SAJDVD Volume 10, Issue 2

SAJDVD

The electronic version of the journal is available at www.diabetesjournal.co.za

The South African Journal of Diabetes & Vascular Disease

June 2013

Volume 10 Number 2

Featured in this issue: Dyslipidaemia in type 2 diabetes Diabetes and the skin Hypertension in elderly South Africans Cardiovascular disease risk evaluation in diabetes Tighter control in hypothyroid disorders Improving cholesterol management Vitamin D and diabetes Youth with Diabetes camps

Reviews

Ethics Focus

Achieving Best Practice

Diabetes Educator’s Focus

News

ISSN 1811-6515

THE SOUTH AFRICAN JOURNAL OF HYPE

RINSULINAEMIA

Diabetes & vascular disease VOLUME 10 NUMBER 2 • JUNE 2013 www.diabetesjournal.co.za

Corresponding Editor Dr FA Mahomed Greys Hospital, Pietermaritzburg Consulting Editor Dr L Lombard National Editorial Board DR A AMOD Centre for Diabetes, Endocrinology and Metabolic Diseases, Life Healthcare, Chatsmed Gardens Hospital, Durban SR K BECKERT Diabetes Nurse, Paarl

CONTENTS

Editorial

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Non-communicable disease: an ongoing challenge L Lombard

PROF F BONNICI Emeritus Professor, Faculty of Health Sciences, University of Cape Town and President of Diabetes South Africa

Reviews

PROF R DELPORT Department of Family Medicine, University of Pretoria

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Dyslipidaemia in type 2 diabetes

DR L DISTILLER Director of the Centre of Diabetes and Endocrinology, Houghton, Johannesburg

D Blom

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DR F MAHOMED Department of Endocrinology, Grey’s Hospital, Pietermaritzburg PROF WF MOLLENTZE Head of Department of Internal Medicine, University of the Free State, Bloemfontein PROF CD POTGIETER Specialist Nephrologist, University of Pretoria and Jakaranda Hospital, Pretoria PROF K SLIWA Associate Professor of Medicine and Cardiology, Baragwanath Hospital, University of the Witwatersrand, Johannesburg PROF YK SEEDAT Emeritus Professor of Medicine and Honorary Research Associate, University of Natal, Durban International Editorial Board PROF IW CAMPBELL Physician, Victoria Hospital, Kircaldy, Scotland, UK PROF PJ GRANT Professor of Medicine and head of Academic Unit of Molecular Vascular Medicine, Faculty of Medicine and Health, University of Leeds; honorary consultant physician, United Leeds Teaching Hospitals NHS Trust, UK PROF J-C MBANYA Professor of Endocrinology, Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Cameroon and President, International Diabetes Federation PROF N POULTER Professor of Preventive Cardiovascular Medicine, Imperial College, School of Medicine, London, UK DR H PURCELL Senior Research Fellow in Cardiology, Royal Brompton National Heart and Lung Hospital, London, UK

Diabetes mellitus and the skin SM Kannenberg, WI Visser

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Hypertension and associated factors in older adults in South Africa K Peltzer, N Phaswana-Mafuya

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The ADVANCE cardiovascular risk model and current strategies for cardiovascular disease risk evaluation in people with diabetes AP Kengne

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Vitamin D and diabetes – a D-lemna M Conradie

Drug Tends

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Aim for tighter control in hypothyroid disorders P Wagenaar

Patient Information Leaflet

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Improving cholesterol management: lifestyle changes and taking medicine G Hardy

Diabetes Educator’s Focus

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Minimising travel-associated risks in cardiac and diabetic patients J Klotnick

Diabetes News

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Diabetes camps provide fun and education for young people living with the condition P Wagenaar

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Conference Reports

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Cardiology and Diabetes At The Limits – 2013 AJ Dalby, JL Aalbers

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4th All African Conference on Heart Disease, Diabetes and Stroke

11th Pan African Society of Cardiology (PASCAR) Conference A selection of abstracts

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Managing Editor: GLENDA HARDY TEL: 021 976 8129 CELL: 071 819 6425 FAX: 086 610 3395 e-mail: glenda@clinicscardive.com Production Editor SHAUNA GERMISHUIZEN TEL: 021 785 7178 FAX: 086 628 1197 e-mail: shauna@clinicscardive.com Financial & Production Co-ordinator ELSABÉ BURMEISTER TEL: 021 976 8129 CELL: 082 775 6808 FAX: 086 664 4202 e-mail: elsabe@clinicscardive.com Content Manager MICHAEL MEADON (Design Connection) TEL: 021 976 8129 FAX: 086 655 7149 e-mail: michael@clinicscardive.com Gauteng Contributor PETER WAGENAAR CELL: 082 413 9954 e-mail: skylark65@myconnection.co.za Layout RYKIM TEL: 021 715 2449 e-mail: rykim@mweb.co.za

The South African Journal of Diabetes and Vascular Disease is published four times a year for Clinics Cardive Publishing (Pty) Ltd and printed by Durbanville Commercial Printers/Tandym Print. Online Services: Design Connection.

Articles in this Journal are sourced as per agreement with the British Journal of Diabetes and Vascular Disease All correspondence to be directed to: THE EDITOR PO BOX 1013 DURBANVILLE 7551 or info@clinicscardive.com TEL: 021 976 8129 FAX: 086 664 4202 INT: +27 (0)21 976-8129 To subscribe to the journal or change address, email elsabe@clinicscardive.com Full text articles available on: www.diabetesjournal.co.za via www.sabinet.co.za

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The opinions, data and statements that appear in any articles published in this journal are those of the contributors.

The publisher, editors and members of the editorial board do not necessarily share the views expressed herein.

Although every effort is made to ensure accuracy and avoid mistakes, no liability on the part of the publisher, editors, the editorial board or their agents or employees is accepted for the consequences of any inaccurate or misleading information.

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EDITORIAL

Non-communicable diseases: an ongoing challenge LANDI LOMBARD

T

he global burden of cardiovascular disease and diabetes presents a major challenge to health systems and human development. A series of five papers on non-communicable diseases (NCDs), recently published in Lancet, presents the latest results and ideas from some of the world’s most eminent scientists.

In the first Series paper, Sir George Alleyne and fellow researchers highlight the fundamental link between health and development and the disproportionate effect that NCDs have on poor people.

According to Alleyne, “Health is essential to the ability of people to contribute to sustainable development, productivity, economic growth; and to adapt to environmental change. Since NCDs are a major contributor to ill health… any realistic attempt to make human development sustainable must take NCDs into account.”

This is of particular concern in South Africa where we face dual epidemics of NCDs and infectious disease (HIV and TB), in hand with the demographic transition of an ageing population. Impoverished and marginalised populations are more likely to be exposed to risk factors for NCDs such as smoking, alcohol abuse, obesity and high blood pressure. Consequently, a higher burden of disease is found in low- to middle-income countries, yet there are fewer resources to deal with them.

People with low socioeconomic status have worse access to health care for timely diagnosis and treatment of NCDs. The need for chronic care and the consequent burden imposed on families can contribute to social disruption. Chronic caregivers are usually women and girls, who may forego education or employment opportunities to meet this need. People with NCDs are likely to be less productive at work, lose their employment or retire early; thereby decreasing household earnings and increasing the risks of poverty.

Long periods of ill health are costly to family finances; with hidden costs of care imposing catastrophic expenditure that impoverishes many households. Spending on chronic care for NCDs (and money spent on consumption of products causing NCDs) displaces funds that may otherwise have been used for education and food.

Our ageing population is also at higher risk for NCDs. An ageing society has greater levels of multimorbidity and health systems have to manage patients with new comorbid disease patterns. This highlights the need of health systems to provide person-centred care with improved outreach and self-management of risk factors, illness episodes and multimorbidity over many years. In order to deliver preventive interventions and to enable early detection and treatment of NCDs, universal high-quality primary care should be financially and physically accessible. The economic implications of NCD are a challenge for all health budgets and first world countries (USA and UK) also struggle to fund optimal management of NCDs. In South Africa, a rapidly growing population where the vast Correspondence to: Dr Landi Lombard Netcare Kuils River Hospital, Cape Town Tel: +27 0(21) 900-6350 e-mail: lclombard@mweb.co.za S Afr J Diabetes Vasc Dis 2013; 10: 47

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majority do not have access to health care, funding optimal care for NCDs will probably not be achievable in the near future. Prevention however, can be achieved with considerably fewer funds and legislative changes; regulation of the food and beverage industries and advertising campaigns can make a big difference. Education of the public on NCD risk factors and the implications of poor diet and obesity can have a huge impact on prevalence.

Cardiovascular disease (CVD) is the most common cause of mortality in those with type 2 diabetes. Knowledge gained from CVD risk evaluation may motivate patients to adopt healthy lifestyle measures and/or observe prescribed risk modifying treatments. In this issue, existing approaches to CVD risk evaluation in diabetes are critically examined by Dr Andre Kengne. CVD risk models developed from the Framingham Heart Study, the UKPDS study and the ADVANCE cohort are discussed. Evidence suggests that existing popular models derived from older cohorts were less accurate for CVD risk evaluation in contemporary populations with diabetes. New CVD risk models, including the ADVANCE model, show improved predictive accuracy for people with diabetes. The growing diabetes epidemic in South Africa will surely impact on the prevalence of CVD. Accurate CVD risk prediction is very important in order to spend our limited health Rands on those most at risk.

Little attention has been focused on hypertension in the elderly in Africa. Older adults in South Africa face a disproportionate rate of hypertension, with an increased risk of CVD. In this issue, a paper from Dr’s Karl Peltzer and Nancy Phasawana-Mafuya indicates that the percentages of older hypertensive subjects who were aware, treated and controlled were very low, underscoring the urgent need to strengthen public health education and improve blood pressure monitoring systems. Hypertension is a very serious modifiable CVD risk factor and treatment is cost-effective and can prevent many complications down the line. Access to health care and both the limitation of health care professionals and funding is, however, restrictive.

Dyslipidaemia is an important atherosclerotic risk factor that is very common in type 2 diabetes. Dr Dirk Blom reviews dyslipidaemia, atherosclerosis and type 2 diabetes in this issue; discussing the clinical concerns of prevention and treatment. The skin may provide vital clues in the diagnosis of diabetes and may portend advanced disease. Recognising various skin signs is therefore critical in the management of patients with diabetes. A review from Drs Kannenberg and Visser on diabetes mellitus and the skin considers the diagnosis and management of some skin conditions.

Included amongst recommended effective actions to reduce NCD inequalities are childhood education programmes. Youth with Diabetes is a non-profit organisation registered with the South African Department of Social Welfare, largely run by young people, mostly with diabetes themselves. Being diagnosed with diabetes at a young age can be devastating and having the support of this wonderful group of young people can make a big difference in the lives of many. This organisation has been established with the express purpose of saving lives of young people in South Africa who have diabetes. In this issue, read about their weekend camps that take place in major centres throughout the country; and to find out more about their school awareness campaign see www. youthwithdiabetes.com

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Dyslipidaemia in Type 2 Diabetes DIRK J. BLOM Head of Division of Lipidology, Department of Medicine, University of Cape Town Abstract Cardiovascular disease is the commonest cause of death in patients with type 2 diabetes (T2DM) and dyslipidaemia is an important atherosclerotic risk factor. Dyslipidaemia is very common in T2DM and is characterized by mild to moderate hypertriglyceridaemia, low high density lipoprotein cholesterol (HDL-C) and the presence of small dense low density lipoprotein (LDL) particles. Almost all patients with T2DM will require lipid lowering therapy with statins aiming for a target LDLcholesterol of 1.8 mmol/l in the majority of patients. Younger patients with a shorter duration of diabetes and no other risk factors can be treated to a target of 2.5 mmol/l. The role of statin and fibrate combination therapy in reducing residual risk by ameliorating hypertriglyceridaemia and low HDLcholesterol that may persist despite statin monotherapy is not well defined and is not included in guideline recommendations.

Diabetes is the commonest secondary cause of severe hypertriglyceridaemia that may trigger acute pancreatitis.

Patients with severe hypertriglyceridaemia require good glycaemic control, a very low fat diet and a fibrate.

Introduction Conventionally, doctors have viewed T2DM primarily as a disorder of glucose metabolism and hyperglycaemia as the central defining feature. An alterative viewpoint would be to think of T2DM primarily as a vascular disorder in which high blood glucose is an essential, but not the sole defining component. The pathophysiology of T2DM is complex (and not uniform in all patients) but dyslipidaemia and hypertension often result from the same pathophysiological processes that lead to hyperglycaemia. The combination of dyslipidaemia, hyperglycaemia, hypertension and other factors creates a ‘toxic’ vascular environment that damages both small and large vessels.

Microvascular damage leads to retinopathy, nephropathy and neuropathy while macrovascular damage causes atherosclerotic cardiovascular disease (ASCVD). ASCVD is responsible for the highest number of life years lost in T2DM when compared to age matched controls without diabetes; and is, in fact, the major cause of death accounting for about 50-75% of all deaths in those with T2DM.1,2 Submitted 6/5/2013, accepted 1/6/2013 Correspondence to: Dr Dirk Blom Lipid Laboratory 5th Floor Chris Barnard Building UCT Health Sciences Faculty Anzio Road 7925 Observatory Cape Town Fax: + 27 21 4066396 E-mail: dirk.blom@uct.ac.za Tel: +27 21 4066055 S Afr J Diabetes Vasc Dis 2013; 10: 48–50

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Dyslipidaemia is an important contributor to the pathogenesis of ASCVD in patients with T2DM. This article will review dyslipidaemia in diabetes, focussing on patients with T2DM.

Atherosclerosis in type 2 diabetes Atherosclerosis in T2DM is often diffuse and extensive. Studies have shown that the coronary arteries of those with T2DM are smaller, have a higher plaque burden and show inadequate compensatory remodelling when compared to those of non-diabetic patients with coronary artery disease.3 It is thus not surprising that patients with T2DM have poorer outcomes following acute myocardial infarction or other acute coronary syndromes. Vascular interventions are associated with a higher complication rate which is at least in part due to the smaller vessels and the diffuse atherosclerosis that characterizes T2DM. Although the short term risk of coronary artery bypass grafting (CABG) is higher than that of percutaneous intervention (PCI) with stenting, a recent study has confirmed that CABG should be the preferred option for many diabetics requiring coronary revascularization as PCI only deals with a discrete focal area of disease while CABG bypasses multiple diseased vascular segments.4

Dyslipidaemia and atherosclerosis Dyslipidaemia is an important contributor to the pathogenesis of atherosclerosis and extensive basic sciences, epidemiological and clinical evidence supports the causative role of elevated levels of apolipoprotein B100 (apoB)-containing lipoproteins in the development of atherosclerosis. ApoB-containing lipoproteins range in size and density from very low density lipoproteins (VLDL) to intermediate density lipoproteins (IDL) to low density lipoproteins (LDL). VLDL are large, triglyceride (TG)-rich lipoproteins secreted by the liver. In the circulation, VLDL undergo progressive delipidation (TG removal) and are transformed into IDL and subsequently LDL. The latter two lipoproteins are smaller and relatively enriched in cholesterol when compared to VLDL. LDL account for the majority of circulating apoB-containing lipoproteins in humans due to their long half life of around 3-4 days. LDL are thus the major circulating pro-atherosclerotic apoBcontaining lipoproteins and in clinical practice the contribution of other apoB-containing lipoproteins is often ignored. This is a reasonable approach as long as VLDL and IDL are not elevated.

Patients with elevated levels of VLDL and IDL usually have elevated TGs as these lipoproteins are TG enriched when compared to LDL. LDL-C reflects the amount of cholesterol carried in LDL particles in a given volume of serum or plasma. Because LDL particles may differ in size, and therefore the amount of cholesterol they carry, the correlation of LDL-C with LDL particle number is only approximate.

The same amount of cholesterol may be carried in many small LDL particles or fewer large LDL particles. Particle size influences atherosclerotic risk as smaller particles penetrate the endothelium more readily, have longer plasma half lives and are more prone to oxidative damage.5

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Diabetic dyslipidaemia is characterized by elevated levels of VLDL and IDL as well as a preponderance of small LDL particles (see below). Many authors have thus argued that LDL-C alone does not adequately reflect the atherogenic burden in diabetic dyslipidaemia and have proposed alternative lipid markers.

The two best known markers are apoB and non-high density lipoprotein cholesterol (non-HDL-C). ApoB levels reflect the total number of atherogenic particles while non-HDL-C is a measure of cholesterol found in all apoB-containing lipoproteins. Non-HDL-C is calculated by subtracting HDL-C from total cholesterol (TC).

LDL-C currently remains the primary lipid target in most guidelines; as most of the outcome evidence has been gathered for LDL-C, it is well established and understood by physicians and because apoB measurements are not yet universally available.6 In this article I will primarily focus on LDL-C target values but indicate apoB and non-HDL-C target values where appropriate.

Extensive epidemiological evidence indicates that low HDL-C is associated with an increased risk of ASCVD. However, HDL has proven to be a difficult therapeutic target and a much more complex lipoparticle than the apoB-containing lipoparticles.

Although raising HDL-C intuitively makes sense, none of the trials examining HDL-C raising strategies has thus far been an unequivocal success.

Dyslipidaemia in diabetes Lipid phenotypes in patients with T2DM may vary considerably and are subject to the same genetic and environmental influences as in non-diabetic patients. However, T2DM is often accompanied by a characteristic constellation of lipid abnormalities which is known either as ‘diabetic dyslipidaemia’ or the ‘atherogenic lipid phenotype (ALP)’.7 The ALP includes mild to moderate TG elevations in the range of 2-5 mmol/l (reflecting increased amounts of VLDL and the presence of large VLDL that are particularly TG rich + elevated concentrations of remnant lipoproteins), low HDL-C (usually in the range of 0.7-1.0 mmol/l) and LDL-C that is usually within the population range but with a predominance of small dense LDL particles.8-10 On superficial inspection the lipogram associated with the ALP may not appear to be particularly abnormal, particularly if the focus is only on TC and LDL-C. The latter two variables are usually not markedly abnormal and atherosclerotic risk may be underestimated. The combination of small dense LDL particles, low and often dysfunctional HDL-C, and elevated levels of other apoB-containing lipoproteins (VLDL and remnants) is highly atherogenic.

The pathophysiology of the ALP is complex but one of the major lipoprotein mechanisms involves hepatic overproduction of large, TG-rich VLDL particles as a result of the elevated levels of free fatty acids that are characteristic of T2DM. Cholesterol ester transfer protein (CETP) exchanges cholesterol esters from HDL (and a lesser extent LDL) into VLDL in exchange for TGs. The resultant TG-rich HDL and LDL undergoes further metabolic processing with lipases removing much of the TG content and the formation of small dense LDL and HDL particles. This process is particularly active in the presence of TG-rich VLDL.11 Diabetes is also the most common secondary cause of severe hypertriglyceridaemia (TG > 10-15 mmol/l). Hypertriglyceridaemia in T2DM is usually multifactorial in origin. Mechanistically there is both overproduction of TG-rich lipoproteins together with impaired clearance. Clinically high dietary TG intake, poor

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glycaemic control and certain medications can aggravate the hypertriglyceridaemia. Severe hypertriglyceridaemia only develops in genetically and metabolically predisposed patients and the majority of patients with poorly controlled T2DM do not develop severe hypertriglyceridaemia.

Clinical Aspects Dyslipidaemia is asymptomatic in most patients. Dyslipidaemia management is thus not aimed at alleviating symptoms but risk reduction is the focus of management. The two major risks that need to be addressed are atherosclerosis and acute pancreatitis.

Because treating dyslipidaemia does not improve wellbeing in the short term, and may be associated with side effects, long term adherence to lipid-lowering therapy remains an ongoing problem and challenge for the clinician and patient.

Atherosclerosis As indicated above, patients with T2DM are at very high risk of developing ASCVD. Lipid treatment guidelines designate T2DM as ‘coronary risk equivalent’ indicating that the ten year risk of a cardiovascular event in patients with T2DM is equivalent to that of a recurrent event in non-diabetic patients who have already survived an event. This short term risk equivalence probably does not apply to all populations, especially in younger diabetics; but as lifetime risk is markedly elevated with T2DM, assigning all type 2 diabetics ‘very high risk’ status remains clinically useful and appropriate.12,13 Because all patients with T2DM are considered as ‘very high risk’, Framingham risk scoring is neither appropriate nor required. The diagnosis of T2DM is the indication for lipid lowering therapy. Put differently, the question every doctor needs to consider is not ‘Should this patient with T2DM be on a statin?’ but ‘Is there any reason why I am not prescribing a statin for this patient?’

