Dr Kotecha. ‘All of the decision aids in AF Manager are based on ESC guidelines so we hope this will encourage guideline implementation. Patients will have the option to anonymously donate their data, which will enable us to assess the guideline adherence rate.’ The apps are linked to allow transfer of data between patients and healthcare professionals via a secure server at the University of Birmingham, UK. Patients control who can view and edit their data. When data sharing is enabled, updates are synced on both apps. All shared information is encrypted and password protected. Dr Kotecha said: ‘We know that effective management of atrial fibrillation is suited to shared decision making and we have created the apps in the hope of facilitating this process. Sharing information should save clinicians time and enable them to devote consultations to choosing the best treatments.’ He concluded: ‘The dynamic nature of this technology will allow us to modify and update the features and content to reflect feedback from users, as well as future versions of the ESC atrial fibrillation guidelines.’ Source: European Society of Cardiology Press Office

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

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Upper limb ischaemia: a South African single-centre experience Tinus du Toit, Kathryn Manning, Nadraj G Naidoo

Abstract Objective: The aims of this study were to report on our experience with upper limb ischaemia (ULI), to define the pattern and distribution of disease, describe key demographic features and report on conventional clinical outcomes. Methods: This was a single-centre, retrospective, descriptive study. All patients (n = 64) who underwent a surgical intervention for ULI over a 12-year study period were included. Findings were analysed and compared with the current literature. Results: A male:female ratio of 0.60 was reported. Two major subgroups of patients were identified. The patients in the thrombo-embolic subgroup (n = 30) were notably younger than expected (mean age 55 years) compared to those in the atherosclerotic occlusive disease subgroup (n = 12, mean age 57 years). Presentation overall was generally late, with 8.6% of acute ULI and 48.3% of chronic ULI patients presenting with irreversible ischaemia and tissue loss, respectively. Thrombo-embolism was the dominant vascular pathology reported in this case series (47%). Ninety-five procedures were performed in 64 patients (89 open, six endovascular). Peri-operative (30-day) mortality rate was 7.8%. Systemic and procedure-related complications were observed in 13 and 23%, respectively. The overall major amputation rate was 10.9%. Adherence to follow up was poor (51% at six months). Conclusion: Although few firm conclusions could be drawn, this review has expanded our overall perspective of ULI, specific to the population we serve. Collaboration between African vascular units should be encouraged in an attempt to further define the pattern of ULI by identifying distinct geographical confounders. Keywords: upper limb, acute ischaemia, chronic ischaemia, revascularisation, non-traumatic Submitted 11/7/17, accepted 7/11/17 Published online 8/12/17 Cardiovasc J Afr 2017; 29: 88–92

Methods Consecutive patients who underwent a surgical intervention for ULI over a 12-year period were identified from the Vascular Unit’s prospectively maintained operative database. Patients presenting with primary Reynaud’s phenomenon and traumatic vascular injuries were excluded. The Trauma Unit at our facility published extensively on this topic within the study period and duplication of data was a concern.3-5 Qualitative and quantitative data were collected and appropriately coded to assist data analysis using Stata/SE version 13.1 (StataCorp®, College Station, Texas). Frequencies and percentages were calculated for categorical data. Means with minimum and maximum range were calculated for continuous data.

www.cvja.co.za

DOI: 10.5830/CVJA-2017-049

Department of Surgery, Groote Schuur Hospital, Cape Town, South Africa Tinus du Toit, MB ChB, FCS (SA), MMed (UCT), dutoitjm@yahoo.com

Department of Medicine, Groote Schuur Hospital, Cape Town, South Africa Kathryn Manning, BSc, MSc (Med) (UCT)

Vascular Unit, Department of Surgery, Groote Schuur Hospital, Cape Town, South Africa Nadraj G Naidoo, MB ChB, FCS (SA)

Upper limb ischaemia (ULI) is a relatively uncommon but well recognised vascular clinical entity caused by a wide range of vascular pathologies.1 Upper-limb revascularisation procedures comprise approximately 4% of all vascular procedures performed.2 Contemporary vascular literature has focused predominantly on vascular occlusive disorders of the lower extremity. The occupational ramifications and impact on quality of life in those affected can be substantial, often resulting in loss of independence and/or livelihood. A thorough understanding of this condition is essential if significant improvement in surgical outcome and limb functionality is to be made. Series that combine acute and chronic ischaemia are rare, with most publications reporting on either a single clinical (acute or chronic) or aetiological (traumatic or non-traumatic) aspect of ULI. The majority of publications originate from developed countries, with no reports identified from the African continent to date. Ethnic, demographic and geographic confounders may influence vascular disease development, necessitating further investigation rather than extrapolation. Accordingly, we report on our institutional experience in the context of the current literature and offer a glimpse into several distinctive features specific to the population we serve.

Results Sixty-four patients presenting with ULI were evaluated and managed surgically from January 2000 to December 2011. Forty females (62.5%) with a mean age of 51 years (range 15–84 years) and 24 males (37.5%) with a mean age of 46 years (range 15–76 years) were included in the study, reflecting a male-to-female ratio of 0.60 (as opposed to 0.96 in the general Western Cape population).6 Fig. 1 represents the ethnic distribution within the study group, in comparison with the general population.6,7 A wide range of vascular pathologies was identified, with noticeable demographic differences between groups (Table 1). A total of 30 patients presented with thrombo-embolic disease, with all but two patients presenting with acute ULI.

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The majority of embolic occlusions occurred at the level of the brachial artery bifurcation (n = 17). Nine patients presented with more proximal (two subclavian artery, seven axillary artery) and three with more distal occlusions (two radial artery, one ulnar artery). One patient presented with a blue-finger syndrome. A left-sided predominance was noted across all levels of obstruction with a right-to-left-sided ratio of 1:2. A distinct proximal distribution of atherosclerotic lesions was observed, with the subclavian artery involved in eight, the axillary artery in one and the brachial artery in three patients. As observed in the thrombo-embolic subgroup, clear left-sided predominance was noted with a right-to-left ratio of 1:5. Morphologically, six lesions were described as stenotic and five as occlusions. Arterial thoracic outlet syndrome: seven of eight patients presented with underlying bony pathology (five cervical ribs, one anomalous first rib and one old clavicle fracture resulting in a pseudo-arthrosis). Six patients presented with chronic and two with acute ULI. Four patients were diagnosed with Takayasu’s disease. Three patients presented with upper-limb claudication. One of these claudicants suffered an ipsilateral ischaemic cerebrovascular accident prior to presentation. Level of disease ranged from stenosis of the innominate artery with occlusion of its outflow (one patient) to proximal left common carotid artery stenosis with associated left subclavian artery occlusion (two patients). One patient presented with prosthetic graft sepsis complicated by an acute anastomotic bleed following previous aortic arch reconstruction for aneurysmal disease. Thrombo-angiitis obliterans: four patients with active digital ulceration due to Buerger’s disease were evaluated and surgically 60 50

managed during the study period. The average smoking history was 36 pack years. Small-vessel disease: two patients presented with active digital ulceration in combination with Reynaud’s symptoms and one presented with Reynaud’s symptoms alone. The vascular pathologies identified were a vasculitis (Lupus), a hypothenar hammer syndrome and an atherosclerotic small-vessel disease.

Clinical presentation Thirty-five patients (54.7%) presented with acute ULI necessitating surgical intervention. Three patients (8.6%) had signs of irreversible ischaemia (Rutherford grade III ULI) and a further nine (25.7%) were diagnosed with Rutherford grade IIb ULI. Twenty-nine patients presented with chronic ULI. Fourteen patients (48.3%) presented with tissue loss. Other clinical

Table 2. Procedures performed according to aetiology (excluding minor and ablative procedures) Procedures performed

No.

Thrombo-embolic disease

Thrombo-embolectomy (fasciotomy in eight)

Brachial–brachial/–distal bypass (autologous vein graft)

Catheter-directed/intra-operative thrombolysis

Stent–graft placement

Aortic arch reconstruction (Gelsoft® Dacron)

Veinpatch angioplasty of veingraft Atherosclerotic occlusive disease

Brachial–distal/brachial–brachial bypass graft

Subclavian–axillary/subclavian–brachial bypass graft

Axillary–brachial bypass graft

Common carotid–axillary/common carotid–brachial bypass graft

Graft thrombectomy

Percentage

ATOS (each row represents a patient)

30 20 10 0

Mixed-race

Caucasian

Current study

Black

Indian

Census 2001

Census 2011

Table 1. Comparative demographic details according to vascular pathology Pathology

Thrombo-embolectomy + fasciotomy; Ipsilateral TO decompression

Common carotid–brachial RSBG bypass

Subclavian–axillary PTFE bypass + brachial–ulnar RSVG bypass

Subclavian–axillary PTFE bypass

Ipsilateral TO decompression

Subclavian–axillary PTFE bypass

Common carotid–brachial Dacron® bypass + brachial–ulnar RSVG bypass + fasciotomy

Redo aortic arch reconstruction SilverGraft®

Axillary–axillary PTFE bypass

Thoracoscopic sympathectomy

Mean age (range)

Male:female ratio

Thrombo-embolic disease

55 (37–80)

0.43

Atherosclerotic disease

57 (39–84)

0.71

Thoracic outlet syndrome

28 (15–59)

1.67

Takayasu’s disease

27 (20–36)

0.33

Thrombo-angiitis obliterans

46 (36–53)

3.00

Small-vessel disease

32 (31–49)

0.50

Iatrogenic

–

1.00

Polymyositis compartment syndrome

–

Aortic arch reconstruction AlboGraft®

Thrombo-angiitis obliterans

Number of patients

1 11

Thrombo-embolectomy + fasciotomy; Ipsilateral TO decompression; contralateral TO decompression

Takayasu’s disease

Fig. 1. Racial prevalence.

1 19

Subclavian artery stent placement

Subclavian artery balloon angioplasty 40

Small-vessel disease

2 2 3

Thoracoscopic sympathectomy

Brachial–distal RSVG bypass

Iatrogenic (each row represents a patient)

Fasciotomy

Thrombo-embolectomy + fasciotomy

Polymyositis compartment syndrome Fasciotomy

1 1

TO: thoracic outlet; RBVG: reverse basilic vein graft; RSVG: reverse saphenous vein graft; PTFE: polytetrafluoroethylene.

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presentations in this group included claudication (31%), rest pain (13.8%) as well as neurovascular symptoms (6.9%).

Surgical interventions Ninety-five procedures were performed in 64 patients. Of these, 89 were open procedures with six cases managed by means of an exclusively endovascular approach. A distinction should be made between minor procedures (10 in total; wound debridements, evacuation of haematomas, closure of fasciotomy wounds and excision/ligation of bypass grafts), attempts at revascularisation (77 in total; see Table 2) and ablative procedures (18 in total; see Table 3). Surgical outcome was reported by quantifying the mortality, morbidity and amputation rates, and functional outcome at certain time intervals post-initial procedure. Unfortunately, follow-up appointments were poorly attended, restricting the interpretation of long-term data (Table 3). In the first 30 days, 18 amputations were performed in 64 patients. Ten amputations were performed primarily (at initial surgical procedure) in patients presenting with irreversible tissue necrosis. Eight secondary amputations (four major, four minor) were performed within 30 days following an initial attempt at revascularisation. A total of six patients (9.4%) required a major amputation at 30 days, of whom three presented with acute ULI. At six month’s follow up, five patients presented with bypass graft occlusion (resulting in one above-elbow amputation) and one with re-occlusion of native vessels post-embolectomy. Functionally, four patients presented with contractures, one with motor weakness (affecting activities of daily living) and two with

Table 3. Summary of 30-day, six-month and long-term outcome Outcome measure Adherence to follow up Mortality

30-day n (%)

6-month n (%)

Long-term n (%)

53 (83.0)

30 (50.8)

17 (28.8)

5 (7.8)

–

Acute coronary syndrome

Acute kidney injury

Acute respiratory failure

Morbidity Systemic complications

8 (12.5)

Acute kidney injury

Acute respiratory insufficiency

Acute coronary syndrome

Cerebrovascular incident Procedural complications

1 18 (23.4)

Surgical site haematoma

Superficial surgical site infection

Bypass graft occlusion

Pseudo-aneurysm post-angiogram

Delayed fasciotomy

Neuropraxia

Re-thrombosis of native vessels

claudication. Twenty-three patients were assessed as having a fully functional ipsilateral upper limb. After six months, one patient developed bypass graft occlusion as part of an agonal event. Thirteen patients reported normal function, two presented with contractures, one with persistent motor weakness and one with claudication symptoms. Five patients died within 30 days of admission, resulting in a 30-day all-cause mortality rate of 7.8%. No further mortalities or systemic complications were noted at the six-month follow up. One patient died of lung carcinoma two years after initial presentation with ULI.

Discussion We report on the first institutional experience with surgical management of ULI from the African continent, in an attempt to identify ethnic, demographic and geographic confounders. However, several research limitations resulted in the generation of multiple, tentative assumptions to direct future research, rather than robust scientific conclusions. Firstly, by attempting to discuss distinctly different aetiopathological processes in unison, important individual characteristics may be obscured. Adherence to follow up was poor, limiting the interpretational value of long-term data. With this in mind, a few relevant findings will be discussed. The true incidence of ULI in South Africa remains speculative. A major limiting factor is the paucity of data on non-surgical management of ULI. In the current series, subjects were retrospectively selected from a surgical database without capturing those managed non-surgically. The singlecentre nature of this series does not allow for any firm conclusion regarding the regional and race-specific incidence of ULI as the number and ethnicity of patients seeking medical attention from private healthcare facilities are currently unknown. Despite the above-mentioned limitations, a clear escalating trend was observed, with 56% of surgically managed patients referred within the last four years of the study period. An increase in the absolute number of referrals is the most conceivable explanation for the observed trend. A less likely explanation may be that a more aggressive surgical approach was followed during the last four years of the study. Anecdotally though, the indications for surgical intervention have remained unchanged. The largest surgical series investigating patients undergoing revascularisation procedures for ULI was published by Deguara et al.1 in 2005. A total of 172 patients were included over a 20-year period, with 53 cases related to upper-extremity trauma (excluded in the current series). Comparison of data between the two series makes for interesting discussion, especially when

Table 4. Demographic and outcome comparisons of thrombo-embolic and atherosclerotic occlusive disease

Amputation rate Primary amputation (2 major, 8 minor) Secondary amputation (4 major, 4 minor)

Mean age Number (years)

10 (15.6) 8 (12.5)

Contracture

M:F ratio

30-day mortality rate (%)

Amputation rate (%)

Current series

Functional outcome Normal

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Thrombo-embolic

1:2.3

16.7

13.3

Atherosclerotic occlusive

1:1.4

8.3

Deguara et al.1

Claudication symptoms

Thrombo-embolic

1:1.1

18.2

Motor weakness

Atherosclerotic occlusive

1:1.9

6.9

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thrombo-embolic and atherosclerotic occlusive disease subgroups are analysed (Table 4). Multiple publications support the view that patients with thrombo-embolic ULI, when compared to atherosclerotic occlusive disease, present at a more advanced age.1,8 Interestingly, this finding was not observed in our series. Possible explanations include the assumed impact that a relatively low life expectancy (57.7 years for males and 61.4 years for females)6 may have, as well as the suspicion of a different risk-factor profile compared to other research populations. Both tuberculosis9 and HIV infection10 have been identified as acquired hypercoagulable states. Therefore, with the prevalence of tuberculosis (25/1000)11,12 and antenatal HIV infection (33%)13 in the Western Cape on the rise,14 it is conceivable that the study population is at higher risk of developing thrombo-embolic disease. In the absence of a national registry, a prospective survey specifically designed to evaluate the impact of tuberculosis and HIV/AIDS on the incidence and pathogenesis of ULI should be performed. Furthermore, all five of the 30-day mortalities were observed in the embolic acute ULI subgroup. The concept that mortality following embolectomy is a consequence of the patient’s co-morbidity rather than the embolus itself, is well supported.1,15 In our series, post-embolectomy mortality was attributable to acute coronary syndrome (n = 2), acute kidney injury (n = 2) and acute respiratory failure (n = 1), resulting in a 30-day all-cause mortality rate of 16.7%. These findings are in keeping with recent international literature, ranging between eight and 19%.1,16,17 The only death observed in the chronic ULI group was as a result of lung carcinoma, documented two years after initial surgery for atherosclerotic occlusive disease. Ablative procedures were reported as either primary (performed at initial procedure) or secondary (following an attempt at revascularisation), with digital (minor) and aboveor below-elbow (major) amputations separately recorded. The 30-day amputation rate following an attempt at revascularisation was 12.5%, with major (both primary and secondary) amputations performed in 6.3%. Patients generally presented late, with 8.6% in the acute ULI group and 48.3% in the chronic ULI group presenting with irreversible ischaemia and tissue loss, respectively. When comparing surgical outcome to that of other case series (see Fig.

2), one has to consider indications for surgery. Units implementing a more aggressive approach to relatively minor symptoms may reflect better surgical outcomes, particularly superior limb-salvage rates. No limbs were amputated in the Deguara1 series, but the indications for intervention were not reported. Of the 64 patients included in this review, seven were confirmed to be HIV positive by HIV Ag/Ab Combo (ELISA) testing. However, only 30 patients underwent testing (as indicated by folder laboratory results sheet or NHLS Disa electronic results system). One patient developed superficial surgical site infection and another died of prosthetic graft sepsis, complicated by an acute bleed. Due to the low rate of HIV testing and small number of patients involved, it is not possible to reach firm conclusions regarding clinical outcome in this subgroup of patients. Candidates for exclusive endovascular management were conservatively selected. Five subclavian artery lesions were managed by primary stent placement, with one lesion stented after failed percutaneous balloon angioplasty. One patient sustained a procedure-related complication in the form of an ipsilateral cerebrovascular incident. All of these patients attended the six-month follow-up appointment and reported normal function of the affected upper limb.

Conclusion Although few firm conclusions could be drawn, this review has expanded our overall perspective of ULI, specific to the population we serve. Collaboration between African vascular units should be encouraged in an attempt to further define the pattern of ULI by identifying distinct geographical confounders. Dr PE Eloff is acknowledged for the initial identification of participants from a surgical database.

References 1.

Deguara J, Ali T, Modarai B, Burnand KG. Upper limb ischemia: 20 year experience from a single center. Vasc J 2005; 13(2): 84–91. DOI: 10.1258/rsmvasc.13.2.84.

Quraishy MS, Cawthorn SJ, Giddings AE. Critical ischaemia of the upper limb. J R Soc Med 1992; 85: 269–273. PMID: 1433088.

Zellweger R, Hess F, Nicol A, Omoshoro-Jones J, Kahn D, Navsaria P. An analysis of 124 surgically managed brachial artery injuries. Am J

Surg 2004; 188: 240–245. DOI: 10.1016/j.amjsurg.2004.02.005. 4.

Percentage

Gill H, Jenkins W, Edu S, Bekker W, Nicol AJ, Navsaria PH. Civilian penetrating axillary artery injuries. World J Surg 2011; 35: 962–966. DOI: 10.1007/s00268-011-1008-8.

Sobnach S, Nicol AJ, Nathire H, Edu S, Kahn D, Navsaria PH. An Analysis of 50 surgically managed penetrating subclavian artery inju-

ries. Eur J Vasc Endovasc Surg 2010; 39; 155–159. DOI: 10.1016/j. 20

ejvs.2009.10.013. 6.

10 0

South African Census report 2011. http://www.statssa.gov.za/publications/P03014/P030142011.pdf.

7. Tissue necrosis Current

Claudication

Rest pain

Roddy et al

Fig. 2. Summary of chronic ULI presentations.

Hughes et al

South African Census report 2001. https://www.datafirst.uct.ac.za/dataportal/index.php/catalog/96.

Neuro-vascular

Kim S, Kwak H, Chung G, Han Y, et al. Acute upper limb ischemia due to cardiac origin thromboembolism: the usefulness of percutaneous aspiration Thromboembolectomy via a transbrachial approach. Korean J Radiol 2011; 12(5): 595–601. DOI: 10.3348/kjr.2011.12.5.595.

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Kechaou I, Cherif E, Ben Hassine L, Khalfallah N. Deep vein thrombosis and tuberculosis: a causative link? Br Med J Case Rep 2014; 2014. DOI: 10.1136/bcr-2013-200807.

10. Shen YM, Frenkel EP. Thrombosis and a hypercoagulable state in HIV-infected patients. Clin Appl Thromb Hemost 2004; 10(3): 277–280. PMID: 15247986. 11. Wood R, Middelkoop K, Myer L, Grant AD, Whitelaw A, et al. Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control. Am J Resp Crit Care Med 2007; 175(1): 87–93. DOI: 10.1164/rccm.200606-759OC. 12. Den Boon S, Van Lill SWP, Borgdorff MW, Enarson DA, Verver S, et al. High prevalence of tuberculosis in previously treated patients, Cape Town, South Africa. Emerg Infect Dis 2007; 13(8): 1189. DOI: 10.3201/ eid1308.051327. 13. Draper B, Pienaar D, Parker W, Rehle T. Recommendations for policy in the Western Cape province for the prevention of major infectious diseases, including HIV/AIDS and tuberculosis. Cape Town. 2007. http://www. capegateway.gov.za/eng/pubs/reports_research/W/157844. 14. World Health Organisation. Global Tuberculosis Control 2011.

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Geneva. [Internet website]. Available: http://apps.who.int/iris/bitstre am/10665/44728/1/9789241564380_eng.pdf. 15. Savelyev VS, Zatevakhin MD, Stepanov MD. Artery embolism of the upper limbs. Surgery 1977; 81: 367–375. PMID: 847643. 16. Sultan S, Evoy D, Eldin AS, Eldeeb M, Elmehairy N. Atraumatic acute upper limb ischemia: a series of 64 patients in a Middle East tertiary vascular center and literature review. Vasc Surg 2001; 35: 181–197. PMID: 11452344. 17. Licht PB, Balezantis T, Wolff B, Baudier JF, Røder OC. Longterm outcome following thrombembolectomy in the upper extremity. Eur J Vasc Endovasc Surg 2004; 28(5): 508–512. DOI: 10.1016/j. ejvs.2004.08.007. 18. Hughes K, Hamdan A, Schermerhorn M, Giordano A, Scovell S, Pomposelli F Jr. Bypass for chronic ischemia of the upper extremity: results in 20 patients. J Vasc Surg 2007; 46(2): 303–307. DOI: 10.1016/j. jvs.2007.04.035. 19. Roddy SP, Darling RC, Chang BB, Kreienberg PB, Paty PS, Lloyd WE, et al. Brachial artery reconstruction for occlusive disease: a 12-year experience. J Vasc Surg 2001; 33: 802–805. DOI: 10.1067/mva.2001.112705.

Smartphone app directs first responders to cardiac arrest three minutes before ambulance A novel smartphone application (app) has been developed that can direct first responders to cardiac arrest victims more than three minutes before the emergency services arrive. Each minute increases the chance of survival by 10%. The EHRA First Responder app was created by the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC). It was released during EHRA EUROPACE – CARDIOSTIM 2017. ‘Sudden cardiac arrest is lethal within minutes if left untreated,’ said EHRA spokesperson Dr Christian Elsner. ‘In Europe, the emergency services arrive around nine minutes after a cardiac arrest. Every minute earlier raises the probability of survival by 10% and reduces the risk of brain injury, which starts four minutes after cardiac arrest.’ If cardiopulmonary resuscitation (CPR) is initiated by a member of the public, this will in essence shorten the time between cardiac arrest and the urgently needed resuscitation measures. However, bystander resuscitation occurs in just of 30–60% of patients who have a cardiac arrest outside hospital. The EHRA First Responder app was developed to increase the rate of bystander resuscitation and reduce the time between cardiac arrest and resuscitation. Based on GPS tracking technology, the app is used by existing emergency services (reached in many countries by dialling 112) to locate trained ‘app rescuers’ and then automatically direct them to the scene of cardiac arrest. The target is for an app rescuer to arrive three to four minutes after the cardiac arrest. In a typical scenario, after the cardiac arrest, a bystander calls the emergency services. The operator dispatches an emergency crew and simultaneously locates nearby app

rescuers. The nearest app rescuers are notified on their smartphones and the quickest responder is given directions, via the app, to the patient and then performs CPR. Other app rescuers can then additionally bring a nearby automated external defibrillator (AED). The app was tested in Lübeck, Germany, where around 600 app rescuers were recruited. In 36% of cardiac arrests, an app rescuer arrived more than three minutes before the emergency services. App rescuers were recruited through a local media campaign and 70% were already medically trained. The 30% without medical training took a basic lifesupport course and committed to retaking it every two years. ‘Recruitment of the app rescuers was no problem at all because people want to help,’ said Dr Elsner. Project organisers are now asking emergency dispatch units (fire departments and hospitals) across Germany to connect to the app so that they have free access to the fleet of app rescuers. ‘The software has a standard interface and can be easily connected to most emergency alert systems in Europe in just a few steps,’ said Dr Elsner. ‘We provide insurance for app users and we have a guarantee of data security from the German Department for Data Security in SchleswigHolstein.’ Dr Elsner concluded: ‘Ultimately we will roll the app out across Europe. We hope to raise bystander resuscitation rates to 70–90% and for cardiac arrest patients to be resuscitated in three to four minutes on average.’ For more information, visit: www.firstresponderapp.com Source: European Society of Cardiology Press Office

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Comparison of carotid intima–media thickness and coronary artery calcium score for estimating subclinical atherosclerosis in patients with fatty liver disease Hyun-Jin Kim, Hyung-Bok Park, Yongsung Suh, Yoon-Hyeong Cho, Eui-Seok Hwang, Deok-Kyu Cho, Tae-Young Choi

Abstract Introduction: Fatty liver disease (FLD) is correlated with cardiovascular disease. Carotid intima–media thickness (CIMT) and coronary artery calcium score (CACS) can noninvasively identify subclinical atherosclerosis and predict risk for cardiovascular events. This study evaluated CIMT and CACS measurements to detect subclinical atherosclerosis in patients with and without FLD. Methods: Patients who underwent carotid and abdominal ultrasounds as well as cardiac computed tomography (CT) scans were evaluated retrospectively. The differences between the mean CIMT value and CACS measurements in patients with FLD and those with normal livers were estimated. Results: Among 819 patients (average age of 53.3 ± 11.2 years), 330 had FLD. The CIMT was greater in patients with FLD compared to the controls (0.79 ± 0.17 vs 0.76 ± 0.17 mm, p = 0.012), and carotid plaques were more commonly seen in patients with FLD. The incidence of a composite of larger CIMT (≥ 75th percentile) plus plaque presence was higher in FLD patients (43.3 vs 36.0%, p = 0.041). Particularly among young patients (≤ 50), the CIMT was larger in patients with FLD than in the controls. FLD increased the risk of a composite of large CIMT plus plaque presence in young patients (odds ratio 1.92, 95% confidence interval 1.05–3.49, p = 0.034). However, patients with FLD had no greater incidence of CACS of over 100 than the controls. Conclusion: CIMT was a better marker of underlying subclinical atherosclerotic risk among patients with FLD than CACS. FLD particularly, increases the risk of subclinical atherosclerosis in patients younger than 50 years of age. These patients should undergo screening CIMT to detect atherosclerosis and modify risk factors. Keywords: atherosclerosis, carotid intima–media thickness, coronary artery calcium score, fatty liver Submitted 3/3/17, accepted 19/11/17

Cardiovasc J Afr 2017; 29: 93–98

www.cvja.co.za

DOI: 10.5830/CVJA-2017-052

Fatty liver disease, a common hepatic manifestation of the metabolic syndrome, is linked to an increased risk for cardiovascular disease and is proposed to be an independent risk factor for cardiovascular disease.1-3 Patients with fatty liver disease also have increased cardiovascular mortality rates regardless of other traditional risk factors,4 and have increased incidence of subclinical atherosclerosis.3 Although the biological mechanism that explains the relationship between fatty liver disease and atherosclerosis has not been fully proven, recent studies have shown that it may be related to hepatic insulin resistance, chronic inflammation, oxidative stress and dyslipidaemia, including low adiponectin levels.5-7 Carotid intima–media thickness (CIMT), as measured by carotid ultrasound, has been used as a surrogate measurement of subclinical atherosclerosis.8 This measurement is correlated with risk for cardiovascular events.9 Coronary artery calcium score (CACS), as measured by cardiac computed tomography (CT) scan, is also a known marker of atherosclerosis, and the clinical risk for all-cause mortality and cardiovascular disease events increases with increasing CACS.10 In addition, CACS over 100 is a known predictor of coronary events.11,12 Although previous studies have shown that fatty liver disease is associated with coronary artery calcification,13,14 there are no specific guidelines recommending screening for subclinical atherosclerosis in patients with fatty liver disease. Further evaluations should assess the progression of atherosclerosis in young patients with fatty liver disease, even in the absence of other traditional risk factors. This study evaluated the efficacy of CIMT measurements and CACS in detecting subclinical atherosclerosis in patients with fatty liver disease.

Published online 8/12/17

Methods Department of Cardiology, Myongji Hospital, Goyang-si, South Korea Hyun-Jin Kim, MD Hyung-Bok Park, MD Yongsung Suh, MD Yoon-Hyeong Cho, MD Eui-Seok Hwang, MD Deok-Kyu Cho, MD

Department of Internal Medicine, Cardiovascular Centre, Myongji Hospital, Goyang-si, South Korea Tae-Young Choi, MD, tchoicardio@gmail.com

This was a retrospective cohort study and the sample was made up of patients who visited our healthcare centre to undergo routine healthcare maintenance evaluations between June 2011 and December 2013 (n = 23 474). Inclusion criteria were performance on the same day of carotid and abdominal ultrasounds as well as cardiac CT scans evaluating for coronary calcifications (n = 1 064). Patients were excluded from the study if they had conditions that could lead to chronic liver disease, including hepatitis B surface antigen positivity (n = 60), hepatitis C antibody positivity (n = 6), or excessive alcohol consumption (≥ 20 g/day)15 (n = 179).

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The study population was composed of 819 patients. Their clinical features and laboratory findings were collected using electronic medical records. The study was approved by the local institutional review board and was conducted according to the Declaration of Helsinki. The institutional review board exempted written informed patient consent (MJH 2015-01-068). Carotid artery examination was performed using a Vivid E9 ultrasound system (GE Healthcare, Little Chalfont, UK) and an 11L linear probe. Mean CIMT measurements were performed by an experienced ultrasonographer on the far wall of both common carotid arteries at end-diastole along an arterial segment of 10 mm in length located 10 mm proximal to the carotid bulb, using semi-automated border detection software. Carotid plaques were defined as focal and isolated areas of abnormal intima protruding into the lumen, greater than 15 mm or 50% of the surrounding IMT value.16 Carotid plaque-free segments were evaluated for CIMT analysis. The mean CIMT value was calculated by averaging the CIMT measurements of the left and right common carotid arteries. For evaluating carotid plaque, the common carotid arteries, carotid bifurcations and external and internal carotid arteries were scanned. We also evaluated the incidence of a composite of a CIMT value higher than the 75th percentile plus the presence of carotid plaque. We defined this composite as subclinical atherosclerosis. The 75th percentile values of the mean CIMT value were estimated according to gender. Abdominal ultrasound is the most commonly used imaging tool for diagnosing fatty liver disease.17 Abdominal ultrasound examination was performed by an experienced ultrasonographer using an Acuson Sequoia 512 ultrasound system (Siemens Medical Solutions, USA) and a 4C1 curved probe. Normal liver echogenicity was equal to the echogenicity of the cortex of the right kidney.18 Fatty liver disease was diagnosed if the liver echogenicity was diffusely increased compared to the cortex echogenicity of the right kidney.19,20 Calcium score CT was performed to evaluate for coronary artery calcifications (GE LightSpeed VCT, USA). CT images were obtained with a 2.5-mm slice thickness from the carina to the bottom of the heart. The CACS from all calcified plaques in the coronary tree was calculated by an automated program according to the Agatston method.21 We also evaluated the incidence of a CACS over 100, which was a threshold in a previous study, known to increase the risk of atherosclerotic cardiovascular disease.22

Statistical analysis All data were summarised as frequencies and percentages or means and standard deviations. The laboratory findings of liver function and lipid profiles were summarised as median and interquartile range. The Pearson chi-square test was used to compare categorical variables. The Student’s t-test was used to compare continuous variables and the Mann-Whitney U-test was used when the sample size of at least one group was less than 30. The mean CIMT value, CACS value and the presence of carotid plaques were stratified by age. Univariate followed by multivariate logistic regression analyses were performed to evaluate the association between subclinical atherosclerosis and fatty liver disease, with adjustments for

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individuals following traditional risk factors for atherosclerosis: age, hypertension, diabetes and dyslipidaemia. A p-value of less than 0.05 was considered statistically significant. All analyses were performed using SPSS 18.0 (SPSS Inc, Chicago, IL).

Results Among a total of 819 patients (mean age: 53.3 ± 11.2 years old) who met the inclusion criteria for this study, 330 (40.3%) patients had fatty liver disease. Patients’ baseline characteristics are presented in Table 1. Patients with fatty liver disease had significantly larger waist and hip circumferences and body mass indices than patients without fatty liver disease. In addition, patients with fatty liver disease had a higher incidence of medical co-morbidities, including hypertension, diabetes and dyslipidaemia and had worse clinical laboratory findings, including haemoglobin A1c, homocysteine, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase levels than patients without fatty liver disease. Of the 819 patients, the mean CIMT was 0.77 ± 0.17 mm; 194 (23.7%) patients had carotid plaques (Table 2). The CIMT was significantly higher in patients with fatty liver disease than among patients with normal livers (0.79 ± 0.17 vs 0.76 ± 0.17 mm, p = 0.012). Carotid plaques were identified more commonly in patients with fatty liver disease, but did not reach statistical significance (27.0 vs 21.7%, p = 0.094). The incidence of a composite of larger CIMT (≥ 75th percentile) plus the presence of carotid plaque was significantly higher in patients with fatty liver disease (43.3 vs 36.0%, p = 0.041). The 75th percentile CIMT value of male patients was 0.92 mm and that of female patients was 0.88 mm. Among 819 patients, 561 (68.5%) had a CACS of zero. The mean CACS was 53.07 ± 250.14 (Table 2). Conversely, there were no significant differences in the mean CACS and in the incidence of a CACS greater than 100 between patients with fatty liver disease and those with normal livers. Table 3 shows the mean CIMT values, the presence of carotid plaques, and the CACS according to the age groups. Interestingly, among patients under 50 years old (n = 310), the CIMT value was significantly higher in the group with fatty livers than among those with normal livers. These young patients with fatty liver disease had increased risk of subclinical atherosclerosis [odds ratios (OR) 1.92, 95% confidence interval (CI): 1.05–3.49, p = 0.034]. After adjustment for age, hypertension, diabetes and dyslipidaemia, fatty liver disease also increased the risk of subclinical atherosclerosis in young patients (OR 1.90, 95% CI: 1.01–3.59, p = 0.047]. However, there were no significant differences in CACS and carotid plaque presence among patients with fatty liver disease compared to those with normal livers according to age group. Young patients with fatty liver disease did not have a significantly increased incidence of CACS > 100 (OR 0.79, 95% CI: 0.14–4.37, p = 0.785) or incidence of carotid plaque presence (OR 1.65, 95% CI: 0.74–3.70, p = 0.221). Of the patients with a CACS of zero (n = 561), the patients with fatty liver disease (n = 212) had a significantly higher mean CIMT value than the patients with normal livers (n = 349) (0.77 ± 0.15 vs 0.72 ± 0.16 mm, p = 0.002) (Fig. 1). In addition, among

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

Table 1. Baseline patient characteristics All (n = 819)

Fatty liver disease (n = 330)

Normal livers (n = 489)

Age (years)

53.25 ± 11.20

53.44 ± 10.87

53.13 ± 11.42

Male, n (%)

415 (50.7)

212 (64.2)

206 (41.5)

< 0.001

Waist circumference (cm)

81.66 ± 9.39

87.07 ± 7.88

77.99 ± 8.53

< 0.001

Hip circumference (cm)

94.56 ± 6.14

97.02 ± 6.02

92.89 ± 5.65

< 0.001

Waist-to-hip ratio

0.86 ± 0.07

0.90 ± 0.06

0.84 ± 0.07

< 0.001

BMI (kg/m2)

25.07 ± 3.41

26.88 ± 3.19

23.85 ± 2.98

< 0.001

SBP (mmHg)

121.95 ± 13.11

125.9 ± 12.38

119.25 ± 12.91

< 0.001

DBP (mmHg)

74.67 ± 9.80

77.95 ± 9.12

72.46 ± 9.63

< 0.001

Hypertension, n (%)

263 (32.1)

141 (42.17)

122 (24.9)

< 0.001

Diabetes, n (%)

108 (13.2)

70 (21.2)

38 (7.8)

< 0.001

p-value 0.698

Previous history

263 (32.1)

141 (42.7)

122 (24.9)

< 0.001

Fasting blood glucose (mg/dl)

Dyslipidaemia, n (%)

99.54 ± 18.95

105.04 ± 20.85

95.82 ± 16.57

< 0.001

(mmol/l)

(5.52 ± 1.05)

(5.83 ± 1.16)

(5.32 ± 0.92)

5.75 ± 0.68

5.96 ± 0.78

5.62 ± 0.57

< 0.001

10.5 (8.9–12.4)

11.1 (9.3–13.2)

10.2 (8.7–12.0)

< 0.001

191.0 (170.0–214.0)

194.0 (174.0–218.0)

186.0 (167.0–211.5)

(mmol/l)

[4.95 (4.40–5.54)]

[5.02 (4.51–5.65)]

[4.82 (4.33–5.48)]

Triglycerides (mg/dl)

115.0 (77.0–17.01)

146.0 (102.8–212.8)

95.0 (59.0–143.0)

(mmol/l)

[1.30 (0.87–0.19)]

[1.65 (1.16–2.40)]

[1.07 (0.67–1.62)]

HbA1c (%) Homocysteine (μmol/l) Total cholesterol (mg/dl)

0.001 < 0.001

LDL cholesterol (mg/dl)

112.0 (93.0–131.0)

116.5 (98.0–134.0)

107.0 (91.0–129.0)

(mmol/l)

[2.90 (2.41–3.39)]

[3.02 (2.54–3.47)]

[2.77 (2.36–3.34)]

0.001

AST (IU/l)

23.0 (19.0–27.0)

25.0 (20.0–31.0)

21.0 (18.0–26.0)

< 0.001

ALT (IU/l)

20.0 (14.0–29.0)

27.0 (19.0–40.3)

17.0 (13.0–23.0)

< 0.001

Gamma-GTP (IU/l)

25.5 (17.0–42.0)

35.5 (24.0–59.0)

21.0 (15.0–31.0)

< 0.001

ALP (IU/l)

83.0 (53.0–193.0)

85.0 (56.8–201.3)

79.0 (52.0–182.0)

0.023

BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; HbA1c: haemoglobin A1c; LDL cholesterol: low-density lipoprotein cholesterol; AST: aspartate aminotransferase; ALT: alanine aminotransferase; Gamma-GTP: gamma-glutamyl transpeptidase; ALP: alkaline phosphatase. Table 2. Difference in CIMT and CACS between the two groups All (n = 819)

Fatty liver disease (n = 330)

Normal liver (n = 489)

p-value

CIMT (mm)

0.77 ± 0.17

0.79 ± 0.17

0.76 ± 0.17

0.012

Presence of plaque, n (%)

195 (23.8)

89 (27.0)

106 (21.7)

0.094

CIMT ≥ 75th percentile or presence of plaque, n (%)

319 (38.9)

143 (43.3)

176 (36.0)

0.041

53.07 ± 250.14

73.85 ± 323.29

39.05 ± 184.20

0.077

73 (8.9)

32 (9.7)

41 (8.4)

0.518

Cardiac CT calcium score Cardiac CT calcium score > 100, n (%)

CIMT: carotid intima–media thickness; CACS: coronary artery calcium score. Table 3. CIMT, carotid plaque and CACS according to age group Fatty liver disease

Normal liver

p-value

< 30 (20)

0.66 ± 0.11 (4)

0.54 ± 0.11 (16)

0.056

31–40 (98)

0.70 ± 0.15 (43)

0.63 ± 0.14 (55)

0.022

41–50 (192)

0.76 ± 0.17 (73)

0.69 ± 0.16 (119)

0.006

51–60 (295)

0.80 ± 0.16 (123)

0.80 ± 0.15 (172)

0.951

61–70 (158)

0.85 ± 0.15 (65)

0.85 ± 0.14 (93)

0.936

> 70 (56)

0.89 ± 0.14 (22)

0.87 ± 0.16 (34)

0.661

Age group, years (n) CIMT (mm) (n)

CACS < 30

–

31–40

1.21 ± 4.06

2.25 ± 14.62

0.650

41–50

16.62 ± 73.57

18.37 ± 133.82

0.918

51–60

82.89 ± 412.46

28.67 ± 117.79

0.158

61–70

93.32 ± 300.54

94.85 ± 337.18

0.977

311.00 ± 521.03

89.18 ± 197.92

0.028

> 70 Carotid plaque, n (%) < 30

–

31–40

3 (7.0)

4 (7.3)

1.000

41–50

10 (13.7)

9 (7.6)

0.167

51–60

32 (26.0)

36 (20.9)

0.306

61–70

32 (49.2)

40 (43.0)

0.440

> 70

12 (54.4)

17 (50.0)

0.740

patients with a CACS under 100, the mean CIMT value was also significantly higher among patients with fatty liver disease (n = 298) compared to those with normal livers (n = 448) (0.78 ± 0.17 vs 0.75 ± 0.17 mm, p = 0.013).

Discussion The clinical characteristics of patients with fatty liver disease were worse than those of patients with normal livers in our study. The carotid ultrasound images reflected these findings that an increased mean CIMT value was associated with fatty liver disease, and that a composite incidence of larger CIMT (≥ 75th percentile) plus the presence of carotid plaque was also associated with fatty liver disease. Interestingly, young patients (less than 50 years of age) with fatty liver disease showed an increased risk of subclinical atherosclerosis proven by carotid ultrasound rather than by CACS. CIMT was a sensitive marker in identifying atherosclerosis in patients with fatty liver disease, even with a CACS of zero or less than 100. The pathogenesis of fatty liver disease has been not fully elucidated, but insulin resistance and subclinical inflammation are known to be key mechanisms in the development of fatty

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

1.0

p = 0.002

p = 0.013

CACS 0

CACS <100

Carotid IMT (mm)

0.8 0.6 0.4 0.2 0.0

Fatty liver

Normal liver

Fig 1. CIMT values according to the presence of fatty liver disease in patients with a CACS of zero and less than 100. The mean CIMT value was significantly higher among patients with fatty liver disease compared to those with normal livers in both groups. CACS: coronary artery calcium score; CIMT: carotid intima–media thickness.

liver disease.3 Fatty liver disease and the metabolic syndrome share many pathophysiological mechanisms and co-morbidities, such as dyslipidaemia, type 2 diabetes mellitus, insulin resistance and obesity. As demonstrated in our study, patients with fatty liver disease had more metabolic co-morbidities than those without fatty liver disease. The metabolic syndrome promotes the progression of atherosclerosis and increases the risk of cardiovascular disease.23 Moreover, fatty liver disease has been found to be associated with increased mortality rates due to cardiovascular disease and was an independent risk factor for atherosclerosis.24,25 The association of fatty liver disease with the development of cardiovascular disease indicates the importance of early detection and close follow up of atherosclerosis in patients with fatty liver disease. The goal of clinical medicine is to prevent as well as cure disease. However, guidelines do not exist regarding which method of screening should be performed in patients with fatty liver disease and how often they should be evaluated to prevent complications caused by atherosclerosis. Prior studies have shown that the measurement of CIMT using carotid ultrasound and of CACS using cardiac CT can detect subclinical atherosclerosis in fatty liver disease patients.9,26 Increased CIMT in the carotid artery reflects the onset of early atherosclerotic change in the arterial wall. It is known that CIMT measurement by carotid ultrasound in asymptomatic individuals can independently predict future cardiovascular events.27,28 Importantly, by showing a significant increase in CIMT values in patients with fatty liver disease compared to those with a normal liver, our study demonstrated that the development of subclinical atherosclerosis had already been initiated in patients under 50 years of age with fatty liver disease. In addition, it revealed that CIMT evaluation can effectively detect subclinical atherosclerosis in patients with a CACS of zero or below 100. These findings have important implications for screening and prevention of cardiovascular disease in asymptomatic young patients. An elevated CACS is also an independent risk factor for coronary artery disease.22 Moreover, as coronary artery

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calcification is associated with a higher incidence of major and minor cardiovascular events, CACS estimation may serve as an important tool in cardiovascular risk assessment. Because arterial calcification represents end-stage changes in vascular atherosclerosis,29 the absence of calcifications does not mean that the artery is free of atherosclerosis or non-calcified plaque. Our study also suggests that there was no significant difference in the CACS or in the presence of carotid plaques between patients with fatty liver disease and those with normal livers, despite a difference in CIMT values. Prior studies have also demonstrated that coronary artery calcification was more strongly correlated with carotid plaque burden than with CIMT values in patients with asymptomatic subclinical atherosclerosis.30,31 In earlier studies, the CACS has been shown to be the best predictor of total cardiovascular disease, while the CIMT or presence of carotid plaque have been found to be slightly better than the CACS in predicting cerebrovascular events.32-34 Both cardiovascular and cerebrovascular events can be especially catastrophic for young patients with underlying metabolic disease. Therefore, a sensitive method for early detection of subclinical atherosclerosis is needed for patients with fatty liver disease in order to predict the likelihood of vascular complications and to intervene with preventative therapies. The main limitation of this study is that inclusion required that patients had all examinations performed, including carotid and abdominal ultrasound and calcium score CT, therefore our results may not be generalisable to other subjects with the same clinical characteristics. Another limitation of this study is its crosssectional design. A long-term, causal study is needed to assess the impact of atherosclerosis screening on patient outcomes.

Conclusion CIMT was a better marker of underlying subclinical atherosclerotic risk among patients with fatty liver disease than CACS. The measurement of CIMT was especially useful in evaluating the risk of subclinical atherosclerosis in young patients less than 50 years of age. Young patients with fatty liver disease should undergo screening CIMT to detect atherosclerosis so that their risk factors can be modified.

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Participation in research improves overall patient management: insights from the Global Rheumatic Heart Disease registry (REMEDY) EA Prendergast, S Perkins, ME Engel, B Cupido, V Francis, A Joachim, M Al Kebsi, F Bode-Thomas, A Damasceno, A Abul Fadl, A El Sayed, B Gitura, N Kennedy, A Ibrahim, J Mucumbitsi, AM Adeoye, J Musuku, E Okello, T Olunuga, S Sheta, BM Mayosi, LJ Zühlke, for the REMEDY investigators

Abstract Background: Rheumatic heart disease (RHD) is a major public health problem in low- and middle-income countries (LMICs), with a paucity of high-quality trial data to improve patient outcomes. Investigators felt that involvement in a recent large, observational RHD study impacted positively on their practice, but this was poorly defined. Aim: The purpose of this study was to document the experience of investigators and research team members from LMICs who participated in a prospective, multi-centre study, the global Rheumatic Heart Disease Registry (REMEDY), conducted in 25 centres in 14 countries from 2010 to 2012. Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa EA Prendergast, BA S Perkins, MS A Joachim, RN LJ Zühlke, MB ChB, FCPaeds, Cert Card, MPH, FESC, FACC, PhD, Liesl.zuhlke@uct.ac.za

Department of Medicine, Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa ME Engel, BSc (Med) Hons, MPH, PhD V Francis, BA (Nursing) B Mayosi, MB ChB, FESC, DPhil LJ Zühlke, MB ChB, FCPaeds, Cert Card, MPH, FESC, FACC, PhD

Division of Cardiology, Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

Methods: We conducted an online survey of site personnel to identify and quantify their experiences. Telephone interviews were conducted with a subset of respondents to gather additional qualitative data. We asked about their experiences, positive and negative, and about any changes in RHD management practices resulting from their participation in REMEDY as a registry site. Results: The majority of respondents in both the survey and telephone interviews indicated that participation as a registry site improved their management of RHD patients. Administrative changes included increased attention to follow-up appointments and details in patient records. Clinical changes included increased use of penicillin prophylaxis, and Cardiothoracic Surgery Department, Al Shaab Teaching Hospital and Faculty of Medicine, Alzaiem Alazhari University, Khartoum, Sudan A El Sayed, MD A Ibrahim, MD, MSc (Echo), Dip Cardiol (London)

Cardiology Unit, Department of Medicine, Kenyatta National Teaching and Referral Hospital, Nairobi, Kenya B Gitura, MD

Department of Paediatrics and Child Health, College of Medicine, University of Malawi, Blantyre, Malawi; Centre for Medical Education, Queen’s University, Belfast; Royal Belfast Hospital for Sick Children, Belfast, Ireland N Kennedy, MB ChB, MMed Sci

Paediatric Cardiology Unit, Department of Paediatrics, King Faisal Hospital, Kigali, Rwanda J Mucumbitsi, MD

Division of Cardiology, Department of Medicine, University College Hospital, Ibadan, Nigeria AM Adeoye, MD

B Cupido, MB ChB, Cert Card, MPhil B Mayosi, MB ChB, FESC, DPhil LJ Zühlke, MB ChB, FCPaeds, Cert Card, MPH, FESC, FACC, PhD

University Teaching Hospital, Department of Paediatrics and Child Health, University of Zambia, Lusaka, Zambia

Faculty of Medicine and Surgery, University of Sana’a, Al-Thawrah, Cardiac Centre, Sana’a, Yemen

Uganda Heart Institute, Kampala, Uganda

M Al Kebsi, MD, PhD

Department of Medicine, Federal Medical Centre, Abeokuta, Nigeria

Departments of Paediatrics, University of Jos and Jos University Teaching Hospital, Jos, Nigeria F Bode-Thomas, MD

Department of Medicine, Eduardo Mondlane University, Maputo, Mozambique A Damasceno, MD, PhD

J Musuku, MD E Okello, MD, PhD

T Olunuga, MD

Department of Paediatrics, Division of Paediatric Cardiology, Faculty of Medicine, Cairo University Children’s Hospital, Cairo, Egypt S Sheta, MD, PhD

Faculty of Medicine, Benha University, Cairo, Egypt

Dean of Faculty of Health Sciences, University of Cape Town, South Africa

A Abul Fadl, MD

BM Mayosi, MB ChB, FESC, DPhil

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

more frequent INR monitoring and contraceptive counselling. Conclusions: Our study demonstrates that participation in clinical research on RHD can have a positive impact on patient management. Furthermore, REMEDY has led to increased patient awareness and improved healthcare workers’ knowledge and efficiency in caring for RHD patients.