Lipid-lowering therapy is initiated based on the high cardiovascular risk of patients with T2DM, even if their lipid values appear to be ‘normal’.

Atherosclerosis prevention Lifestyle modification remains the cornerstone of managing T2DM. Many of the interventions that improve glycaemic control such as increased exercise, weight reduction and dietary modification also reduce cardiovascular risk. Smoking cessation and blood pressure control are especially important in patients with T2DM. Good glycaemic control can reduce cardiovascular events in the long term14, but attempting very tight glycaemic control in elderly patients with established cardiovascular disease may increase mortality.15 In patients with relatively long standing diabetes, lipid and blood pressure control are associated with larger reductions in cardiovascular outcomes than glycaemic control and are also usually easier.16 This does not mean that glycaemic control should be neglected; achieving tight control early after the diagnosis will benefit patients many years down the line.14 In addition to lifestyle modifications, patients with T2DM also require lipid lowering therapy. There is extensive data to support the safety and efficacy of statin therapy in patients with T2DM.17,18 Statins are therefore the agents of first choice, except for patients with severe hypertriglyceridaemia in whom a different treatment approach is required (see below).

LDL-C is the best validated lipid target and LDL-C control therefore remains the primary target of lipid lowering therapy,

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although the ALP is characterized by multiple lipid abnormalities.

The recently updated SEMDSA guidelines19 for the management of T2DM suggest the following two LDL-C targets: 1. 1.8 mmol/l is the target for most patients with T2DM. 2. Patients who fulfil all of the following criteria can be treated to a LDL-C of 2.5 mmol/l: No cardiovascular disease or chronic kidney disease, no other cardiovascular risk factors, less than forty years old or duration of diabetes less than 10 years.

ApoB levels of 0.8 g/l and 1.0 g/l correspond to the LDL-C targets of 1.8 mmol/l and 2.5 mmol/l respectively. The non-HDL-C targets are 0.8 mmol/l higher than the LDL-C targets, i.e. 2.6 mmol/l and 3.3 mmol/l respectively. Triglycerides should ideally be less than 1.7 mmol/l, while HDL-C should be more than 1.2 mmol/l in females and more than 1.0 mmol/l in men.6,19 The choice of statin and starting dose depends on the baseline LDL-C, the risk of interaction with other drugs the patient may be taking and individual tolerability. Following statin initiation, patients require regular follow-up (at 6-12 weekly intervals) and statin dose adjustment if they have not reached their target LDL-C. Patients who are unable to reach target despite high doses of potent statins such as atorvastatin or rosuvastatin, or who are unable to tolerate the statin dose required to reach target, can be treated with the combination of a statin and ezetimibe. Stable patients at LDL-C goal can be followed up annually for their lipids.

Although statins are highly effective therapy they do not prevent all vascular events (residual risk). Statins do not deal with all the components of the ALP and there has been much interest in combining statins with other lipid lowering therapies that more specifically address issues such as hypertriglyceridaemia and low HDL-C. A full review of these studies is beyond the scope of this article. The two therapies that have been best studied in combination with statins are fibrates and niacin. The ACCORD study examined the utility of adding fenofibrate or placebo in simvastatin treated type 2 diabetics with added vascular risk, irrespective of baseline lipids. The study overall failed to show any benefit from adding fenofibrate. In a post-hoc analysis, a subgroup of patients with high TGs (defined as TG > 2.30 mmol/l) and low HDL-C (defined as HDL-C < 0.88 mmol/l) seemed to benefit from fibrate therapy.20 The HPS-THRIVE II study examined the utility of adding modified release niacin with laropiprant to simvastatin (+ ezetimibe if required) based aggressive lipid lowering therapy (the baseline LDL-C before randomization was 1.64 mmol/l) in high-risk patients. About 32% of patients included had T2DM. Niacin did not improve cardiovascular outcomes and was associated with a significant excess of adverse events.21,22 The role of combination therapy in diabetes is thus currently not well defined and there are no clear guidelines when, and if, a second lipid lowering agent should be added to statin based therapy. Controlling the LDL-C remains critical and additional therapy should only be considered once the LDL-C is adequately controlled. Good glycaemic control and lifestyle changes may aid in improving hypertriglyceridaemia and increasing HDL-C. Acute Pancreatitis Severe hypertriglyceridaemia (TG > 10-15 mmol/l) may trigger acute pancreatitis. Acute pancreatitis occurs unpredictably in patients with severe hypertriglyceridaemia. The correlation between the severity of hypertriglyceridaemia and the onset of acute pancreatitis is not clear cut. Some patients with severe hypertriglyceridaemia never develop pancreatitis while others may have recurrent attacks.

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Hypertriglyceridaemic pancreatitis is associated with significant morbidity and mortality.

Clinical clues that help identify patients with severe hypertriglyceridaemia include eruptive xanthomata (figure 1), a lipaemic specimen (figure 2) or a very high TC value on screening. Severe hypertriglyceridaemia is secondary to accumulation of chylomicrons and VLDL, which do contain cholesterol in addition to TG, and marked accumulation of these lipoproteins can thus raise TC substantially. Many, but not all, diabetics with severe hypertriglyceridaemia have poorly controlled diabetes.

Eruptive xanthomata Legend: Eruptive xanthomata are associated with severe hypertriglyceridaemia.

They are usually asymptomatic and found on the flexor surfaces of the elbows and knees. They also commonly occur on the buttocks, thighs and flanks.

Lipaemic plasma Legend: Lipaemia is caused by the accumulation of large, TG-rich lipoproteins (chylomicrons and VLDL) and indicates that patients are at risk of developing hypertriglyceridaemic pancreatitis.

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Diabetes mellitus and the skin SM Kannenberg, WI Visser Abstract

Table 1. Skin conditions associated with Diabetes Mellitus

The skin may provide vital clues for the diagnosis of diabetes mellitus (DM). Certain skin signs may even portend advanced disease. Skin complications associated with DM may lead to severe impairment in the quality of life. Recognising various skin signs is critical in the diagnosis and management of patients with DM. This review will aim to overview the diagnosis and management of some of the important skin conditions associated with DM.

Introduction Diabetes Mellitus and the skin may be associated in various ways: the skin signs may provide the initial clue to the diagnosis of DM, the skin may be affected by long term pathophysiological changes caused by DM and the skin may be affected by diabetic medications.

Moreover, DM found in combination with specific skin signs may be diagnostic of certain syndromes (e.g. necrolytic migratory erythema in glucagonoma syndrome). Some skin findings may be more specific to the diagnosis of DM (e.g. necrobiosis lipoidica) and others less so (e.g. periungual telangiectasias). The skin lesions can arbitrarily be classified into either early or late associations (Table 1), where ‘early’ would include conditions commonly preceding the diagnosis of and aiding in the diagnosis of DM; and ‘late’ those conditions found in a known diabetic patient, often with end-organ involvement.

Certain conditions are more common in, although not exclusive to, type 1 DM such as necrobiosis lipoidica and vitiligo. Others are more common in type 2 DM, such as diabetic cheiroarthropathy and eruptive xanthomas (Table 2). This review will aim to give an overview of the diagnosis and management of some of the skin conditions associated with DM.

Acanthosis nigricans Acanthosis nigricans presents as velvety, hyperpigmented plaques especially in the flexures. The pathogenesis is thought to be related to high levels of circulating insulin, which binds to insulin-like growth Submitted 2/5/2013, accepted 23/5/2013 Correspondence to: Dr SM Kannenberg Dermatologist (Private Practice, Kuils River, Cape Town), Sessional Consultant Dermatologist, Tygerberg Academic Hospital and Stellenbosch University PO Box 5659, Tygervalley, 7536 e-mail: drskannenberg@gmail.com Dr WI Visser Consultant Dermatologist, Head of Division of Dermatology, Tygerberg Academic Hospital and Stellenbosch University S Afr J Diabetes Vasc Dis 2013; 10: 51–53

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Early Acanthosis nigricans Acrochordons (skin tags) Necrobiosis lipoidica Diabetic dermopathy Eruptive xanthomas Infections such as erythrasma, cellulitis and necrotizing fasciitis Late Diabetic cheiroarthropathy Scleredema diabeticorum of Buschke Diabetic bullae Lower leg ulcers (neuropathic, arterial or venous) Acquired perforating disorder Infections such as mucor, malignant otitis externa Secondary infections of other diabetes mellitus complications Diabetic foot Controversial associations Granuloma annulare and Lichen planus Medication related Lipoatrophy at insulin injection site Photosensitivity Lichenoid drug reactions Erythema multiforme Syndromes Polycystic Ovarian Syndrome/Hyperandrogenism Insulin Resistance Acanthosis Nigricans Syndrome – DM with hirsutism Glucagonoma syndrome – DM with necrolytic migratory erythema Polyglandular Autoimmune Syndrome Type II – DM with vitiligo

Table 2. Skin conditions more commonly associated with type 1 and type 2 DM Type 1 DM Periungual telangiectasia Necrobiosis lipoidica Diabetic bullae Vitiligo Lichen planus Type 2 DM Diabetic cheiroarthropathy Skin tags Acanthosis nigricans Diabetic dermopathy Acquired perforating dermatoses Eruptive xanthomas Granuloma annulare

factor receptors. If asymptomatic, no treatment is required. Weight reduction and exercise may reduce insulin resistance and thereby improve the acanthosis nigricans. Ointments containing salicylic acid or urea may reduce thicker lesions in areas of maceration. This may decrease malodor and relieve discomfort.

Acrochordons (Skin tags) Skin tags are soft pedunculated lesions occurring on the axillae, neck and eyelids. In a large study of patients with skin tags, more than 25% had diabetes and 8% had impaired glucose tolerance. If treatment is required, skin tags can be removed with small scissors, cryotherapy, or electrodessication.

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Necrobiosis lipoidica

Diabetic dermopathy

Necrobiosis lipoidica (NL) is an uncommon condition with only 0.31.6% of patients with DM developing NL (Figs 1, 2). However, more than 66% of patients with NL have diabetes and therefore it should be regarded as a cutaneous marker of DM until proven otherwise.

NL has other associations as well and these include sarcoidosis, rheumatoid arthritis, inflammatory bowel disease and adult-onset Still’s disease.

Diabetic dermopathy is also known as ‘shin spots’ and pigmented pretibial papules. This is the most common skin lesion occurring in DM, although not specific for DM as 20% of healthy individuals may have similar lesions. Prevalence in patients with DM varies from 7% to 70%. Men are affected more often than women. This condition is important as it may precede abnormal glucose metabolism.

Although commonly presenting on the extensor aspects of the lower limbs, they may rarely occur elsewhere as well. The clinician usually sees only the end result of atrophic and hyperpigmented plaques. The active lesions tend to be red and polycyclic. Treatment is not effective and some lesions resolve spontaneously.

Eruptive xanthomas Eruptive xanthomas (Fig. 3) present as small (1-2 mm) yellow papules, often with erythematous borders. Their development is associated with elevated levels of triglyceride-rich lipoproteins and they tend to resolve rapidly with control of the metabolic disturbance.

Figure 1. Necrobiosis lipoidica – early stage.

NL starts as a non-scaling red papule and spreads centrifugally, with the yellow discoloration and atrophy developing centrally. The yellow colour follows as a consequence of the underlying fibrosis in the dermis.

Figure 3. Eruptive xanthomas.

Note the multiple red papules and nodules with a yellowish hue on the extensor surfaces of the forearms. The yellow hue is due to foamy macrophages containing lipid found in the infiltrate.

Diabetic cheiroarthropathy

Figure 2. Necrobiosis lipoidica – advanced stage.

A large plaque of NL clearly demonstrating atrophy in the centre with a prominent red border.

NL classically presents as a non-scaling plaque with an atrophic yellow centre, which may ulcerate in 35% of cases, and a red elevated border. The pretibial region is the area typically affected, but it may occur elsewhere as well. Women are affected more often than men and those with type 1 DM tend to develop NL earlier than type 2 DM. Metabolic control has no proven effect on the course of this condition. NL is very resistant to treatment and options include application of a topical steroid with or without occlusion; and intralesional steroids into the active border.

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Diabetic cheiroarthropathy, also known as diabetic stiff hand syndrome or limited joint mobility syndrome, is characterized by thickened waxy skin and limited joint mobility of the hands and fingers, leading to flexion contractures. Patients are unable to press their palms together completely. A gap remains between opposed palms and fingers. This is called the ‘prayer sign’. Patients may also present with multiple minute papules, grouped on the extensor side of the fingers, on the knuckles, or on the periungual surface; known as pebbled knuckles or Huntley papules. Dupuytren’s contracture may further complicate diabetic hand syndrome. Diabetic cheiroarthropathy is observed in about 30% of DM patients with longstanding disease and prevalence increases with the duration of diabetes. This condition is predictive of other diabetic complications.

The pathogenesis includes increased glycosylation of collagen in the skin and periarticular tissue, decreased collagen degradation, diabetic microangiopathy and possibly diabetic neuropathy. Unfortunately, this is not a treatable condition.

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Scleroedema diabeticorum Scleroedema diabeticorum (Fig. 4) is an unusual condition occurring in 2.5% to 14% of people with DM and seems to be more common in men than women. It is characterised by a symmetrical diffuse induration of the upper part of the body, in particular the posterior neck and upper back, with overlying redness. The skin often has a peau d’orange appearance. Occasionally, the induration may extend to the deltoid and lumbar regions. Onset is subtle and the involvement is persistent with no specific treatment available.

Histologically, it is characterised by a thickened dermis with thick collagen bundles and mucin deposition. Diabetes control has no influence on the prognosis. No effective treatment is known for scleroedema diabeticorum although sparse reports of phototherapy affording some relief can be found in the literature.

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diagnosis. Thorough evaluation regarding the vascular status of the patient should be performed by appropriate specialists. Simple wound care, combined with occasional debriding agents if needed, and careful surveillance for secondary infection is important in the management of the ulcers. An experienced wound care nursing sister can be invaluable in this regard.

Granuloma annulare Granuloma annulare (GA) (Fig. 5) and its association with DM are controversial. Some studies have been able to demonstrate a stronger association between generalised, chronic relapsing GA and DM versus the localised variant of GA and DM. The cause is unknown. The lesions start as red papules, which expand centrifugally and resolve centrally, resulting in annular or polycyclic plaques. The dorsa of the hands and arms are the sites usually affected. The histology is comparable to that of necrobiosis lipoidica except for the presence of mucin in GA. Localised lesions often resolve spontaneously, whereas the generalised form has a more protracted and relapsing course and rarely shows spontaneous resolution. Treatment options include corticosteroids (topical, intralesional or systemic) and phototherapy amongst others.

Figure 4. Scleroedema diabeticorum.

The lighter crease in the mid back is often found in skin conditions associated with induration/thickening of the skin.

Diabetic bullae Diabetic bullae, also known as bullosis diabeticorum, are very rare occurring in 0.5% of diabetic patients. It is found more commonly in those with type 1 DM, in men and in patients with longstanding diabetes and peripheral neuropathy. The bullae appear spontaneously, commonly on the dorsa and sides of the lower legs, especially the feet. Occasionally, similar lesions may be found on the forearms and hands. Bullae may range from millimeters to a few centimeters. The lesions are often bilateral, containing clear sterile fluid, with no surrounding erythema. These blisters are not the result of trauma or infection and this is a diagnosis of exclusion.

The cause of this rare manifestation of diabetes is unknown.

Treatment is symptomatic and conservative. In cases of discomfort, the bullae can be aspirated leaving the blister roof intact. Most lesions resolve in 2 to 3 weeks without residual scarring, although they may recur.

Lower leg ulcers Although the neuropathic ulcers are the type of ulcer that comes to mind when considering diabetes, one has to remember that the commonest ulcer by far still remains venous insufficiency ulcers.

Due to the macrovascular complications associated with diabetes, arterial ulcers also need to be considered in the differential

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Figure 5. Granuloma annulare.

GA starts as a non-scaly red papule, spreads centrifugally and clears centrally to form polycyclic plaques.

Conclusion Recognising skin signs in DM are important because they may be the initial clues to the diagnosis, they may portend advanced disease, they may lead to severe discomfort and impairment in the quality of life of the patient; and they may even contribute to the patient’s demise. Assistance of a dermatologist in the management of patients with DM may be invaluable and is certainly advisable in many cases.

Further reading 1. Van Hattem S, Bootsma AH, Thio HB. Skin manifestations of diabetes. Clev Clin J Med 2008;75(11):772-787.

2. Ahmed I, Goldstein B. Diabetes mellitus. Clin Dermatol 2006;24:237–246.

3. Ferringer T, Miller F. Cutaneous manifestations of diabetes mellitus. Dermatol Clin 2002;20:483–492.

4. Sreedevi1 C, Car N, Pavliæ-Renar I. Dermatologic lesions in diabetes mellitus.

Diabetologica Croatia 2002;31(3):147-159.

5. Perez MI, Kohn SR. Cutaneous manifestations of diabetes mellitus. J Am Acad Dermatol 1994;30:519–530.

6. Jelinek JE. Cutaneous manifestations of diabetes mellitus. Int J Dermatol 1994;33:605–617.

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Hypertension and associated factors in older adults in South Africa KARL PELTZER, NANCY PHASWANA-MAFUYA Abstract Background: Older adults are disproportionately affected by hypertension, which is an established risk factor for cardiovascular disease. Little attention has been focused on hypertension and associated factors among older adults in Africa. Therefore, this study aimed to investigate the prevalence and associated factors of hypertension in a national sample of older South Africans who participated in the Study of Global Ageing and Adults’ Health (SAGE) in 2008.

Methods: In 2008 we conducted a national, population-based, cross-sectional study of a sample of 3 840 subjects aged 50 years or older in South Africa. The questionnaire included socio-demographic characteristics, health variables, and anthropometric and blood pressure measurements.

Results: The prevalence of hypertension in the sample population was 77.3% (male 74.4%, female 79.6%). The rates of awareness, treatment and control among the hypertensive participants were 38.1, 32.7 and 17.1%, respectively. The results of multivariate logistic regression analysis revealed that the prevalence of hypertension was associated with being in the Coloured population group, having had a stroke, being overweight or obese and having had five or more outpatients care visits in the past 12 months. Hypertension was inversely associated with current alcohol use.

Conclusion: This study revealed high rates of hypertension among older adults (50 years and more) in South Africa, which puts them at risk for cardiovascular disease. The percentages of hypertensive subjects who were aware, treated and controlled were very low. These data underscore the urgent need to strengthen the public health education and blood pressure-monitoring systems to better manage hypertension among older adults in South Africa.

Keywords: hypertension, risk factors, older adults, South Africa Submitted 7/4/12, accepted 11/1/13

High blood pressure in South Africa is estimated to have caused 46 888 deaths and 390 860 disability-adjusted life years in 2000.1 Hypertension alone is the leading reason for attending primary care Correspondence to: HIV/AIDS/SIT and TB (HAST), Human Sciences Research Council, Pretoria, South Africa Karl Peltzer, PhD E-mail: kpeltzer@hsrc.ac.za Department of Psychology, University of Limpopo, Turfloop, South Africa and ASEAN Institute for Health Development, Mahidol University, Salaya, Thailand Nancy Phaswana-Mafuya, PhD Office of the Vice Chancellor, Nelson Mandela Metropolitan University, Port Elizabeth, South Africa S Afr J Diabetes Vasc Dis 2013; 10: 54–58

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and is the most common diagnosis (13.1%) in South Africa.2 In population-based surveys, high rates of hypertension were found among older adults in South Africa, 44.0–52.0% among men and 51.6–60.4% among women in 1998.3 In other countries, in Dakar, Senegal, 65.4% of subjects had hypertension,4 in urban Zimbabwe 72%.5 In Malawi, Rwanda and Tanzania, hypertension was found in 41.0% of men and 36.6% of women.6 In Costa Rica, 65% were hypertensive,7 and 42.4% of women in Accra, Ghana had hypertension.8 In Brazil, self-reported hypertension was 55%,9 in rural China it was 57–64.9%,10 and in another study in China it was 24.2–43.8%.11 In Turkey 71.2–82.2% of subjects had hypertension,12 and in Taiwan 31.1–38.0%.13 Various factors have been found to be associated with hypertension, including socio-demographics (older age, female gender, lower education level, lower household income),13-16 geolocality (urban residence),17 other risk factors or behaviour, including stroke,18 diabetes,19,20 higher body mass index (BMI),5,10,13,14 physical inactivity,16,22,23 insufficient fruit and vegetable intake,13,23-25 smoking and drinking,10,16,22 greater limitations on activities of daily living (ADLs) and instrumental activities of daily living (IADLs),26 higher frequency of doctor visits,4 and less social cohesion.27 In general, it is estimated that in South Africa only 26% of men and 51% of women are aware of their hypertension.1 Among older adults in Senegal, half of those suffering from high blood pressure were aware of their problem, and among the latter, 70% said they were on treatment. However, of these, only 17% had controlled arterial blood pressure.4 Among rural older adults in China, the rates of awareness, treatment and control were very low (overall 35.2, 28.7 and 1.0%, respectively).10 Few studies exist investigating hypertension among older adults in low- and middle-income countries. Yet, research studies ‘demonstrate a clear evolution in the prevalence, awareness, treatment and control of hypertension during the ageing process’.4 Therefore, this study aimed to investigate the prevalence and associated factors of hypertension in a national sample of older South Africans who participated in the Study of Global Ageing and Adults’ Health (SAGE) in 2008.

Methods We conducted a national, population-based, cross-sectional study with a sample of 3 840 subjects aged 50 years or older in South Africa in 2008. The SAGE sample design entailed a two-stage probability sample that yielded national and sub-national estimates to an acceptable precision at provincial level, by locality type (urban and rural) and population group (including black, Coloured, Indian or Asian, and white). The overall response rate among those aged 50 years or older was 60%.

The Global Study on Ageing (SAGE) survey was carried out in South Africa in partnership with the World Health Organisation (WHO), the National Department of Health, and the Human Sciences Research Council (HSRC). The study was approved by the Human Sciences Research Council Research Ethics Committee and the national Department of Health. Blood pressure (systolic and

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diastolic) was measured three times on the right arm/wrist of the seated respondent using an automated recording device (OMRON R6 Wrist Blood Pressure Monitor, HEM-6000-E, Omron Healthcare Europe, BV, Hoofddorp and The Netherlands).

Out of three measurements, the average of the last two readings was used. In accordance with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, individuals with systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or who reported the current use of antihypertensive medication were considered to be suffering from high blood pressure.28 Awareness was defined as history of hypertension based on diagnosis by a healthcare provider. Treatment was defined as taking any medication or other treatment for hypertension in the last two weeks prior to the survey, and control was defined as blood pressure < 140 and < 90 mmHg at the time of the survey.

Lifetime tobacco users were asked ‘Do you currently use (smoke, sniff or chew) any tobacco products such as cigarettes, cigars, pipes, chewing tobacco or snuff?’ The response options were ‘Yes, daily’, ‘Yes, but not daily’ and ‘No, not at all’. Daily tobacco use was coded = 1, and not daily and not at all = 0.29 Lifetime alcohol users were asked about current (past month) alcohol use. Past month alcohol use was coded = 1 and no past month alcohol use = 0.

Height and weight were measured. Body mass index (BMI) was used as an indicator of obesity (≥ 30 kg/m2), calculated as weight in kg divided by height in metres squared. Overweight and/or obesity were defined as BMI ≥ 25 kg/m2 and underweight as < 18.5 kg/m2.

Social cohesion was measured with nine items, starting with the introduction ‘How often in the last 12 months have you… e.g. attended any group, club, society, union or organisational meeting?’

All nine items were summed to get a social cohesion index. Response options ranged from never = 1 to daily = 5. Cronbach alpha for the social cohesion index in this sample was 0.73.

Physical activity was measured using the General Physical Activity Questionnaire (GPAQ). The instrument gathers information on physical activity in three domains (activity at work, travel to and from places, and recreational activities), as well as time spent sitting.

The questionnaire also assesses vigorous and moderate activities performed at work and for recreational activities. Information on the number of days a week spent on different activities, and time spent in a typical day for each activity was also recorded.30 Cronbach alpha for the GPAQ in this sample was 0.77.

For physical activity, in addition to the total minutes of activity, the activity volume was also computed by weighting each type of activity by its energy requirement in metabolic equivalents (METs).

One MET was defined as the energy cost of sitting quietly, and was equivalent to a caloric consumption of 1 kcal/kg/h. A METminute showed the total activity volume on a weekly basis, and was calculated by multiplying the time spent on each activity during a week by the MET-values of each level of activity. MET-values for different levels of activities were set as 4 MET for moderate intensity physical activity, 8 MET for vigorous physical activity, and 4 MET for transport-related walking or cycling.

The total physical activity for GPAQ2 was calculated as the sum of the total moderate, vigorous, and transport-related activities per week. The number of days and total physical activity MET-minutes per week were used to classify respondents into three categories of low, moderate and high level of physical activities. Less than 600 MET-minutes per week was classified as low physical activity.30

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Fruit and vegetable consumption was assessed with the questions ‘How many servings of fruit do you eat on a typical day?’ and ‘How many servings of vegetables do you eat on a typical day?’

Insufficient fruit and vegetable consumption was defined as less than five servings of fruits and/or vegetables a day.

Overall self-rated health status was based on respondents’ assessment of their current health status on a five-point scale in response to the question: ‘In general, how would you rate your health today?’ Response categories were: very good, good, moderate, bad and very bad. Very good and good were grouped together and coded = 1, moderate = 2 and bad and very bad were grouped together and coded = 3.

Activity limitation (difficulty an individual may have in executing task or actions) was assessed with one item ‘Overall in the last 30 days, how much difficulty did you have with work or household activities?’ Response options ranged from 1 = none to 5 = extreme/ cannot do. None were coded = 1, mild = 2, moderate = 3 and severe and extreme were grouped together and coded = 4.

Finally, participants were asked about a list of chronic and other conditions they had been diagnosed with, including diabetes, hypertension, stroke, angina and arthritis. Of participants who responded to having been diagnosed with hypertension, the question was asked, ‘Have you been taking any medication or other treatment for it during the last two weeks?’ Other treatment might include a weight-loss programme or change in eating habits.

Attendance at out-patient care was assessed with the question, ‘Over the last 12 months, did you receive ant healthcare not including an overnight stay in hospital or long-term care facility?’

Of those who indicated ‘yes’ they had to report the number of times they had received healthcare or consultation in the last 12 months. Frequency of attendance at out-patient care was grouped into none = 0, one to four = 2, five or more = 3.

To estimate economic or wealth status, a random-effects probit model was used to identify indicator-specific thresholds that represent the point on the wealth scale above which a household is more likely to own a particular asset than not. This enabled an estimation of an asset ladder. These estimates of thresholds, combined with actual assets observed to be owned for any given household, were used to produce an estimate of household-level wealth status. This was used to create wealth quintiles.31 Lowest and second-lowest wealth quintiles were grouped together as low = 1, the middle wealth quintile was medium = 2 and the fourth and highest wealth quintiles were grouped together as high = 3.

Statistical analysis The data were entered using CSPro and analysed using STATA Version 10. The data were weighted using post-stratified individual probability weights based on the selection probability at each stage of selection. Individual weights were post-stratified by province, gender and age groups according to the 2009 medium mid-year population estimates from Statistics South Africa, available at: http://www.statssa.gov.za/publications/ P0302/P03022009.pdf.

Computed estimates and odds ratios were reported with 95% confidence intervals and a two-tailed p-value of 0.05 was used as the cut-off point for statistical significance. Associations between key outcomes of hypertension, and socio-demographic and health variables were evaluated calculating odds ratios (OR).

Multivariate logistic regression was used for evaluation of the impact of explanatory variables for key outcome of hypertension (binary dependent variable). All variables statistically significant at

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p < 0.05 in bivariate analyses were included in the multivariable models. In the analysis, weighted percentages were reported.

Table 1. Sample characteristics and prevalence rate of hypertension among older South Africans

Results

The total sample included 3 840 South African subjects 50 years or older, 44.1% were men and 55.9% were women. The most prevalent population group was black Africans (74%), and almost half (49.9%) were between 50 and 59 years old. The educational level of most participants (71.6%) was lower than secondary school education and almost two-thirds (64.9%) lived in an urban area.

A large group (72.4%) of older adults were overweight or obese, 20.4% were daily tobacco users, 4.0% had had a stroke, and 9.2% had diabetes. More than half (52.2%) engaged in low physical activity, two-thirds (67.7%) ate insufficient fruit and vegetables, and a small proportion (13.7%) were current alcohol users. A sizeable proportion (17.5%) rated their health status as bad or very bad, 10.7% reported severe or extreme activity limitation and 28.1% were out-patients five times or more. The prevalence rates of hypertension were 77.3% (male 74.4%, female 79.6%) (Table 1).

The results of the multivariate logistic regression analysis revealed that the prevalence of hypertension was associated with being in the Coloured population group, having had a stroke, being overweight and having had five or more out-patients care visits in the past 12 months. Prevalence of hypertension was inversely associated with current alcohol use (Table 2).

Overall, 30.3% of older hypertensive people were aware of their diagnosis, 24.8% of older hypertensives were taking treatment in the past two weeks to lower their blood pressure, and 48.8% of those who were taking antihypertensive treatment had their blood pressure controlled. Women, older age and more frequent outpatient visits in the past 12 months were associated with awareness of their hypertensive status and were taking treatment to lower their blood pressure in the past two weeks.

However, there were no statistical differences in gender, age and out-patient visits among those who were taking antihypertensive treatment and had their blood pressure controlled. Of the total 2 841 hypertensive participants, 1 081 (38.1%) were aware of their hypertension, 985 (32.7%) were being treated, and 486 (17.1%) had their hypertension under controll (Table 3).

All Age (years) 50–59 60–69 70 and over

1695 (49.9) 520 (71.3) 682 (77.9) 1202 (74.9) 1233 (30.6) 391 (79.4) 563 (81.6) 954 (80.6) 912 (19.5) 248 (75.1) 438 (80.5) 686 (78.4)

Population group African black White Coloured Indian or Asian

2053 (74.0) 269 (9.3) 655 (12.8) 307 (3.8)

575 (73.1) 92 (75.6) 195 (88.1) 97 (74.1)

975 (80.0) 101 (83.0) 350 (83.1) 117 (78.5)

1550 (77.3) 193 (79.6) 545 (85.0) 214 (76.8)

Marital status Single Married Separated/divorced Widow

512 (14.3) 2007 (55.9) 230 (5.9) 1020 (23.9)

97 (71.5) 870 (74.2) 60 (66.0) 120 (84.8)

292 (83.1) 571 (74.2) 116 (82.3) 667 (82.6)

389 (80.1) 1441 (74.2) 176 (77.7) 787 (82.9)

Educational level No schooling Less than primary Primary Secondary

854 (25.2) 803 (24.0) 779 (22.4) 923 (28.3)

231 (78.3) 227 (69.4) 232 (79.2) 261 (74.9)

422 (81.2) 404 (85.6) 364 (79.3) 337 (76.5)

653 (80.2) 631 (78.9) 596 (79.2) 598 (75.8)

Wealth Low Medium High

1482 (40.6) 429 (71.1) 646 (78.7) 1075 (75.4) 731 (18.2) 197 (74.7) 377 (79.9) 574 (78.3) 1608 (41.2) 525 (77.1) 651 (80.2) 1176 (78.6)

Geolocality Rural Urban

1276 (35.1) 392 (75.9) 524 (78.7) 916 (77.5) 2561 (64.9) 766 (73.7) 1157 (80.1) 1923 (77.2)

Discussion The study found significant rates of hypertension of 77.3% (male 74.4%, female 79.6%) among older adults (50 years and older) in South Africa. These rates seemed to be higher than in a previous survey in South Africa (men 44.0–52.0% and women 51.6–60.4%) in 1998,3 and similar to other studies such as in urban Senegal (65.4%),4 urban Zimbabwe (72%),5 and Turkey (71.2–82.2%).12 The rates were higher than in a number of other countries including rural Malawi, Rwanda and Tanzania (36.6– 41.0%),6 Brazil (55%),9 China (24.2–64.9%),10,11 and Taiwan (31.1–38.0%).13 The study further found that regarding socio-demographics, with multivariate analysis, being in the Coloured population group was associated with higher rates of hypertension. This confirms previous studies in women.3 Further initiatives are required to address the high rate of hypertension in this population group. Unlike in other studies,13-15,17 this study did not find any effect of gender, age, level of education and geolocality on hypertensive status.

In terms of health variables, this study was in agreement with other studies,4,10,13,14,18,31 that having had a stroke, being overweight

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Other conditions Stroke Angina Diabetes Overweight

(BMI ≥ 25 kg/m2) Underweight

(BMI < 18.5 kg/m2) Arthritis Daily tobacco use

Prevalence rate of hypertension Total sample 3840

Male Female (n = 1638) (n = 2202) Total 1159 (74.4) 1683 (79.6) 2842 (77.3)

139 (4.0) 48 (88.2) 71 (91.5) 119 (90.0) 219 (5.2) 62 (76.2) 114 (76.2) 176 (76.2) 360 (9.2) 107 (88.4) 202 (90.2) 309 (89.6) 2505 (72.4) 745 (77.3) 1253 (82.8) 1998 (80.5) 184 (4.3) 51 (64.4) 63 (66.8) 114 (65.5) 851 (24.7) 198 (81.8) 472 (83.0) 670 (82.6) 810 (20.4) 295 (74.6) 315 (76.3) 610 (75.4)

Alcohol use (past month) 557 (13.7) 248 (66.6) 151 (77.5) 399 (70.3) Physical activity Low Moderate High

2100 (52.2) 567 (73.2) 940 (79.0) 1507 (76.6) 692 (16.6) 233 (79.6) 302 (76.9) 535 (78.1) 1044 (31.2) 357 (73.4) 440 (82.1) 797 (78.1)

Insufficient fruit and vegetables

2817 (67.7) 834 (77.3) 1245 (77.0) 2079 (77.1)

Subjective health status Very/good Moderate Bad/very bad

1469 (37.9) 486 (71.3) 565 (75.4) 1051 (73.4) 1681 (44.9) 495 (78.2) 834 (80.9) 1329 (79.8) 617 (17.5) 177 (73.9) 281 (84.4) 458 (79.9)

Activity limitation None Mild Moderate Severe/extreme

1465 (38.5) 625 (16.7) 1275 (34.2) 370 (10.7)

Social cohesion index (range 9–72); mean (SD) Outpatient visits in past 12 months 0 1–4 5 or more

487 (73.6) 191 (71.6) 369 (75.9) 103 (78.5)

566 (74.8) 297 (80.5) 628 (81.0) 178 (89.6)

1053 (74.2) 488 (76.5) 997 (78.9) 281 (85.8)

22.1 (6.5) 21.9 (6.2) 21.4 (6.1) 21.6 (6.1)

1176 (38.2) 372 (72.2) 464 (74.5) 836 (73.3) 908 (33.7) 271 (76.2) 414 (79.2) 685 (77.9) 941 (28.1) 282 (80.4) 513 (86.4) 795 (84.2)

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Table 2. Multiple logistic regression of hypertension prevalence in older South Africans

Gender Female Male

UOR (95% CI)

AOR (95% CI)

1.00 0.75 (0.57–0.98)*

1.00 0.85 (0.80–1.63)

Age (years) 50–59 60–69 70 and over

1.00 1.40 (1.12–1.75)** 1.22 (0.87–1.70)

1.00 1.30 (0.94–1.79) 1.19 (0.80–1.78)

Population group African black White Coloured Indian or Asian

1.00 1.14 (0.64–2.05) 1.66 (1.07–2.59)* 0.97 (0.59–1.60)

1.00 1.23 (0.66–2.30) 1.89 (1.04–3.44)* 0.82 (0.47–1.42)

Marital status Single Married Separated/divorced Widow

1.00 0.71 (0.43–1.18) 0.86 (0.43–1.72) 1.20 (0.66–2.19)

Educational level No schooling Less than primary Primary Secondary

1.00 1.15 (0.74–1.81) 1.18 (0.86–1.60) 0.97 (0.71–1.31)

Wealth Low Medium High

1.00 1.18 (0.78–1.77) 1.20 (0.80–1.80)

Geolocality Rural Urban

1.00 0.98 (0.59–1.65)

Other conditions Stroke Angina Diabetes Overweight (BMI ≥ 25 kg/m2) Underweight (BMI < 18.5 kg/m2) Arthritis Daily tobacco use Alcohol use (past month) Physical activity Low Moderate High

4.48 (1.48–13.59)**

1.67 (1.41–1.98)***

1.52 (1.15–2.01)**

0.53 (0.30–0.97)* 1.49 (1.06–2.11)*

0.77 (0.36–1.64) 1.13 (0.75–1.69)

1.30 (0.86–1.98)

0.85 (0.56–1.30) 0.64 (0.49–0.84)**

1.00 1.01 (0.70–1.45) 0.92 (0.66–1.27)

Insufficient fruit and vegetables 0.96 (0.65–1.43) Subjective health status Very/good Moderate Bad/very bad

1.00 1.43 (1.12–1.83)** 1.44 (0.77–2.68)

1.00 1.41 (0.95–2.10) 1.27 (0.62–2.58)

Activity limitation None Mild Moderate Severe/extreme

1.00 1.13 (0.84–1.52) 1.30 (0.90–1.88) 2.10 (1.12–3.93)*

1.00 0.92 (0.59–1.45) 0.92 (0.58–1.48) 1.60 (0.70–3.64)

Social cohesion index (range 9–72); mean (SD)

1.01 (0.9-1.03)

Outpatient visits in past 12 months 0 1.00 1–4 1.28 (0.84–1.96) 5 or more 1.94 (1.34–2.81)*** ***p < 0.001; **p < 0.01; *p < 0.5.

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1.00 1.14 (0.80–1.63) 1.93 (1.48–2.51)***

Awareness (30.3%) AOR (95% CI)

Treatment (24.8%) AOR (95% CI)

Control of treated (48.8%) AOR (95% CI)

Gender Female Male

1.00 1.00 1.00 0.68 (0.51–0.90)** 0.67 (0.50–0.88)** 1.09 (0.81–1.46)

Age 50-59 60-69 70 and over

1.00 1.00 1.00 1.70 (1.16–2.48)** 1.89 (1.38–2.58)*** 0.73 (0.55–0.95) 1.77 (1.22–2.59)** 2.15 (1.40–3.30)*** 0.73 (0.50–1.06)

Population group African black 1.00 White 0.81 (0.40–1.62) Coloured 1.00 (0.65–1.52) Indian or Asian 1.08 (0.56–2.07) Marital status Single Married Separated/ divorced Widow

2.67 (1.10–6.47)* 0.92 (0.56–1.51) 2.65 (1.86–3.78)***

0.64 (0.47–0.85)**

Table 3. Multivariate logistic regression of awareness treatment and control rates of hypertension among older adults in South Africa

1.00 1.00 0.97 (0.52–1.83) 0.89 (0.44–1.80) 1.09 (0.73–1.63) 0.80 (0.58–1.10) 1.45 (0.73–2.91) 1.25 (0.64–2.45)

1.00 1.38 (0.83–2.29)

1.00 1.00 1.50 (0.85–2.66) 1.44 (0.90–2.29)

1.17 (0.69–1.97) 1.67 (0.96–2.92)

1.11 (0.62–1.99) 1.11 (0.65–2.45) 1.45 (0.81–2.62) 1.51 (0.93–2.46)

Educational level No schooling 1.00 Less than primary 0.96 (0.65–1.52) Primary 1.10 (0.72–1.68) Secondary 0.94 (0.65–1.38)

1.03 (0.67–1.58) 0.99 (0.64–1.54) 1.03 (0.65–1.61) 1.04 (0.73–1.49) 1.09 (0.75–1.59) 1.54 (1.04–2.27)*

Wealth Low Medium High

1.00 1.43 (0.98–2.08) 1.55 (1.00–2.40)*

1.00 1.00 1.36 (0.84–2.20) 0.75 (0.49–1.15) 1.34 (0.75–2.40) 0.93 (0.64–1.33)

Geolocality Rural Urban

1.00 1.27 (0.95–1.71)

1.00 1.00 1.30 (0.84–2.01) 1.17 (0.87–1.58)

1.00

1.00

Outpatient visits in past 12 months 0 1.00 1.00 1.00 1–4 1.85 (1.10–3.11)* 1.94 (1.20–3.12)** 0.85 (0.61–1.17) 5 or more 4.49 (3.02–6.66)*** 5.95 (3.96–8.95)*** 0.87 (0.63–1.19) ***p < 0.001; **p < 0.01; *p < 0.5.

and having had more out-patients care visits in the past 12 months were associated with hypertension. Unlike some other studies,10,13,21,2325,33 this study did not find insufficient fruit and vegetable intake, smoking, being physically inactive and having more limitations in activities of daily living to be associated with hypertension. The finding that current alcohol use was protective for hypertension in this study may be in line with some previous studies where lightto-moderate alcohol consumption decreased hypertension risk in women and increased the risk in men.21 The rates of awareness, treatment and control among the hypertensive participants in the present study (38.1, 32.7 and 17.1%, respectively) were as low as in some studies in rural China (35.2, 28.7 and 1.0%),10 Senegal (49.5, 37.0 and 5.7%),4 and Italy (65.6, 59.5 and 10.5%).18 They were however lower than in studies in Costa Rica (74.9% aware and more than half controlled)7 and in the USA (74% aware and 51.6% controlled among men and 37% controlled among women).34

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As found in some other studies, in this study, women were more frequently aware of their hypertension and more frequently treated.7,35 They were not significantly more frequently controlled than men, though, as found in other studies.7,36 In the group of individuals who were unaware of their hypertension, it may have been because of multiple factors, such as never having been screened for hypertension, having been previously diagnosed but had forgotten the diagnosis, the medical provider had not considered their blood pressure levels to be sufficiently elevated to warrant the diagnosis, or had had inadequate health education and limited access to healthcare services.9,35 Therefore, more efforts, such as public health education and a blood pressuremonitoring system should be included for the older age group, particularly men, to improve their unsatisfactory awareness, treatment and control of hypertension.10

Limitations of the study This study had several limitations. Firstly, the self-report of health variables such as tobacco or alcohol use should be interpreted with caution; it is possible that respondents under-reported, especially females. As in many studies, arterial blood pressure was measured three times during a single session (two hours), which may have led to an overestimation of the prevalence of hypertension. In addition, the awareness and treatment rate of hypertension was solely assessed by individual self-report. Furthermore, this study was based on data collected in a crosssectional survey. We cannot, therefore, ascribe causality to any of the associated factors in the study.