Table 1. Challenges and opportunities: the REMEDY study (online survey) Section 1: Personal details 1. Name 2. Role 3. Site/centre number 4. Name of hospital/facility 5. Country 6. Would you be interested in participating in the telephone interview? 7. If yes, how would you prefer to be contacted?

Keywords: rheumatic heart disease, REMEDY study, clinical research, low- and middle-income countries, implementation

Section 2: About your site 9. How would you describe your site? 10. Before REMEDY, had your site ever conducted a local/single-site research study before?

Submitted 30/7/17, accepted 19/11/17 Published online 19/3/18 Cardiovasc J Afr 2018; 29: 98–105

8. Please specify your contact details and best time/day for calling

www.cvja.co.za

11. Before REMEDY, had your site ever conducted a multi-centre research study before? 12. How many members of staff on your site participated in REMEDY?

DOI: 10.5830/CVJA-2017-054

13. Was a GCP course offered on-site? 14. If yes, how many members of staff completed a GCP course? 15. If no, did any of your staff complete GCP training as part of REMEDY?

Rheumatic heart disease (RHD) is the principal cause of valvular heart disease-related mortality and morbidity in lowand middle-income countries (LMICs). It predominantly affects children and young adults and is potentially responsible for approximately 233 000 deaths per year worldwide.1 However, contemporary data documenting the presentation, clinical course, complications, and ‘real-world’ treatment of RHD are relatively scarce. The Global Rheumatic Heart Disease Registry (REMEDY) was a prospective registry of 3 343 patients with RHD from 25 sites in 14 LMICs that was conducted from January 2010 to November 2012.2 It documented both clinical and echocardiographic characteristics of the patients, and outcomes and current treatment practices, with particular reference to adherence to secondary prophylaxis with penicillin and oral anticoagulation regimens.3,4 The outcomes of REMEDY have drawn attention to a number of concerns. First, although patients were young, two-year case fatality rate was high.4 Second, post-primary school education level is associated with lower risk of death, and third, patients from low- and lower-middle-income countries have higher ageand gender-adjusted mortality rates than patients from uppermiddle-income countries. Fourth, valve surgery is more frequently undertaken in upper-middle-income countries than in low- and lower-middle-income countries. These findings have motivated further research and changes in clinical practice relating to RHD at many of the original REMEDY investigation sites.5-8 It is well known that clinical outcomes of patients who participate in clinical research are superior to those in realworld practice.9 In randomised trials, this effect may relate to selective enrolment but the explanations in registry studies are poorly defined. Therefore, our study aimed to identify the major challenges and opportunities encountered by investigators and members of the research teams during the study and to provide a useful reference for researchers working on future similar projects in LMICs.

Methods We created an online survey comprising four sections, with a total of 45 questions (Table 1). The online survey addressed questions concerning patient follow up, administration and

16. Did you attend a REMEDY investigator meeting? 17. If yes, how far do you agree with the following statement? ‘The investigator meeting was productive and supportive, providing an opportunity for learning and clarification. Adequate time was provided to give and receive feedback. I felt confident to continue with the conduct of the study after the meeting.’ 18. Did you have a site initiation visit from a representative from the UCT project coordination office? 19. If yes, how useful did you find it? ‘I felt I was given complete information and adequate time to learn and ask questions. I was confident to conduct the study at the end of the visit.’ 20. Did you have an on-site monitoring visit from a representative from the UCT project coordination office? 21. If yes, how useful did you find it? ‘The visit was productive and supportive, providing an opportunity for learning and clarification. Adequate time was provided to give and receive feedback. I felt confident to continue with the conduct of the study after the visit.’ 22. What would you change about the training you received? Section 3: Organisation and accessibility 23. Was INR available on-site? 24. If yes, on-site INR results were generally available 25. Results were made available by 26. If not available on-site, where was testing performed? 27. If not available on-site, how long did it take to receive results? 28. What supplies/equipment did you purchase specifically for conducting the REMEDY study? 29. What type of echo equipment did you use? 30. Did you have easy access to an ECG machine? 31. Did you have access to ECG paper? 32. CRFs were sent to the UCT project coordination office 33. During the study, my access to REMEDY email and internet was 34. During the study, medical records at my site were 35. Did you change the way you manage your RHD patients as a result of participating in the REMEDY study? 36. Please check any administrative changes due to the REMEDY study 37. Please check any clinical changes due to the REMEDY study Section 4: Patients 38. Where were baseline ECGs conducted? 39. Where were baseline echos conducted? 40. Did your site experience stock-out problems for penicillin during the study? 41. Did your site experience stock-out problems for anticoagulants during the study? 42. Did your site experience stock-out problems for other cardiac drugs during the study? 43. What were the most difficult challenges you faced upon following up patients? 44. Did you experience any other challenges not mentioned above upon following up patients? 45. How did you resolve them?

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Table 2. Challenges and opportunities: the REMEDY study Telephone interview questions 1. For many of the REMEDY sites, it was their first time participating in a multi-centre research project. Was this the case for your site? 2. Some participants have said that REMEDY had an impact on the clinical, research, academic and administrative aspects of their sites. For example, some reported that it changed the way in which they ran clinics. What impact did REMEDY have on your site? 3. Were you able to obtain additional resources by the fact that you were in the REMEDY study? 4. Did REMEDY have any impact on your relationship with the Ministry of Health? 5. Some members of staff have said that they acquired some skills as a result of the REMEDY study. Was this the case at your site? 6. Have you/they used these skills in other contexts? 7. Would you have liked an opportunity to learn anything else during the study? 8. What was your experience with ethics and institutional approval processes? 9. What, if any, impact has REMEDY had on your RHD patients? 10. Is there anything else that you would like to tell me that REMEDY did or did not do for your site?

their experiences during the study (Table 2). The telephonic questionnaire focused on clinical management, research participation, administration, research and clinical skills, ministry of health collaborations, patient–public interactions, inter-site variations and ethics approvals (Fig. 2). Fig. 1. P articipants from 22 sites completed the survey.

clinical management, staff training, and on-site resources. The majority of questions (34/45) followed a multiple-choice format to quantify the challenges and opportunities encountered by investigators during the study. Thirty participants from 22 sites completed the survey (Fig. 1). Most survey respondents (19/30) also participated in a followup telephonic interview (conducted by Skype, telephone or WhatsApp call) comprising 10 qualitative questions concerning

Fig. 2. Information-gathering methods and their components.

Results Online survey Patient follow up: all respondents (30/30) experienced significant difficulties with the follow up of their RHD patients. Participants identified invalid telephone numbers (24/30), long distances (24/30), medical costs to patients (20/30) and language barriers (7/30) as common problems (Fig. 3). Other barriers included late ethics committee approvals, lack of study funding, lack of support from other on-site staff and difficulty in tracing patients’ addresses.

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35 30 5

Respondents

4 20 15

15 24

10 5 0

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7 Invalid telephone numbers Challenging

Long distances

Medical costs to patients

Not challenging

Language barriers Not answered

Fig. 3. C ommon barriers to follow up.

Strategies to reduce losses to follow up included initiation of home visits to patients who had missed appointments, collection of several telephone numbers from patients and relatives, initiation of telephone reminders before clinics, sketching patient residences on a map in the absence of a formal address system and educating patients about the importance of regular follow up. Administration and clinical management: the majority of responses (24/30) were positive when asked whether participation in REMEDY changed their management of RHD patients (Fig. 4). Administrative changes included increased frequency of follow-up appointments (14/24), increased information noted in patient records (13/24), and changes to clinic times and booking systems (6/24). Clinical changes included more rigorous prescribing practices for penicillin prophylaxis (15/24) and warfarin (6/24), more frequent international normalised ratio (INR) monitoring (11/24), and increased efforts to provide contraceptive counselling to post-menarchal females (9/24). Staff training: in total, 8/30 respondents’ sites offered a good clinical practice (GCP) course on-site that was completed by the

majority of staff at 5/8 sites. On-site GCP training was unavailable to 18/30 respondents. Nevertheless, 10/18 respondents stated that staff completed GCP courses via other mechanisms, such as online courses. Twenty-four/30 respondents attended a REMEDY investigator meeting; 21/24 agreed that the meeting was productive and supportive, that adequate time was provided to give and receive feedback and that they felt confident to continue with the study after the meeting. Ten/30 respondents received a site initiation visit from a representative of the project coordination office (PCO); 10/10 agreed that they were given adequate information and time to learn during the visit and that they felt confident to conduct the study afterwards. Thirteen/30 received an on-site monitoring visit from a representative of the PCO. Of these, 12/13 agreed that the visit was productive and supportive, provided opportunity for learning, clarification and feedback, and increased their confidence to continue with the study. When asked whether they would change anything about the training they received, most (19/30) respondents did not answer, 3/30 stated that they would not change anything and 8/30 made suggestions for future related studies that included clarification about specific medical terminology, drug categories and diagnostic tests, increased numbers of investigator meetings and monitoring visits, mandatory GCP courses and increased online communication. On-site resources: most (26/30) respondents’ sites had participated in single-site research before REMEDY. Most (20/26) had also participated in multi-centre research. As a result, different sites had different capacities to conduct research over two years. For example, numbers of staff greatly varied across REMEDY sites. Fourteen/30 respondents’ teams comprised one to five individuals, 8/30 comprised five to 10 individuals, 2/30 comprised 10 to 15 individuals, and 2/30 had over 15 members of staff dedicated to the project (Fig. 5). INR monitoring was available on 23/30 respondents’ sites. On-site INR results were available at point of care (5/23), on the same day as patient visits (9/23), after visits (6/23) or at times not specified on the survey, such as the day before visits (3/23). Results were made available by telephone (4/23), hardcopy printouts (16/23) or electronic devices (1/23). INR was not available on-site for 7/30 respondents and instead was performed at nearby hospitals, private laboratories or non-governmental organisation-run clinics. Off-site results were received on the

10% 4 10%

80%

No impact

1 to 5

Impact

5 to 10

No answer

10 to 15 Over 15

Fig. 4. O nline survey: impact of REMEDY on patient management.

No answer

Fig. 5. Online survey: numbers of on-site REMEDY staff.

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Percentage of survey respondents

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63.3

63.3 ECG machine

62 60

Echo machine

56.7

Stationery

56 54 52

Scanner

Penicillin

Anticoagulants

Other (e.g. digoxin)

Airtime

Fig. 6. O nline survey: drug stock-out problems.

same day as patient visits (1/7), between one and seven days after visits (5/7) or over seven days after visits (1/7). The majority of sites had access to adequate resources for conducting electrocardiograms (ECGs) and echocardiograms (echos). Baseline echos were conducted on-site at 27/30 respondents’ sites and baseline ECGs were conducted on-site at 26/30 sites. While 26/30 respondents always or usually had access to ECG machines, 2/30 sometimes or seldom had access. Twentyfive/30 respondents always or usually had access to ECG paper while 2/30 sometimes or seldom had access. The majority of respondents experienced drug stock-out problems for their RHD patients, including penicillin (19/30), anticoagulants (17/30) and other cardiac drugs such as digoxin, ACE inhibitors, spironolactone and captopril (19/30) (Fig. 6). On-site internet access varied across sites. For example, REMEDY e-mail was either provided by respondents’ work facilities (15/30) or by personal devices and funds (13/30) throughout the study. Several sites purchased supplies for conducting the REMEDY study. Items bought included telephones (6/30), computers (6/30), airtime (10/30), scanners, copiers and fax machines (13/30), patient binders, files and stationery (11/30), echo machines (5/30), ECG machines (6/30) and other supplies not mentioned in the survey (1/30) such as furniture. Seven/30 respondents did not purchase anything for conducting REMEDY (Fig. 7).

Computer

Telephone

Other

1 0

Fig. 7. Online survey: items purchased during REMEDY.

Research participation: for 15/19 respondents, REMEDY encouraged further participation in rheumatic and congenital heart disease projects and collaboration with researchers in these fields. At least eight sites have continued working with REMEDY investigators on subsequent studies (INVICTUS, RHDGen and Afrostrep) while independent sub-projects have focused on pre-school screening for RHD, atrial fibrillation, primary prevention measures for RHD, and co-morbid associations with hepatitis B.10 Administration: results varied when participants were asked whether participation in REMEDY changed administrative structures at their sites. Some (5/19) stated that it changed systems for the filing of patient records and recording the

Telephone interview Clinical management: almost all responses (17/19) were positive when asked whether participation in REMEDY changed their management of RHD patients (Fig. 8). Changes included more rigorous use of penicillin prophylaxis and anticoagulation, increased efforts to reduce loss to follow up, establishment of independent RHD clinics, more regular INR management, higher-quality standards for echocardiography, improved knowledge concerning early symptoms of RHD, and increased efforts to provide family planning counselling to post-menarchal females. For example, one participant remarked, ‘Before REMEDY, we were not very keen on important interventions like family planning and mandatory injections. REMEDY led us to be more vigilant, to encourage family planning and to make sure our RHD patients are getting regular medications. It has improved the care for these patients’.

Impact

90%

No impact No answer

Fig. 8. Telephone interview: impact of REMEDY on patient management.

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echocardiographic findings, 9/19 stated that it had no impact and 5/19 did not comment on its effect. New research and clinical skills: approximately two-thirds of respondents (14/19) acquired research skills as a result of REMEDY, such as protocol preparation, data management and creation of case report forms, while 8/19 acquired new clinical skills, such as improved interpretation of echocardiograms. The vast majority (16/19) used these skills subsequently in other contexts. Moreover, 14/19 remarked that they would have valued the opportunity to learn further skills during the study. One researcher suggested that their site would have benefitted from an introductory research course to familiarise the research team with the chronology of the study, required steps and study timelines. Other suggestions included increased site-initiation training, on-site visits to ensure quality control, statistical analysis courses, increased guidance on how to perform echocardiography, and more training in anticoagulant management. Ministry of Health collaborations: for 11/19 researchers, REMEDY had an impact on their site’s relationship with the Ministry of Health. One investigator shared their site’s data with the national Ministry of Health in order to procure assistance in drawing up guidelines for the detection and prevention of RHD. At a different site, the findings of REMEDY led to the creation of a national RHD registry and investment in echocardiography machines by the local Ministry of Health. Another site used REMEDY results to collaborate with the Ministry of Health in securing approval for RHD screening in schools. Patient–public interaction: almost all participants (18/19) responded positively when asked whether participation in REMEDY had an impact on interaction with their RHD patients (Fig. 9). For example, investigators at the Groote Schuur and Red Cross War Memorial Children’s Hospitals (Cape Town) presented the outcomes of REMEDY to their RHD patients in 2014. The hospital now hosts an annual event for its RHD patients, which aims to empower patients by improving their understanding of the disease and compliance with treatment. Additionally, a patient community advisory board has been established as a community liaison between patients and clinical researchers. Similarly, the Uganda Heart Institute established a patient support group in which long-term RHD patients support clinicians in counselling newly diagnosed patients. Such groups

Impact

95%

No impact

Fig. 9. T elephone interview: impact of REMEDY on patient behaviour.

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build patient confidence and empower them to manage their disease. Inter-site variations: Although the telephone findings were largely consistent across study sites, wide variation in previous exposure to multi-centre research, patient volume, and access to healthcare resources provided a unique set of challenges and opportunities at each centre. For example, 11/16 respondents who had previously participated in multi-centre research (and 9/11 who had already conducted specific cardiology research) employed pre-existing administrative, human and material resources during REMEDY. Furthermore, on-site support for REMEDY varied greatly from one site to the next, with team sizes ranging from 20 members of staff to one principal investigator acting alone. Those with limited support found the study taxing on their time and resources and expressed that REMEDY had limited impact on their site as a result. Several methods were employed by investigators to resolve this challenge. For example, 8/19 sought additional resources from non-governmental organisations, other hospitals and pharmaceutical companies. One site established a research committee with the intent of employing full-time administrative staff to relieve pressure experienced by clinicians in the course of research activities. Ethical approval: given that REMEDY is a prospective, non-interventional registry, 13/19 sites experienced little difficulty in obtaining ethical clearance. Those that experienced difficulties were unable to recruit large numbers of patients for the study, demonstrating the importance of early application for ethical and institutional approval.

Principal investigator responses The principal investigators of REMEDY were asked an additional question about unexpected challenges during the course of the study. A common problem was the variation in availability of patient identifiers (such as date of birth, thumbprints and formal addresses) across sites. Similarly, clinical records for each patient’s history of stroke, HIV and contraceptive use differed across sites, leading to underestimation of their incidence. Political situations also impacted on the study’s progress. Halfway through the study, South Sudan became an independent nation, resulting in a 30% loss of Sudanese patients from the registry. Furthermore, the civil war in Yemen and the Arab Spring unrest in Cairo significantly hindered follow up of REMEDY patients in these countries. Both principal investigators therefore stressed the importance of start-up and progress meetings in the course of a multicentre research project. Although challenging to implement, monitoring and evaluation strategies allow investigators to identify and address challenges encountered by individual sites. For example, a monitoring visit to Zambia allowed the Project Coordination Office to update REMEDY patient files on site, while visits to other sites resulted in grants for fax machines, cellphone data and laptop computers to enable the transmission of REMEDY data to Cape Town.

Discussion The impact of REMEDY on everyday practice in a variety of geographical and clinical settings demonstrates that RHD

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research has a positive effect on patient management. Clinical practices established during REMEDY, such as closer follow up, increased provision of family planning counselling and the promulgation of independent RHD clinics have continued since original publication of the study. For example, one participant remarked, ‘Before REMEDY we didn’t realise what proportion of patients stopped coming for follow up. Some of them were not regular in attending their clinic and nobody really noticed, but because we had to keep track of them during REMEDY, it improved their engagement with the healthcare system and their follow-up attendance’. Involvement in REMEDY also resulted in the acquisition of new research skills by the study team members and improved sites’ ability to conduct RHD research, as demonstrated by the increase in RHD projects post-REMEDY. Furthermore, publication of the results of REMEDY3,4,11 increased public awareness of RHD and advocacy for its prevention among higher medical and political authorities, such as local and national ministries of health. Involvement in a project with such widespread impact boosted morale among staff at sites with high volumes of RHD patients. For example, one researcher commented, ‘When you’re faced with tides and tides of patients and you’re on your own, it can feel quite disheartening. REMEDY encouraged participants, it gave job satisfaction and it improved motivation in general’. Several factors impeded the study’s progress. Unavoidable situations such as informal address systems and political unrest in several countries where REMEDY sites were based resulted in loss to follow up of REMEDY patients. Furthermore, the majority of survey respondents (22/30) had small on-site teams (0–10 individuals) to assist them in conducting the REMEDY study. Those with limited on-site support remarked in the telephone interview that they found the study taxing on their time and resources and that, as a result, they were unable to perform critical tasks such as timely application for ethical approval. On-site support for GCP training courses was also lacking for 18/30 survey respondents. Given the positive feedback and advocacy from both survey and telephone interview respondents for more GCP training, site initiation and monitoring visits, future related projects should dedicate time and funding to on-site visits and training in order to educate investigators about the project and to assess each site’s resources individually. Our study has several implications for future research and clinical practice. First, the rise in rheumatic and congenital heart disease projects and ensuing collaboration among cardiologists as a result of REMEDY has greatly increased global awareness of RHD. This growing research network is a major advocacy tool for the disease and demonstrates the importance of continuing efforts to conduct and facilitate RHD research. Second, our results indicate that observational registries such as REMEDY have significant value. Not only did the publication of the findings of REMEDY increase public awareness of RHD but it also directly improved clinicians’ and patients’ understanding of the disease. In resource-limited countries, the initiation of local and national registries is the cornerstone of the RHD prevention and control programmes recommended by the World Health Organisation and the World Heart Federation. Finally, the majority of survey and telephone interview respondents used their experiences during REMEDY to propose suggestions for future related studies. Their ideas provide a

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valuable resource to researchers working on similar projects and demonstrate the importance of involving clinicians who are active in the field (and not just those in principal academic centres) in programmes of clinical research. Our study highlights these important implications but is of course limited by the subjective impression from investigators and research staff, rather than stringent monitoring and evaluation processes running alongside the original study. We suggest therefore that these are incorporated into future studies in LMICs to demonstrate the additional benefits (or disadvantages) of research to communities, research personnel and patients.

Conclusions Researchers in the field should draw confidence from our findings that RHD research improves overall patient management and advocacy for the disease. The important lessons learnt were strategies employed by the REMEDY investigators to reduce loss to follow up, the benefits of early application for ethics approval, and the importance of on-site initiation and monitoring during multi-centre projects. The authors acknowledge the work of the original REMEDY investigators*, especially the key investigators (Salim Yusuf, Koon Teo, Ganesan Karthikeyan, Bongani Mayosi), and are grateful to all those who responded to the questionnaire and participated in the telephonic interviews. *Liesl Zühlke, Ganesan Karthikeyan, Mark E Engel, Sumathy Rangarajan, Pam Mackie, Blanche Cupido, Katya Mauff, Shofiqul Islam, Rezeen Daniels, Veronica Francis, Stephen Ogendo, Bernard Gitura, Charles Mondo, Emmy Okello, Peter Lwabi, Mohammed M Al-Kebsi, Christopher Hugo-Hamman, Sahar S Sheta, Abraham Haileamlak, Wandimu Daniel, Dejuma Yadeta Goshu, Senbeta G Abdissa, Araya G Desta, Bekele A Shasho, Dufera M Begna, Ahmed ElSayed, Ahmed S Ibrahim, John Musuku, Fidelia BodeThomas, Christopher C Yilgwan, Ganiyu A Amusa, Olukemi Ige, Basil Okeahialam, Christopher Sutton, Rajeev Misra, Azza Abul Fadl, Neil Kennedy, Albertino Damasceno, Mahmoud Sani, Okechukwu S Ogah, Taiwo Olunuga, Huda HM Elhassan, Ana Olga Mocumbi, Abiodun M Adeoye, Phindile Mntla, Dike Ojji, Joseph Mucumbitsi, Koon Teo, Salim Yusuf, Bongani M Mayosi. In addition, we thank Gabriel Zühlke for the creation of Fig. 3, and acknowledge the assistance of the Children’s Heart Disease Research Unit at the Red Cross War Memorial Children’s Hospital in conducting this study.

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Zühlke LJ, Karthikeyan G, Engel M, Cupido B, Joachim A, Daniels R, et al. The Rheumatic Heart Disease Global Registry (REMEDY) study – Preliminary report. Circulation 2012; 125: e723. (Oral presentation: World Congress of Cardiology, Dubai, UAE. 18–21 April 2012 ).

Zuhlke L, Engel ME, Karthikeyan G, Rangarajan S, Mackie P, Cupido B, et al. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study). Eur Heart J 2015; 36(18):

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Addis Ababa communique. Cardiovasc J Afr 2016. 27: 1–5.

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heart disease from 14 low and middle income countries: 2-year follow-up

Ethiopia: A multisite echocardiography-based screening. Int J Cardiol

Circulation 8 Nov 2016. Okello E, Karkande B, Sebatta E, Kayima J, Kuteesa M, Mutatinu B, et al. Socioeconomic and environmental risk factors among rheumatic heart disease patients in Uganda. PLoS One 2012; 7(8): e43917. 6.

2016. 221: 260–263. 9.

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infection registry: the AFROStrep study. Br Med J Open 2016; 6(2):

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e010248. 11. Karthikeyan G, Zühlke L, Engel M, Rangarajan S, Yusuf S, Teo K, et

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The REMEDY study. Am Heart J 2012; 163(4): 535–540.

Anabolic androgenic steroids may be associated with early coronary artery disease Anabolic androgenic steroids may be associated with early coronary artery disease, according to research presented at the Brazilian Congress of Cardiology (SBC 2017). The annual congress of the Brazilian Society of Cardiology (SBC) was held in São Paulo from 3 to 5 November 2017. Experts from the European Society of Cardiology (ESC) presented a special programme. ‘Anabolic androgenic steroid abuse among young people is a widespread problem worldwide, and adverse events such as sudden cardiac death and heart attack have been reported in athletes,’ said lead author Francis Ribeiro de Souza, PhD student, Heart Institute (Instituto do Coração; InCor), Medical School, University of São Paulo (Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; HCFMUSP), Brazil. ‘In Brazil, around one million people have used anabolic androgenic steroids at least once, and they are the seventh most commonly used drug in the country,’ he added. This study examined whether anabolic androgenic steroids could be associated with early coronary artery disease. It also tested whether reduced high-density lipoprotein (HDL) function could be a mechanism leading to coronary artery disease in anabolic androgenic steroid users. The study included 51 men with an average age of 29 years (range 23–43 years). Of those, 21 did weight lifting and had taken anabolic androgenic steroids for at least two years, 20 did weight lifting but did not take steroids, and 10 were healthy but sedentary. Participants underwent computed tomography coronary angiography (a type of imaging used to visualise the arteries) to assess the presence of atherosclerosis in the coronary arteries. A urine test was performed in all participants to confirm steroid use. Blood samples were taken to measure lipid levels including HDL. The researchers used cell cultures to measure the ability of each participant’s HDL to perform its normal function of removing cholesterol from the macrophages.