Conclusion This study revealed high rates of hypertension among older adults (50 years and more) in South Africa, which put them at risk for cardiovascular disease. The percentages of hypertensives who were aware of, treated for and controlled were very low. These data underscore the urgent need to strengthen the public health education and blood pressure-monitoring systems to better manage hypertension among older adults in South Africa. Community healthcare workers in their new role in South Africa could screen for hypertension among older adults using a primary care ‘highrisk’ approach once every two years. This screening process would enable the health system to identify and cater for the needs of this vulnerable population group.37 Funding was provided predominantly from the National Department of Health with additional funding provided by the United States National Institute on Aging through an interagency agreement with the World Health Organisation, and the Human Sciences Research Council, South Africa.

References 1.

2.

3.

4.

5.

6.

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Rayner B. Hypertension: detection and management in South Africa. Nephron Clin Pract 2010; 116(4): c269–273.

Mash B, Fairall L, Adejayan O, et al. A morbidity survey of South African primary care.

PLoS One 2012; 7(3): e32358.

Steyn K, Gaziano TA, Bradshaw D, et al. Hypertension in South African adults: results from the Demographic and Health Survey, 1998. J Hypertens 2001; 19(10): 1717– 1725.

Macia E, Duboz P, Gueye L. Prevalence, awareness, treatment and control of hypertension among adults 50 years and older in Dakar, Senegal. Cardiovasc J Afr 2011; 22: 1–5.

Mufunda J, Scott LJ, Chifamba J, et al. Correlates of blood pressure in an urban Zimbabwean population and comparison to other populations of African origin. J Hum Hypertens 2000; 14(1): 65–73.

Negin J, Cumming R, de Ramirez SS, et al. Risk factors for noncommunicable diseases among older adults in rural Africa. Trop Med Intern Health 2011; 16(5): 640–646.

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7. Méndez-Chacón E, Santamaría-Ulloa C, Rosero-Bixby L. Factors associated with hypertension prevalence, unawareness and treatment among Costa Rican elderly.

BMC Public Health 2008; 8: 275.

8. Duda RB, Anarfi JK, Adanu RM, et al. The health of the ‘older women’ in Accra, Ghana: results of the Women’s Health Study of Accra. J Cross Cult Gerontol 2011; 26(3): 299–314.

9. Lima e Costa MF, Peixoto SV, et al. Health behaviors among older adults with hypertension, Brazil, 2006. Rev Saude Publica 2009; 43(Suppl 2): 18–26.

10. Pang W, Li Z, Sun Z, et al. Prevalence of hypertension and associated factors among older rural adults: results from Liaoning Province, China. Med Princ Pract 2010; 19(1): 22–27.

11. Ruixing Y, Jiaqiang D, Dezhai Y, et al. Effects of demographic characteristics, healthrelated behaviors and lifestyle factors on the prevalence of hypertension for the middle-aged and elderly in the Guangxi Hei Yi Zhuang and Han populations. Kidney Blood Press Res 2006; 29(5): 312–320.

12. Erem C, Hacihasanoglu A, Kocak M, et al. Prevalence of prehypertension and hypertension and associated risk factors among Turkish adults: Trabzon Hypertension Study. J Public Health (Oxf) 2009; 31(1): 47–58.

13. Tsai AC, Liou JC, Chang MC. Interview to study the determinants of hypertension in older adults in Taiwan: a population based crosssectional survey. Asia Pac J Clin Nutr 2007; 16(2): 338–345.

14. Hendriks ME, Wit FW, Roos MT, et al. Hypertension in sub-Saharan Africa: crosssectional surveys in four rural and urban communities. PLoS One 2012; 7(3): e32638.

15. Kaplan MS, Huguet N, Feeny DH, McFarland BH. Self-reported hypertension prevalence and income among older adults in Canada and the United States. Soc Sci Med 2010; 70(6): 844–849.

16. Teo GS, Idris MN. Prevalence of hypertension among Chinese elderly and its relationship to behavioural and nutritional factors. Med J Malaysia 1996; 51(1): 33–40.

17. Agyemang C. Rural and urban differences in blood pressure and hypertension in Ghana, West Africa. Public Health 2006; 120(6): 525–533.

18. Ngoungou EB, Aboyans V, Kouna P, et al. Prevalence of cardiovascular disease in Gabon: A population study. Arch Cardiovasc Dis 2012; 105(2): 77–83.

19. Prencipe M, Casini AR, Santini M, et al. Prevalence, awareness, treatment and control of hypertension in the elderly: results from a population survey. J Hum Hypertens 2000; 14(12): 825–830.

20. Long AN, Dagogo-Jack S. Comorbidities of diabetes and hypertension: mechanisms and approach to target organ protection. J Clin Hypertens (Greenwich) 2011; 13(4): 244–251.

21. Giday A, Tadesse B. Prevalence and determinants of hypertension in rural and urban areas of southern Ethiopia. Ethiop Med J 2011; 49(2): 139–147.

22. De Ramirez SS, Enquobahrie DA, Nyadzi G, et al. Prevalence and correlates of hypertension: a cross-sectional study among rural populations in sub-Saharan Africa.

J Hum Hypertens 2010; 24(12): 786–795.

23. Wang L, Manson JE, Gaziano JM, et al. Fruit and vegetable intake and the risk of hypertension in middle-aged and older women. Am J Hypertens 2012; 25(2): 180– 189.

24. Zhao D, Qi Y, Zheng Z, et al. Dietary factors associated with hypertension. Nat Rev Cardiol 2011; 8(8): 456–465.

25. Caskie GI, Sutton MC, Margrett JA.The relation of hypertension to changes in ADL/ IADL limitations of Mexican american older adults. J Gerontol B Psychol Sci Soc Sci 2010; 65B(3): 296–305.

26. Mujahid MS, Diez Roux AV, Morenoff JD, et al. Neighborhood characteristics and hypertension. Epidemiology 2008; 19(4): 590–598.

27. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee of Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206–1252.

28. World Health Organisation (WHO). Guidelines for controlling and monitoring the tobacco epidemic. Geneva, Switzerland: WHO, 1998.

29. World Health Organisation (WHO). Global Physical Activity Surveillance. (http://www. who.int/chp/steps/GPAQ/en/index.html, accessed 2 December 2010), 2009.

30. Chatterji S, Kowal P, Mathers C, et al. The health of aging populations in China and India. Health Aff (Millwood) 2008; 27(4): 1052–1063.

31. Mufunda J, Mebrahtu G, Usman A, et al. The prevalence of hypertension and its relationship with obesity: results from a national blood pressure survey in Eritrea. J Hum Hypertens 2006; 20(1): 59–65.

32. Banda JA, Clouston K, Sui X, et al. Protective health factors and incident hypertension in men. Am J Hypertens 2010; 23(6): 599–605.

33. Sesso HD, Cook NR, Buring JE, et al. Alcohol consumption and the risk of hypertension in women and men. Hypertension 2008; 51(4): 1080–1087.

34. Ostchega Y, Dillon CF, Hughes JP, et al. Trends in hypertension prevalence, awareness, treatment, and control in older US adults: data from the National Health and Nutrition Examination Survey 1988 to 2004. J Am Geriatr Soc 2007; 55(7): 1056–1065.

35. Brindel P, Hanon O, Dartigues JF, et al. Prevalence, awareness, treatment, and control of hypertension in the elderly: the Three City study. J Hypertens 2006; 24(1): 51–58.

36. Satish S, Markides KS, Zhang D, Goodwin JS. Factors influencing unawareness of hypertension among Older Mexican Americans. Preventive Med 1997; 26: 645– 650.

37. John J, Muliyil J, Balraj V. Screening for hypertension among older adults: a primary care ‘high risk’ approach. Indian J Community Med 2010; 35(1): 67–69.

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The ADVANCE cardiovascular risk model and current strategies for cardiovascular disease risk evaluation in people with diabetes Andre Pascal Kengne Abstract Purpose: To critically examine existing approaches to cardiovascular disease (CVD) risk evaluation in people with diabetes, and discuss the use of accurate and validated absolute CVD risk tool as an appropriate basis for CVD prevention in people with diabetes.

Methods: Narrative review, using evidence from the ADVANCE study and all relevant publications identified via PubMed MEDLINE. Results: There is sufficient evidence that diabetes does not confer a CVD risk equivalent to that in non-diabetic people with existing CVD in all circumstances. In people with diabetes, CVD risk follows a gradient. Reliably capturing this gradient depends upon an adequate combination of several risk factors. Many global CVD risk tools applicable to people with diabetes have been developed. Those derived from older cohorts are less accurate in contemporary populations and many newer tools have not been tested. The ADVANCE risk engine, recently developed from the large multinational ADVANCE study, showed acceptable performance on the ADVANCE population and largely outperformed the popular Framingham risk equation when tested on the multinational DIAB-HYCAR cohort of people with type 2 diabetes.

Conclusions: The high-risk status conferred by diabetes does not preclude estimation of absolute CVD risk using tools such as the ADVANCE risk engine and its use as the basis for initiating and intensifying CVD preventative measures.

Adopting such an accurate and validated tool will likely improve prescriptions and outcomes of diabetes care.

Keywords: diabetes mellitus, cardiovascular disease, risk evaluation, ADVANCE, absolute risk Submitted 6/5/2013, accepted 10/6/2013

Introduction Cardiovascular disease (CVD), the leading global killer, is multifactorial by nature. No single risk factor taken alone is able to Correspondence to: Dr Andre Pascal Kengne South African Medical Research Council, PO Box 19070, Tygerberg,7505, Cape Town, South Africa E-mail: andre.kengne@mrc.ac.za S Afr J Diabetes Vasc Dis 2013; 10: 59–64

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distinguish people who will go on to develop a cardiovascular event from those who will not. This consideration forms the basis of the contemporary multifactorial approaches to CVD risk evaluation and reduction. A key aim of CVD risk evaluation is to identify those in the population who’s health outcomes can be modified by performing more medical tests, starting treatments to reduce the level of risk factors or increasing the doses of prescribed risk reducing therapies.1,2 Estimated risks are also used to educate patients about their chances of experiencing a cardiovascular event within a given time period (for example, five or ten years). Equipped with this knowledge, patients are likely to be more motivated to adopt healthy lifestyle measures and/or to observe prescribed risk modifying treatments. These patients are also more likely to regularly report back to their healthcare provider for monitoring and adaptation of treatments, to lower and maintain their risk factors at optimal levels. Concerning CVD in people with diabetes, healthcare providers who see these patients on a routine basis are interested in gauging the chances of their patients developing any major CVD event over a reasonable period of time (often five to ten years); and not just specific components such as stroke or myocardial infarction. These busy healthcare providers are also interested in assessing the CVD risk of their patients using accurate and validated global CVD risk evaluation tools.3-5 In the general population, efforts to develop reliable tools for evaluating CVD risk based on a combination of several risk factors have paralleled efforts to improve our understanding of the determinants of CVD, and the more efficient ways to control them.6 These efforts were initially led by the Framingham investigators, and more recently by investigators from other parts of the world.6,7 The first attempts to develop such tools from the Framingham study date back to the year 1967.8 These first tools however, did not account for diabetes status, nor for any other indicator of chronic hyperglycaemia. Although many subsequent Framingham tools took diabetes status into consideration, the uptake of the Framingham tools in people with diabetes around the world has remained very limited, resulting in the adoption of multivariable CVD tools in people with diabetes to lag behind the general population. One reason was the lack of trust among researchers on the validity of the Framingham tools in people with diabetes, due to the relatively small number of people with diabetes in the Framingham cohort; and the non-inclusion of other indicators of exposure to chronic hyperglycaemia in the Framingham tools.9 Another major reason was the publication in the late 1990’s of a study from Finland suggesting that people with diabetes but no history of cardiovascular disease, had a future risk of CVD similar to the risk of non-diabetic people who have survived from a CVD event in the past.10 This study inspired the concept of diabetes as a ‘CVD risk equivalent’ based on which, people with diabetes should be treated with cardiovascular risk reducing therapies such as statins or aspirin without taking into consideration their absolute CVD risk

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Fax: +27(0)11 525 3401. References: 1. The ADVANCE Collaborative Group. N Engl J Med. 2008; 358: 2560-2572 2. SEMDSA Guidelines 2012 3. Al Sifri S et al. Int J Clin Pract. 2011;11 :1132-1140 8. 4. Aravind SR et al. Curr Med Res Opin. 2012;28:1-8.

5.Perkovic V et al. Kidney Int. 2013 Jan 9. Epub ahead of print.

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levels. However, the concept of diabetes as a CVD risk equivalent has been losing ground in recent years, with the accumulating evidence challenging its validity in all circumstances11 and supporting the importance of absolute risk estimation in people with diabetes as the appropriate basis for CVD risk factor modification. Such an approach is further supported by the gradual shift in the management of diabetes mellitus from a glucocentric focus to an intensive multifactorial strategy targeting reduction in the risk of both macrovascular and microvascular complications of diabetes.12,13 The growing recognition of the importance of global CVD risk in people with diabetes has generated interest among researchers to develop tools with improved performance to estimate absolute risk in people with diabetes, or to establish the validity of the existing ones and refine their performance.7 The following development is a discussion on the rationale and strategies for global CVD risk estimation in people with diabetes, with emphasis on the specificities and limitations of those strategies. The discussion is largely inspired by new knowledge gained from CVD risk modeling in ADVANCE study.3,14

Global cardiovascular risk assessment: overview Global cardiovascular risk assessment is based on th=e combination of predictive information from several cardiovascular risk factors, using mathematical equations (also called models). In those models, the coefficient of each included risk factor indicates their relative contribution to the overall (global) CVD risk.2,15 A model can be used to estimate the risk that a disease is present (diagnostic model) or to estimate the risk that a particular disease or health event will occur within a given time period (prognostic models). The focus of the current paper is on prognostic models.

Once developed, a cardiovascular risk model normally requires a validation both on the sample population that was used to develop the model (internal validation) and on independent populations (external validation). Validation consists of testing whether the prognostic model accurately estimates the risk of future events in one or several populations. 2,15 The performance of absolute cardiovascular risk models in validation studies is commonly assessed in terms of discrimination, calibration and more recently reclassification. 2,15 Discrimination is the ability of the model to distinguish people who go on to develop a cardiovascular event and those who remain event free. 2,15 For example, for two individuals with diabetes with one developing a cardiovascular event after 10 years of follow-up and the other remaining CVD-free within that same time period; a discriminating model will systematically assign, at the start of the follow-up, a higher absolute risk to the first subject compared to the second. Discrimination is commonly assessed using the C-statistic, which ranges from 0.5 (lack of discrimination) to 1.0 (perfect discrimination).1,2,15 In general, a C-statistic 0.7 or greater is considered acceptable.

Calibration describes the agreement between estimated and observed risks. It is assessed by comparing absolute risk estimates from the model with the actual event rates in the test population.

1,2,15 For illustration, a 10-year estimated absolute risk of CVD of 20% for a patient indicates that, in a given group of patients with similar characteristics, 20% will experience a cardiovascular event within a 10-year period of follow-up. The most commonly reported measure of the calibration is the Hosmer-Lemeshow statistic. Estimates of calibration are sensitive to differences in the

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background levels of risk across populations. For example, if a given CVD risk model is developed in a high-risk population but tested in a low risk population; the estimated absolute risks will be unreliably high. Recalibration of the risk model by adjusting the baseline risk estimates to fit the target population may help correcting the overor underestimation of risk. 1,15

Global cardiovascular risk estimation in people with diabetes Global CVD risk has been estimated in people with diabetes using essentially three main approaches.16 In the ‘CVD risk equivalent’ approach described above, the presence of diabetes mellitus is considered to confer a 10-year absolute CVD risk of 20% or more, which is approximately the 10-year CVD event rate observed in non-diabetic individuals with a prior history of CVD. Such an approach appears to be counterintuitive as the CVD risk is not uniformly distributed among people with diabetes. This is further supported by many studies showing multivariable risk estimation to be significantly better than classification of diabetes as a cardiovascular risk equivalent. 17,18 In the second approach, also termed ‘step approach’, unifying CVD risk estimation models are developed both for people with diabetes and those without the condition. This approach assumes that major risk factors for CVD are related to future occurrence of CVD in a similar way, regardless of the status for diabetes mellitus. Stated otherwise, everything else being equal an individual with diabetes will always have a higher risk of CVD (by a constant amount) than the non-diabetic subject with the same level of other risk factors (e.g. blood pressure or lipid levels). This has been the basis for models such as the popular Framingham cardiovascular absolute risk models.16 In the last approach, also known as ‘interaction approach’, CVD risk models are constructed separately for people with and without diabetes.

This approach suggests that risk factors are related to future CVD risk in different ways in people with and without diabetes. This approach in people with diabetes was initially used by the UKPDS investigators.9,19 Available studies largely suggest that classical cardiovascular risk factors (including smoking, blood pressure, lipid variables) and even some novel risk factors16,20-23, affect the risk of CVD in similar ways in people with and without diabetes, with no evidence of interaction.

Some risk factors or characteristics are likely to be more frequent in people with diabetes and may justify separate cardiovascular risk models for people with diabetes. These diabetes-specific characteristics include prescriptions of cardiovascular risk reducing therapies, which may differ in people with and without diabetes.

Additional specific factors are haemoglobin A1c (HbA1c), urinary albumin excretion and markers of microvascular complications of diabetes in general (especially retinopathy). These have been demonstrated to be associated with CVD risk and can contribute useful information to predictions.24-29

Performance of popular CVD risk models and the ADVANCE study At the time the ADVANCE study was conducted, CVD risk prediction models in the general population were dominated by models developed from the Framingham Heart Study, which for many could also be used in people with diabetes.7 CVD risk models specific to people with diabetes were also available, particularly those from the UKPDS study.7 However, the clinical utility and comparative

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performance of these popular CVD risk models in contemporary populations with diabetes in diverse settings were still to be established.