The researchers found that 24% of steroid users had atherosclerosis in their coronary arteries, compared to none of the non-users and sedentary participants. The steroid users with atherosclerosis also had significantly reduced HDL levels and HDL function. Mr Ribeiro de Souza said: ‘Our study suggests that anabolic androgenic steroid use may be associated with the development of coronary artery disease in apparently healthy young people. Steroids may have an impact on the ability of HDL to remove cholesterol from macrophages, thereby promoting atherosclerosis.’ ‘This was a small, observational study and we cannot conclude that steroid use causes atherosclerosis,’ he continued. ‘Larger studies with longer follow up are needed to confirm these results.’ Mr Ribeiro de Souza concluded: ‘We observed coronary atherosclerosis in young anabolic androgenic steroid users, which in combination with lower HDL levels and reduced HDL function, could increase the risk of cardiovascular events. Greater awareness is needed of the potential risks of these drugs.’ Dr Raul Santos, scientific chair of SBC 2017, said: ‘This study, despite its small sample size, is well done and calls attention to a possible important health problem in Brazil and elsewhere, since it shows not only the classical lipid disturbances induced by steroids but actually associates them with subclinical atherosclerosis presence, something that we are not supposed to find in young individuals.’ Professor Fausto Pinto, ESC immediate past president and course director of the ESC programme in Brazil, said: ‘This is an important issue in cardiovascular prevention, which deserves further study. During SBC 2017, ESC experts highlighted hot topics in prevention and other fields of cardiology that were presented at ESC Congress 2017 in Barcelona. Source: European Society of Cardiology Press Office

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Prevalence of cardiometabolic risk factors among professional male long-distance bus drivers in Lagos, south-west Nigeria: a cross-sectional study Casmir E Amadi, Tim P Grove, Amam C Mbakwem, Obianuju B Ozoh, Oyewole A Kushimo, David A Wood, Michael Akinkunmi

Abstract Background: Professional drivers are known to be at high risk of cardiovascular disease (CVD). This study was carried out to highlight these risk factors and their predictors among male long-distance professional bus drivers in Lagos, southwest Nigeria, with a view to improving health awareness in this group. Methods: Socio-demographic data, anthropometric indices, blood pressure, fasting plasma blood glucose levels and lipid and physical activity profiles of 293 drivers were measured. Results: Mean age of the study population was 48 ± 9.7 years; 71.0 and 19.5% of the drivers used alcohol and were smokers, respectively; and 50.9% were physically inactive. The prevalence of overweight and obesity was 41.7 and 21.1%, respectively, while 39.7 and 13.9% were hypertensive and diabetic, respectively. Ninety (31.3%) subjects had impaired fasting glucose levels while 56.3% had dyslipidaemia. Predictors of hypertension were age and body mass index (BMI). BMI only was a predictor of abnormal glucose profile. Conclusion: Professional male long-distance bus drivers in this study showed a high prevalence of a cluster of risk factors for CVD. Keywords: cardiovascular disease, risk factors, long-distance drivers Submitted 26/5/17, accepted 14/1/18 Published online 19/2/18 Cardiovasc J Afr 2018; 29: 106–114

www.cvja.co.za

DOI: 10.5830/CVJA-2018-006

Department of Medicine, College of Medicine, University of Lagos, Nigeria Casmir E Amadi, MD, acetalx@yahoo.com Amam C Mbakwem, MD Obianuju B Ozoh, MD

National Heart and Lung Institute, Imperial College, London Tim P Grove, MSc David A Wood, PhD

Department of Medicine, Lagos University Teaching Hospital, Nigeria Oyewole A Kushimo, MD Michael Akinkunmi, MD

Atherosclerotic cardiovascular disease (CVD), typified by coronary heart disease (CHD) and stroke, is a pre-eminent cause of preventable and premature mortality globally, accounting for about 30% of global deaths.1 This is expected to increase by almost 50% by 2030.2 It is also a major cause of mass disability and a somatic cause of loss of productivity globally, with over 150 million disability adjusted life years (DALYS).3 About 80% of this burden from CVD is borne by low- and middle-income countries (LMIC).1 Globally, CVD prevalence is on the increase, remarkably so in the LMIC. This is largely due to increased urbanisation and its corollary of better socio-economic opportunities and Westernisation of lifestyles, such as sedentary living, unhealthy dietary choices, tobacco use, psycho-social stress and harmful use of alcohol.4 These behavioural risk factors predispose to intermediary or metabolic risk factors, such as hypertension, abnormalities in blood glucose levels, dyslipidaemia, overweight and obesity.5,6 One of the socio-economic consequences of urbanisation is mass transit of people, goods and services across regions and long distances via land, air and waterways. The consequence of this is the creation of effective road transport systems in urban areas, with an increase in the number of people engaged in professional driving. Professional drivers as an occupational group are at increased risk of CVD. Morris et al., in their seminal research in 1953, documented that London bus drivers were at increased risk for CHD compared to the more active bus conductors.7 Several other occupational epidemiological studies have provided evidence that professional drivers (short- and long-distance drivers) suffer more and die from CVD.8-11 This excess of CVD morbidity and mortality risk among this group is attributable to a high prevalence of CVD risk factors, such as obesity, hypertension, sedentary living, diabetes, smoking and unhealthy diets found in them.12-14 Beyond these conventional risk factors for CVD, various driving-related activities, such as traffic congestion, ergonomic factors, long-distance driving, shift work, and anxiety and tension from the job of driving have also been implicated. These are known to cause various neuroendocrine and neurocardiological responses, such as increased secretion of cortisol and catecholamines, and decreased heart rate variability, which may also be possible mediators of CVD.15,16 They can also be considered a vulnerable group with social gradients of inequalities; they usually belong to the lower socio-economic class, are not well educated/informed and are not usually covered by public health policies. They also work under immense anxiety and stress. These further heighten their risk for CVD. Lagos is the second most populous city in Nigeria, the second fastest growing city in Africa and the seventh in the world.17 It is

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the economic hub of the country with well-developed intra-city, inter-city and trans-African highway routes for easy mass transit of people, goods and services across geographical barriers,18 making road transportation and the transportation business important features of its economy. Therefore many companies engage in long-distance transportation, with professional drivers employed to provide this service. In Nigeria there are few studies on the CVD risk profile of this important but vulnerable group. These studies show that long-distance drivers have a significant burden of hypertension and overweight/obesity, comparable to or even higher than in the general population.19-21 Hypertension is a common and important CVD risk factor. Its prevalence among long-distance bus drivers in Nigeria is 22.5%,19 which was also the pooled prevalence of hypertension in the general population in 2012.22 However, none of these studies screened the drivers for diabetes/ abnormal glucose profiles or dyslipidaemia. Considering the potential risk associated with professional driving, the importance of bus drivers to the country’s socio-economic development and the paucity of data on the cardiovascular risk profile of long-distance bus drivers, it became necessary to investigate the prevalence of cardiometabolic and lifestyle-related risk factors for CVD and their predictors in this segment of the Nigerian working population in Lagos, southwest Nigeria. The findings from this study will also help create awareness of their risk burden and possibly help shape policies to address this risk.

Methods This was a cross-sectional study involving male long-distance bus drivers in major motor parks in Lagos. The parks were selected based on their size and the routes they serve. Long-distance driving was defined as a distance of 160-km radius from the terminal of departure.23 The calculated sample size was 268 based on the prevalence of hypertension in the general population.22 To allow for 15% attrition rate, the sample size was increased to 308. However, 15 of the drivers did not have complete data and were not included in the data analysis, giving a response rate of 95%. Therefore 293 was the final sample size used in the data analysis. Ethical approval for the study was obtained from the Health Research Ethics Committee of the Lagos University Teaching Hospital. We used a stratified cluster-sampling method to recruit longdistance drivers registered with the Transport Workers’ Union from selected motor parks in Lagos between March and July 2015. The motor parks were then stratified based on whether or not they organised mandatory annual health and safety training for their drivers (AHS motor parks). Only two motor parks employing 400 drivers met this criterion. The drivers in the AHS motor parks only operate from their company terminals. We selected one of these for inclusion in the study because its annual health and safety programme coincided with the study period. All 168 drivers agreed to participate but three (1.8%) later declined. The second category of (non-AHS) motor parks comprised independent drivers and drivers working for small transport companies that operate from general and less regulated motor parks in Lagos and who do not routinely receive formal health and safety checks. We divided these motor parks into two;

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those serving the northern and southern parts of the country, respectively. We then randomly selected two motor parks from each of these strata for inclusion in the study, thereby selecting four in total. Finally, we used a convenience sample of 50 drivers from each of these four parks and recruited 143 of them (71.5% response rate). Those who declined did so due to time constraints and undisclosed personal reasons. Fig. 1 shows the consort diagram on how the participants were recruited. On a mutually agreed day, the consenting drivers were approached in groups and were given a talk on the importance of healthy living and they were also briefed on the usefulness of the study. They were told to observe an overnight fast on the day of the medical screening. We used a structured questionnaire administered by trained interviewers to obtain their sociodemographic data and relevant medical history. Those who couldn’t read or write were assisted to complete the questionnaire by interviewers who could speak their native languages. Thereafter their body weights were measured in kilograms with an Omron HN289 (Osaka, Japan) digital weighing scale, placed on a firm, flat ground, with participants wearing light clothing and with no footwear or cap. Measurements were taken to the nearest 0.5 kg, after ensuring that the scale was always at the zero mark. Their heights were measured in centimetres with a Seca model 216 (GmbH, Hamburg, Germany) stadiometer with the participant standing erect, back against the height metre rule and occiput and heels making contact with the height metre rule. BMI was calculated as weight in kilograms divided by height squared in metres.24 BMI was categorised as underweight < 18.0 kg/m2; normal weight 18.0–24.9 kg/m2; overweight 25.0–29.9 kg/ m2; class I obesity 30.0–34.9 kg/m2; class II obesity 35.0–39.9 kg/ m2 and class III obesity > 40.0 kg/m2. Participants’ waist circumferences were measured with an inextensible, inelastic 1-cm-wide tape snug around the body at the level of the midpoint between the lower margin of the last palpable rib and the top of the anterior iliac crest. Measurements were taken at the end of normal respiration and ≥ 102 cm was regarded as abdominal obesity.25 Their neck circumferences were also measured with an inextensible, inelastic 1-cm-wide tape at the level of the cricoid cartilage. A neck circumference ≥ 40 cm defined obesity.26 The blood pressure (BP) of the participants was measured by the research assistants after five minutes of rest, with the participant seated comfortably, feet on the floor, arm at the level of the heart and free of any constricting clothing. Appropriate-sized cuffs and bladder connected to an Omron HEM7233 (Osaka, Japan) digital sphygmomanometer were used in measuring the BP, which was taken initially on both arms, and the arm with the higher value was used in subsequent measurements. Three BP readings were taken at two- to three-minute intervals. The average of three readings was taken for analysis. Hypertension was defined as BP ≥ 140/90 mmHg, self-volunteered history of hypertension and/or use of anti-hypertensives. Venepuncture was done on each participant while observing aseptic techniques. Five millilitres of venous blood was put in fluoride oxalate and lithium heparin vacutainer specimen bottles for fasting plasma glucose and fasting lipid profiles, respectively, and sent to the laboratory for processing and analysis with a Beckman (Pasadena, CA, USA) automated clinical chemistry autoanalyser using standard reagents/kits from Randox

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8 900 LDD operate from Lagos

Two companies identified (n = 400) have access to yearly health and safety checks

8 500 drivers without access to periodic health checks working out of 25 motor parks in Lagos

One company selected (annual health check coincided with period of study and drivers from across the country could be accessed). Total drivers = 168 and all invited to participate

Three excluded due to refusal

Five parks serving mostly northern routes (2 500 drivers)

17 parks serving mainly southern routes (6 000 drivers)

Two parks randomly selected (1 000 drivers) and 100 drivers approached to participate

Two parks randomly selected (2 000 drivers) and 100 drivers approached to participate

34 excluded due to refusal to participate

23 excluded due to refusal to participate

66 drivers recruited

77 drivers recruited

165 LDD with access to regular health and safety checks agreed to participate

143 LDD without access to regular health and safety checks agreed to participate 15 questionnaires were voided

293 was used for analysis

Final study sample (n = 308). All completed questionnaire

Fig. 1. C onsort diagram describing how participants were recruited into the study. LDD: long-distance commercial drivers.

Laboratories.27 Participants with a fasting plasma glucose value of ≥ 126 mg/dl (6.99 mmol/l), self-volunteered history of diabetes and or use of insulin/oral hypoglycaemic agents were regarded as diabetic, while a fasting plasma glucose level between 100 and 125 mg/dl (5.55–6.94 mmol/l) was regarded as impaired fasting glucose.28 For the purpose of this study, abnormal glucose profile was defined as a combination of impaired fasting glucose and frank diabetes. Abnormal lipid profile was determined from the ATP III guidelines of 2001; total cholesterol (TC) ≥ 240 mg/dl (6.22 mmol/l), high-density lipoprotein cholesterol (HDL-C) ≤ 40 mg/ dl (1.04 mmol/l), and low-density lipoprotein cholesterol (LDLC) > 160 mg/dl (4.14 mmol/l) and triglycerides > 150 mg/dl (1.70 mmol/l).29 Atherogenic dyslipidaemia was defined by the Castelli index as TC/HDL-C > 3.4.30 The physical activity level of participants was assessed with the World Health Organisation (WHO) Global Physical Activity Questionnaire-2 (GPAQ-2), which assesses physical activity in four domains of work, travel, recreational and resting.31 The product of the exercise intensity in metabolic equivalents (METs), duration of activity in hours and the number of times per week, expressed as METs/hour was regarded as exercise volume. A MET/hour value less than 600 per week was taken as physical inactivity.31

Statistical analysis Data entry and analysis were done with the Statistical Package for the Social Sciences 17.0 version (SPSS, Inc, Chicago, IL, USA). Continous data are presented as mean and standard deviation. Categorical variables are expressed as proportions. Pearson’s correlation was used to determine how some independent numerical variables (age, BMI, number of years of professional driving and number of driving hours/week) correlated with the major outcome variables (systolic and diastolic BP, and abnormal glucose profile). Furthermore, the independent variables were dichotomised to look for an association between them and the outcome variables, hypertension and abnormal glucose profile using the chi-squared test. Level of statistical significance was set at p < 0.05 and confidence interval at 95%. Multivariate analysis was done using a forward stepwise binary logistic regression in order to assess for independent predictors of hypertension and abnormal glucose. We included predictor variables with associations at a significance level of p ≤ 0.2 on univariate analysis in order to accommodate for important risk factors.

Results A total of 308 drivers were recruited for the study. Fifteen were

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Table 1. Socio-demographic characteristics of the subjects Parameters

Mean ± SD

Age (years)

44.8 ± 9.7

n (%)

25–44

147 (50.2)

45–64

139 (47.4)

> 65

7 (2.4)

Educational level Primary

77 (26.3)

Secondary

177 (60.4)

Tertiary

37 (12.6)

Marital status Married

265 (90.4)

Single

22 (7.5)

Widowed

3 (1.0)

Divorced

3 (1.0)

Number of years as a professional driver

20.0 ± 10.4

Number of hours driven per week

41.9 ± 28.7

Smoking pattern Active smokers

57 (19.5)

Non-smokers

217 (74.1)

Ex-smokers

19 (6.5)

Alcohol use User

208 (71.1)

Teetotaler

85 (29.0)

excluded due to incomplete data. Therefore 293 were used for data analysis, giving a response rate of 95.1%. The age range of the study population was between 25 and 76 years with a mean of 44.8 ± 9.7 years. Two hundred and eightysix (97.6%) of the subjects were aged between 25 and 65 years. The rest of their socio-demographic characteristics is shown in Table 1. Fifty-seven of the drivers (19.5%; 95% CI: 14.9–24.0%) were active smokers while 217 (74.1%) and 19 (6.5%) were non-smokers and ex-smokers, respectively. The prevalence of alcohol intake was 71.1% (95% CI: 65.7–76.2%). The majority consumed various types of alcoholic beverages: beer, spirits and

Table 2. Measures of obesity, BP and glucose profile of the subjects Parameter

Mean ± SD

BMI (kg/m2)

27.2 ± 9.6

Waist circumference (cm)

96.4 ± 0.9

Proportion < 102 cm

alcohol-based herbal medications. The intake of alcohol was about four bottles of beer per week (Table 1). The mean BMI of the subjects was 27.2 ± 9.6 kg/m2, with 121 (41.7%) and 61 (21.1%) being in the overweight and obese categories, respectively. The prevalence of overweight and obesity were 41.7% (95% CI: 36.0–47.4%) and 21.1% (95% CI: 16.3–25.6%), respectively, giving a combined prevalence of 62.8% (95% CI: 57.2–68.3%) (Table 2). Fig. 2 shows the frequency of the various classes of obesity. The mean waist circumference (WC) of the study population was 94.9 ± 11.9 cm, while the prevalence of abdominal obesity,WC ≥ 102 cm, was 24.1% (95% CI: 19.2–29.0%). The mean neck circumference of the study population was 39.2 ± 2.8 cm, with 28.8% having a neck circumference ≥ 40 cm (Table 2). The mean systolic blood pressure (SPB) and diastolic blood pressure (DBP) of the subjects were 136.3 ± 20.9 and 83.2 ± 13.6 mmHg, respectively. One hundred and sixteen cases of hypertension were identified, giving a prevalence rate of 39.7% (95% CI: 34.0–45.25%). Eighty-eight (75.9%) were detected for the first time during the study. Twenty-eight (24.1%) were previously known hypertensives, with six (21.4%) having good BP control (Table 2). The mean fasting blood glucose level (FBG) of the study population was 108.2 ± 39.7 mg/dl (6.01 ± 2.2 mmol/l). Forty of the subjects (13.9%; 95% CI: 9.7–17.6%) had diabetes and seven (2.4%) were previously known diabetics. Ninety (31.3%) had impaired fasting glucose levels. Prevalence of abnormal glucose profiles (diabetes + impaired FBG) was 45.2% (95% CI: 39.3–50.7%) (Table 2). The mean TC of the study population was 218.4 ± 33.2 mg/ dl (5.66 ± 0.86 mmol/l). The overall lipid profile is presented in Table 3. One hundred and twenty-eight (43.7%) of the subjects had normal lipid profiles while 165 (56.3%) had one form of dyslipidaemia or another. The prevalence of dyslipidaemia in the study was 56.3% (95% CI: 50.6–62.0%), while the prevalence of atherogenic dyslipidaemia, i.e. elevated TC/HDL-C was 33.1% (95% CI: 27.7–38.5%) (Table 3). The mean METs/hour of the subjects was 638.8 ± 565.5, with 66% of them spending most of their time in the travel domain

n (%) 70 168 (66.4) 125 (43.3)

Proportion < 40 cm

171 (59.6)

Proportion ≥ 40 cm

131 (41.6)

Proportion ≥ 102 cm 39.2 ± 2.8

Blood pressure SBP (mmHg)

136.3 ± 20.9

DBP (mmHg)

83.2 ± 13.6

Total number of hypertensives

116 (39.7)

Newly diagnosed

88 (75.9)

Previously known hypertensives

29 (9.6)

40 30 20 10

Blood glucose Fasting blood glucose (mg/dl)

Prevalence (%)

Neck circumference (cm)

108.2 ± 39.7

Normoglycaemia Impaired fasting glucose Total number of diabetics

158 (54.9) 90 (31.3) 40 (13.9)

Newly diagnosed diabetics

33 (82.5)

Previously known diabetics

7 (17.5)

SBP: systolic blood pressure; DBP: diastolic blood pressure.

Normal

Overweight

Class I obesity

Class II obesity

Class III Overweight/ obesity obese

BMI categories

Fig. 2. Prevalence of the various categories of BMI.

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Table 3. Pattern of lipid profiles of the subjects

Mean ± SD Parameter

mmol/l

218.4 ± 33.2

5.66 ± 0.86

LDL-C

136.4 ± 33.6

3.53 ± 0.87

HDL-C

57.7 ± 15.3

1.49 ± 0.40

122.7 ± 64.1

1.39 ± 0.72

Non-HDL-C

161.0 ± 31.5

TC/HDL-C

3.8 ± 1.9

TG/HDL

3.7 ± 2.6

n (%)

70 60 Prevalence (%)

mg/dl

Abnormal profiles Elevated TC

81 (27.8)

Elevated LDL-C

72 (24.6)

Low HDL-C

19 (6.5)

Elevated TC/HDL-C

96 (33.1)

Elevated TG/HDL-C

38 (13.0)

50 40 30 20 10 0

TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides.

(Fig. 3). The prevalence of physical inactivity in the study population, defined as total METs/hour in all four domains < 600 per week was 50.9% (95% CI: 53.1–64.3%). Two hundred and thirty-four (80.4%) of the subjects were inactive, 56 (19.2%) were low active, while one (0.3%) was medium active. None was highly active. One hundred and thirty-two (45.1%) subjects had co-occurrence of two or more risk factors. The most prevalent combination was the duo of hypertension and abnormal glucose profile. Fig. 4 shows the common single risk factors, while common risk factor combinations are shown in Fig. 5. Alcohol use and physical inactivity were the commonest behavioural risk factors, while overweight/obesity, hypertension and dyslipidaemia were the three most common metabolic risk factors in the subjects (Fig. 6). Pearson’s correlation was used to determine how some independent numerical variables (age, BMI, number of years of professional driving and number of driving hours/week) correlated with the major outcome variables (SBP, DBP and fasting blood glucose level). Age correlated significantly with SBP (r = 0.362, p < 0.001) and DBP (r = 0.335, p < 0.001). BMI also correlated significantly with SBP (r = 0.288, p < 0.001) and DBP (r = 0.208, p < 0.001). BMI alone correlated significantly with fasting glucose (r = 0.136, p = 0.021).

Dyslip- Obesity Physical Athe- Smoking Alcohol HyperAbrogen tension normal idae

Fig. 4. Prevalence of single risk factors among the subjects

Furthermore, the independent variables were dichotomised to look for an association between them and outcome variables of hypertension and abnormal glucose profile. In this model only age, BMI, number of years of professional driving and waist circumference had significant associations with hypertension, while none of these except BMI had a significant association with abnormal glucose levels (Table 4). Multivariate analysis was done using a forward stepwise binary logistic regression in order to assess for independent predictors of hypertension and abnormal blood glucose levels. We included predictor variables with associations at a significance level of p ≤ 0.2 on univariate analysis in order to accommodate for important risk factors. The final logistic regression model (Table 5) showed that as age and BMI increased, the chances of becoming hypertensive increased 1.09 and 2.99 times (OR 1.09; 95% CI: 1.06–1.1, p < 0.0001; OR 2.99; 95% CI: 1.69–5.31, p < 0.0001), respectively.

40 34,8

35 5%

Travel

29% 66%

Recreation Work

Prevalence (%)

30 25 20

11,3

10 3,4

5 0

0,3 0

Number of risk factors

Fig. 3. C ontributions of the GPAQ2 domains to total physical activity of the subjects.

Fig. 5. Prevalence of multiple risk factors among the subjects.

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HTN, abnormal glucose, high WC, smoking, high TC/HDL

Table 5. Logistic regression on predictors of hypertension and abnormal glucose levels

n = 293 (%)

Hypertensiona

1 Variables Age

HTN, abnormal glucose, high WC, smoking

Overweight/obesity

Abnormal glucose levelsb

OR (95% CI)

p-value

OR (95% CI)

1.090 (1.058–1.23)

< 0.0001

p-value ns

2.99 (1.69–5.32)

< 0.0001

2.39 (1.33–4.3)

0.04

Variables excluded from the final model were: physical activity, number of driving hours, waist circumference and professional driving years. b Variables excluded from the final model were: age, physical activity, number of driving hours, waist circumference and professional driving years. a

HTN, abnormal glucose, high WC

14 (4.8%)

HTN, abnormal glucose, smoking

8 (2.73%)

HTN, abnormal glucose, TC/HDL ratio

8 (2.73%)

5% CI: 1.33–4.30; p = 0.004). Other variables such as physical activity, number of driving hours, waist circumference and professional driving years were not independently associated with our outcome parameters and were excluded from the final regression model.

HTN, abnormal glucose

36 (12.3%)

None

59 (20.1%) 0

Fig. 6. P revalence of different combinations of risk factors in the subjects. HTN: hypertension; WC: waist circumference; TC: total cholesterol; HDL: high-density lipoprotein cholesterol.

For abnormal glucose level with increasing BMI, the chances of having abnormal glucose level increased 2.5 times (OR 2.39; Table 4. Association between independent variables and hypertension and abnormal glucose levels Hypertension Parameter

% (95% CI)

Driving hours/week

Abnormal glucose levels

p-value

% (95% CI)

0.250

≥ 36

42.9 (35.0–50.9)

< 36

36.3 (28.5–44.2)

0.076 35.6 (27.9–43.2) 25.9 (18.6–33.2)

< 0.001

Years of professional driving ≥ 20

56.2 (43.1–64.4)

< 20

23.1 (16.2–30.0)

Physical activity

0.320 33.1 (25.4–40.8) 27.7 (20.3–35.0)

0.279

< 600 METs/week

42.6 (34.6–50.5)

≥ 600 METs/week

36.3 (28.5–44.2)

0.205 27.6 (20.3-34.9) 34.5 (26.7-42.3)

< 0.001

BMI Overweight/obese

48.4 (41.1–55.6)

Normal

25.9 (17.7–34.2)

Alcohol use

0.002 37.8 (30.7–44.9) 19.8 (12.2–27.4

0.840

Yes

40.1 (33.4–46.8)

38.8 (28.5–49.2)

Smoking

0.807 31.2 (24.9–37.6) 29.8 (20.0–39.5)

0.477

Yes

43.9 (31.0–56.7)

38.7 (28.5-49.2)

0.808 32.1 (19.9-44.4) 30.5 (24.6-36.4)

< 0.001

WC (cm) > 102

61.4 (50.0–72.8)

≤ 102

33.0 (26.8–39.2)

0.076 39.7 (28.1–51.3) 28.3 (22.3–34.3)

< 0.001

Age

p-value

0.499

≥ 45

54.5 (46.4–62.6)

32.6 (25.0–40.3)

< 45

25.2 (18.2–32.2)

29.0 (21.6–36.3)

BMI: body mass index; WC: waist circumference; METs: metabolic equivalents.