Therefore, one of the major initial steps was to conduct extensive validation studies of the Framingham and UKPDS CVD risk models, using the unique features of the ADVANCE cohort.3 These validation studies revealed that, in the cohort of ADVANCE participants who had no known history of CVD at their enrolment in the trial, the 4-year absolute risk of cardiovascular events and components was largely overestimated by the Framingham-Anderson30, FraminghamD’Agostino31 and UKPDS risk models9,19. This overestimation was also observed in men and women, Caucasians and non-Caucasians, and the double placebo cohort (i.e. those assigned to the placebo group in the blood pressure lowering arm and the standard care group of the blood pressure control arm).3 Discrimination of the Framingham and UKPDS risk models in predicting CVD events in ADVANCE was poor for stroke, and modest-to-acceptable for coronary heart disease and total CVD. Recalibration substantially attenuated the magnitude of risk overestimation by the Framingham and UKPDS risk models in ADVANCE. Discrimination was unaffected as expected, indicating the need for new CVD risk models with improved predictive accuracy for people with diabetes, particularly those who are receiving many contemporary cardiovascular risk reducing therapies.

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Table 1. Beta coefficients (95% confidence interval) and standard errors for predictors in the ADVANCE CVD prediction model.14 Variable

Parameter estimate (standard error)

P value*

Age at diagnosis (per 1 year increase)

0.062 (0.008)

< 0.001

Sex (women vs. men)

-0.474 (0.098)

< 0.001

Known duration of diabetes (per 1 year increase)

0.083 (0.010)

< 0.001

Pulse pressure (per 1 mmHg increase)

0.007 (0.003)

0.016

Retinopathy (yes vs. no)

0.383 (0.101)

< 0.001

Atrial fibrillation (present vs. absent)

0.601 (0.154)

< 0.001

HbA1c (per 1% increase)

0.099 (0.027)

< 0.001

Log of urinary albumin/creatinine ratio (per 1 log mg/g increase)

0.193 (0.033)

< 0.001

Non-HDL cholesterol (per 1 mmol/l increase)

0.126 (0.034)

< 0.001

Treated hypertension (yes vs. no)

0.242 (0.106)

0.022

Development of the ADVANCE cardiovascular risk model In developing a new model for risk prediction, it is critical to account for the limitations of existing ones, in order to improve performance. The inclusion in ADVANCE of participants from many countries provided the opportunity to account for the substantial variation in the care of diabetes and CVD around the world. Available models so far had been derived from homogenous populations. The ADVANCE model targets total CVD and therefore captures the interrelation between components of CVD such as CHD or stroke; unlike many existing models that have focussed specifically on these components. The complexity of the relationship between chronic hyperglycaemia and cardiovascular risk has been less fully addressed in existing models. Some improvement was achieved in the ADVANCE model through integration of risk factors to capture both the exposure to chronic hyperglycaemia prior to and after the clinical diagnosis of diabetes. Statistical method is an important component of model development. Trusted statistical methods were used to select the potential risk factors and test their suitability for inclusion in the ADVANCE risk model.14 Risk factors considered for inclusion in the ADVANCE model were: age at clinical diagnosis of diabetes, duration of diagnosed diabetes, sex, blood pressure (BP) indices (systolic BP, diastolic BP, mean arterial (MAP) and pulse (PP) pressures), lipid variables (total, HDL and non-HDL cholesterol, ratio total/HDL cholesterol and triglycerides), body mass index (BMI), waist circumference, waistto-hip ratio, BP lowering medication (i.e. treated hypertension), statin use, current smoking, retinopathy, atrial fibrillation (past or present), urinary albumin/creatinine ratio (ACR) and serum creatinine ( S cr ), HbA1c, fasting blood glucose and randomised treatments (BP lowering and glucose control regimens). Ten of these candidate risk factors were included in the final ADVANCE risk model. Age at diabetes diagnosis and known duration of diabetes were preferred to age at baseline to improve the applicability of the ADVANCE risk model to other populations. The beta coefficients and accompanying standard error for risk factors in the ADVANCE risk model are shown in Table 1.14

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Performance of the ADVANCE risk model14 The applicability of the ADVANCE risk model tested on the same population used to develop the model (i.e. internal validation) and on an independent external sample for which the DIAB-HYCAR cohort32 was used. In both internal and external validations, the discrimination of the ADVANCE model was acceptable. In comparison with existing total CVD models, the ADVANCE model largely outperformed the Framingham-Anderson and FraminghamD’Agostino models. The calibration of the ADVANCE model was excellent in internal validation and good in external validation, with only a modest risk underestimation. This is likely explained by the difference in the levels of preventive therapies between ADVANCE and DIAB-HYCAR population. Interestingly, the agreement between predictions by the ADVANCE models and the observed CVD events was consistent across different cut-offs or predicted risk of CVD. For comparison, the two Framingham equations overestimated the risk of CVD in the DIAB-HYCAR cohort by 65% (Anderson equation) and 99% (D’Agostino equation). Using a cut-off for 4-year predicted risk of ≥ 8% (which is approximately equivalent to a 10-year predicted risk of 20% and above), the ADVANCE model would reliably identify the 22% of the ADVANCE participants and 39% of the DIAB-HYCAR participants in whom 48% and 66% of CVD events respectively occurred during follow-up. Further intensifying treatment in such groups on top of any baseline therapy could achieve significant gain in terms of CVD risk reduction.

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Dissemination of the ADVANCE risk model To facilitate the uptake of the ADVANCE model in clinical practice, a handheld calculator and a risk scoring chart (Figure 1) have been developed.14 Other tools from this model, including an online calculator are available at the website of the model to improve its uptake.33 Extensive validations have been conducted to assure that these tools provide estimates similar to those from the full ADVANCE risk equation.

Performance of existing global risk tools for cardiovascular risk estimation in people with diabetes Two systematic reviews have examined the performance of CVD risk evaluation models applicable to people with diabetes.7,34 The most recent and comprehensive review identified 45 risk CVD models applicable to people with diabetes.7 Of these, 12 were specifically developed for people with type 2 diabetes (including the

ADVANCE model) and 33 were developed in the general population accounting for diabetes as a risk factor. These models vary greatly in their quality and the methodology used to develop them. Only about a third of the existing CVD risk tools applicable to people with diabetes have been externally validated in a population with diabetes. The discriminative ability of both diabetes-specific CVD prediction models and general population prediction models that use diabetes status as a predictor was generally acceptable-to-good (i.e. C-statistic â&#x2030;Ľ 0.70). The discrimination of prediction models designed for the general population was moderate (C-statistic: 0.59 to 0.80) and their calibration generally poor. The most commonly validated models were the general population-based Framingham cardiovascular risk equations and the diabetes-specific UKPDS risk engines. The Framingham prediction models also showed a lowto-acceptable discrimination and a poor calibration. Although the discriminative power of UKPDS engines was acceptable, it has a poor calibration and a tendency toward systematic overestimation

Figure 1. Major cardiovascular disease points and 4-year predicted risk by the ADVANCE Model equation.14 Step 1

Step 5

Step 11

Age at diagnosis, y

Points

Retinopathy

Points

29-34 35-39

0

No

0

1

Yes

40-44

2

1

45-50

3

51-56

4

Treated hypertension

Points

57-62

5

No

0

63-68

6

Yes

1

69-74

7

75-80

8

81-86

9 Step 2

Step 6

Sum up points from steps 1 through 10

Look up predicted 4-year risk of major CVD in the table

Step 7 Pulse pressure, mmHg

Points

< 50

0

50-110

1

111 +

2

Known duration, y

Points

0

0

1-5

1

6-10

2

HbA1c

11-15

3

16-20

Predicted 4-year risk of Major CVD

Total points

4-year risk, %

5 or less

< 0.5%

Points

6

0.5%

< 6%

0

7

0.7%

4

6-<9

1

8

1.0%

21-25

5

9+

2

9

1.4%

26-30

6

10

2.1%

31-35

7

11

3.0%

36+

8 Step 3

Sex

Points

Men

0

Women

-1 Step 4

Step 8

Step 9 Albuminuria

Points

12

4.3%

Normoalbuminuria

0

13

6.2%

Microalbuminuria

2

14

8.9%

Macroalbuminuria

3

15

12.6%

16

17.8%

17

24.7%

Step 10 Non HDL-c, mmol/L

Points

18

33.7%

<3

0

19

41.9% 57.8%

Atrial fibrillation

Points

3-<6

1

20

No

0

6-<9

2

21

71.4%

Old or present

2

9+

5

22

Above 83%

As an illustration of the use of the risk scoring chart, a male subject, diagnosed with diabetes 3 years previously at the age of 50, who has a pulse pressure of 50 mmHg and is currently treated for hypertension; also has retinopathy, atrial fibrillation and microalbuminuria, an HbA1c of 7% and a non-HDL cholesterol of 3.3 mmol.L-1; will receive a total score of 13 points: 0 for sex, 3 for age at diagnosis, 1 for known duration, 1 for pulse pressure, 1 for treated hypertension, 1 for retinopathy, 2 for atrial fibrillation, 2 for microabuminuria, and 1 for HbA1c and non-HDL cholesterol each. A score of 13 points is equivalent to a 4-year estimated risk of 6.2%, which is similar to the risk estimated for the same patient using the full equation.

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of risk, particularly in recent cohorts. The models with best external validity were more contemporary, but these had been validated in other patient populations only once.7

Conclusion The quest for the appropriate approaches to assess cardiovascular risk and thus prevent vascular complications in individuals with diabetes is a continuing pursuit. Diabetes mellitus is not a cardiovascular risk equivalent in all circumstances. The CVD risk is not uniformly distributed in individuals with diabetes, but rather follows a gradient. Adequately capturing this gradient depends on the combination of individual risk factors. Global risk assessment appears to be the way forward for managing CVD risk among people with diabetes. Both the ADVANCE and subsequent studies have provided evidence that existing popular models derived from older cohorts were less accurate for cardiovascular risk evaluation in contemporary population with diabetes.7 The recognition of this non-optimal performance and other limitations of existing models have stimulated efforts to develop new cardiovascular risk models (including the ADVANCE model14) with improved predictive accuracy for people with diabetes. The ADVANCE model continues to enjoy the unique property that it was developed from a contemporary multinational cohort of people with diabetes, and has been successfully validated in another recent multinational cohort of individuals with diabetes. Inclusion of participants from developing countries in the ADVANCE cohort highlight the potential of the ADVANCE risk model for assisting cardiovascular risk stratification efforts in many settings around the world.

References 1

Moons K, Kengne AP, Grobbee DE, Royston P, Vergouwe Y, Altman D, Woodward M. Risk prediction models: II. External validation, model updating, and impact assessment. Heart. 2012: doi:10.1136/heartjnl-2011-301247.

2 Moons K, Kengne AP, Woodward M, Royston P, Vergouwe Y, Altman D, Grobbee DE. Risk prediction models: I. Development, internal validation, and assessing the incremental value of a new (bio)marker. Heart. 2012; doi:10.1136/heartjnl-2011301246.

3 Kengne AP, Patel A, Colagiuri S, Heller S, Hamet P, Marre M, Yu Pan C, Zoungas S, Grobbee DE, Neal B, Chalmers J, Woodward M. The Framingham and UKPDS risk equations do not reliably estimate the probability of cardiovascular events in a large ethnically diverse sample of patients with diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) Study. Diabetologia. 2010; 53: 821-31.

4 Echouffo-Tcheugui JB, Kengne AP, Sobngwi E. Cardiovascular risk evaluation tools specific to population with diabetes. Arch Intern Med. 2012; 172(6): 523-4.

5 Kengne AP, Echouffo-Tcheugui JB, Sobngwi E. Coronary artery calcium for guiding statin treatment. Lancet. 2012; 379: 60140-8.

6 Kengne AP, Turnbull F, MacMahon S. The Framingham Study, diabetes mellitus and cardiovascular disease: turning back the clock. Prog Cardiovasc Dis. 2010; 53: 45-51. 10.1016/j.pcad.2010.02.010.

7 Van Dieren S, Beulens JW, Kengne AP, Peelen LM, Rutten GE, Woodward M, Van der Schouw YT, Moons KG. Prediction models for the risk of cardiovascular disease in patients with type 2 diabetes: a systematic review. Heart. 2012; 98: 360-9. heartjnl-2011-300734 [pii] 10.1136/heartjnl-2011-300734.

8 Truett J, Cornfield J, Kannel W. A multivariate analysis of the risk of coronary heart disease in Framingham. J Chronic Dis. 1967; 20: 511-24.

9 Stevens RJ, Kothari V, Adler AI, Stratton IM. The UKPDS risk engine: a model for the risk of coronary heart disease in Type II diabetes (UKPDS 56). Clin Sci (Lond).

2001; 101: 671-9.

10 Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998; 339: 229-34.

11 Bulugahapitiya U, Siyambalapitiya S, Sithole J, Idris I. Is diabetes a coronary risk equivalent? Systematic review and meta-analysis. Diabet Med. 2009; 26: 142-8.

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12 Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008; 358: 580-91.

13 Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003; 348: 383-93.

14 Kengne AP, Patel A, Marre M, Travert F, Lievre M, Zoungas S, Chalmers J, Colagiuri S, Grobbee DE, Hamet P, Heller S, Neal B, Woodward M. Contemporary model for cardiovascular risk prediction in people with type 2 diabetes. Eur J Cardiovasc Prev Rehabil. 2011. 10.1177/1741826710394270.

15 Lloyd-Jones DM. Cardiovascular risk prediction: basic concepts, current status, and future directions. Circulation. 2010; 121: 1768-77. 121/15/1768 [pii] 10.1161/CIRCULATIONAHA.109.849166.

16 Echouffo-Tcheugui JB, Ogunniyi MO, Kengne AP. Estimation of absolute cardiovascular risk in individuals with diabetes mellitus: rationale and approaches.

ISRN Cardiol. 2011; 2011: 242656. 10.5402/2011/242656.

17 Howard BV, Best LG, Galloway JM, Howard WJ, Jones K, Lee ET, Ratner RE, Resnick HE, Devereux RB. Coronary heart disease risk equivalence in diabetes depends on concomitant risk factors. Diabetes Care. 2006; 29: 391-7.

18 Wannamethee SG, Shaper AG, Whincup PH, Lennon L, Sattar N. Impact of diabetes on cardiovascular disease risk and all-cause mortality in older men: influence of age at onset, diabetes duration, and established and novel risk factors. Arch Intern Med. 2011; 171: 404-10. 171/5/404 [pii] 10.1001/archinternmed.2011.2.

19 Kothari V, Stevens RJ, Adler AI, Stratton IM, Manley SE, Neil HA, Holman RR. UKPDS 60: risk of stroke in type 2 diabetes estimated by the UK Prospective Diabetes Study risk engine. Stroke. 2002; 33: 1776-81.

20 Asia Pacific Cohort Studies Collaboration. Systolic blood pressure, diabetes and the risk of cardiovascular diseases in the Asia-Pacific region. J Hypertens. 2007; 25: 1205-13.

21 Asia Pacific Cohort Studies Collaboration. Cholesterol, diabetes and major cardiovascular diseases in the Asia-Pacific region. Diabetologia. 2007; 50: 2289-97.

22 Asia Pacific Cohort Studies Collaboration. Smoking, diabetes and cardiovascular diseases in men in the Asia-Pacific Region J Diabetes. 2009; 1: 173-81.

23 Kengne AP, Batty GD, Hamer M, Stamatakis E, Czernichow S. Association of C-reactive protein with cardiovascular disease mortality according to diabetes status: pooled analyses of 25,979 participants from four U.K. prospective cohort studies. Diabetes Care. 2012; 35: 396-403. 10.2337/dc11-1588.

24 Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care.

1999; 22: 233-40.

25 Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, Golden SH. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med. 2004; 141: 421-31.

26 Miettinen H, Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Retinopathy predicts coronary heart disease events in NIDDM patients. Diabetes Care. 1996; 19: 1445-8.

27 van Hecke MV, Dekker JM, Stehouwer CD, Polak BC, Fuller JH, Sjolie AK, Kofinis A, Rottiers R, Porta M, Chaturvedi N. Diabetic retinopathy is associated with mortality and cardiovascular disease incidence: the EURODIAB prospective complications study. Diabetes Care. 2005; 28: 1383-9.

28 Targher G, Bertolini L, Tessari R, Zenari L, Arcaro G. Retinopathy predicts future cardiovascular events among type 2 diabetic patients: The Valpolicella Heart Diabetes Study. Diabetes Care. 2006; 29: 1178.

29 Juutilainen A, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Retinopathy predicts cardiovascular mortality in type 2 diabetic men and women. Diabetes Care. 2007; 30: 292-9.

30 Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J. 1991; 121: 293-8.

31 Dâ&#x20AC;&#x2122;Agostino RB, Sr., Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, Kannel WB. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008; 117: 743-53.

32 Marre M, Lievre M, Chatellier G, Mann JF, Passa P, Menard J. Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study). Bmj. 2004; 328: 495.

33 The ADVANCE Collaborative Group. ADVANCE Risk ENgine. Available at http:// www.advanceriskengine.com/index.html. Accessed on 04.06.2012 34 Chamnan P, Simmons RK, Sharp SJ, Griffin SJ, Wareham NJ. Cardiovascular risk assessment scores for people with diabetes: a systematic review. Diabetologia.

2009; 52: 2001-14.

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Vitamin D and diabetes – a D-lemna MARLI CONRADIE Introduction

Measurement of vitamin D status

The worldwide prevalence of diabetes, most notably Type 2 diabetes (T2DM), is increasing rapidly. Estimated projections for Sub-Saharan Africa are a prevalence of 18.6 million by 2030.1 Most strategies to halt this increase have been aimed at preventing or treating obesity as a major risk factor for the development of diabetes.

Unfortunately, most efforts have failed and the prevalence of obesity remains alarmingly high.1 Novel risk factors for the development of diabetes have been described.2 Included are adipose-derived factors (e.g. adiponectin and leptin), liver-derived factors (e.g. CRP and ALT/GGT ratio), endothelial-derived factors, inflammatory markers and nutritional factors. To be considered amongst the nutritional factors is the link between hypovitaminosis D and diabetes.

The 25-OH vitamin D level reflects the body’s overall vitamin D status. It is more stable than 1,25-(OH)2 vitamin D, with a much longer half-life.8 Assays in South Africa are not standardized at the present time and a variety of methods (RIAs, enzyme linked assays such as ELISA and liquid chromatography with mass spectrometry) are used, with different reference ranges and units.

Normal vitamin D status is currently defined as a serum level between 30-76 ng/ml (65-190 nmol/l).8 The lower limit of normal still remains a topic of much debate. The term vitamin D insufficiency has more recently been introduced to describe suboptimal levels of 25-OH vitamin D, typically between 10-30 ng/ml (25-65 nmol/l), associated with adverse outcomes.3 The vitamin D status of the South African population is not known at the present time.

What we do know about vitamin D?

A role in Type 1 diabetes?

Vitamin D exists in two forms (D2 or ergocalciferol and D3 or cholecalciferol) and also as numerous circulating metabolites thereof. Vitamin D3 is produced in the skin under the influence of ultraviolet light (80%) or can be obtained from the diet (fatty fish, egg yolks etc.). Vitamin D2 is found in plant sources or produced commercially by the fortification of yeast.3 Supplementation can either be with vitamin D2 or D3. Both forms can be stored in adipose tissue or alternatively undergo hydroxylation in the liver, producing 25-OH vitamin D (calcidiol). This form is converted mostly in the kidney via 1– hydroxylase to 1,25-(OH)2 vitamin D (calcitriol). This is the biologically active form of vitamin D. The vitamin D receptor (VDR) is a nuclear receptor of the thyroid hormone receptor superfamily which is expressed by all tissues.4 Many tissues including colon, pancreas, breast, prostate, immune system, macrophages, vascular endothelium, epidermis, placenta and others also possess the enzymes to produce calcitriol locally.

This may explain why vitamin D appears to play an essential role in overall health.4,5 Different polymorphisms of VDR have been associated with diabetes (type 1 and type 2), metabolic syndrome, impaired fasting glucose and impaired glucose tolerance. Furthermore, 1,25-(OH)2 vitamin D regulates the expression of over 200 genes, including those related to apoptosis and immune modulation.6 Potential mechanisms for the role of vitamin D in diabetes include its action on insulin secretion (both directly, as well as through its role in calcium homeostasis), insulin action (both directly and indirectly) and a beneficial effect on systemic inflammation.7

It has been shown that there is an immunomodulatory effect of 1,25-(OH)2 vitamin D, inhibiting upregulation of Th cells that are crucial in the pathogenesis of type 1 diabetes mellitus (T1DM).9 An inverse relationship between vitamin D intake in infants and the subsequent prevalence of T1DM was found in large population based studies in Finland.10 Interestingly, the incidence of T1DM also increases as one moves further away from the equator, typically reflecting the amount of sunlight received.11 However, no cause and effect have been demonstrated.