Discussion The major finding of this study was that male long-distance bus drivers had a higher prevalence of clustering of cardiometabolic risk factors than the general population, and in addition, most them were unaware of their risk status.12,14 This clustering places them at a higher risk for CVD and contributes significantly to the already burgeoning CVD burden in the general population. Importantly, a CVD event in a driver while driving portends grave danger to him, the passengers and other road users. The prevalence of hypertension in this study was 39.7%, with 75.9% being newly diagnosed. This is higher than the recent pooled national prevalence rate of 28.9% but lower than the 44.9% prevalence from a national study on blindness and hypertension.32,33 Previous local studies reported prevalence rates ranging from 21.4 to 33.5%.19-21 Studies from Brazil and Iran reported prevalence rates of 45.6 and 44.6%, respectively, much higher than their national prevalence rates.12,13 Professional drivers, by nature of their occupation, are largely sedentary and indulge in dietary indiscretions, which could lead to obesity. From this study, obesity was a predictor of hypertension. Furthermore, BMI and longer duration of years of professional driving significantly correlated with the risk of hypertension, similar to findings by Sangaletti et al.12 This association is plausible, as drivers who drive for long hours over many years tend to gain weight inappropriately due to physical inactivity and dietary indiscretion. In addition to high prevalence of hypertension, optimal blood pressure control was equally low among the subjects. Among the 9.6% previously known hypertensives, only 21.4% had optimal BP control. BP control is generally very low in Nigeria, ranging between five and 29.4%.34,35 Ignorance, long travel times, poor access to standard medical care, the asymptomatic nature of hypertension and the relative lack of self-care among males have been suggested as possible causes of poor BP control among long-distance drivers.12 The prevalence of abnormal glucose profiles in this study was 45.2%, comprising 31.3 and 13.9% for impaired fasting gliucose levels and diabetes mellitus (DM), respectively. Most of the diabetics were diagnosed for the first time during this study. There are no local studies for comparison but the reported prevalence of DM from this study is much higher than the 4.5% reported by the International Diabetes Federation (IDF) and the eight to 10% from a study on the general population.36,37 In Iran,

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the prevalence of DM among drivers was 17.5%, comparable to the value obtained from this study, but higher than the 8.5% prevalence reported by the IDF in 2014.13 Obesity is a risk factor for type 2 DM. From our study, BMI was a predictor of abnormal glucose profiles, similar to the findings by Sangaletti et al.12 The prevalence of dyslipidaemia in this study was 56.3%, comparable to the national average of 60.1%.38 The predominant dyslipidaemia was elevated TC levels in 27.8% of the subjects, followed by elevated LDL-C levels in 24.6%, elevated triglycerides in 24.6% and low HDL-C levels in 6.5%. There are no local studies of lipid abnormalities in professional drivers. The pattern obtained is at variance however with patterns reported in local studies in apparently healthy Nigerians, in which the predominant dyslipidaemia was low HDL-C levels.38 In Iran, professional drivers have been shown to have predominantly hypertriglyceridaemia and central obesity, attributable to stressful working conditions.13 The combined prevalence of overweight and obesity, measured by BMI in this study, was 62.8%, comparable to the 63.4 and 64.4% reported by similar local studies,19-21 but higher than the reported prevalence of 31 to 48% in the general Nigerian population.39,40 Similar international studies documented a prevalence of combined overweight and obesity to be between 62.1 and 78.2%.13,41,42 Using waist circumference, the prevalence of obesity from this study was 24.1%. This was lower than the 58.2 and 63.3% from studies in Brazil and Iran, respectively.12,41 This difference might be methodological. In these countries the cut-off for abdominal obesity is 88 cm, less than the 102 cm used in our study.43,44 Prolonged work stress and long hours at work contribute to the development of obesity and abdominal obesity in professional drivers.13 The prevalence of physical inactivity in this study was 50.9%, comparable to the 53.4% from a local study,20 but lower than the 72.8% reported by similar international studies.12,45 Both studies were among truck drivers who probably do not have to stop on the way for passengers to alight for refreshments. Physical inactivity and dietary habits of professional drivers are known to predispose to obesity. Obesity increases the risk of hypertension and abnormal glucose profiles, as shown in this study. It is also known to increase the risk of road traffic accidents among professional drivers due to its association with obstructive sleep apnoea and excessive daytime sleepiness, consequent fatigue and reduction in alertness while driving.46 The prevalence of smoking in this study was 19.5%. Reported prevalence in similar local studies is between 17.8 and 31.3%, all higher than the 15% in the general population.20,21,47,48 The lower prevalence from this study might be due to dilution effect from the ‘no smoking within the bus terminal’ policy of one of the transport companies used in this study. Secondly, the subjects may not have been truthful in their responses to the question on smoking status. Comparable rates of 20 and 15.6% were reported in similar international studies.12,45 Alcohol consumption was very common in this study group, with a prevalence rate of 71.1%. Reported local prevalence in this group ranged from 34 to 84.4%.20,48,49 These figures are much higher than the 7.6 and 9.1% reported in the general male population.50,51 A recent local study from Muslim-dominated north-west Nigeria documented a prevalence of 5.5% among

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inter-city bus drivers.21 This very low figure might be related to a religious obligation that forbids Muslims from consuming alcohol. It is pertinent to note that in this study, CVD risk factors co-occurred, as has been documented in the past.52 This clustering of risk factors increases the overall CVD risk of the individual and also makes control difficult due to problems of pill burden.53,54 In this study 45.1% of the subjects had more than two risk factors clustered together. Clustering of CVD risk factors has been documented in the general population, with prevalence rates between 12.9 and 27.5%, depending on the study population. The commonest risk-factor combinations are hypertension, obesity, abnormal glucose profile and atherogenic dyslipidaemia.55-57 Our findings are similar to the above pattern, although the combination of hypertension and abnormal glucose level was most prevalent. These findings are similar to the pattern reported in similar studies.12,13 There were some limitations in this study. The use of glycosylated haemoglobin would have been helpful in assessing the quality of glycaemic control among the diabetic subjects. Bus drivers with poor control of both BP and glucose levels were not assessed for medication adherence.

Conclusion Long-distance professional drivers in Nigeria are at a higher risk for CVD than the general male population on account of the higher prevalence of a plethora of risk factors they harbour: hypertension, abnormal glucose profiles, overweight/obesity, alcohol use, smoking and atherogenic dyslipidaemia. These risk factors not only co-occur in a large number of drivers, but most are unaware of their risk. Overweight/obesity is the common driver of hypertension and abnormal glucose profiles among them, while age ≥ 45 years increases the risk of developing hypertension. Contributing to their risk is the social gradient of inequality, which affects their access to healthcare and adherence to medical intervention. There is therefore a need to increase CVD risk awareness in this vulnerable yet important segment of our population through public awareness campaigns, banning of smoking and selling of alcoholic beverages in motor parks, compulsory annual health screening, defined maximum driving hours per week, provision of facilities to promote physical activity in the motor parks and medical facilities to diagnose, treat and monitor risk-factor control. Universal health insurance coverage as a national health policy would also help in providing healthcare/health promotional services to this group, who at the moment are not covered by the health insurance scheme. The authors thank Drs Igebu, Anyakpele, Oyatokun, Eluogu and Oshuntokun for helping out with data collection, and Chimamaka Chibuike and Joy Alozie for their help in preparing the manuscript.

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Notes 2010; 3(11): 1–7. 57. Oladapo OO, Falase AO, Salako L, Sodiq O, Shoyinka K, Adedapo K. A prevalence of cardiometabolic risk factors among a rural Yoruba southwestern Nigerian population: a population-based survey. Cardiovasc J Afr 2010; 21(1): 26–31.

Any physical activity in elderly better than none at all for reducing cardiovascular risk Any physical activity in the elderly is better than none at all for reducing cardiovascular risk, according to an 18-year study in more than 24 000 adults published recently in the European Journal of Preventive Cardiology. ‘We know that regular physical activity has major health benefits,’ said first author Dr Sangeeta Lachman, a cardiologist at the Academic Medical Centre, Amsterdam, the Netherlands. ‘Healthy adults are advised to do at least 150 minutes a week of moderate-intensity or 75 minutes a week of vigorousintensity aerobic exercise to reduce their risk of cardiovascular disease,’ she continued. ‘These recommendations are based primarily on research in middle-aged adults and we wanted to know whether regular physical activity yields comparable cardiovascular health benefits in elderly people.’ This study compared the association between different levels of physical activity and the risk of cardiovascular disease in middle-aged to elderly individuals. The hypothesis was that exercise would be equally beneficial in reducing cardiovascular risk in middle-aged and elderly individuals. The study included 24 502 adults aged 39 to 79 years who participated in the European Prospective Investigation into Cancer (EPIC) Norfolk cohort, a prospective population study that is part of the 10-country collaboration EPIC study. The cohort was primarily designed to assess dietary and other determinants of cancer, but data were also collected on determinants of cardiovascular disease. Participants were recruited between 1993 and 1997 from registries of general practices in the county of Norfolk, UK. On enrolment into the study, participants completed a health and lifestyle questionnaire, underwent a standardised physical examination and gave blood samples. Physical activity during work and leisure time was assessed with a questionnaire and participants were categorised as active, moderately active, moderately inactive and inactive.

Patients were followed up until 31 March 2015 for hospitalisation or death from cardiovascular events (coronary heart disease or stroke), which were identified by linking the participant’s unique National Health Service number with the East Norfolk Health Authority (ENCORE) database. Physical activity levels and time to cardiovascular events were investigated in three age categories: less than 55, 55–65 (middle-aged), and over 65 years of age (elderly). During a median follow up of 18 years, there were 5 240 cardiovascular disease events. In elderly participants, hazard ratios for cardiovascular events were 0.86, 0.87 and 0.88 in moderately inactive, moderately active and active people, respectively, compared to inactive people. In those aged 55–65 and less than 55 years, the associations were directionally similar, but not statistically significant. Dr Lachman said: ‘We observed an inverse association between physical activity and the risk of cardiovascular disease in both elderly and middle-aged people. As expected, there were more cardiovascular events in elderly participants, which could explain why the association only reached significance in this age category.’ ‘Elderly people who were moderately inactive had a 14% reduced risk of cardiovascular events compared to those who were completely inactive,’ continued Dr Lachman. ‘This suggests that even modest levels of physical activity are beneficial to heart health. Elderly people should be encouraged to at least do low-intensity physical activities such as walking, gardening and housework.’ She concluded: ‘Given our aging population and the impact of cardiovascular disease on society, a broader array of public health programmes are needed to help elderly people engage in any physical activity of any level and avoid being completely sedentary.’ Source: ESC Press Office

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PASCAR Report Status of cardiac arrhythmia services in Africa in 2018: a PASCAR Sudden Cardiac Death Task Force report MA Talle, A Bonny, W Scholtz, A Chin, G Nel, KM Karaye, JB Anzouan-Kacou, A Damasceno, YR Lubenga, MU Sani, BM Mayosi

Abstract Background: There is limited information on the availability of health services to treat cardiac arrhythmias in Africa. Methods: The Pan-African Society of Cardiology (PASCAR) Sudden Cardiac Death Task Force conducted a survey of the burden of cardiac arrhythmias and related services over two months (15 October to 15 December) in 2017. An electronic questionnaire was completed by general cardiologists and electrophysiologists working in African countries. The questionnaire focused on availability of human resources, diagnostic tools and treatment modalities in each country.

Cardiology Unit, Department of Medicine, University of Maiduguri Teaching Hospital, Maiduguri, Nigeria MA Talle, MD

University of Douala, Cameroon Cardiovascular Research Network, Douala, Cameroon; Hopital Forcilles, FerollesAttilly, France A Bonny, MD, MSc

Pan-Africa Society of Cardiology (PASCAR) W Scholtz, BSc (Hons) G Nel, MSc

Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa

Results: We received responses from physicians in 33 out of 55 (60%) African countries. Limited use of basic cardiovascular drugs such as anti-arrhythmics and anticoagulants prevails. Non-vitamin K-dependent oral anticoagulants (NOACs) are not widely used on the continent, even in North Africa. Six (18%) of the sub-Saharan African (SSA) countries do not have a registered cardiologist and about one-third do not have pacemaker services. The median pacemaker implantation rate was 2.66 per million population per country, which is 200-fold lower than in Europe. The density of pacemaker facilities and operators in Africa is quite low, with a median of 0.14 (0.03–6.36) centres and 0.10 (0.05–9.49) operators per million population. Less than half of the African countries have a functional catheter laboratory with only South Africa providing the full complement of services for cardiac arrhythmia in SSA. Overall, countries in North Africa have better coverage, leaving more than 110 million people in SSA without access to effective basic treatment for cardiac conduction disturbances. Conclusion: The lack of diagnostic and treatment services for cardiac arrhythmias is a common scenario in the majority of SSA countries, resulting in sub-optimal care and a subsequent high burden of premature cardiac death. There is a need to improve the standard of care by providing essential services such as cardiac pacemaker implantation.

A Chin, MD

Keywords: cardiovascular diseases, cardiac arrhythmias, Africa, management, services

Bayero University and Aminu Kano Teaching Hospital, Department of Cardiology, Kano, Nigeria

Submitted 28/4/18, accepted 18/4/18

KM Karaye, BM BCh, PhD MU Sani, MD

Cardiovasc J Afr 2018; 29: 115–121

Felix Houphouet Boigny University, Abidjan, Ivory Coast; Cardiology Institute of Abidjan, Ivory Coast

DOI: 10.5830/CVJA-2018-027

www.cvja.co.za

JB Anzouan-Kacou, MD

Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique A Damasceno, MD

Department of Cardiology, University Hospital of Kinshasa, Democratic Republic of Congo YR Lubenga, MD

Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa BM Mayosi, DPhil, FCP (SA), bongani.mayosi@uct.ac.za

Cardiovascular diseases (CVD) including cardiac arrhythmias are a major public health problem in low- and middle-income countries (LMICs) to which all sub-Saharan African (SSA) countries belong.1,2 Lack of adequate data on the real burden of cardiac arrhythmias and the need for expensive equipment and drugs poses a great impediment to the management of patients with arrythmogenic diseases in SSA. Accurate diagnosis and treatment of cardiac arrhythmias require monitoring of electrical activity of the heart, drug challenges to unmask paroxysmal/concealed arrhythmias, and non-invasive and invasive imaging techniques, which are not

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affordable in many African countries. In addition, there are disparities in cardiovascular healthcare between countries, which are not properly documented. These disparities need to be established for developing south–south collaboration between more developed countries and those with a lack of facilities. The first studies of pacemaker and implantable cardioverter defibrillator implantation rates in SSA were conducted about 20 years ago.3-5 These studies, together with a recent evaluation of access and use of cardiac implantable electronic devices (CIED) and catheter ablation procedures show very low levels of use and access to CIEDs in SSA. The Pan-African Society of Cardiology (PASCAR) Sudden Cardiac Death Task Force has conducted the first pan-African survey on human resources, diagnostic tools and treatment for cardiac arrhythmias across African countries.

Methods We conducted a survey across African countries using an electronic questionnaire (Table 1) between 15 October and 15 December 2017. This was completed by general cardiologists and electrophysiologists from the PASCAR community. The questionnaire focused on availability of human ressources, diagnostic work up and treatment in each country. Blinded multiple responders per country were requested as much as possible. In case of significant disparities in the information from multiple responders, they were invited to revise their responses. For countries in SSA that do not have cardiac physicians, information was obtained from official authorities such as the embassy of the country in question.

Results Of the 55 African countries, data from 33 countries were available. In 19 (63%) of the countries, data were provided from at least two responders.

Human resources To the best of our knowledge, six (18%) countries did not have a registered cardiologist in 2017. These were Central African Republic, Equatorial Guinea, Liberia, Malawi, Somalia and Swaziland. In addition, 11 (33.3%) countries had no trained physicians capable of performing pacemaker implantations (Fig. 1). Fellowship training courses in cardiac pacing for physicians and technologists to provide the required expertise were available in all North African countries, in contrast to SSA countries where this exists in South Africa only. As shown in Fig. 2, most operators obtained their baseline skills in Europe, followed by their own country or another African country, and the minority in Asia or North America. More importantly, almost 60% of these experts did not receive any postgraduate training overseas, and only one-third benefited from a fellowship programme in Europe (Fig. 3). The University of Cape Town has trained three fellows in cardiac pacing from Tanzania, Sierra Leone and Kenya as part of the PASCAR fellowship in cardiac pacing, and a similar training programme has been launched at the University of Gaston Berger, Saint Louis, Senegal.

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Table 1. Questionnaire administered for the survey of arrhythmia services in Africa 1. In which country are you currently practicing medicine? 2. In which centre are you performing electrophysiology and/or pacing? Select all applicable options. a. Public non-teaching hospital b. Teaching hospital c. Private sector 3. In how many centres in your country are patients able to receive a. Pacemaker implantation b. CRT (cardiac resynchronisation therapy) c. ICD (implantable cardioverter–defibrillator) d. Catheter ablation procedures? 4. What is the percentage of public hospitals in your country that supply electrophysiology and/or pacing? 5. Where did you receive your training in electrophysiological procedures and/ or pacing? a. Current country b. Another African country (please specify) c. Asia d. Europe e. America 6. Have you travelled abroad for a short-term fellowship in electrophysiological procedures and/or pacing? If yes, where? a. No b. Another African country (please specify) c. Asia d. Europe e. America f. Australasia 7. Which of the following procedures you are able to perform? Select all applicable options. a. Pacemaker b. CRT (cardiac resynchronisation therapy) c. ICD (implantable cardioverter–defibrillator) d. Catheter ablations e. None 8. How many physicians in your country are able to a. Implant pacemakers b. Implant ICD c. Implant CRT d. Perform ablation procedures? 9. Which of the following diagnostic drugs are available in your country? Please select all applicable options a. Ajmaline iv b. Flecanide iv c. Other, please specify 10. Which of the following anti-arrhythmia drugs are available in your country? Please select all applicable options a. Amiodarone iv b. Xylocaine iv c. Beta-blockers iv d. Digoxine iv e. Procainamide f. Flecainide g. Hydroquinidine 11. Which of the following are used in the treatment of atrial fibrillation/flutter in your country? Please select all applicable options a. Aspirin b. Clopdiogrel c. VKA (Vitamin K antagonist) d. Apixaban e. Rivaroxaban f. Dabigatran g. Electrical cardioversion h. Flutter ablation i. AV node ablation j. AF ablation (pulmonary vein isolation) 12. Which of the following diagnostic tools are used in your country? Please select all applicable options a. 12-lead ECG b. Signal-averaged ECG c. Holter ECG d. 2D echo e. Tilt-table testing f. Exercise testing g. Nuclear imaging h. Coronary angiography i. Right ventricle angiography j. Cardiac CT scan k. Cardiac MRI 13. Which of the following invasive therapies are used in your country? Please select all applicable options a. Pacemaker implantation b. CRT implantation c. ICD implantation d. Flutter ablation e. AV nodal re-entry ablation f. Accessory pathway ablation g. AF ablation (pulmonary vein isolation) h. Complex ablation requiring 3D mapping (ventricular tachycardia, PVCs, atrial tachycardia) 14. Please provide contact details (voluntary) to allow us to keep you abreast of developments a. Title, name and surname b. Institution name c. E-mail address d. Mobile number

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Fig. 1. A vailability of various cardiac arrhythmia services across the African continent. PMK = pacemaker; ICD = implantable cardioverter defibrillator; CRT = cardiac resynchronisation therapy. Ablation includes radiofrequency ablation for atrial flutter and junctional tachycardia (simple ablation) as well as catherter ablation for atrial fibrillation (complex ablation).

Diagnostic facilities and challenges Electrocardiography (ECG): as shown in Table 2, ECG was widely available in all African countries, although mainly in secondary and tertiary health facilities. Signal-averaged ECG (SA-ECG), which detects arrhythmogenic late potentials for the diagnosis of arrhythmogenic right ventricular cardiomyopathy/ dysplasia (ARVC/D) was available only in South Africa and in Maghreb. Ambulatory ECG monitoring (24-hour Holter-ECG) and exercise treadmill testing were not routinely performed in many countries. These tests were available in only 76 and 61% of the countries, respectively, and they were very expensive. For instance, in Cameroon, they cost approximately US$180, about 2.7-fold higher than the minimum monthly wage. Other diagnostic techniques: echocardiography was the most commonly used imaging technique to rule out or confirm structural heart diseases. Although widely available in Africa (Table 2), its use was limited to tertiary centres in larger cities. Tilt-testing to rule out vaso-vagal syncope was available in only six (18.2%) countries (Table 2).

Electrophysiological procedures (EP) for the diagnosis of paroxysmal advanced heart blocks or tachyarrhythmias were routinely performed only in countries from North Africa, Kenya, Senegal and South Africa. Other SSA countries with implantation activity were able to supply pacemaker implantations to only patients with overt conduction system disturbances, excluding the remaining population with unexplained syncope. A catheter laboratory was not available in 19 (57.6%) countries (Fig. 1). Drug challenge aims to unmask silent phenotypes of inheritable arrhythmogenic diseases such as Brugada syndrome. However, this test was largely unavailable in many countries of SSA, with anecdotal reports on ajmaline or flecanide use in some countries (Fig. 4).

Treatments Anti-arrhythmia drugs: as shown in the Table 3, digoxin and amiodarone were the most commonly used medications. Vaughan Williamâ&#x20AC;&#x2122;s class I anti-arrhythmic drugs were in short supply, apart from flecainide, which was present in about 50% of the

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3% 17% 2% 34%

Asia

Asia 34%

USA

42% 5%

Africa (current country)

Europe

AFRICA

58%

Europe USA

Africa (another country)

Africa (another country) 2%

Fig. 2. C entres where primary training in cardiac pacing was obtained by cardiologists practicing in Africa. More than 50% of the cardiologists were trained in Africa.

countries. In general, parenteral medications were less available, making the management of life-threatening arrhythmias quite challenging. Anticoagulants: the increasing burden of atrial fibrillation (Afib) in Africa underscores the need for proper diagnosis and management in order to better prevent stroke and heart failure.

Fig. 3. Centres where short-term fellowship in cardiac pacing was obtained by cardiologists practicing in Africa; 58% have not had formal fellowship training in cardiac pacing.

Vitamin K antagonists (VKAs) were widely available in Africa (Table 4) but their optimal use is challenging. Two-thirds of the REMEDY Afib study patients with a CHA2DS2 â&#x20AC;&#x201C;VASC score > 1 were on oral anti-coagulation but only 27.4% had INR in the therapeutic range.5

Fig. 4. A vailability of drugs used for unmasking covert cardiac arrhythmias.

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Holter ECG

2D echo

Tilt-table testing

Exercise testing

Country

Digoxine

Amiodarone

Beta-blockers

Flecainide

Xylocaïne iv

Procainamide iv

South Africa

Sudan

Tunisia

Algeria

Sudan

Tunisia

Côte d’ivoire

Senegal

Algeria

Côte d’ivoire

Burkina Faso

Kenya

Nigeria

Gabon

Mauritius

Uganda

Cameroon

Tanzania

Angola

Sierra Leone

Tanzania

Angola

Mozambique

Nigeria

Sierra Leone

Senegal

Burkina Faso

Niger

Zimbabwe

Burundi

Mauritius

Uganda

Mozambique

Benin

Burundi

Gabon

Mauritania

Chad

Benin

Congo Republic

Cameroon

Mali

Guinea Conakry

Togo

Congo Republic

Mauritania

Mali

Equatorial Guinea

Togo

Guinea Conakry

Liberia

Somalia

Chad

Niger

Equatorial Guinea

Malawi

Somalia

Swaziland

Malawi

Liberia

Swaziland

Central Africa Republic

SA-ECG and tilt-table test are available in a minority. ECG = electrocardiography ; SA-ECG = signal-averaged electrocardiography; 2D echo = two-dimentional echocardiography.

Non-vitamin K-dependent oral anticoagulants (NOACs) were not available in the majority of countries, including NorthAfrican countries such as Tunisia (Table 4). Invasive treatment: considerable heterogeneity in the access to invasive arrhythmia treatment was observed across Africa (Fig. 1). About one-third of the PASCAR countries did not perform pacemaker implantations: Burundi, Central African Republic, Chad, Equatorial Guinea, Guinea Conakry, Liberia, Malawi, Niger, Republic of Congo, Sao Tome et Principe, Swaziland and Somalia. In 2014, the median pacemaker implantation rate was 2.66 per million population per country.7 The 2017 PASCAR survey showed that the density of pacemaker facilities and operators in SSA was quite low, with a median of 0.14 centres per million population and 0.10 operators per million population.7 Implantable cardioverter-defibrillator (ICD) and cardiac resynchronisation therapy (CRT) were performed in 11/33 (33.3%) and 10/33 (30%) of the countries respectively.7 Electrophysiological studies and ablation techniques were unavailable in all SSA areas, apart from South Africa. Here

Hydroquinidine

Countries

SA-ECG

Table 3. Availability of various anti-arrhythmic drugs in various African countries

ECG

Table 2. Routine diagnostic techniques available in the various African countries

Procainamide and hydroquinidine are largely unavailable; iv = intravenous.

complex ablations requiring three-dimensional mapping were routinely carried out, as in countries of the Maghreb (Table 5). Marked variation in cost (up to 1 000-fold) was observed across countries, with an inverse correlation between implant rates and the procedural fees standardised to the gross domestic product (GDP) per capita.7 Poverty, lack of facilities/equipment, prohibitive costs of procedures, paucity of trained health professionnals, and non-existent fellowship programmes were the main drivers of under-utilisation of interventional cardiac arrhythmia care.