Submitted 7/5/2013, accepted 27/5/2013 Correspondence to: Dr Marli Conradie MBChB MMed (Int Med) FCP (SA) Cert Endo & Metab (Phys) Consultant Physician and Endocrinologist University of Stellenbosch Dept of Medicine Tygerberg Academic Hospital E-mail: marliconradie@sun.ac.za S Afr J Diabetes Vasc Dis 2013; 10: 65–66

VOLUME 10 NUMBER 2 • JUNE 2013

Type 2 diabetes The epidemiology of T2DM corresponds with that of vitamin D deficiency, being more prevalent in the older population as well as in subjects with darker skins. Also, a seasonal variation in diabetes control has been demonstrated, with control being worse in winter.12 Whether this is due to the general lack of sunlight, or the fact that patients are more inclined to consume carbohydrate loaded diets in winter, is of course not clear.

There is an overwhelming amount of research, mostly observational, trying to link vitamin D deficiency with diabetes. A systematic review and meta-analysis evaluating 19 cross-sectional studies concluded that there were inverse associations between levels of 25-OH vitamin D and measurements of glycaemia or prevalence of T2DM; however, this was not consistent and not present in all populations.13 By combining data reporting on level of 25-OH vitamin D and diabetes prevalence, a non-significant inverse association was found (OR 0.54, 95% CI: 0.23-1.27 for highest vs. lowest 25-OH vitamin D concentration). Similarly, in the Nurses’ Health Study, it was found that those with the highest intake of both vitamin D and calcium had the lowest incident relative risk for diabetes.14 Other population based research also showed associations between low vitamin D levels and markers of cardiometabolic risk (blood pressure, lipids and hyperglycaemia) when adjusted for obesity.15,16 In addition, low vitamin D levels were associated with markers of insulin resistance17 as well as showing a non-linear inverse association with HbA1c.18 The problem with these observational studies is the huge variability in study cohorts as well as the presence of important confounders

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like obesity. Also, in case-control and cross-sectional studies, the measurement of vitamin D is done after the diagnosis of diabetes and not before, making impossible the proving of causality.

A meta-analysis looking at 11 prospective studies concluded that there was a combined relative risk for diabetes comparing the highest with the lowest quartiles of 25-OH vitamin D of 0.59 (0.520.67).19 Also, an analysis of 25-OH vitamin D levels done during the DPP, found a higher concentration was associated with lower risk of incident diabetes, after adjusting for lifestyle interventions (HR 0.72, 95% CI: 0.56-0.90).20 Interventional studies are mostly lacking and there is variability in reporting. No clear benefit of supplementation of vitamin D with the aim to prevent diabetes has been demonstrated yet.21 It was shown that there may be a small benefit on insulin resistance markers in patients who already have impaired fasting glucose.22 A randomized controlled trial evaluating the secretion and sensitivity of insulin with vitamin D supplementation showed a potential benefit,23 but another trial in obese African American patients demonstrated no improvement in glycaemia after 3 months.24

Diabetes complications An increase in both the all-cause mortality as well as cardiovascular mortality in T2DM is associated with lower 25-OH vitamin D levels.25 However, in this study severe vitamin D deficiency at baseline did not predict progression to micro- or macroalbuminuria. Also, a systematic review of 15 trials concluded that there was insufficient evidence to draw conclusions regarding micro- and macrovascular events in T2DM.22 Similarly, though an increased mortality has been demonstrated in T1DM with a lower vitamin D level, severe vitamin D deficiency at baseline did not predict the development of microvascular complications such as nephropathy and retinopathy.26

Cardiovascular outcomes Low 25-OH vitamin D levels have been associated with stroke, peripheral vascular disease, chronic heart failure and myocardial infarction in cross-sectional and longitudinal data.27 The question remains whether this is indeed cause or effect. To date, interventional studies have been inconclusive and results of larger trials such as the VITAL and VIDAL studies are awaited.

Recommendations and conclusion Guidelines as to which patients to test for vitamin D deficiency, as well as recommendations for vitamin D intake in various subgroups, are available.28 The most effective source of vitamin D remains sunlight exposure, but recent concerns regarding the disadvantages of UV exposure has made this undesirable. However, it must be said that the amount of sunlight needed to produce a significant amount of vitamin D is very little.28 In conclusion, vitamin D has proven effects on insulin secretion and sensitivity. Observational data supports an association between vitamin D deficiency and diabetes, but this does not prove causality.

Interventional trials to resolve the question of benefit, either on development or outcome of diabetes, are still largely lacking. Therefore, testing and subsequent vitamin D supplementation for diabeticrelated outcomes is at presently not recommended in patients.

References 1.

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Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world—a growing challenge. N Engl J Med 2007; 356(3): 213-215.

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2. Sattar N, Wannamethee S, Forouhi N. Novel biochemical risk factors for type 2 diabetes: pathogenic insights or prediction possibilities? Diabetologia 2008; 51(6): 926-940.

3. Adams JS, Hewison M. Update in Vitamin D. J Clin Endocrinol Metab 2010 February 1; 95(2): 471-478.

4. Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc 2011 01/01; 86(1): 50.

5. Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med 2008 Dec; 29(6): 361-368.

6. Cavalier E, Delanaye P, Souberbielle J, Radermecker R. Vitamin D and type 2 diabetes mellitus: Where do we stand? Diabetes Metab 2011; 37(4): 265-272.

7. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 2007 Jun; 92(6): 2017-2029.

8. Rosen C. Vitamin D Insufficiency. N Engl J Med 2011 Jan 20; 364(3): 248.

9. Mathieu C, Gysemans C, Giulietti A, Bouillon R. Vitamin D and diabetes.

Diabetologia 2005; 48(7): 1247-1257.

10. Hyppönen E, Läärä E, Reunanen A, Järvelin M, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. The Lancet 2001; 358(9292): 1500-1503.

11. Mohr S, Garland C, Gorham E, Garland F. The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. Diabetologia 2008; 51(8): 1391-1398.

12. Ishii H, Suzuki H, Baba T, Nakamura K, Watanabe T. Seasonal variation of glycemic control in type 2 diabetic patients. Diabetes Care 2001; 24(8): 1503-1503.

13. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The Role of Vitamin D and Calcium in Type 2 Diabetes. A Systematic Review and Meta-Analysis. J Clin Endocrinol Metab 2007 June 1; 92(6): 2017-2029.

14. Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett WC, Manson JE, et al.

Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care 2006; 29(3): 650-656.

15. Reis JP, von Mühlen D, Miller ER, Michos ED, Appel LJ. Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics 2009; 124(3): e371-e379.

16. Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL, et al. Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes 2010; 59(1): 242-248.

17. Zhao G, Ford ES, Li C. Associations of serum concentrations of 25-hydroxyvitamin D and parathyroid hormone with surrogate markers of insulin resistance among US adults without physician-diagnosed diabetes: NHANES, 2003–2006. Diabetes Care 2010; 33(2): 344-347.

18. Kositsawat J, Freeman VL, Gerber BS, Geraci S. Association of A1C Levels With Vitamin D Status in US Adults Data from the National Health and Nutrition Examination Survey. Diabetes Care 2010; 33(6): 1236-1238.

19. Forouhi N, Ye Z, Rickard A, Khaw K, Luben R, Langenberg C, et al. Circulating 25-hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies. Diabetologia 2012; 55(8): 2173-2182.

20. Pittas AG, Nelson J, Mitri J, Hillmann W, Garganta C, Nathan DM, et al. Plasma 25-Hydroxyvitamin D and Progression to Diabetes in Patients at Risk for Diabetes: An ancillary analysis in the Diabetes Prevention Program. Diabetes Care 2012; 35(3): 565-573.

21. Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, et al. Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med 2010 Mar 2; 152(5): 307-314.

22. George P, Pearson E, Witham M. Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta–analysis.

Diabetic Med 2012; 29(8): e142-e150.

23. Mitri J, Dawson-Hughes B, Hu FB, Pittas AG. Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. Am J Clin Nutr 2011; 94(2): 86-494.

24. Harris SS, Pittas AG, Palermo NJ. A randomized, placebo–controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans. Diabetes, Obesity and Metabolism 2012; 14(9): 789-794.

25. Joergensen C, Gall M, Schmedes A, Tarnow L, Parving H, Rossing P. Vitamin D levels and mortality in type 2 diabetes. Diabetes Care 2010; 33(10): 2238-2243.

26. Joergensen C, Hovind P, Schmedes A, Parving H, Rossing P. Vitamin D levels, microvascular complications, and mortality in type 1 diabetes. Diabetes Care 2011; 34(5): 1081-1085.

27. Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA. Vitamin D deficiency and supplementation and relation to cardiovascular health. Am J Cardiol 2012; 109(3): 359-363.

28. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96(7): 19111930.

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DRUG TRENDS

Aim for tighter control in hypothyroid disorders

W

hen it comes to the management of hypothyroid disorders, it’s important to aim for tighter control and to get thyroidstimulating hormone (TSH) levels to target.

This is the message conveyed by Dr Sindeep Bhana, a Johannesburg endocrinologist who works in the public sector. He was speaking at the Johannesburg launch of Abbott Laboratories’ Synthroid, a new levothyroxine sodium formulation that gives healthcare professionals an additional option for the treatment of hypothyroidism.

The thyroid gland may be a small organ but it drives the entire body’s metabolism, affecting inter alia carbohydrate, protein, lipid and bone metabolism, cardiovascular and cognitive function as well as fertility, among many other functions.

Hypothyroidism affects 5-10% of elderly women in some studies. Predisposing factors include age, female gender, subacute lymphocytic thyroiditis and Turner’s disease.

Chronic autoimmune thyroiditis is the commonest cause of hypothyroidism, but the following are a few other causes: • Thyroidectomy • Radioactive iodine treatment • Iodine therapy, including amiodarone • External radiation therapy • Infiltrative causes (although these are rare) • Enzyme defects Hypothalamic and pituitary pathology are secondary causes of hypothyroidism.

“Treatment requires the use of levothyroxine with the aim of restoring the metabolic state,” says Dr Bhana. “The dosage can vary from 25 to 300 micrograms, but the average is 112 micrograms. It’s important to remember, however, that patients are not average and that we need to titrate according to individual patient needs. The optimal dose depends on clinical criteria and a very narrow TSH band. TSH levels need to be measured six-weekly until they fall within the normal range and thereafter six-monthly.

“Where secondary causes are involved, we need to look at T4 levels alone and aim for the upper third of normal.”

When individualising treatment, various factors need to be taken into account, including age, weight, race, underlying cardiovascular health and other co-morbidities. There are various levothyroxine formulations on the market to choose from. “With elderly patients, start with a low dose of 25 micrograms and double that every 3-4 weeks until

VOLUME 10 NUMBER 2 • JUNE 2013

TSH levels normalise, as increasing the metabolic rate too quickly, with higher doses of thyroxine, may precipitate an infarct,” says Dr Bhana.

A number of factors may increase levothyroxine requirements. These include pregnancy, small bowel disease, drugs and dietary supplements that reduce absorption, drugs that increase metabolism and drugs that reduce T4 to T3 conversion. “It’s important to be aware of drug interactions, particularly with those used for treating upper gastrointestinal tract symptoms,” cautions Dr Bhana.

He advises doctors not to swap patients from one product to another if the TSH levels are within a tight range. “If a patient is well controlled on a specific product, stay with it.”

Dr Bhana describes subclinical hypothyroidism (SH) as a ‘whole new ballgame’, characterised by a TSH level up to 10, in the presence of a normal T4 level. The condition is more common in women than in men. Type 1 diabetes is also a predisposing factor. Its aetiology is usually autoimmune, but it can occur post ablative therapy for hyperthyroidism or be the result of surgery. Most commonly, as the Colorado study showed, inadequate replacement therapy is the aetiology. “Some 37% of patients with hypothyroidism are not receiving adequate or appropriate replacement therapy, and in this context swapping products may allow us to address matters.”

If SH is untreated, there is the likelihood of the condition progressing to overt hypothyroidism. Different studies show different progression rates, and population and iodine status evidently matter. Dr Bhana feels that most of the randomised controlled trials were not adequately designed to answer the gaps in this field. “In treating SH, we see mixed outcomes with regard to echocardiogram parameters. And while T4 replacement has been associated with improved endothelial function and increased intima media function, there were no significant changes in other measures of cardiovascular function.”

SH is associated with weight gain, as shown in the Rotterdam study. It also poses risks in pregnancy and fertility by increasing the possibility of miscarriage, preterm birth, poor developmental outcomes and ovulatory dysfunction.

Summarising the management of hypothyroidism, Dr Bhana observes that while various guidelines are not in total agreement, the following is generally accepted. Treat symptomatic patients under 65 who have

TSH levels of 4-10 mU/l; treat asymptomatic patients under 65 who have TSH levels of 4-10 mU/l and have high antibody levels; treat patients who are pregnant, who wish to fall pregnant, are infertile or have ovulatory dysfunction. But the evidence to treat patients over the age of 65 is not clear.

Key messages • Aim for tighter control of hypothyroid disorders • Get TSH levels to target, titrating therapy as required • Make therapy as convenient for the patient as possible The goal is to aim for TSH target levels in normal range – 0.5-2.5 in younger patients, 3-5 in the elderly. There are three levothyroxine brands now available in South Africa – the first comes in dosages of 50 and 100 micrograms (not scored), the second in dosages of 25, 50 and 100 micrograms (scored).

The third – the newly launched Synthroid – comes in five doses, viz. 25, 50, 88, 100 and 112 micrograms (partially scored and colour coded). “If patients are well controlled and symptom free, don’t change brands,” advises Dr Bhana. “However, 60% of patients suffering from thyroid conditions are not, and we now have more options. Make the dose as convenient as possible and titrate until normal levels are reached.”

Priority patients requiring treatment for their subclinical hypothyroidism • • •

Symptomatic patients under 65 years, with TSH levels of 4-10mU/L Asymptomatic patients, under 65 years, with TSH of 4-10mU/L and high antibody levels Pregnant patients or those wishing to fall pregnant, are infertile or have ovulatory dysfunction

The evidence to treat patients over the age of 65 is not clear

Synthroid is a levothyroxine sodium formulation available in 14 dosages in the USA. The five dosages now available in South Africa were chosen by local key opinion leaders and give healthcare professionals more options for titration. “Our aim is to simplify treatment and make it more accessible,” says product manager Ntebeng Ramushi. “The 88 microgram dose especially has become very popular.”

P Wagenaar, Gauteng correspondent

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Patient information leaflet

S Afr J Diabetes Vasc Dis 2013; 10: 68–69

Keep and Copy Series IMPROVING CHOLESTEROL MANAGEMENT: LIFESTYLE CHANGES AND TAKING MEDICINE

M

any factors can cause unhealthy cholesterol levels. Most of these factors can be modified, but some cannot be changed. High blood cholesterol can be inherited, but even so, action can be taken to lower levels of bad (LDL) cholesterol. Cholesterol levels also rise as we age and in the case of women, menopause may elevate cholesterol levels too. Factors under our control include diet, weight and levels of physical activity.

Of equal importance, if taking cholesterol-lowering medicines, we need to learn to take them properly.

Diet Minimise or eliminate your intake of bad fats Saturated fats are responsible for raising bad cholesterol levels more than anything else in the diet. These fats are usually solid at room and fridge temperatures and mostly originate from animals. The worst culprits are fatty cuts of meat, poultry skin, whole-milk dairy products and lard. Some vegetable oils such as coconut and palm oil are also saturated fats.

Trans fats or hydrogenated vegetable oils are found in hard margarines and shortenings, baked products such as cookies and breads; and fried foods. Check the labels of processed foods to see if they contain partially hydrogenated oil.

The most concentrated sources of cholesterol in food include organ meats, egg yolks and whole milk products.

Increase your intake of soluble fibre Although your body isn’t nourished by fibre, it is vital to good health. Soluble fibre dissolves into a gel-like substance in the intestines, preventing cholesterol and fats from being absorbed into the blood stream. It is better

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to increase the amount of fibre in your diet gradually so as to avoid abdominal cramping or bloating. See Box 1 for quick ways to add fibre to your diet.

Eat foods rich in omega-3 fatty acids Omega-3 fatty acids can help to lower bad cholesterol. Fish (salmon, mackerel and herring) and nuts (walnuts, almonds and ground flaxseed) are good sources of omega-3 fatty acids.

OVERWEIGHT/OBESITY Excess weight increases levels of bad cholesterol and lowers levels of good (HDL) cholesterol. Promises of rapid and dramatic weight loss are tempting, but don’t fall for fad diets and gimmicks. When it comes to weight loss, a slow and steady approach is easier to maintain over the long term, with better results. Involve your doctor or nurse in helping you set weight goals that are right for your health and any medicines you may be taking. Weight loss of 0.5-1.0 kg a week is usually recommended.

A good eating plan is flexible and does not forbid certain foods or food groups. Diets eliminating entire food groups may result in nutritional and further health problems. A good eating plan should include Box 1. Quick ways to add fibre to your diet • Choose breakfast cereals such as oatmeal and oat bran.

• Add a fruit to your breakfast cereal.

• Eat a whole fruit instead of, or in addition to, drinking the juice.

• Whole fruit contains more fibre.

• Carry dried fruits with you, a handy high-fibre snack.

• Add beans or lentils to salads.

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a variety of foods from all the major food groups, easily found at the local grocery store. Most importantly, your diet should include foods that you like and will continue to enjoy eating.

PHYSICAL ACTIVITY Physical inactivity contributes to obesity and can raise levels of bad cholesterol. If you have not been physically active, the key to success is starting slowly. Gradually incorporate more physical activity into your daily routine.

Use the stairs instead of taking the lift. Take a walk during lunch hour or in the evening with friends and family. Gradually increase the length or the pace of your walks. Finding an exercise buddy or joining an exercise group can help keep you motivated. There are so many other benefits to increasing our activity levels that it seems quite foolish not to (Box 2).

MEDICINES Sometimes, regardless of changes in lifestyle, drug therapy is still needed to help keep cholesterol levels low. Keep up with lifestyle changes anyway, as this will ensure that you are taking the lowest necessary dose of medicine and it will also benefit other risk factors for heart disease.

Box 2. Benefits of regular physical activity • • • • • • • •

Physical activity helps to lower bad cholesterol levels.

Physical activity is good for your heart.

It is easier to control your weight when you are active.

Physical activity can boost your ability to make other improvements in lifestyle such as diet changes.

You feel and look better when you are physically active.

Physical activity helps to beat stress and depression.

You’ll have more energy.

You can share physical activities with friends and family, it can be lots of fun.

There are a number of types of drugs used to control cholesterol, working in different ways. The best drug for you will depend on other medicines you may be taking (prescribed, over-the-counter and home/natural remedies) and whether or not the drug gives you side effects.

Most people are initially prescribed a statin, which works by blocking the liver from making cholesterol. Other cholesterol-lowering drugs work by decreasing the amount of fat absorbed from food (bile acid binders and cholesterol absorption inhibitors) or by helping the liver to break down bad cholesterol (fibrates). If taking one drug does not lower your cholesterol enough, a second medicine may be added.

Minor side effects of these medicines include heartburn and diarrhoea.

These often go away after taking the medicine for a few days. It is important to tell your doctor if these symptoms (or any others) are severe or do not go away. Serious side effects are rare, but can occur.

It is very important to know how to take your medicine properly (Box 3). If you are having trouble understanding your doctor, take a friend with to help you. It is also important to tell the doctor if you think that the medicine is not working. If this is the case, the doctor needs to find out why and make any changes that may be needed. Don’t stop taking your medicine without speaking to the doctor or nurse first.

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PATIENT INFORMATION LEAFLET

Box 3. Taking medicine the right way Important things to find out about • Why am I taking the medicine?

• When do I need to take the medicine?

• How often do I need to take the medicine?

• How many pills do I need to take?

• Do I need to take the medicine with food or on an empty stomach?

• What happens if I don’t take the medicine properly?