Discussion The paradigm shift in the epidemiology of disease burden in Africa towards the predominance of non-communicable diseases (NCDs) emphasises the need for appropriate health policies to address the changing pattern of diseases. The steady increase in the incidence of heart diseases and their risk factors, such as hypertension, ischaemic heart disease, diabetes and heart failure mechanistically impact significantly on the burden of

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Country

VKA

Apixaban

Rivaroxaban

Dabigatran

Electrical cardioversion

Flutter ablation

AV node ablation

AF ablation (pulmonary vein isolation)

Tunisia

Country

PMK

CRT

ICD

Flutter ablation

AV nodal re-entry ablation

Accessory pathway ablation

AF ablation

Complex ablation requiring 3D mapping

Table 5. Electrophysiological procedures including complex catheter ablations

Aspirin

Table 4. Treatments available for atrial fibrillation and atrial flutter

South Africa

Sudan

Algeria

Kenya

Gabon

Tunisia

Sierra Leone

Senegal

Nigeria

Sudan

Mauritius

Côte d’ivoire

Algeria

Nigeria

Senegal

Mauritius

Côte d’ivoire

Uganda

Tanzania

Cameroon

Angola

Benin

Zimbabwe

Tanzania

Cameroon

Mozambique

Uganda

Sierra Leone

Niger

Angola

Mozambique

Burkina Faso

Zimbabwe

Chad

Mali

Guinea Conakry

Togo

Congo Republic

Mauritania

Mali

Gabon

Togo

Chad

Burundi

Somalia

Mauritania

Malawi

Benin

Swaziland

Central Africa Republic

Liberia

Equatorial Guinea

Burundi

Somalia

Central Africa Republic

Malawi

Equatorial Guinea

Swaziland

Guinea Conakry

Liberia

Congo Republic

Niger

Ablation (simple and complex) remains largely unavailable in the region. VKA = Vitamin K antagonist; AV = atrioventricular; AF = atrial fibrillation.

cardiac arrhythmogenic disorders.8-11 Therefore, health policies in Africa should be aligned towards better management of cardiac arrhythmias. Unfortunately, the current situation in many African countries is very worrisome. Our results show that there was a significant heterogeneity in both access to care and use of CIEDs and EP procedures across the African continent. In fact, the only SSA country with the full armamentarium of arrhythmia services was South Africa. This illustrates the magnitude of the challenge facing many African countries as they set out to improve and potentially expand cardiac arrhythmia care. Given the high incidence of thromboembolic events among patients with rheumatic heart disease, the use of anticoagulation for Afib and INR monitoring need to be especially encouraged. So is the use of proven and relatively simple therapeutic options such as beta-blockers, amiodarone and class Ic antiarrhythmic drugs, as well as external electrical cardioversion for haemodynamically compromised cardiac arrhythmias, which require neither specific facilities nor technical expertise. This is

Ablation (simple and complex) remains largely unavailable in the region. PMK = pacemaker; CRT = cardiac resynchronisation therapy; ICD = implantable cardioverter defibrillator; AV = atrioventricular; AF = atrial fibrillation.

the starting point for the treatment of tachyarrhythmias in those areas where resources are scarce. On the other hand, digoxin, which is the first-line agent for rate control of Afib in most SSA countries (Table 3), should be used cautiously, particularly in the setting of SSA where facilities for monitoring serum digoxin concentration are particularly lacking.12-14 There is a clear need to promote contemporary cardiac arrhythmia care in Africa and to address the disparity that exists between different regions and countries. This will be a huge and multi-faceted challenge. In Europe, the White Book data have been used successfully to raise awareness about inequalities in the treatment of arrhythmias, not only within the cardiology community but also among healthcare administrators, policymakers and other stakeholders.15 Similar steps now also need to be taken in Africa, using data from the first PASCAR arrhythmia report and the results of this survey, and focusing first on developing widespread basic arrhythmia services. 7

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Given the disparities in care already in place, it is obvious that the requirements for improvement in various regions will differ substantially. One might also question how realistic it is to promote arrhythmia care in those areas where the healthcare infrastructure is weak, and even primary care is poorly organised and underfunded. Ideally, basic arrhythmia services would include non-invasive diagnostic work up, intravenous and oral anti-arrhythmia drugs (including parenteral ones), anticoagulants (including NOACs), procedures such as pacemaker implantations, ICDs for secondary prevention, CRT and simple radiofrequency catheter ablations. Re-use of cardiac devices should be promoted to a greater extent, to include those unable to afford new devices.16 This will require significant investment in facilities and training of physicians in some areas. For this reason, the development of arrhythmia services could initially be congregated in a few selected centres in Africa as centres of excellence, which could eventually also function as training sites for arrhythmia specialists. In this regard, countries of North Africa, Kenya, Senegal and South Africa are well equiped to drive such a south–south cooperation. In addition, telemedicine and e-cardiology, including ECG monitoring, will help to diagnose cardiac arrhythmias in patients living in poorresource settings lacking healthcare professionals.

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Mohamed Awad Awad, Elbadri Azza, Anas Babiker, Ibrahim Lway, Eltalib Khalid, Ali Mustafa Ibrahim Mohammed, Mohammed Murtada, Elsayed Osman, Khaleifa Sahar and Mohamed Khadja Abdalhakam Taifour; Tanzania: Mohamed Hanee Mehboob.  We thank Marcus Ngantcha from Cameroon for data managment. Mr Musi Ngidjol Pierre Joseph from Cameroon designed the figures.

References 1.

Mensah GA, Sampson UK, Roth GA, et al. Mortality from cardiovascular diseases in sub-Saharan Africa, 1990–2013: a systematic analysis of data from the Global Burden of Disease Study 2013. Cardiovasc J Africa 2015; 26(Suppl 1): 6–10.

Bestawros M. Electrophysiology in the developing world. Challenges and opportunities. Cardiol Clin 2017; 35: 49–58

Mayosi BM, Scott-Millar R. The 1995 survey of cardiac pacing in South Africa. S Afr Med J 1988; 88(Suppl 4): C207–C211.

Mayosi BM, Scott-Millar RN. Permanent cardiac pacing in Africa. East Afr Med J 2000; 77: 339.

Zühlke L, Engel ME, Karthikeyan G, et al. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study). Eur Heart J 2014; 36(18): 1115–1122.

Bonny A, Ngantcha M, Jeilan M, Okello E, Kaviraj B, Talle MA, et al. Statistics on the use of cardiac electronic devices and interventional elec-

Study limitations

trophysiological procedures in Africa from 2011 to 2016: report of the

The data of the survey highlighting availability of facilities and treatments were mainly obtained on a declarative basis. Also, some countries in SSA had multiple responders while some had none or only one responder. These may have resulted in incomplete data. However, the data still provide an insight into the availability of cardiac arrhythmia services in Africa, which could be used for advocacy and planning.

and Pacing Task Forces. Europace. 2017; Dec 21. doi: 10.1093/europace/

Pan-African Society of Cardiology (PASCAR) Cardiac Arrhythmias eux353. [Epub ahead of print]. 7.

Sliwa K, Wilkinson D, Hansen C, et al. Spectrum of heart disease and risk factors in a black urban population in South Africa (the Heart of Soweto Study): a cohort study. Lancet 2008; 371(9616): 915–922.

Tefera YG, Abegaz TM, Abebe TB, et al. The changing trend of cardiovascular disease and its clinical characteristics in Ethiopia: hospitalbased observational study. Vasc Health Risk Manag 2017; 13: 143–151

Conclusion This new pan-African survey on managing arrhythmias in Africa describes the current status and challenges of managing cardiac arrhythmias in different geographical regions of Africa. There are also huge disparities in diagnostic and treatment facilites in Africa. The increasing burden of cardiac arrhythmias and premature cardiac death calls for better understanding of cardiac arrhythmias, promoting awareness of the importance of arrhythmogenic cardiac disorders in the spectrum of tropical cardiac diseases, and improved cardiac arrhythmia services in Africa.

Carlson S, Duber HC, Achan J, Stergachis A, Wollum A, Bukhman G, et al. Capacity for diagnosis and treatment of heart failure in subSaharan Africa. Heart 2017; 103(23): 1874–1879.

10. Bloomfield GS, Barasa FA, Doll JA, et al. Heart failure in sub-Saharan Africa. Curr Cardiol Rev 2013; 9(2): 157–173. 11. Ouyang AJ, Lv YN, Zhong HL, Wen JH, Wei XH, Peng HW, et al. Meta-analysis of digoxin use and risk of mortality in patients with atrial fibrillation. Am J Cardiol 2015; 115: 901–906. 12. Van Veldhuisen DJ, van Gelder IC, Ahmed A, Gheorghiade G. Digoxin for patients with atrial fibrillation and heart failure : paradise lost or not? Eur Heart J 2013; 34: 1468–1470. 13. Lopes RD, Rordorf R, de Ferrari GM, et al. Digoxin and mortality in patients with atrial fibrillation. J Am Coll of Cardiol 2018; 71(10):

The database of this survey was obtained through the collective efforts of

1063–1074.

several medical doctors and local distributors, to whom we are immensely

14. Raatikainen MJ, Arnar DO, Merkely B, Nielsen JC, Hindricks G,

grateful. The following physicians participated in the study by collecting

Heidbuchel H, et al. A decade of information on the use of cardiac

relevant data from their countries:

implantable electronic devices and interventional electrophysiological

Algeria: Yazid Aoudia; Angola: Sandra Castelo; Burkina Faso: Georges

procedures in the European Society of Cardiology countries: 2017

Millogo and Jonas Kologo; Cameroon: Anastase Dzudie; Kenya: Mohammed

report from the European Heart Rhythm Association. Europace 2017;

Jeilan; Mauritius: Kaviraj Bundhoo; Niger: Ibrahim Toure Ali; Nigeria: Aje

19(suppl 2): ii1–90.

Akinyemi; Senegal: Adama Kane; Sierra Leonne: Russell James Baligeh

15. Sani MU, Mayosi BM. The Pacemaker and ICD Reuse Programme of

Walter; South Africa: Adele Greyling and Andrew Thornton; Sudan:

the Pan-African Society of Cardiology. Heart 2017; 103(23): 1844–1845.

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Review Article The aetiology of cardiovascular disease: a role for mitochondrial DNA? Marianne Venter, Francois H van der Westhuizen, Joanna L Elson

Abstract Cardiovascular disease (CVD) is a world-wide cause of mortality in humans and its incidence is on the rise in Africa. In this review, we discuss the putative role of mitochondrial dysfunction in the aetiology of CVD and consequently identify mitochondrial DNA (mtDNA) variation as a viable genetic risk factor to be considered. We then describe the contribution and pitfalls of several current approaches used when investigating mtDNA in relation to complex disease. We also propose an alternative approach, the adjusted mutational load hypothesis, which would have greater statistical power with cohorts of moderate size, and is less likely to be affected by population stratification. We therefore address some of the shortcomings of the current haplogroup association approach. Finally, we discuss the unique challenges faced by studies done on African populations, and recommend the most viable methods to use when investigating mtDNA variation in CVD and other common complex disease.

have contributed to identifying genetic loci involved in CVDs, and their association with behavioural and biological risk factors.2-7 Despite the numerous nuclear DNA (nDNA) variants identified, only a small portion of the heredity of CVDs can thus far be accounted for by variants discovered with GWAS studies.8 For instance, the 46 loci identified for coronary artery disease (CAD) only account for about six to 13% of CAD hereditability.9-11 The mitochondrion is the only other source of DNA apart from the nucleus. Mitochondrial DNA (mtDNA) encodes for 22 tRNAs, two rRNAs and 13 polypeptides thought important in the catalytic cores of complexes I, III, IV and V of the oxidative

Keywords: mitochondrial DNA, cardiovascular disease, MutPred, mutational load, African Submitted 7/11/16, accepted 31/7/17 Published online 24/8/17 Cardiovasc J Afr 2017; 29: 122–132

www.cvja.co.za

DOI: 10.5830/CVJA-2017-037

Mitochondrial DNA Cardiovascular disease (CVD) remains the main noncommunicable cause of morbidity and mortality in humans.1 While environmental factors and lifestyle choices play a major role in CVD, it is also recognised that genetic factors contribute significantly to the aetiology thereof. In this regard, several studies, most recently genome-wide association studies (GWAS),

Human Metabolomics, North-West University, Potchefstroom, South Africa Marianne Venter, PhD, 20196946@nwu.ac.za Francois H van der Westhuizen, PhD Joanna L Elson, PhD

Institute of Genetic Medicine, Newcastle University, United Kingdom Joanna L Elson, PhD

Fig. 1. mtDNA encodes for 22 tRNA and two rRNA molecules, as well as 13 polypeptide sub-units of the OXPHOS enzyme complexes, as indicated by colour. Enzyme complexes I–IV are involved in a series of redox reactions, which transfer electrons from carriers nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) to oxygen molecules. During these catalytically favourable reactions, H+ ions are pumped from the mitochondrial matrix into the mitochondrial intermembrane space to create a proton-motor force across the inner mitochondrial membrane. This force is used by complex V to catalyse the phosphorylation of adenosine diphosphate (ADP) to adenosine triphosphate (ATP). Complex I: NADH dehydrogenase; complex II: succinate dehydrogenase; complex III: cytochrome c reductase; complex IV: cytochrome c oxidase; complex V: ATP synthase.

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phosphorylation (OXPHOS) system (Fig. 1). In humans, mtDNA contains 16 569 bps and is double stranded.12 Depending on the energy needs of a specific tissue, each cell can contain hundreds to thousands of copies of mtDNA.13 mtDNA is maternally inherited and has a much higher mutation rate than nDNA, possibly 10 to 17 times higher.14 Maternal inheritance results in a lack of bi-parental recombination and therefore the evolution of mtDNA is defined by the emergence of distinct lineages called haplogroups. Multi-copy makes possible a condition called heteroplasmy, where more than one genotype is present in the same cell/ tissue/organism; homoplasmy then, is where all mtDNA copies carry the same allele. Notably, mtDNA is largely overlooked in GWASs, and could possibly contribute to the missing heredity of CVDs. Next we will consider two main arguments on the possible role of mtDNA variants in CVDs.

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some improvements in disease presentation of hypertension and diabetes have been observed in studies where chronic antioxidant treatment is applied.18,28,29 Another mechanism by which inflammation might be altered by mitochondrial dysfunction is through the resultant release of mtDNA into the cytosol and circulation. Because mtDNA is similar to bacterial DNA and not methylated,30 released mtDNA molecules are thought to induce an inflammatory state, which contributes to atherosclerosis and other inflammatory diseases.31-35

Mitochondrial dysfunction and mtDNA damage in vascular health When considering mtDNA as a possible contributor to the aetiology of CVD, it should also be considered from a biological perspective. Much investigation has been conducted in an attempt to elucidate the risk factors and physiological mechanisms involved in the development of CVDs, such as sub-clinical atherosclerosis, hypertension, cardiomyopathy and type 2 diabetes.15-20 An important common feature in all these conditions is inflammation in some form or another (Fig. 2). This inflammatory state is thought to be caused by oxidative stress, due to excessive levels of reactive oxygen species (ROS). ROS can be produced in several pathways, including by enzymes such as NADPH oxidase, nitric oxide synthase, and enzyme complexes of the electron transport chain (ETC).21 The general mechanism of ROS involvement in CVDs is ascribed to oxidative effects. For example, ROS contributes to atherosclerotic lesion formation by oxidising lipids, promoting vessel wall uptake of inflammatory cells, and enhancing proliferation and hypertrophy of vascular smooth muscle cells (VSMC).21 Several studies have shown increased levels of ROS in hypertensive humans and rats.16,22,23 In cultured VSMCs for example, ROS has been shown to cause changes in cellular signalling pathways, favouring vasoconstriction.15 A mechanism for this could be that ROS reduces nitric oxide (NO) bioavailability via quenching, impairing endotheliummediated vasodilation.21,22,24 However, ROS along with other factors of a dysfunctional mitochondrial energy metabolism (e.g. nucleotides, Ca2+) also act as effectors of retrograde signalling and the so-called cell danger response.25-27 Mitochondria are considered the major producers of ROS within the cell. In a recent article, Lopez-Armada et al.18 reviewed the role of mitochondrial dysfunction in the inflammatory response and consequently in the pathology of various diseases, including CVDs. The authors described how mitochondrial dysfunction may modulate inflammatory processes by activating redox-sensitive inflammatory pathways and the NLRP3 inflammasome. In the vasculature, these alterations lead to disturbed endothelial homeostasis, which has been implicated in the pathology of CVDs, such as atherosclerosis.18 Indeed,

Fig. 2. M itochondrial dysfunction and mtDNA damage affect vascular health in several ways. (1) ROS aids in lesion formation by oxidising lipids, increasing the uptake of inflammatory cells into the vascular wall and enhancing proliferation and hypertrophy in VSMC. (2) During endothelium-dependant vasodilation, EC-released NO activates sGC in VSMC to produce cGMP, signalling a vasodilation response. ROS inhibits this mechanism by quenching bioavailable NO molecules. (3) Endothelial homeostasis is disturbed and plaque formation promoted when mitochondrial dysfunction leads to ROS formation and activates redox-sensitive inflammatory pathways. (4) Circulating cell-free mtDNA is similar in structure to bacterial DNA and invokes an inflammatory response, contributing to atherosclerosis. (5) Independent from ROS formation, mtDNA damage leads to aberrant ETC function and reduced ATP levels in VSMC. When cell viability is compromised, apoptosis of VSMC occurs, accelerating plaque growth and decreasing plaque integrity. (6) Through the same mechanisms, apoptosis of monocytes occurs, releasing inflammatory cytokines, contributing to inflammation and consequently, increasing plaque formation and vulnerability. ATP: adenosine triphosphate; cGMP: cyclic guanosine monophosphate; EC: endothelial cell; ETC: electron transport chain; NO: nitric oxide; ROS: reactive oxygen species; sGC: soluble guanylyl cyclase; VSMC: vascular smooth muscle cells.

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mtDNA damage has also been shown to promote atherosclerosis directly, in the absence of oxidative stress. In a study by Yu et al.,36 VSMCs showed increased apoptosis and decreased proliferation in a proof-reading deficient PolG-/-/ ApoE-/- mouse model. Increased secretion of pro-inflammatory factors, tumour necrosis factor-α and interleukin-1β were also reported and implicated in mtDNA release into the cytosol and subsequent activation of the inflammasome. The authors went on to test the applicability of their findings in humans and concluded that an alternative mechanism for mtDNA defects mediate atherosclerosis development, independent of ROS; mtDNA defects lead to aberrant ECT function and consequently reduce ATP content in VSMCs, which then promote apoptosis and inhibit cell proliferation, leading to increased atherosclerosis and risk of plaque rupture.36,37 Plaque vulnerability is further promoted by mtDNA defects via monocyte cell death and the resultant increased release of inflammatory cytokine.38 From these studies, it can be seen that mitochondrial dysfunction, possibly as a result of mtDNA variants or damage, can directly be implicated in mechanisms that encumber vascular health.

mtDNA point mutations and cardiac involvement Clinically proven mtDNA mutations are also an important cause of inherited disease.39 To date, more than 250 deleterious point mutations and deletions of the mitochondrial genome have been clinically proven to be associated with certain disease phenotypes (www.mitomap.org). In several of these diseases, cardiovascular symptoms are an important part of the aetiology. Due to the very high levels of mtDNA population variation seen, both within and between human populations, the identification of mutations causing clinically manifesting disease proves to be a challenge, despite the small size of the mitochondrial chromosome. Initially, DiMauro and Schon had set specific criteria for defining the pathogenicity of mtDNA mutations.40 The list has subsequently been updated to include important methods such as functional testing and singlefibre analysis, which can more specifically link genotype to phenotype.41,42 Notably, a pathogenicity scoring system for mitochondrial tRNAs was devised by McFarland et al.41 and further refined by Yarham et al.43 Mitchell et al.44 also devised a pathogenicity scoring system using variants in complex I mtDNA genes, but this can be applied to any structural mtDNA mutation. A list of these criteria is given in Table 1. It should be noted that there are mtDNA mutations that are exceptions to all the ‘rules’ in Table 1, and this was a critical motivation for algorithms or clinical scoring systems to help weigh the evidence that is presented for each mutation.43,44 For a clinically proven mutation to manifest as a diseased phenotype, as in the case of primary mitochondrial disorders, the allele frequency (heteroplasmy) needs to exceed a certain threshold, usually above 60%, referred to as the phenotypical threshold effect.45 The biochemical threshold effect then refers to the ability of the oxidative phosphorylation (OXPHOS) system to resist the metabolic expression of deficiencies therein.45,46 These deficiencies may be caused by various factors involved in the expression and regulation of the OXHPOS complexes.

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There are many complexities to the expression of mtDNA mutations; a classic example is the mitochondrial tRNA mutation m.3243A>G, the most common of the mtDNA mutations causing mitochondrial disease. The m.3243A>G mutation can result in a vast array of clinical phenotypes affecting multiple systems within the body, causing two distinct clinical syndromes: maternally inherited diabetes and deafness (MIDD), and mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode (MELAS) syndrome in severe cases. Furthermore, the age of onset of m.3243A>G-associated phenotypes spans more than 50 years. The impact of several confounding factors, including heteroplasmy levels, remains unclear.47 Another group of well-studied mutations are those that cause the disease Leber’s hereditary optic neuropathy (LHON). In contrast to the m.3243A>G mutation, LHON has a tissuespecific phenotype manifesting as bi-lateral blindness. Several mtDNA mutations have been implicated in LHON, while three of these mutations, namely m.3460G>A, m.11778G>A and m.14484T>C located in subunits ND1, ND4 and ND6 of complex I, respectively, account for 90 to 95% of cases.48 Unusually, these mutations can be detected as homoplasmic variants without exerting a phenotype. Rather, disease penetrance is significantly influenced by confounding factors such as gender and environment (clinical penetrance is increased to 93% in smoking men),49 and mtDNA haplogroup background (haplogroup J, K and M7 increase risk of clinical penetrance).50,51 The heart has especially high energy needs and relies heavily on OXPHOS-derived ATP, such that one-third of cardiomyocyte volume consists of mitochondria.52 Not surprisingly then, the myocardium is frequently affected in primary mitochondrial disorders.53 In a retrospective review study by Yaplito-Lee et al.,54 33% of paediatric patients with definitive OXPHOS disorders had cardiac manifestations. Several mtDNA mutations (Fig. 3, Table 2 [online]) have also been shown to exhibit cardiac involvement, either as part of a multi-system syndrome (most frequently seen in MELAS), or as isolated occurrences, such as in the absence of associated CVDs or risk factors thereof.53,55,56 Hypertrophic cardiomyopathy (hCM) and pulmonary artery hypertension (PAH) are the two phenotypes most commonly seen as isolated cardiac manifestations of primary mitochondrial Table 1. Criteria for defining the pathogenicity of mtDNA mutations Criteria for pathogenicity of mtDNA mutations include • The mutation must be present only in patients and not in controls • The mutation must be present in varied mitochondrial genetic backgrounds • The mutation must be the best mtDNA candidate variant to be pathogenic • The mutation must affect functionally important domains • Transfer of the mutated mtDNA to another cell line must be accompanied by transfer of the cellular or molecular defect • The mutation must not be a recognised, non-pathogenic, single-nucleotide polymorphism • The mutation must alter an area that is known to be highly conserved throughout evolution • The mutation must occur at varying levels within the cells (i.e. must be heteroplasmic) • A larger proportion of mutant mtDNA must correspond to a more severe phenotype • Single-fibre polymerase chain reaction must be performed by comparing normal and abnormal fibres from muscle • The secondary structure of the tRNA molecule must also be taken into account when determining mt-tRNA mutation pathogenicity These criteria need to be met in order for a mtDNA mutation to be classified as ‘disease causing’ for either structural or mt-tRNA mutations.40-43

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disorders.53 If clinically proven mtDNA mutations can directly lead to cardiac dysfunction, is it plausible to think that other mtDNA variants, such as population variants of mildly deleterious effect, might also lead to or alter severity/penetrance of complex cardiovascular disease phenotypes. From the substantial supportive evidence of mitochondrial involvement in cardiovascular disease, it is therefore evident that genetic investigations on the aetiology of CVD should include consideration of mtDNA variations. In the following sections, we present a number of approaches (plus findings from such investigations) on how mtDNA variation is investigated/ associates in/with disease, with a specific focus on the approaches more likely to show its putative contribution to the risk of CVD development.

Current approaches used for investigating mtDNA involvement in disease Mitochondrial DNA copy number mtDNA copy number can be used as an indicative marker of mitochondrial biogenesis, which is thought to increase in response to increased energy demands, such as exercise, but also as a compensatory method for mitochondrial dysfunction.89 On the other hand, mtDNA copy number has been shown to decrease with aging,90 and has been significantly correlated

Fig. 3. m tDNA morbidity map indicating clinically proven mtDNA mutations that present with syndromic or isolated cardiac involvement. aCAR: abnormal cardiac autonomic regulation; CM: cardiomyopathy; hCM: hypertrophic cardiomyopathy; dCM: dilated cardiomyopathy; HF: heart failure; hiCM: histiocytoid cardiomyopathy; iCM: infantile cardiomyopathy; ishCM: isolated hypertrophic cardiomyopathy; LBBB: left bundle branch block; LVA: left ventricle abnormalities; LVH: left ventricular hypertrophy; LVHT: left ventricular hyper-trabeculation/ non-compaction; mCM: mitochondrial cardiomyopathy; PAH: pulmonary artery hypertension; RRF: ragged red fibres; S&FCA: structural and functional cardiac abnormality; SSS: sick sinus syndrome; VD: ventricular dysfunction; VPB: ventricular premature beats; VSD: ventricular septal defect; WPW: Wolff–Parkinson–White syndrome. See Table 2 for a detailed list of mutations, phenotype, references and pathogenicity scores, as described in Mitchell et al.44 and Yarham et al.43

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with late-onset diseases, such as Parkinson’s disease.91,92 As mentioned above, cell-free circulating mtDNA may also act as an inflammatory agent that contributes to CVDs.33 Altered mtDNA copy number measured in peripheral blood cells have been shown to be associated with different complications of diabetes (diabetic retinopathy and diabetic nephropathy).93,94 Also, an association between telomere length and mtDNA copy number suggests a co-regulatory mechanism for these two parameters, both of which are implicated in aging.95 mtDNA depletion and impaired mitochondrial biogenesis have been shown to be a constant factor in the early stages of heart failure96,97 and other diseases thought to be related to aberrant ROS production.98 While the exact mechanisms behind mtDNA content regulation are still unclear, it seems changes in either direction can be causative or indicative of disease.99 Measurement of mtDNA copy number can be done accurately by real-time PCR methods, making this a useful approach for investigating the role of mitochondrial metabolism in disease phenotypes.

Common mtDNA population variants mtDNA variants accumulated over time differ between population groups that have been separated for several thousand years. Consequently, distinct lineages (mtDNA haplogroups) can be drawn according to these sets of unique changes in mtDNA, referred to as common population variants. The full human mtDNA phylogeny can be accessed at www.phylotree.org.100 Much of the variation seen in modern humans is to be found in the African haplogroups L0 to L6, but this variation has not been as fully described as the variation on other continents. European (e.g. I, J, K, H, T, U, V, W, X) and Asian (e.g. A, B, C, D, F, G) haplogroups fall within super haplogroups M and N, which in turn fall within L3. mtDNA haplogroup association studies aim therefore to associate these common mtDNA population variants with risk for various complex diseases, such as diabetes, hypertension or Parkinson’s disease.101 mtDNA background has been shown to correlate with the severity of cardiomyopathy caused by nDNAencoded mitochondrial protein mutations,102 and increases the penetrance of LHON-causing pathogenic mutations.50,51 It has been proposed that mtDNA population variants could contribute to the adaptability of population groups to their environment by altering mitochondrial enzyme function.103,104 By analysing non-synonymous variants in 104 complete mtDNA sequences from across the globe, Mishmar et al.103 found that the ATP6 and cytochrome b genes were particularly variable in arctic and temperate zones, respectively, leading them to believe that positive selection had taken place. Stressors, such as sudden changes in environment, could then influence the degree of disease susceptibility of these environmentally adapted population groups.105 However, this hypothesis was contested by others who have shown that there are significant differences in the same measure in haplogroups from the same environment.106,107 Additionally, Amo and Brand108 put forward evidence to suggest that certain bioenergetic parameters did not significantly differ between mitochondria from arctic versus tropical haplogroups. In contrast to the action of positive selection, the action of negative or purifying selection on mtDNA has been established for almost a decade.107,109 One important point to consider is that

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positive or directional selection could not have acted identically on all lineages, and therefore would result in a different rate of accumulation of variants on haplogroup lineages, thus affecting our ability to time divergence events by counting the mutational events between lineages. On the other hand, it is possible that negative or purifying selection could act evenly across lineages and not impact on our use of mtDNA as a molecular clock; the reliability of mtDNA as a molecular clock has been widely discussed.110 Because of the central role that mitochondria play in cell signalling and apoptosis, mitochondria have been implicated in several age-related diseases, including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and psoriasis.101,111,112 CVDs are also classified as late-onset diseases and mitochondria have also been implicated in CVDs. Consequently, haplogroup association studies on CVD phenotypes are plentiful, but, as will be revealed, also prone to pitfalls. Crispim et al.113 reported an association of European haplogroup cluster J/T with insulin resistance and type 2 diabetes in a Caucasian-Brazilian cohort. On the other hand, Li et al.114 found no association between mtDNA variation and risk for developing diabetes, while Chinnery et al.115 found no association with type 2 diabetes and major European haplogroups in a large study using 897 cases and 1 010 controls. Rather, Achilli et al.116 found that the risk for developing specific types of diabetes complications (disease outcome) was significantly associated with different mitochondrial haplogroups. Several mtDNA population variants in cytochrome c oxidase and NADH dehydrogenase subunit genes have been associated with body mass index (BMI) in adults.117 In a very large study using a second cohort, Chinnery et al.118 found no significant associations between mtDNA haplogroups and ischaemic heart disease, hypertension, diabetes or the metabolic syndrome, but did find a significant association of sub-haplogroup K with risk of cerebral ischaemic vascular effects. Therefore, while some studies investigating phenotypes included in CVDs have reported results that support a role for mtDNA in CVD,116,117,119,120 there are also conflicting reports.115,118,121 This is not only common in CVD-related literature, but all areas where haplogroup association studies have been applied. This is an indication of the many difficulties that need to be overcome when considering mtDNA variation in the context of disease.122 The unique way in which mtDNA is inherited (lack of bi-parental recombination), which results in the emergence of numerous unique haplogroups, contributes to the complexity encountered when investigating mtDNA involvement in disease. Non-biological factors such as differences in approach to statistical analysis;123 difficulty in proper case and control matching; small effective population size, which results in a higher likelihood of population stratification; and insufficient cohort size,122 further undermine the consistency of these studies. Meta-analysis of data generated by several studies with overlapping phenotypes can be employed to overcome sample size difficulties, but these bring along challenges of their own, as independent studies have different goals/methods, and do not necessarily generate directly comparable datasets.101 So, while haplogroup association studies might have fulfilled an important role in the ongoing pursuit of the involvement of mtDNA variation in disease, it is now well recognised that the field needs to consider alternative models.

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Rare mtDNA population variants It has been shown that negative or purifying selection plays a significant role in mtDNA evolution, with deleterious variants being removed from the population over time,107 and that the power of selection has been equally effective in all human lineages.124 Consequently, rare mtDNA population variants are more likely to be mildly deleterious than common variants, as selection has had less time to remove them from the populations. Indeed, rare mtDNA variants have been linked to changes in CVDs and risk factors. In a study by Govindaraj et al.,120 complete mtDNA analysis revealed 10 non-synonymous variants present in hypertrophic cardiomyopathy patients, but not present in controls or on databases. Seven of these variants were classified as likely ‘pathogenic’, using several online scoring tools such as PolyPhen-2, PMUT and PROVEAN, and were therefore thought to be involved in the development of cardiomyopathy. Rare variants m.5913G>A and m.3316G>A have both been suggested to be associated with increased fasting blood glucose levels, while m.5913G>A was shown to also be associated with increased blood pressure in a selected Framingham heart study subset, all of whom were of European descent.7 In addition, several rare mtDNA variants, such as m.3316G>A,7,125 have been implicated in diabetes mellitus, of which an up-to-date list can be found on www.mitomap.org. Another possibility is that the effect of an accumulation of mildly deleterious variants may only become clinically significant once a population is challenged by a rapid change of confounding factors, such as diet or other environmental factors (toxins).126,127 In conclusion, several approaches are currently in use for investigating the role of mtDNA in common complex disease. mtDNA copy number is an emerging approach that might become more prevalent in studies concerning CVDs as well. In terms of mtDNA variants, rare population variants have been linked to several disease phenotypes, including CVD-related diseases such as cardiomyopathy and diabetes mellitus, and might be found to be associated with other CVDs or risk factors such as hypertension. Rare population variants are more likely to be mildly deleterious,124 but might not have a high enough impact on their own to alter disease onset; rather, these variants might be more likely to alter disease progression or outcomes. For common population variants, several haplogroup association studies have been done in CVDs, but have also been marred by the challenges these types of studies face.122 It seems then that an alternative approach to investigating the role of mtDNA variation in disease is needed when investigating common complex disease.

Alternative approach for investigating mtDNA involvement in disease: the adjusted mutational load hypothesis An alternative approach, the mutational load hypothesis was put forward in Elson et al.111 Mutational load refers to the synergistic effect of several changes in, for example, a specific gene or functionally related set of genes. It does not look for associations with a specific variant but rather a summative effect. While some mtDNA variants might be of little effect on their own, an increased mutational load might be associated with increased risk for a certain disease. mtDNA mutational loads can then

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be adjusted to reflect the position within the phylogeny, since there are large differences in the average number of common population variants between haplogroups. This approach can also further be modified to, for example, exclude low-impact variants, highlighting the role of likely deleterious functional variants. Determining the likely impact or pathogenicity of mtDNA variants can be achieved by using several computational pathogenicity-predicting methods.128 An example of such a method is the MutPred system, which assigns a MutPred score to any protein-coding mtDNA variant, according to 14 gain/ loss properties of protein structure and function.129 The use of this system has been widely validated in the context of mtDNA studies,124 and performs better in an accuracy test when compared with several other methods.128 Therefore the question can be asked whether individuals in the disease group are impacted on by a combination of rare (mildly deleterious) variants or simply whether such variants are more common in the disease cohort than in the controls. The mutational load approach moves away from the study of haplogroups and looks at the collective effect of rare (or recent) variants, which are more likely to be deleterious. It distils the likely impact of a person’s mtDNA variation into a single value on a continuous scale rather than a letter. Consequently it will have more statistical power than conventional haplogroupassociation studies, as more powerful parametric statistics can be applied and fewer comparisons are required.130 It offers an alternative method to explore the involvement of mtDNA variants in disease phenotypes, including diseases thought to be related to mitochondrial dysfunction, such as CVDs.

The unique challenges faced by studies in African populations While communicable diseases are still the leading causes of mortality in sub-Saharan Africa (SSA), CVD particularly is a growing concern here, since the prevalence has risen markedly in recent times as more populations of developing countries become urbanised and are exposed to a diet and lifestyle that increase risk factors for CVD.131 Taking into account the many differences among ethnic groups in the onset and development of CVD,132,133 genomic investigations have also been used to investigate these disparities.131,134-136 However, the number of well-powered genetic studies on CVDs in African populations or people of African descent is much lower than in European populations. As yet, no conclusive nDNA genetic factor/s has been identified to help understand these disparities.137 Current Eurocentric reference panels used in GWAS studies to examine the involvement of population variants in disease have been shown to be of limited use in even common SSA population groups.138 This is indicative of the lack of African representation in our current databases. This lack extends to mtDNA as well. Of the more than 30 000 mtDNA sequences available on GenBank, only 13% of these are of African lineages (L0–6). This bias in published data results in the resolution of the phylogenetic tree being much higher in the European branches (especially super-haplogroup N descendant) than in the African roots,139 despite greater diversity within the latter. Comparatively few studies have been done where the involvement of mtDNA variation in CVD has been considered.135,136,140-142

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Although of small size, one such study helps to highlight the challenges posed by these gaps in our current data. Ameh et al.142 could not find the tRNA mutation m.3243A>G in Nigerian type 2 diabetes patients, despite an association being previously reported in other European and Asian populations. This and other studies143 illustrate the difficulty of extrapolating genetic risk factors for disease from one population group to the next, and the need for population-specific studies.

Conclusion SSA is facing a growing burden of CVD, while the discrepancies in onset and progression between different ethnicities are still poorly understood. Additionally, there are large data gaps when genetic studies on Africans are considered, especially for complex disease phenotypes. The unique genetic backgrounds of different populations also make it difficult to apply advances made in well-studied populations to understudied populations. While great efforts are being made to address these data gaps by initiatives such as the Human Heredity and Health in Africa (H3Africa) initiative,131 the Southern African Human Genome Programme, and the African Genome Variation Project,138 there is an urgent need for even more large-scale African-specific investigations (which should also consider mtDNA variation) to be undertaken if we are to provide the necessary care to all vulnerable groups.144 Realistically, for some time still, it is likely that studies in African populations will be hampered by financial and logistic/infrastructural difficulties,144 limiting the sizes thereof. Fortunately, these studies can benefit from retrospective lessons we have learned thus far in other populations, highlighted in the above discussions. New studies could particularly benefit by asking better-formulated questions, and using alternative approaches that aim to address the challenges associated with many of the classic approaches used, when the role of mtDNA in common disease is investigated.

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Key messages • Cardiovascular disease (CVD) is a leading global cause of morbidity and mortality, and its incidence is on the rise in sub-Saharan Africa. • Discrepancies in the onset and progression of CVDs exist between different ethnic and population groups, which nuclear genetic studies have so far failed to explain. Mitochondrial DNA (mtDNA) offers a viable alternative target for genetic studies concerning common complex disease. • Many approaches can be taken to investigate the role of mtDNA in disease, but not all are suited for studies influenced by moderate cohort size or population stratification. The adjusted mutational load hypothesis offers an alternative approach, which could be of particular value for much-needed studies on CVDs in under-represented sub-Saharan African populations.

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Cardiovascular Topics Absolute cardiovascular risk of women using hormonal contraception in Porto-Novo Arnaud Sonou, Mathieu Ogoudjobi, Philippe Mahouna Adjagba, Corine Houehanou, Richard Aniglé, Léopold Codjo, Murielle Hounkponou, Rosaire Bognon, Salimatou Assani, Daniel Amoussou-Guénou, Dèdonougbo Martin Houénassi

Abstract Introduction: The purpose of this work was to determine the absolute cardiovascular risk (ACVR) of women using hormonal contraception in Porto-Novo.

Departmental University Hospital of l’Ouémé-Plateau, Porto-Novo, Bénin Arnaud Sonou, MD, arnsonou@gmail.com Mathieu Ogoudjobi, MD Corine Houehanou, MD, PhD Richard Aniglé, MD Daniel Amoussou-Guénou, MD

National University Hospital Centre of Hubert Koutoukou Maga, Cotonou, Bénin

Methods: We carried out a descriptive, cross-sectional study, including women at the time of renewal of a hormonal contraceptive method. Blood pressure, fasting venous blood glucose level, body mass index and electrocardiographic left ventricular hypertrophy were studied. The determination of ACVR was dual based on the World Health Organisation (WHO/ISH) and the European Society of Cardiology (ESC/ ESH) models. Results: The mean age of the women was 35.3 ± 8.2 years. Blood pressure and blood glucose levels were high in 24 and 1.5% of cases, respectively. Left ventricular hypertrophy was present in 7.1% of cases. A high ACVR was found in 5.2% of these women, using the ESC/ESH model. Conclusion: The occurrence of women with high ACVR in this group raises the problem of cardiovascular eligibility to the contraceptive method used.

Philippe Mahouna Adjagba, MD Murielle Hounkponou, MD Rosaire Bognon, MD Salimatou Assani, MD Dèdonougbo Martin Houénassi, MD

Keywords: absolute cardiovascular risk, hormonal contraception, eligibility

Departmental University Hospital of Borgou-Alibori, Parakou, Bénin

Published online 27/3/18

Submitted 15/3/17, accepted 5/3/18 Cardiovasc J Afr 2018; 29: e1–e4

Léopold Codjo, MD DOI: 10.5830/CVJA-2018-016

www.cvja.co.za

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

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Risque cardiovasculaire absolu des femmes sous contraception hormonale à Porto-Novo Arnaud Sonou, Mathieu Ogoudjobi, Philippe Mahouna Adjagba, Corine Houehanou, Richard Aniglé, Léopold Codjo, Murielle Hounkponou, Rosaire Bognon, Salimatou Assani, Daniel Amoussou-Guénou, Dèdonougbo Martin Houénassi

Résumé Introduction: Le but du présent travail était de déterminer le risque cardiovasculaire absolu (RCVA) des femmes utilisant une contraception hormonale à Porto-Novo. Méthode: Nous avons mené une étude transversale descriptive incluant des femmes au moment du renouvellement d’une méthode contraceptive hormonale. La pression artérielle, la glycémie veineuse à jeun, l’indice de masse corporelle et l’hypertrophie ventriculaire gauche électrocardiographique ont été étudiées. La détermination du RCVA a été double basée sur les modèles de l’Organisation Mondiale de la Santé (OMS/ISH) et de la Société Européenne de Cardiologie (ESC/ ESH). Résultats: L’âge moyen des femmes était de 35.3 ± 8.2 ans. La pression artérielle et la glycémie étaient élevées dans respectivement 24 et 1.5% des cas; 23.2% étaient obèses. L’hypertrophie du ventricule gauche était présente dans 7.1% des cas. Un RCVA élevé était retrouvé chez 5.2% de ces femmes selon le modèle de l’ESC/ESH. Conclusion: L’existence de femmes à RCVA élevé dans ce groupe soulève le problème de l’éligibilité cardiovasculaire à la méthode contraceptive utilisée.

Mots clés: risque cardiovasculaire absolu, contraception hormonale, éligibilité Submitted 15/3/17, accepted 5/3/18 Published online 27/3/18 Cardiovasc J Afr 2018; 29: e1–e4

www.cvja.co.za

DOI: 10.5830/CVJA-2018-016

Centre Hospitalier Universitaire Départemental de l’Ouémé-Plateau, Porto-Novo, Bénin Arnaud Sonou, MD, arnsonou@gmail.com Mathieu Ogoudjobi, MD Corine Houehanou, MD, PhD Richard Aniglé, MD Daniel Amoussou-Guénou, MD

Centre National Hospitalier Universitaire Hubert Koutoukou Maga, Cotonou, Bénin Philippe Mahouna Adjagba, MD Murielle Hounkponou, MD Rosaire Bognon, MD Salimatou Assani, MD Dèdonougbo Martin Houénassi, MD

Centre Hospitalier Universitaire Départemental du BorgouAlibori, Parakou, Bénin Léopold Codjo, MD

Les méthodes contraceptives hormonales, du fait de leurs mécanismes d’action, ne sont pas sans risque sur l’organisme particulièrement sur la fonction cardiovasculaire et le métabolisme glucido-lipidique.1 Une augmentation mineure des chiffres de pression artérielle (5 à 7 mmHg) a été notée sous œstroprogestatifs. L’hypertension artérielle franche apparaît chez 0.6 à 2.8% de ces utilisatrices.2 L’identification des principaux facteurs de risque athéromateux bien que nécessaire avant le choix d’une méthode contraceptive hormonale, n’est pas systématique sous nos cieux. En Afrique et précisément au Bénin, peu de travaux se sont intéressés au profil de risque cardiovasculaire des femmes sous contraception hormonale, raison pour laquelle nous avons initié l’étude du risque cardiovasculaire absolu (RCVA) de ces femmes à Porto-Novo.

Méthode Nous avons réalisé une étude descriptive transversale de mars à juin 2016. Ont été incluses de façon exhaustive et consécutive toutes les femmes se présentant à l’Association Béninoise pour la Promotion de la Famille (site de Porto-Novo), pour le renouvellement d’une méthode hormonale de contraception. La taille minimale prédéterminée de l’échantillon, obtenue par la formule de Schwartz était de 384 sujets. La collecte des données a été faite par un étudiant en fin de formation en médecine. Une entrevue face à face a eu lieu entre l’enquêteur et l’enquêté (en français ou en langue locale ‘goun’), grâce à un questionnaire standardisé écrit en français. Elle a permis de recueillir les données sociodémographiques et comportementales, notamment la recherche d’un tabagisme actif de moins de 12 mois. Les paramètres anthropométriques ont été mesurés (poids, taille, tour de taille). La pression artérielle (PA) a été prise grâce à un tensiomètre semi-automatique testé et validé. La glycémie à jeun a été dosée sur un prélèvement veineux sanguin et un électrocardiogramme a été enregistré en utilisant un appareil C3000 de marque Bionet. La PA élevée a été retenue en cas de traitement médicamenteux hypotenseur en cours ou pour une PAS ≥ 140 et/ou une PAD ≥ 90 mmHg. La répartition des chiffres de pression artérielle s’est basée sur la classification de la Société Européenne de Cardiologie (ESH/ESC).3 L’hyperglycémie de type diabétique a été retenue en cas de traitement médicamenteux du diabète ou pour une glycémie plasmatique veineuse à jeun ≥ 1.26 g/l.4 L’intolérance au glucose est définie quant à elle par une glycémie à jeun comprise entre 1.02 et 1.25 g/l. Le tour de taille représentant le pourtour abdominal, a été mesuré au niveau d’un point situé à égale distance du bord

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inférieur de la dernière côte et de la crête iliaque. La mesure était notée à la fin d’une expiration. Une obésité abdominale a été retenue pour un tour de taille > 88 cm.3 L’obésité et la surcharge pondérale ont été définies à partir du calcul de l’indice de masse corporelle (IMC) grâce à la formule poids (kg)/taille² (m2). Les femmes ayant un IMC compris entre 25 et 29.9 kg/m2 ont été considérées comme étant en surcharge pondérale alors que celles ayant un IMC ≥ 30 kg/m2 ont été considérées comme obèses.3 L’hypertrophie ventriculaire gauche a été définie à l’électrocardiogramme (ECG) par un indice de Sokolow–Lyon (SV1 ou SV2 + RV5 ou RV6) ≥ 35 mm ou par un indice de Cornell (SV3 + RVL) ≥ 20 mm.5 L’évaluation du risque cardiovasculaire absolu (RCVA) a été faite, utilisant dans un premier temps sur le diagramme de l’OMS et de la Société Internationale d’Hypertension Artérielle (WHO/ ISH),6 et dans un second temps la méthode de l’ESH/ESC.2 La méthode WHO/ISH a permis de classer les femmes selon leur RCVA en cinq catégories (< 10%, entre 10 et 20%, entre 20 et 30%, entre 30 et 40% et > 40%). La méthode ESC/ESH a permis quant elle, de les classer en cinq catégories de risque (faible, faible à modéré, modéré, modéré à élevé et élevé).7 Ces pourcentages définissent la probabilité de présenter au cours des 10 années suivantes, un accident cardiovasculaire majeur fatal ou non. La saisie et l’analyse des données ont été faites sur logiciel Epi-Info 3.1. Les variables quantitatives ont été exprimées en moyenne ± écart-type. Les comparaisons entre sous-groupes ont été faites avec un seuil de significativité de 5%. Les autorisations administratives ont été obtenues auprès des responsables de l’ABPF Porto-Novo. Le consentement écrit des femmes a été obtenu avant inclusion dans l’enquête. Les données des femmes ont été collectées et traitées en toute confidentialité.

Résultats L’enquête a porté sur 375 femmes soit 97.7% de la taille minimale prédéterminée de l’échantillon. Elles étaient âgées en moyenne de 35.3 ± 8.2 ans avec des extrêmes de 18 et 55 ans. Les facteurs de risque cardiovasculaire: La consommation de

Effectif

tabac au cours des 12 précédents mois a été identifiée chez une femme soit une prévalence de 0.3%. L’obésité était retrouvée dans 23.2% des cas (tableau 1). L’obésité abdominale a été retrouvée chez 47.5% des enquêtées (178 cas). Le diabète de type 2 a été retrouvé chez 1.5% (6 cas) des enquêtées tandis que l’intolérance au glucose était présente chez 3.1% (11 cas) d’entre elles. Le tableau 2 montre la répartition des femmes en fonction de leur pression artérielle. Le pourcentage cumulé des 3 grades d’hypertension artérielle donne 24% d’enquêtées à PA élevée. L’hypertrophie ventriculaire gauche a été diagnostiquée chez 27 femmes soit 7.1%. Risque cardiovasculaire absolu: Selon la méthode WHO/ISH, 97.6% (319 femmes) des enquêtées avaient un risque < 10 et 2.4% (8 femmes) un risque compris entre 10 et 20%. Le tableau 3 montre la répartition du RCVA des enquêtées, selon la méthode ESH/ESC. L’analyse de ce tableau montre que le RCVA était faible chez 73.9% des enquêtées, faible à modéré chez 6.7%, modéré chez 7.4% des cas, modéré à élevé chez 8.6% et élevé chez 5.2% d’entre elles.

Discussion La prévalence des facteurs de risque athéromateux a été recherchée sur une population féminine jeune non ménopausée. Dans cette population, nous avons obtenu 24% de femmes à pression artérielle élevée, 1.5% ayant une hyperglycémie, 26.9% en surcharge pondérale, 23.2% d’obèses et 47.5% ayant une obésité abdominale. L’étude de ces paramètres en population générale féminine au Bénin a rapporté des chiffres similaires concernant la pression artérielle élevée (26.3%) et l’hyperglycémie (2%) mais moins élevés pour ce qui est de la surcharge pondérale (23%) et de l’obésité (14%).8 La détermination du RCVA basée sur les facteurs de risque étudiés et sur l’hypertrophie ventriculaire gauche, a donné selon Tableau 2. Répartition des femmes en fonction de la pression artérielle selon la classification de l’ESH/ESC, enquête risque cardiovasculaire absolu (RCVA) femmes sous contraceptifs, Porto-Novo 2016 La pression artérielle

Tableau 1. Répartition des femmes selon l’IMC (kg/m2), enquête risque cardiovasculaire absolu (RCVA) femmes sous contraceptifs, Porto-Novo 2016 l’IMC (kg/m2)

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% cumulé

Effectif

% cumulé

Optimale

23.5

Normale

110

29.3

52.8

Normale haute

23.2

76 89.1

1.3

HTA grade 1

13.1

Normal (18.5–24.9)

172

45.9

47.2

HTA grade 2

8.0

Surcharge (25.0–29.9)

111

29.6

76.8

HTA grade 3

2.9

23.2

Maigreur (< 18.5)

Obèse (≥ 30) Total

100

375

Total

97.1 100

375

HTA = hypertension.