DO NOT STOP TAKING YOUR MEDICINE WITHOUT SPEAKING TO YOUR DOCTOR FIRST Tips for remembering to take medicine • Take the medicine at the same time every day.

• It is easier to remember when associating taking the medicine with other daily events like brushing teeth.

• Ask family and friends to help remind you.

• Put a reminder note on your fridge or medicine cabinet.

• Set an alarm reminder on your cell phone or watch.

• There are many different types of pill containers, some even beep when it is time to take your medicine. Speak to your pharmacist about the best type of pill container for you.

• If you are often away from home, remember to carry extra medicine with you in your briefcase or toiletry bag.

A SENSIBLE APPROACH TO MAKING CHANGES Set specific, realistic goals that are smaller steps leading to a larger goal. By progressively achieving small changes, you should stay motivated for the entire journey.

Reward yourself with a well-deserved non-food item or experience with each achievement.

Let loved ones know what you want to achieve. Asides from moral support, they may be able to help in more concrete ways, such as the preparation of healthier meals.

Despite our best intentions; it is not always easy to maintain lifestyle changes over the medium- to long-term. Don’t worry! Everybody tries and tries again. This is a long-term change and small victories are better than no progress.

Think about what led you astray in the first place. The wrong snacks at a party? Too little time to exercise? Consider strategies to manage such circumstances in the future.

Have you tried to do too much at once? Stopped smoking, crash dieting and pulled your hamstring at the fun-run? Break the process down into small steps. Gradually work towards your goal and give yourself the chance to slowly and comfortably adapt to your lifestyle changes. Celebrate your successes!

Resources National Institute of Health. Your guide to lowering cholesterol with TLC (Therapeutic Lifestyle Changes). 2005; http://www.nhlbi.nih.gov/health/public/heart/chol/chol_tlc.pdf University of Ottawa Evidence-based Practice Center. Comparative Effectiveness of Lipid-Modifying Agents. 2009; www.effectivehealthcare.ahrq.gov Mayo Clinic Staff. Top 5 lifestyle changes to reduce cholesterol. 2012; http://www. mayoclinic.com/health/reduce-cholesterol/CL00012/ American Heart Association. http://www.heart.org/HEARTORG/Conditions/Cholesterol/PreventionTreatmentofHighCholesterol/ (Accessed 27 June, 2013)

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Diabetes Educator’s Focus Minimising travel-associated risks in cardiac and diabetic patients Dr Jonathan Klotnick Executive Member: South African Society of Travel Medicine

S Afr J Diabetes Vasc Dis 2013; 10: 70–71.

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ravel, especially when it involves long-haul flights, can be hazardous to some patients with cardiac conditions and diabetes. It is important therefore for their doctors and nurses/educators to be aware of this and advise them accordingly.

Dr Jonathan Klotnick, an executive member of the South African Society of Travel Medicine who runs a travel clinic in Rosebank, Johannesburg, elaborates further. “Stable cardiac patients, who are controlled on their medication, have no real issues when it comes to flying/altitude and are unlikely to decompensate, provided there is no depressurisation of the aircraft cabin. It’s unstable patients that healthcare professionals need to be concerned about.”

The Aerospace Medical Association lists the following contraindications/precautions with regard to flying: • A myocardial infarction (MI) within the previous 2-3 weeks • In the event of a major MI, patients should wait six weeks before travelling • Unstable angina • Severe congestive heart failure • Uncontrolled hypertension • Patients who have undergone coronary artery bypass grafting should wait two weeks before flying • Any uncontrolled arrhythmias or tachycardias make it unsafe to fly • Severe disease of the heart valve may pose a risk in the event of a dip in oxygen saturation Dr Klotnick underscores, however, that this is a guideline only, not a set of black and white rules. Oxygen desaturation and the reduction of aircraft cabin pressures are the major concern when it comes to unstable patients who fulfil any of the abovementioned criteria.

Deep vein thrombosis (DVT) is a risk associated with flying generally, and Dr Klotnick notes that

those on an anticoagulant such as warfarin reduce their risk. He points out, however, that aspirin is not a preventative for DVT, contrary to widely held beliefs. “The idea that taking one or two aspirins a day before undertaking a flight will lower DVT risk is misinformed and wrong. Doctors need to make their patients aware of this.”

Moving away from flying, he says that cardiac patients should factor in altitude differences. “If their destination is at a much higher altitude than their point of origin, they might take time to adjust, experiencing symptoms like shortness of breath. This is not necessarily indicative of a worsening of their condition.” Temperature can also be a factor. “Patients with low blood pressure, who are normally asymptomatic, may develop symptoms like light-headedness and fatigue in very hot climates. Increasing their fluid and salt intake can help alleviate these symptoms.”

It’s vital too to take an adequate supply of medication. Dr Klotnick advises that patients take a two-week supply over and above what they expect to use and to factor in delays in their return and possible nonavailability of medication at their destination.

Patients with pacemakers are often concerned about interference from airport metal detectors. Dr Klotnick reassures them that this is very unlikely. “There is a theoretical risk but there have been very few issues in reality. On the whole, they’re pretty safe.”

Turning to patients with diabetes, he notes that travel and flying are in fact more complicated in these individuals than those with cardiac conditions.

Patients need to advise airlines in advance of their dietary requirements and must ensure they have adequate travel insurance, something that also holds true for cardiac patients.

Non-insulin-dependent diabetics, with stable blood glucose levels and who are not prone to hy-

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per- or hypoglycaemic episodes, are generally at low risk for travel. It’s the insulin-dependent individuals who need to take care. “It’s important to take a sufficient supply of insulin and injectable materials, as well as extra testing strips and extra batteries for the glucometer. Patients should also carry extra snacks in their bags, so that these are handy in the event of a hypoglycaemic episode. Airline staff should be informed of an individual’s diabetic status, so that they are prepared and can take action in the event of an emergency.”

Crossing time zones has implications for insulin requirements, which may need to be adjusted accordingly. “Eastbound flights, which usually take place overnight, are likely to require reduced insulin intake, so as to avert a possible hypoglycaemic episode while asleep. Westbound flights tend to take place during the day, encouraging travellers to eat more than usual. As a result, it may be necessary to increase insulin dosages.” The

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EDUCATOR’S FOCUS

Aerospace Medical Association provides good guidelines for insulin dose adjustment for travellers.

Diabetes in itself is a risk for DVT, and this is aggravated by the fact that many patients are overweight.

Insulin can destabilise at extreme temperatures, both hot and cold.

While travelling, patients need to ensure that they keep their insulin at the correct temperatures as specified by the manufacturer. Diabetics are likely to experience more heat-related issues than healthy travellers, and are more predisposed to symptoms such as headache and dizziness in hot climates. Adequate foot care is also essential, if they’re going to be walking more than usual.

For more information, visit the Aerospace Medical Association website: www.asma.org

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DIABETES NEWS

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Diabetes News Diabetes camps provide fun and education for young people living with the condition

By Peter Wagenaar

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he history of Youth With Diabetes’ camps for young people with the condition goes back to the middle of the last decade, when diabetes nurse educator, Sr Hester Davel, from the Centre for Diabetes and Endocrinology, and paediatric endocrinologist, Dr David Segal, recognised a need for them. “I had always wanted to create a space for children with diabetes where they could play, laugh, sing, paint and just feel at one with each other,” says Hester. “A place where they could experience unconditional love and where everything they needed would be available to them.

In addition, I wanted to raise awareness of diabetes among children.”

The first camp took place in 2005. Today they take place regularly in the major centres all over the country – Johannesburg, Cape Town, Port Elizabeth, East London, George, Bloemfontein and Kimberley – as well as in Botswana.

“Soon after starting the camps, we saw the need for people to help us so that we could run them more often. We realised: who better than their peers? So we developed a course: Diabetes Youth Leader Training,” says Hester. “The first national leaders training course was taken

Young people undertaking fun activities at the Youth With Diabetes camp held in March at Camp Nelu, near Magaliesburg. “They don’t let diabetes stand in their way,” says Sr Hester Davel.

A youth leader helps a child with their art therapy project

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Two youth leaders on a camp

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by 40 motivated youngsters in 2006. The same year we hosted three camps with their help. Our youth leaders are positive, wellcontrolled young adults who inspire and guide young people with diabetes to live well, despite the condition.”

That original group of youth leaders, in turn, decided to form an association that would do something for young people with diabetes, because there was no organisation or real support group for them. This led to the foundation of Youth With Diabetes in 2007. “Youth With Diabetes is a non-profit organisation for young people run in large part by young people,” observes Hester.

Having diabetes is very difficult for children and adolescents. Hester explains further, “They often feel isolated and alone, and very conscious of being different from their peers. At the camps, they feel included because everyone else also has diabetes and everyone tests their blood glucose levels at the same time.” She points out too that teenagers and small children are different from each other and that is why separate

DIABETES NEWS

camps (ages 6-12 and ages 13-18) are held for each group.

The most recent children’s camp for the Johannesburg area took place over the weekend of 15-17 March at Camp Nelu, near Magaliesburg. As usual, the weekend provided a mix of fun and learning activities to foster a sense of community and belonging among those who attended.

The fun outdoor activities may take the form of obstacle courses or guided walks, while the learning may take place in group sessions or even as one-one-one on-thespot education. “We endeavour to allow the young people to learn about diabetes in a creative, fun and interactive way,” continues Hester. “This includes the use of role-play and conversation maps, as well as talks and lectures.

Malcolm Goddard and Heidi Engelbrecht have been attending the camps on a regular basis for a long time. Both are now trained youth leaders. Heidi describes the camps as a safe place to return to, even if only once a year. “It’s so good to know you’re not alone

and that you have the support of those around you. I’ve met so many good people through the camps, including my best friend in the world.” She feels her two years as a leader have helped her to grow. “I find it rewarding to help others, and it’s also broadened my knowledge of diabetes and its treatment – I’ve had to learn how to manage hypoglycaemic episodes in others, for example. I’ve had to become familiar with therapies other than my own, like pumps and injections, and make decisions for others in respect of lowering or increasing their insulin.”

According to Malcolm, the diabetes camps changed his life. “I had difficulty accepting that I had diabetes at first, and attending the camps helped me make peace with the diagnosis.” Like Heidi, he too underscores the important role they play in helping the young person with diabetes not feel alone. “And over and above that, they’re also lots of fun.”

For more information visit www.youthwithdiabetes.com or email Kerry@youthwithdiabetes.com

Camp calendar for 2013 Month

Date

Location

Sep

6-8

Cape Town Teen

13-14

Port Elizabeth

20-22

Joburg Teen

23-25

Leadership training

Oct

11-13

Joburg Kids

What we do on camp: • • • • • •

Realise other young people also have diabetes Learn diabetes management skills Understand how to make healthy choices Enjoy fun and creative activities Learn teamwork and leadership skills Share your story and feelings

No need to worry: You should feel safe sending your child on our camps because we include: • • • •

24 hour access to a medical doctor and diabetes nurse educators Frequent monitoring of blood glucose levels, including overnight Groups facilitated by our trained Diabetes Youth Leaders Monitoring and supervising of Insulin and pump treatment

Contact our Operations Manager, Allison Email: allison@youthwithdiabetes.com

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CONFERENCE REPORT

SA JOURNAL OF DIABETES & VASCULAR DISEASE

Cardiology & Diabetes At The Limits 2013 AJ Dalby, jl aalbers Friday 22nd – Monday 25th March The 15th At The Limits conference was held in Cape Town under the auspices of the Hatter Institute and organised and chaired by Prof Derek Yellon of University College London and Prof Lionel Opie of the University of Cape Town. The meeting was sponsored

by AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, BristolMyers Squibb, Discovery Health, Medtronic, Novo Nordisk, Roche, Servier, Takeda and The Coca-Cola Company.

Friday evening: Early programming of diabetes and cardiovascular disease – an update Alan Lucas, Institute of Child Health, University College London Lucas discussed programming during foetal development and the effect of diet in post-natal period, specifically comparing breast milk vs. formula feeding. Although better foetal growth is associated with better cognitive function, accelerating the growth of small infants in the post-natal period to “catch up” is associated with increases in BP, obesity and risk of CVD. It may therefore be necessary to avoid encouraging weight gain by overfeeding smaller babies.

Expressed breast milk does not represent the composition of suckled breast milk which changes during a feed and, in the longerterm, with the time that breast feeding continues. Recognition of this has led to the reformulation of infant feeds.

Saturday: The Lancet Lecture: The renin-angiotensin-aldosterone system: have we reached the limits?

Marc Pfeffer, Brigham & Women’s Hospital, Boston, USA Marc Pfeffer told of how he had gone to extraordinary academic lengths over many years to undertake and publish over 100 studies dealing with the RAAS system to show that in the end the more extensive studied drugs were the cheaper ACE inhibitors. The more modern ARBs now also have strong supporting data. Overall, both ACE-i and ARBs give a 20% reduction in mortality in vascular disease. The ARBs have specific data for ACE-intolerant patients and for post-infarct heart failure. Combining ACE-i and ARBs has not on the whole given improvements except in one heart failure study

by Pfeffer. He also pointed out that spironolactone and eplerenone were very similar, and that studies (including one by his group) were under way to evaluate whether spironolactone provides the same benefits in heart failure as the now well established but much more costly eplerenone.

To obtain funding for this study, Pfeffer had to gain US government support via NIH. The direct renin inhibitors failed to give any further benefit. “So we are at the limit of blocking the RAAS system, we have tried to inhibit more, with no benefit”, Dr Pfeffer concluded.

This is a personal South African view of the meeting. The full talks and slides are accessible on the Lancet website, so interested CVJA readers can select any talks they would like to see and hear.

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Transcatheter aortic valve implantation (TAVI) surgery – where are the limits?

Axel Linke, University of Leipzig, Germany In inoperable patients, TAVI, using Medtronic Core Valve self-expanding prostheses, offers resolution of severe aortic stenosis, but with complications of stroke (2.9%) major vascular complications (10%) and major bleeding events (10%). TAVI has proved better than balloon valvuloplasty, and also superior to drug therapy in inoperable patients. The future includes valves that are repositionable, retrievable and steerable; attempts are also being made to reduce strokes by using filters to capture calcific debris and to design valves that reduce aortic regurgitation.

What is the future of cardiac intervention – have we reached the limits?

Stephan Windeker, Bern University Hospital, Switzerland In the COURAGE trial PCI which resulted in a reduction in ischaemia was associated with an improvement in longer-term outcome. FAME II showed marked benefit of PCI guided by FFR compared to medical therapy, the endpoint being driven by urgent revascularisation. The ISCHEMIA trial is in progress which may clarify the best approach to treatment.

The comparison of PCI to CABG in SYNTAX showed that risk stratification yielded different results in the different categories. Newer DES may influence future outcomes. Though PCI and CABG seem to offer similar benefits in left main coronary artery (LMCA) stenosis, difficulties remain in choosing the best treatment for patients with multivessel disease. The EXCEL trial is evaluating LMCA PCI vs. CABG. Effective STEMI treatment requires improvements in the management network.

Bioabsorbable stents may result in positive remodelling of the coronary vessel.

The duration of dual antiplatelet therapy (DAPT) remains an open question. One trial is in progress which will compare standard DAPT to ticagrelor given with only one month of aspirin.

Heart failure – where are the new targets?

Martin Cowie, The Royal Brompton Hospital, London There has been a progressive improvement in heart failure survival over the past 2 decades with a currently low rate of mortality in societies able to provide modern treatment. Treatment can be improved by attending to the delivery of care. Triple therapy with ACE-i, beta-blocker and MRA are standard in HeF-REF. Ivabradine has an important role in reducing hospitalisation and improving QoL. New agents being investigated are serelaxin which improves symptoms in AHF with 48 hours of treatment but has no effect on readmission rates. Mortality at 6 months may be reduced.

Ultrafiltration is not beneficial with more adverse effects. (Bart, NEJM, 2012). Other areas of research are the effects of mechanical circulatory support, autonomic modulation with vagal stimulation or renal denervation, the influence of sleep disordered breathing and cardiac myosin activators, ryanodine receptor stabilisers and SERCA2a gene transfection of the myocardium (CUPID 2a).

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Nonetheless the major problem remains the lack of implementation of known therapies.

Exercise and fitness in diabetes and heart disease – when do we reach the limits?

Carl Lavie, John Ochsner Heart and Vascular Institute, New Orleans Cardiorespiratory fitness is graded: low fitness is defined as the lowest quintile of individuals assessed according to their time on treadmill adjusted for gender and age. Small improvements in fitness result in a significant reduction in incidence of diabetes and mortality.

Physical inactivity and low fitness increases total mortality by 1.7-2X in males. Fitness overrides fatness as a cause of cardiovascular disease.

There are multiple mechanisms mediating the effect of fitness. An important factor is improvement in mood and anxiety. The exercise dose is important, more not necessarily being better. Resistance training is important in addition to aerobic exercise. 40 minutes / day of vigorous exercise probably provides the maximal benefit.

Modern drug therapy for Type 2 diabetes: a cardiology perspective Mansoor Husain, Toronto General Hospital Research Institute The DECODE study showed that IGT increases mortality risk.

HbA1C has been shown to correlate with macrovascular disease and heart failure. Reducing HbA1C has not been shown to change this outcome. Good glycaemic control improves quality of life and microvascular disease. Meta-analysis of sulphonylureas showed that they increase in mortality 2.5-3X. There is no convincing data on survival for any other hypoglycaemic therapy.

GLP-1 is rapidly degraded (2½ min), thus only a small proportion reaches the heart. GLP metabolites may be the active substances affecting cardiovascular function. Experimental evidence has shown that DPP4 inhibition and GLP1 agonism improve survival in mice after MI. GLP1 agonism but not DPP4 inhibition has reduced experimental infarct size.

The Hatter Lecture: Blood pressure control in diabetes: what are the limits, what are the drugs and how are they defined?

Morris Brown, University of Cambridge, UK Brown discussed the control of hypertension in diabetics, pointing out that in all hypertensives, the risk for MI is greater than that for stroke, although the less linear relationship of BP to stroke makes it easier to detect changes in the frequency of stroke than of MI when BP is reduced. Masked hypertension occurs more frequently in diabetics and carries a risk equivalent to that of Stage 1 hypertension. Treating BP to target level in diabetics does not restore the CV risk to that of normotensive (untreated) diabetics.

Brown has found evidence of primary hyperaldosteronism in hypertensives. This may be identified by inappropriate suppression of the renin level. Hypokalaemia is found less frequently. About 10% of this group have adrenal microadenomas which may be identified by PET scanning. Early identification and excision may cure the hypertension but is less likely to be effective in those whose blood pressure elevation is long-standing.

Sunday morning debate: Diabetologist: The major aim in the therapy of DM2 lies in limiting microvascular damage vs. Cardiologist: the major aim in the therapy of DM2 lies in limiting macrovascular damage Steven Kahn (Diabetologist) University of Washington, Seattle

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CONFERENCE REPORT

The 10-year mortality rate was 40% in UKPDS. The mortality in diabetes is lower in a high income group of patients. In the high income group, the expenditure on diabetes far exceeds the expenditure in middle and lower income groups. Around 50% of all cause mortality in diabetes is non-cardiovascular. The combination of diabetes and chronic kidney disease has an all cause mortality of 30% compared to 7.5% in a group in whom neither condition is present. Similarly the combination of CKD and albuminuria has a mortality of 47% compared to those with neither condition. The 10-year results of UKPDS showed reductions in both mortality and MI. In the ACCORD study, although negative overall, better results were obtained in the subgroups with albuminuria. The most recent NHANES report on diabetics found worsening percentages of glycaemic control, BP control, control of LDL cholesterol and diminishing numbers on statin therapy, with a very low percentage of patients achieving control of all these parameters.

Bryan Williams (Cardiologist), University College London Increased pulse pressure develops with ageing and begins earlier in diabetes. The presence of an increased pulse pressure in diabetes is strongly correlated with mortality. The pathogenesis involves loss of elastin, collagen deposition and modification of the collagen by advanced glycation end-products which result in cross linkage of collagen, aortic stiffness, loading of the left ventricle and a reduced work capacity. In diabetics there is a loss of the reflected wave in the aorta with transmission of pulsatile flow more distally in the peripheral circulation. This leads to increased pulsatility in the microcirculation and promotes microvascular disease. Diabetes differs from the effects seen in hypertension and ageing in that autoregulation within the microcirculation is impaired.

Beyond warfarin – are there any limits?