Tableau 3. Répartition du risque cardiovasculaire absolu (RCVA) des enquêtées, selon la méthode ESC/ESH, enquête RCVA femmes sous contraceptifs, Porto-Novo 2016 Effectif (%) RCVA

PA normale et optimale

PA normale haute

HTA grade 1

HTA grade 2

Pas d’autre FRCV

85 (27.3)

25 (8)

17 (5.5)

6 (1.9)

1 ou 2 FRCV

68 (21.9)

35 (11.2)

17 (5.5)

≥ 3 FRCV ou hyperglycémie ou HVG

15 (4.8)

6 (1.9)

66 (21.2)

40 (12.9)

Total

168 (54)

HTA grade 3

Total

3 (1)

136 (43.7)

15 (4.8)

4 (1.3)

139 (44.7)

5 (1.6)

4 (1.3)

36 (11.6)

26 (8.4)

11 (3.5)

311 (100.00)

HTA = hypertension, PA = la pression artérielle, HVG = hypertrophie ventriculaire gauche, FRCV = facteur de risque cardiovasculaire, encadré vert-foncé = risque faible, encadré vert-clair = risque faible à modéré, encadré jaune = risque modéré, encadré orange = risque modéré à élevé, encadré rouge = risque élevé.

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la méthode de l’ESC, un risque modéré à élevé dans 8.6% des cas et un risque élevé dans 5.2% des cas. Il a été démontré que la prise d’hormones contraceptives induit une modification du métabolisme des hydrates de carbone, elle-même impliquée dans la prise de poids.2 Soulé au Nigéria a trouvé que la prise du poids en trois ans était plus importante chez des femmes utilisant une contraception hormonale que chez celles utilisant une méthode non hormonale.9 Asaré au Ghana a démontré au cours d’une étude cas témoins que l’usage de contraceptifs hormonaux entrainait de façon significative une prise de poids, une augmentation des taux sanguins de cholestérol total et low-density lipoprotein (LDL) cholestérol ainsi qu’une élévation de la PA diastolique.10 L’interaction entre la contraception hormonale et le risque cardiovasculaire a amené l’Organisation Mondiale de la Santé (OMS) à publier des critères d’éligibilité à l’usage de cette contraception.11 Ces critères ont fait entre autres, du risque cardiovasculaire élevé et de la maladie thromboembolique veineuse, des situations au cours desquelles le risque encouru sous hormone contraceptive est supérieur au bénéfice attendu. Les femmes à risque cardiovasculaire élevé devraient bénéficier d’une prise en charge adéquate, et surtout bénéficier d’une méthode contraceptive respectant les critères d’éligibilité cardiovasculaire établis. Selon la méthode individuelle de l’OMS, aucune femme enquêtée, n’avait un risque supérieur à 20% de développer au cours des 10 années suivantes un évènement cardiovasculaire majeur. Cette différence de résultat ne devrait pas être perçue comme une réelle discordance au vu des items utilisés pour chaque outil d’évaluation du risque.

Références 1.

Le RCVA de cette population de femmes sous hormones contraceptives est élevé chez 5.2% d’entre elles. Ce résultat pose la question de l’éligibilité cardiovasculaire à l’usage des hormones contraceptives dans cette sous-population. Des travaux de recherche seront envisagés afin d’étudier de façon plus précise cette éligibilité.

Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365(9455): 217–223.

Petersen KR, Skouby SO, Pedersen RG. Desogestrel and gestodene in oral contraceptives: 12 months assessment of carbohydrate and lipoprotein metabolism. Obstet Gynecol 1991; 78: 666–672.

Junquero D, Rival Y. Syndrome métabolique: quelle définition pour quel(s) traitement(s)? Médecine/Sciences 2005; 21: 1045–1053.

IDF Global Guideline for Managing Older People with Type 2 Diabetes [Internet]. International Diabetes Federation. [cited 2017 Jan 24]. Available from: http://www.idf.org/guidelines-older-people-type2-diabetes

Casale PN, Devereux RB, Alonso DR, Campo E, Kligfield P. Improved sex-specific criteria of left ventricular hypertrophy for clinical and computer interpretation of electrocadiograms: validation with autopsy findings. Circulation 1987; 75(3): 565–572.

The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). 2013 ESH/ESC Guidelines for the management of arterial hypertension. Eur Heart J 2013; 34: 2159–2219.

World Health Organization/International Society for Hypertension. Pocket guidelines for Assessment and Management of Cardiovascular Risk with WHO/ISH Cardiovascular Risk Prediction Charts for WHO epidemiological Sub-regions SEAR-D.; 2011. Available from: http:// ish-world.com/downloads/activities/colour_charts_24_Aug_07.pdf (last accessed: 14-12-16).

Houinato DS, Gbary AR, Houehanou YC, Djrolo F, Amoussou M, Segnon-Agueh J. Prevalence of hypertension and associated risk factors in Benin. Rev Epidémiol Santé Publique 2012; 60(2): 95–102.

Conclusion

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Sule S, Shittu O. Weight changes in clients on hormonal contraceptives in Zaria, Nigeria. Afr J Reproduct Health 2005; 9(2): 92–100.

10. Asare GA, Santa S, Ngala RA, Asiedu B, Afriyie D, Amoah AG. Effect of hormonal contraceptives on lipid profile and the risk indices for cardiovascular disease in a Ghanaian community. Int J Womens Health 2014; 6: 597–603. 11. WHO | Medical eligibility criteria for contraceptive use [Internet]. [cited 2016 Dec 14].Availablefrom :http://www.who.int/reproductivehealth/ publications/family_planning/Ex-Summ-MEC-5/en/.

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Case Report Partial anomalous pulmonary venous connection with accessory pulmonary veins Vimalarani Arulselvam, Neale N Kalis, Suad R Al Amer

Abstract We present a case of a six-year-old boy with complex partial anomalous pulmonary venous connections with accessory pulmonary veins, where multi-detector computed tomography proved crucial for accurate identification prior to planning for surgical correction. Keywords: partial anomalous pulmonary venous connections, accessory pulmonary veins Submitted 13/12/16, accepted 4/4/17 Cardiovasc J Afr 2018; 29: e5â&#x20AC;&#x201C;e7

www.cvja.co.za

DOI: 10.5830/CVJA-2017-022

Partial anomalous pulmonary venous connection is a rare congenital cardiovascular condition in which some but not all of the pulmonary veins drain into the systemic circulation rather than into the left atrium. Although the pulmonary venous anatomy can be evaluated by echocardiography and cardiac catheterisation, non-invasive modalities such as multi-detector computed tomography and magnetic resonance imaging now play a crucial role in characterisation of the pulmonary veins. We report on a case of partial anomalous pulmonary venous connection of the left superior pulmonary vein with bilateral accessory pulmonary veins.

Case report A six-year-old child who underwent aortic coarctation repair at two years of age was referred to us. He was asymptomatic and weighed 23 kg, with normal oxygen saturation in room air. There was no significant limb blood pressure gradient between the upper and lower limbs. His left radial and brachial pulses were absent. The cardiovascular examination revealed a grade 2/6 systolic murmur.

Mohammed bin Khalifa bin Salman Al-Khalifa Cardiac Centre, Bahrain Defense Forces Hospital, Kingdom of Bahrain Vimalarani Arulselvam, MB BS, DNB (Paeds), FNB (Paed Cardiology) Neale N Kalis, MB ChB, MMed (Paeds), FCP (Paeds) SA, nnkalis@batelco.com.bh Suad R Al Amer, MD, DCh, SSC-P, SF (Paed Cardiology)

Chest X-ray showed mild cardiomegaly. Electrocardiography revealed right atrial and right ventricular enlargement. Echocardiography confirmed a dilated right atrium, ventricle and pulmonary arteries. The estimated right ventricular systolic pressure was 45 mmHg. There was a 20-mmHg gradient across the descending aorta. Evaluation of the pulmonary veins showed two right-sided veins draining normally into the left atrium and one left-sided pulmonary vein connecting to the vertical vein and draining into a dilated innominate vein and superior vena cava. Multi-detector computed tomography (Fig. 1A, B) confirmed normal drainage of the right upper and lower pulmonary veins, a small left middle pulmonary vein, and left lower pulmonary veins draining into the upper poles of the left atrium. A large right-sided accessory pulmonary vein drained from the right upper lobe lung. This accessory pulmonary vein was dilated and had a long superior course to the left side of the heart before joining the left upper pulmonary vein, which made a U-turn around the left pulmonary artery. After joining, both drained superiorly into the innominate vein via a dilated vertical vein, which drained into the dilated right-sided superior vena cava (Fig. 2A, B). Furthermore, the lower branch of this rightsided anomalous accessory pulmonary vein was connected to the right lower pulmonary vein (Fig. 1A, B). The patient was scheduled for surgical redirection of the anomalous pulmonary venous drainage to the left atrium.

Discussion The typical pattern of four pulmonary veins with welldifferentiated ostia is seen in 60 to 70% of the population.1 Atypical anatomical patterns are found in approximately 38% of the population,2 hence it is important to be familiar with them. The prevalence of partial anomalous pulmonary venous connections is 0.4 to 0.6%.3 Patients with partial anomalous pulmonary venous connections are often asymptomatic and are detected incidentally. If the anomaly compromises 50% or more of the pulmonary venous flow, it may become clinically significant. Various normal patterns and variations have been described in studies of pulmonary vein anatomy.1,2 Anatomical variants on the left side are relatively simple, basically consisting of convergence of the left pulmonary veins into a common trunk that drains into the left atrium. Two subtypes of this variant occur: a short or a long left common trunk. The short left common trunk is the second most common normal anatomical pattern, occurring in 15% of the population. Anatomical variants on the right side are less common and more complex, with one or more accessory veins that have their

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IV SVC

V VV AV

AV RVPV

LPA

LVPV

RLPV

RVPV

LMPV LLPV

RLPV

Fig. 1. C T angiogram (anterior view). Normal drainage of the right upper (RUPV) and right lower pulmonary vein (RLPV) into the upper pole of the left atrium (LA), and a small left middle pulmonary vein (LMPV) and left lower pulmonary veins (LLPV) into the left atrium. Large right-sided accessory pulmonary vein (AV) drains into the right upper lobe of the lung. Left upper pulmonary vein (LUPV) makes a U-turn around the left pulmonary artery (LPA) and joins with the anomalous right accessory pulmonary vein draining into the vertical vein (VV). Right-sided anomalous accessory pulmonary vein also connects (CV) with the RLPV.

IV SVC

VV LVPV

VV AV

PA LA

RLPV

PA LVPV

CV LA

RLPV

LLPV

Fig. 2. C T angiogram (posterior view). The left upper pulmonary vein (LUPV), making a U-turn around the left pulmonary artery (LPA), joins the accessory pulmonary vein (AV), which drains via a dilated vertical vein (VV) into the innominate vein (IV) and finally into the dilated right-sided superior vena cava (SVC). RLPV, right lower pulmonary vein; LA, left atrium; LLPV, left lower pulmonary vein; CV, connecting vein.

own connections to the left atrium independently of the superior and inferior pulmonary veins. These variants mainly include (1) one accessory right middle pulmonary vein, (2) two accessory right middle pulmonary veins, and (3) one accessory right middle pulmonary vein and one accessory right upper pulmonary vein. Other infrequent variations are also seen: a superior segment

right lower lobe vein, basilar segments of the right lower lobe, and a right upper pulmonary vein. A right upper pulmonary vein enters the left atrium at a point super-medial to the right superior pulmonary vein and drains into the superior right lower lobe segment, the posterior right upper lobe segment, or both segments.1,4

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In our case, even though four pulmonary veins drained into the left atrium, one accessory pulmonary vein on the right side had dual drainage into the superior vena cava via the vertical vein and into the left atrium via a tortuous connection to the right inferior pulmonary vein. Also there was anomalous connection of the left superior pulmonary vein into the vertical vein. Our case is unique where anomalous drainage from both upper lobe lungs contributed to approximately 66% of the pulmonary blood flow and needed to be corrected surgically. Multi-detector computed tomography proved crucial for accurate identification. To our knowledge there are no published reports with a similar condition.

the need for sedation. Axial and three-dimensional reconstructed images accurately depict the anomalous pulmonary venous structures prior to further surgical management. The authors acknowledge Rajesh Jayakumar and Haya Y Al Amer for reconstructing the CT and line images.

References 1.

Lacomis JM, Goitein O, Deible C, Schwartzman D. CT of the pulmonary veins. J Thorac Imaging 2007; 22(1): 63–76.

Kato R, Lickfett L, Meininger G, et al. Pulmonary vein anatomy in patients undergoing catheter ablation of atrial fibrillation: lessons learned by use of magnetic resonance imaging. Circulation 2003; 107

Conclusion Echocardiography is the initial imaging technique of choice but it is sub-optimal in the complete evaluation of complex pulmonary venous anomalies. Multi-detector computed tomography provides very rapid, safe imaging that may obviate

(15): 2004–2010. 3.

Dillman JR, Yarram SG, Hernandez RJ. Imaging of pulmonary venous developmental anomalies. Am J Roentgenol 2009; 192(5): 1272–1285.

Porres DV, Morenza OP, Pallisa E, et al. Learning from the pulmonary veins, Radiographics 2013; 33(4): 999–1022.

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Case Report Ischaemic heart disease and pregnancy: the tale of two stories Mamotabo R Matshela

Abstract Ischaemic heart disease (IHD) is presumed to be rare in pregnancy. Based on that assumption, patients go undiagnosed or undertreated. IHD in pregnancy frequently occurs as a result of an unusual aetiology, therefore each patient needs to be managed individually since each may present differently. This may pose challenges to the consulting clinician. Pregnancy itself is a risk factor for cardiovascular disease, due to its associated hypercoagulable state. From current reports, the prevalence of IHD in females is increasing due to lifestyle changes, including cigarette smoking, diabetes and stress. In our modern societies, women delay childbearing until they are older, allowing time for risk factors to cluster. Although presumed to be rare in pregnant women, IHD is currently estimated to occur three to four times more often during pregnancy in middle- and high-income women, warranting an extensive review highlighting cases of IHD in pregnancy. Keywords: pregnancy, ischaemic heart disease Submitted 17/8/17, accepted 7/11/17

Case reports

Published online 27/3/18 Cardiovasc J Afr 2018; 29: e8–e12

www.cvja.co.za

DOI: 10.5830/CVJA-2017-050

In the developing world, hypertension and rheumatic disease are the commonest heart diseases encountered in pregnancy. However, the prevalence of adult congenital heart disease and other cardiovascular diseases is increasing. Pregnancy itself is a risk factor for cardiovascular disease due to its associated hypercoagulable state.1,2 The era of human immunodeficiency virus and improved socio-economic lifestyles has ushered in a rise in the frequency of ischaemic heart disease (IHD) in pregnancy. However, many patients go undiagnosed and undertreated due to the assumption that IHD is rare in pregnancy. IHD, particularly acute myocardial infarction in pregnancy, frequently occurs due to an unusual aetiology and as a result, each patient needs to be managed accordingly. University of KwaZulu-Natal, Durban; Mediclinic Heart Hospital, Pretoria, South Africa; London School of Economics and Political Science, London, UK Mamotabo R Matshela, MB ChB, PhD, FESC, mamotabomatsh@gmail.com

Cardiac disease in pregnancy remains a minor yet significant cause of maternal mortality worldwide. Since rheumatic fever is uncommon in affluent societies, most cases in the Western world are the result of congenital heart disease. In the developing world, rheumatic heart disease remains the major cause of cardiac disease in pregnancy.3-7 The National Committee on Confidential Enquiries into Maternal Deaths lists cardiac disease as one of the five major causes of maternal death in southern Africa.8,9 Until recently, IHD or coronary artery disease (CAD) in pregnancy has been described as a rare occurrence. In southern Africa, there have been a few reports on IHD, including acute myocardial infarction (AMI)/acute coronary syndrome (ACS) in pregnancy. The purpose of this article is to describe the challenges one encounters regarding clinical presentation and management of IHD in pregnancy, particularly AMI. We shall also highlight each patient’s clinical presentation and some challenges encountered by cardiologists and obstetricians to provide appropriate care.

Patient 1 was a 42-year-old white female primigravid who presented at 33 weeks of gestation complaining of Canadian Society class (CCS) II angina and New York Heart Association (NYHA) grade II dyspnoea. In addition, she had a past history of an inferior wall ST-segment elevation myocardial infarction six months prior to her pregnancy and she was also epileptic. Her additional risk factors for CAD included type 1 diabetes mellitus and hypertension. The clinical examination was unremarkable and her initial transthoracic electrocardiogram revealed sinus rhythm with poor R-wave amplitude in lead III and T-wave inversion in leads III and V1 (Fig. 1). A transthoracic echocardiogram revealed preserved left ventricular (LV) function with an ejection fraction of 58%, and basal septal wall hypokinesia. An emergency caesarean section was performed during her admission due to worsening symptoms and recurrent episodes of seizures, and foetal distress. The peri-operative period was uneventful and she delivered a 1.8-kg female baby with dimorphism, in keeping with trisomy 21. Patient 2 was a 34-year-old female of Indian descent, gravida 2 and para 1, who presented at 20 weeks of gestation, with a past history of an extensive anterior and inferior myocardial infarction at the age of 25 years. The patient had suffered a spontaneous dissection of the mid-left anterior descending (LAD) artery during her first pregnancy, which was confirmed by an intravascular ultrasound. Her symptoms during her

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Fig. 1. E lectrocardiogram of patient 1 in sinus rhythm showing an isolated T-wave inversion and poor R amplitude in lead III.

current pregnancy included CCS class II angina and NYHA grade III dyspnoea. In addition, she had a past history of hypercholesterolaemia. Her initial electrocardiogram revealed poor R amplitude and T-wave inversion globally, and Q waves in the inferolateral leads (Fig. 2). A transthoracic echocardiogram revealed a dilated left ventricle and impaired LV function with an ejection fraction of 38%, and multiple regional hypokinesia with no evidence of LV mural thrombus. A repeat coronary angiogram performed after delivery revealed normal epicardial coronary arteries with severely impaired LV contractility, with an estimated LV ejection fraction of 35% and a large LV apical (mural) thrombus. The patient delivered a 3.09 kg healthy female baby by an elective caesarean section after 34 weeks of pregnancy. There were no intra-operative or postoperative complications reported. With subsequent follow up, her heart failure had worsened and a repeat transthoracic echocardiography revealed deterioration in her LV function, due to poor compliance. Her anti-failure

Fig. 2. E lectrocardiogram of patient 2 showing sinus rhythm, poor R amplitude and T-wave inversions globally, with a left-axis deviation.

Fig. 3. Electrocardiogram of patient 3 at least 24 hours after the myocardial infarction, in sinus rhythm with Q waves in leads V1–V2 (poor R-wave amplitude in leads V1–V3).

therapy was optimised and her condition improved dramatically, however she was lost to follow up. Patient 3 was a 34-year-old female of Indian descent who presented to her local hospital at 33 weeks of gestation with an acute anterior ST-elevation myocardial infarction. However, the patient was referred to the tertiary hospital at least 24 hours after her initial presentation to her local hospital. In addition, there was a documented history of an acute myocardial infarction a year earlier. Her risk factors for CAD included diabetes mellitus and hypertension. Her initial electrocardiogram revealed extensive ST elevations in the anterior leads. A repeat electrocardiogram on arrival at

Fig. 4. Chest X-ray of patient 3 showing a mildly increased cardiothoracic ratio and clear lung fields.

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our tertiary hospital, which was at least 24 hours later, revealed sinus rhythm with evidence of a recent extensive antero-septal myocardial infarction (Fig. 3). Her chest X-ray is shown in Fig. 4. Echocardiography revealed preserved LV function with an ejection fraction of 62% and regional wall motion abnormalities, including antero-septal and infero-basal hypokinesia. Coronary angiography revealed a sub-totally occluded LAD (Fig. 5). Percutaneous revascularisation was performed where a baremetal stent was successfully deployed with no peri-procedural complications (Fig. 5). Strict radiation protective measures of the foetus were undertaken during the procedure. An elective caesarean section was performed two weeks later, when a 2.2-kg female baby was delivered with no peri-operative

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complications. During her cardiology follow up, she reported severe prolonged rest pain, which was attributed to poor compliance. Her management was optimised and her symptoms improved.

Discussion Acute myocardial infarction In the largest series of AMI in pregnancy where 125 patients were reported, the authors discovered the highest incidence of AMI in the third trimester, and most importantly, in multigravid women older than 33 years of age.1,2,10-12 In the same report, a coronary angiography was performed in 54% of the patients;

Fig. 5. P atient 3. (Aâ&#x20AC;&#x201C;C) Coronary angiogram showing the sub-totally occluded left anterior descending coronary artery (LAD, indicated by the white arrows). (D) Improved flow post-PCI and stenting to the proximal LAD with TIMI 3 flow to the distal vessel (white arrow).

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 2, March/April 2018

43% of these had coronary atherosclerosis and 21% had coronary thrombus without evidence of atherosclerotic disease. In addition, 16% had spontaneous coronary artery dissection, while 29% had normal epicardial coronaries.10,11 Anterior wall myocardial infarction was the most common occurrence to be reported. In earlier reports, myocardial infarction was associated with a maternal mortality rate of 21% or higher. However in recent reports, the mortality rate was estimated to be between 5 and 11%, and most foetal deaths were associated with maternal deaths.1,2,10-12 Most importantly, most maternal deaths occurred at the time of an acute myocardial infarct or within two weeks of the acute event, usually related to labour and delivery. A literature survey by Ladner et al.13 reported a total of 151 women with AMI, yielding an incidence rate of one in 35 700 deliveries. This report was supportive of the study by Roth et al.,10,11 who reported that AMI was more common in women older than 35 years and often in multiparous women. Important independent risk factors for AMI included chronic hypertension, diabetes, advanced maternal age, eclampsia and severe pre-eclampsia. The same authors reported a maternal mortality rate of 7.3% and also indicated that maternal death only occurred in those women with AMI before or at the time of delivery.10,11 In addition, the authors reported that 38, 21 and 41% of the incidences occurred during the antenatal and intrapartum periods and six weeks postpartum, respectively; and the incidence of AMI increased over the 10-year study period.1,2,14 Hankins et al.12 emphasised that delivery within two weeks of infarction was associated with increased mortality rates and in addition, an increased risk of re-infarction occured during labour. The reporters indicated that increased cardiovascular stresses late in pregnancy, especially when intensified by parturition, compromise women with IHD. As a result, efforts should be made to limit myocardial oxygen demand/consumption throughout pregnancy and particularly during parturition.

Percutanous coronary intervention (PCI) during pregnancy James et al.1,2 reported on revascularisation by PCI in a total of 135 patients, with stent deployment in 127 of the patients.1,2 However, information on outcomes was limited. In another study, more data were reported on 92 of 103 patients who had coronary angiography, where 49 and 43 of these patients had the procedure during the antepartum and postpartum periods, respectively.15-17 PCI was subsequently performed in 38 (41%) of the patients (23 antepartum, six peripartum and nine postpartum) with stent placement in only 55% of the patients and bare-metal stents deployed in all patients. Drug-eluting stents should be avoided during pregnancy if possible due to limited information on their safety.15-17

Dufour et al.18 reported data on pregnancy in patients who had had a previous myocardial infarction with or without prior CABG. In the majority of patients who died, their death occurred at the time of myocardial infarction, and maternal mortality rate was the greatest if myocardial infarction occurred late in pregnancy.

Prevalence of acute coronary syndromes (ACS) during pregnancy The prevalence of myocardial infarction during pregnancy was previously estimated at one per 10 000 pregnancies, however current estimates indicate that the prevalence has increased three to four times, more often in middle- and high-income women.19-25 Myocardial ischaemia during pregnancy can mimic typical symptoms related to pregnancy itself, which may be misinterpreted, resulting in under-reporting of the incidence. When myocardial infarction does occur, it may be associated with both maternal and neonatal mortality, and the risk increases during the peripartum period, particularly during labour and within a few weeks of delivery. Although most cases of myocardial infarction in non-pregnant patients are due to coronary atherosclerosis, alternative aetiologies should always be looked for in pregnancy. Pregnancy is a hypercoagulable state, which increases the risk of AMI, as does older age at the time of conception.23-25 Changes in the cardiac, haemodynamic, haemostatic and hormonal milieu during pregnancy and the puerperium period create a spectrum of stresses that may provoke ACS. Spontaneous coronary dissection is one of the commoner and more important causes of ACS in these patients.15,26-41

Conclusion Although IHD was previously presumed to be rare in pregnancy, current reports estimate a three- to four-fold increase, more often in middle- and high-income women. Pregnancy, due to its associated hypercoagulable state, is a major risk factor for cardiovascular disease in the current era. Changes in lifestyle, including cigarette smoking, diabetes and stress, and delayed childbearing until older age further increase the risk of IHD in pregnancy. The management of IHD in pregnancy, particularly AMI, remains controversial due to limited data. Bare-metal stents are reported to be the preferred choice of intervention compared with drug-eluting stents due to limited information and risk of prolonged anticoagulation. In addition, since information regarding the safety of CABG during pregnancy is rather limited, CABG should not be recommended as the first option.

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