Stefan Hohnloser, JW Goethe University, Frankfurt The results of the RE-LY, ROCKET-AF and ARISTOTLE trials were reviewed. Given the reduced stroke risk, diminution in intracranial bleeding and ease of use, Hohnloser preferred the use of one of the novel oral anticoagulants to warfarin, although admitting that cost constraints were problematic. His preference overrode considerations of good control of the INR on warfarin or moderate chronic kidney injury (GFR 30-60 ml/min).

Monday morning: Debate: Life style changes vs. drugs – which best limits cardiovascular disease?

Timothy Noakes, University of Cape Town and Peter Libby, Brigham & Women’s Hospital, Harvard Medical School, Boston The debate between Timothy Noakes and Peter Libby was an excellent closing event, both arguing well. Noakes proposed that life style with increased exercise and a low CHO diet could in his view achieve excellent results on general health including levels of blood glucose and lipids. Thus drug therapy could often be avoided.

However, no controlled studies were presented. Libby agreed that the standard low fat diet recommendation was not the best. He gave his support to the Mediterranean diet (fresh vegetables, high fruit, fish rather than meat, nuts and olive oil). In the first controlled outcome diet study ever (New Engl J Med, April 2013), the Mediterranean diet decreased CV outcomes and total mortality compared with low fat. However, Libby argued, the major problem with any diet was poor long term adherence, less than 40% at one year, so that in clinical practice drug therapy was more effective.

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CONFERENCE REPORT

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4th All African Conference on Heart Disease, Diabetes and Stroke 11th Pan African Society of Cardiology (PASCAR) Conference The 4th All African Conference on Heart Disease, Diabetes and Stroke was hosted in Dakar, Senegal, 16th-20th May, 2013. A record turnout of both registered delegates and number of African nations represented reflected kudos on the co-hosts PASCAR and the Senegalese Society of Cardiology (SOSECAR). Selected abstracts are reported by theme; view the full book of abstracts at http://www.cvja.co.za/onlinejournal/vol24/pascar_2013/ HYPERTENSION WAIST CIRCUMFERENCE: AN ANTHROPOMETRIC MEASURE OF ADIPOSITY IN HYPERTENSIVE AFRICAN POPULATION Adeoye AM*, Adebiyi A, Tayo b, Salako BL, Ogunniyi A, Cooper R Division of Cardiovascular Medicine, Department of Medicine, University College Hospital, Ibadan, Nigeria Introduction: Studies differ on which anthropometric measure of adiposity best correlates with cardiovascular diseases. In this study we re-examined the role of waist circumference as the correlate of elevated blood pressure in an African population.

Subjects and methods: A cross-sectional prospective study was carried out on a total of 1 858 subjects (mean age 49 ± 9; 1 411 females and 447 males) over 2.5 years between June 2009 and December 2011. All subjects underwent a standardised clinical examination and anthropometric measurements. Correlation analysis was used to assess the relationship between blood pressure and body mass index (BMI), waist height ratio and waist circumference respectively.

Results: Females were significantly older, shorter, heavier and had greater arm circumference and heart rates when compared with males. Blood pressure parameters were comparable between the two groups. Anthropometric measurements showed that 587 (34.1%) were overweight, 372 (21.6%) were obese and 186 (10.8%) had morbid obesity. Compared with their male counterparts, females were significantly more obese (p<0.0001). Similarly 51.6% of the subjects had abdominal obesity, with female preponderance (p<0.0001). Compared with other measures of adiposity, waist circumference best correlated with blood pressure (p<0.01).

Interpretation: This study shows that obesity is a major cardiovascular risk factor among the study population. Waist circumference correlates most with blood pressure. Significant reduction in hypertension is possible if the waist size is reduced in this population.

Intervention programmes targeted at waist circumference reduction through lifestyle modification, including exercise and diet, may have significant public health significance in reducing the incidence of hypertension among the population.

EFFECTS OF NEWER V. OLDER ANTIHYPERTENSIVE DRUGS ON CENTRAL HAEMODYNAMICS IN BLACK HYPERTENSIVE PATIENTS LIVING IN SUB-SAHARAN AFRICA: INSIGHT FROM NOAAH STUDY Lemogoum D*, Jacobs,B Anisiuba B, Kamdem MM, Thijs L, Kaptue J, Odili AN, Ezeala-Adikaibe B, M’Buyamba-Kabangu JR, Ulasi II, Staessen JA Service of Cardiology, ULB-Erasme Hospital, Brussels, Belgium

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Introduction: The Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial was designed to compare the efficacy of single-pill combinations of amlodipinevalsartan 5/160 mg (E) and bisoprolol-hydrochlorothiazide 5/6.25 mg (R) drugs on blood pressure (BP) in native black patients living in sub-Saharan Africa. Furthermore, the present ancillary study aimed to explore the effects of E and R drugs on central haemodynamics in 80 of 183 randomised patients (40 per drug arm) aged 30–69 years with uncomplicated hypertension (140–179/90–109 mmHg) recruited from two NOAAH centres.

Subjects and methods: Central pressures, systolic augmentation, augmentation index (AIx), carotid-femoral pulse wave velocity (PWV) were measured using applanation tonometry (SphygmoCor) at inclusion, after 8 and 16 weeks of treatment.

Results: At randomisation age, sex, BP, AIx, and heart rate (HR) were comparable in both regimens, while PWV was faster in E than R p=0.02). Despite similar changes in brachial BP, aortic systolic augmentation was less in E than R: difference = -2.8 mmHg (95% confidence interval (CI) -4.8 to -0.8), p=0.007, while E non-significantly lowered more aortic systolic pressure than R: difference = -4.6 mmHg (95% CI -9.6 to 0.5), p=0.078. Central pulse pressure decreased markedly in the E than R: mean changes = -8.4 ± 1.9 mmHg v. -3.4 ± 2.4 mmHg, p=0.008. AIx standardised for HR significantly decreased in E, whereas it increased in R: mean changes = -8.4 ± 1.6% v. 5.4 ± 5.5%, p=0.0007. Change in PWV was similar between both drug arms (p=0.82).

Interpretation: In black patients the amlodipine-valsartan regimen decreases more central pressures and AIx than the bisoprolol-hydrochlorothiazide combination.

EFFECTS OF MELATONIN TREATMENT ON CARDIAC FUNCTION IN A MODEL OF PULMONARY ARTERIAL HYPERTENSION Maarman G*, Blauwet L, Sliwa K, Lecour S Hatter Institute for Cardiovascular Research in Africa (HICRA), Department of Medicine, University of Cape Town, South Africa Introduction: Pulmonary arterial hypertension (PAH) is a disorder characterised by elevated pulmonary arterial pressure which leads to cardiac hypertrophy and ventricular dysfunction. Current treatments are only marginally effective and additional therapies are required.

Melatonin is a natural product that has been shown to be cardioprotective against hypertension and myocardial infarction. We therefore propose that a chronic melatonin treatment may be cardioprotective in a rat model of monocrotaline (MCT)-induced PAH. Subjects and methods: Male Long Evans rats (150–175 g) received a single subcutaneous injection of MCT (80 mg/kg) which induced

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PAH after 28 days. Melatonin was given in the drinking water (4 mg/ kg/day) for the 28-day period. Cardiac hypertrophy was confirmed with a ratio of the right ventricle weight over heart weight (RVW/ HW). Cardiac functional parameters were assessed at 0 and 28 days using isolated heart perfusion and/or echocardiography. These parameters included right ventricular systolic (SP) and diastolic pressure (DP), ejection fraction (EF) and fractional shortening (FS).

Results: MCT increased RVW/HW, reduced EF (92.84% ± 1.33 v.

60.53% ± 4.23, p<0.0003), FS (28.23% ± 2.68 v. 61.03% ± 2.89, p<0.0002) and increased SP and DP. Chronic administration of melatonin in MCT-treated rats improved EF (60.5% ± 4.2 v. 84.1% ± 1.7, p<0.0008), FS (28.2% ± 2.7 v. 48.7% ± 2.1, p<0.0005), SP and DP. Interpretation: In conclusion our data demonstrate that chronic melatonin improves cardiac function in MCT-induced PAH and suggests a cardioprotective role of melatonin in PAH.

CATHETER-BASED RENAL SYMPATHETIC DENERVATION FOR RESISTANT SYSTEMIC HYPERTENSION: A PILOT STUDY Nguchu H*, Gikonyo AK, Ravi Kumar R Cardiology, Fortis Malar Hospital, Chennai, India Introduction: Resistant systemic hypertension is a major public health problem in India and on the African continent. Since many patients are unable to afford long-term drugs for hypertension, renal sympathetic denervation could be a safe solution for this problem.

Subjects and methods: We studied 10 Indian patients (4 male, 6 female) in the age group 35–58 years with resistant hypertension on a minimum of 3 antihypertensive drugs, including diuretic (thiazide or torsemide) , angiotensin receptor blockers like telmisartan or olmesartan , angiotensin-converting enzyme (ACE) inhibitors like ramipril, beta-blockers (like metoprolol and nebivolol) and alphablockers like prazosin and clonidine (in 2 cases). BP range (on three drugs) was 190/106 to 156/98 (average of 170 systolic and 100 diastolic). Renal artery stenosis and azotaemia were ruled out. All were taken for renal denervation procedure via femoral route in the cardiac catheter laboratory. Mild sedation (injection of midazolam 1 mg) was given during the procedure. A 5F ablation catheter via a 6F femoral arterial sheath was used for the procedure along with a Cordis radiofrequency ablator used to deliver 6-8 watts RF energy.

The ablation was performed in 3 opposite consecutive points in each renal artery about 4 mm apart.

Results: Post ablation patients had reduction in systolic and diastolic blood pressures. After 1 week, BP range (on one or two antihypertensive drugs) was 146/86 to 130/80; average 136/84. After 6 months the BP range on one to two drugs was 140/78 to 130/70.

Five patients who were followed up for 1 year had BP range of 140/80 to 130/76 on 1 or 0 antihypertensive drugs. No complications of the procedure were encountered.

Interpretation: Catheter-based renal sympathetic denervation is a useful procedure for systemic hypertension and may find extensive applications in Africa.

AMBULATORY BLOOD PRESSURE MEASUREMENT IN CAMEROON: HIGH PREVALENCE OF WHITE COAT HYPERTENSION AND INFLUENCE OF BODY MASS INDEX Noah T*, Dzudie A, Ndjebet J, Wawo EG, Kengne AP, Blackett Ngu K

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Department of Internal Medicine, Faculty of Health Sciences, University of Buea, Buea, Cameroon Introduction: Identifying white coat hypertension (WCH) may avoid inappropriate commitment of individuals to lifelong and costly blood pressure (BP) lowering medications. We assessed the prevalence and determinants of WCH in urban clinical settings in Cameroon.

Subjects and methods: Participants were a consecutive sample of adults, who underwent ambulatory BP measurements (ABPM) for the diagnosis of hypertension and evaluation of treatment in three referral cardiac clinics in the cities of Yaoundé and Douala, between January 2006 and July 2011. WCH was defined as a clinic systolic (or diastolic) BP ≥140 (90) mmHg together with an average daytime ambulatory systolic (diastolic) BP <135 (85) mmHg. Results: Of the 500 participants included, 188 (37.6%) were women, 230 (46%) were non-smokers and 53 (10.6%) had diabetes mellitus. The mean age was 51.6 ± 10.2 years. The ABPM readings were higher in men than in women (p<0.05). The prevalence of WCH was 26.4% overall, 39.3% in women and 22.4% in men (p=0.01). In multivariable analysis, body mass index (BMI) was the only significant determinant of WCH (odds ratio 1.15 (95% confidence interval: 1.00–1.43), p<0.05).

Interpretation: The prevalence of WCH was high in our study population and was correlated only with BMI. Accurate measurement of BP and appropriate diagnosis of hypertension using ABPM in this setting may help limiting the consequences of overestimating hypertension severity on individuals, families and health systems.

THE SPECTRUM OF HEART DISEASE IN TWO CITIES IN SUB-SAHARAN AFRICA UNDERGOING SOCIO-ECONOMIC TRANSITION Ojji D*, Stewart S, Ajayi S, Manmak M, Jacob A, Sliwa K Cardiology Unit, Department of Medicine, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria Introduction: With rapid westernisation in sub-Saharan Africa, cardiovascular disease is gradually becoming the major cause of morbidity and mortality in this part of the world. Unfortunately, there is still a dearth of data on the pattern of heart disease in sub-Saharan Africa. We therefore studied the pattern of heart disease in Abuja, Nigeria and compared our findings with similar data derived from the Heart of Soweto study.

Subjects and methods: We prospectively studied 1 515 subjects with confirmed cardiac disease referred to the cardiology clinic of the University of Abuja Teaching Hospital during a 4-year period.

Equivalent data from the Heart of Soweto study in 4 626 subjects were available for comparison.

Results: The mean age of the study cohort was 49.0 ± 13.7 years.

Hypertension was the primary diagnosis in around two-thirds of the study cohort. Hypertension was also the commonest cause of heart failure (HF) accounting for HF in 60.6% of cases. The Abuja cohort were more likely to present with a primary diagnosis of hypertension (adjusted odds ratio (OR) 2.10, 95% confidence interval (CI) 1.85–2.42), hypertensive heart disease/failure (OR 2.48, 95% CI 2.18–2.83; p<0.001 for both comparisons and representing more than two-thirds of presentations in Abuja. Alternatively, they were far less likely to present with coronary artery disease (CAD) (OR 0.04, 95% CI 0.02–0.11), p<0.001.

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Interpretation: Hypertension and its complications is the commonest cardiovascular disease in the Nigerian population in Abuja, and unlike in Soweto, coronary artery disease is not common.

AETIOLOGY OF PULMONARY HYPERTENSION IN AFRICA: PRELIMINARY DATA ANALYSIS AFTER ONE YEAR OF RECRUITMENT: THE PAN AFRICAN PULMONARY HYPERTENSION COHORT STUDY (PAPUCO) Thienemann F*, Blauwet L, Dzudie A, Karaye KM, Mahmoud S, Mbakwem A, Udo P, Mocumbi AO, Sliwa K The PAPUCO Group, Hatter Institute for Cardiovascular Research in Africa, University of Cape Town, South Africa

Introduction: Pulmonary hypertension (PH) is a devastating, progressive disease, with increasingly debilitating symptoms and, usually, shortened overall life expectancy.

Subjects and methods: A prospective observational study of patients with newly diagnosed and previously untreated PH based on echocardiography. Preliminary data analysis after 1 year of recruitment is presented.

Results: Among the 107 recruited cases, the median age was 41 years (range 1–86 years) with a female-to-male ratio of 1.5:1.

Cardiovascular (CV) risk factors were family history of CVD (34%), hypertension (38%), hypercholesterolaemia (7%), diabetes (8%) and smoking (5%). The HIV prevalence of the cohort was 25% with a median CD4 count of 352 cells/µl (interquartile range(IQR) 201–516 cell/µl) at presentation. Twenty-five per cent of patients had previous episodes of TB. Presenting symptoms were shortness of breath (SOB) (93%), fatigue (81%), palpitation (69%), cough (54%), cyanosis (14%) and syncope (or near syncope) (5%); 64% of patients presented at WHO-FC III or IV. The mean right ventricle systolic pressure (RVSP) was 56 mmHg (IQR 46–68 mmHg), whereas the median RVSP in HIV-PH was 60 mmHg (53–73 mmHg, p=0.08). At the time of writing, 6-month follow-up data were available for 33 patients.

Of those, 9 (27%) died within the first 6 months. All but one were HIV-positive. Median time from diagnosis of PH to death was 3.0 months (IQR 1.5–3.7). The median RVSP at baseline was 72 mmHg (IQR 60–83 mmHg) of patients who died within 6 months compared to a median RVSP of 55 mmHg (IQR 45–65) at baseline of patients alive at 6-month follow-up (p=0.03). Final diagnosis according to WHO classification: idiopathic PH (2%), HIV-PH (11%), congenital heart disease PH (5%), PH due to left heart disease (56%), PH due to lung disease and hypoxia (17%), chronic thromboembolic PH (2%) and unclear and/or multifactorial mechanisms (8%).

Interpretation: Left heart disease, HIV, chronic lung disease and congenital heart disease are common contributors to PH in Africa. Disease targeted therapy is not routinely available in the public sector. Outcome of HIV-PH is very poor with RVSP being a prognostic marker.

DIABETES AND OBESITY THE THIKA DIABETES STUDY: DIABETES IN NEWLY ADMITTED PATIENTS AT A REFERRAL COUNTY HOSPITAL IN KENYA Kamotho C* International Clinic, Nairobi, Kenya Introduction: Diabetes is estimated to increase by 161% by the year

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2030 in sub-Saharan Africa as compared with 54% in the established market economies of the West. INTERHEART Africa showed that the odds ratio (OR) of diabetes leading to a new myocardial infarction in Africans was 3.55 (2.53–4.99), higher than in the overall INTERHEART Study, 3.07 (2.84–3.33). A study of black Africans with angiographically evident coronary artery disease showed that diabetes was significantly more prevalent in such individuals (38.5%) than in those with normal coronary arteries (12%, p=0.0002).

Subjects and methods: This prospective, descriptive study of disease prevalence, which was preceded by a pilot study, involved blood sugar measurements of serially admitted patients at Thika Level 5 Hospital, Kenya, in January 2010. A total of 145 patients were studied and results of 141 were analysed. Random blood sugar measurements were done for patients on admission followed by fasting blood sugar (FBS) assessments.

Results: Of the 141 patients, a total of 46 (32.6%) patients had FBS of 7.0 mmol/l and above, hence had diabetes mellitus; 13 (9.2%) were known diabetics and 33 (23.4%) of the 141 were newly diagnosed diabetics. Nineteen (13.5%) patients had impaired fasting glucose, defined by FBS from 6.1 to 6.9 mmol/l. Only one of these 19 patients was a known diabetic, all the others being newly diagnosed with the abnormality. Therefore an important 65 (46%) of all the patients in the study had abnormal glucose metabolism, and a total of 51 (36%) were newly diagnosed with hyperglycaemia.

Interpretation: The prevalence of diabetes mellitus (and impaired fasting glucose) in newly diagnosed patients admitted at this county hospital in Kenya was found to be considerably high. More concerning still was the very high prevalence of newly diagnosed diabetics. It is recommended therefore that aggressive screening be done at the admission points of such hospitals to pre-empt cardiovascular complications.

DO ENVIRONMENTAL FACTORS, INCLUDING SLEEPING PATTERNS, AFFECT THE PREVALENCE OF OBESITY IN AN URBAN AFRICAN POPULATION? Pretorius S*, Sliwa K, Stewart S, Carrington M, Crowther NJ Soweto Cardiovascular Research Unit, University of the Witwatersrand, Johannesburg, South Africa Introduction: Urbanisation and the nutrition transition in South Africa are accompanied by an increase in CVD risk factors, particularly obesity, in African populations. Furthermore, environmental factors other than food intake and urbanisation are also known to affect the prevalence of obesity. The aim of this study was to examine the relationship of these environmental factors (education, employment, exercise, smoking, sleeping patterns) with obesity in an urban population of African subjects.

Subjects and methods: We systematically collected data on 1 311 consecutive patients attending two pre-selected primary health care clinics in Soweto, South Africa. Education, employment status, level of exercise, smoking habits and variables related to sleep duration were obtained using questionnaires. Weight and height were measured using standard procedures and body mass index (BMI) was calculated.

Results: The prevalence of obesity was 45.4% in females and 11.3% in males. A multiple regression model was designed using variables that correlated with BMI in a univariate analysis with p<0.20. These variables were: age, gender, smoking, education,

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employment status, exercise, time of going to bed and daytime napping. Backward, stepwise multiple regression analyses demonstrated that of these variables the principal determinants of BMI (log) were: age (beta=0.003, p<0.0001), female gender (beta=0.07, p<0.0001), smoking (beta=-0.03, p<0.0001) and napping during the day (beta=0.015, p=0.04). An ANCOVA adjusted for gender and age demonstrated that subjects who currently smoked had a lower BMI (median [interquartile range (IQR)]: 22.6 [5.6]) than both non- (27.6 [10.5]; p<0.0001) and ex-smokers (25.1 [12.7]; p<0.0005).

Interpretation: Our data further confirm the higher prevalence of obesity in females than males. The negative effect of smoking on BMI has been reported in other studies, and suggests that after smoking cessation precautions should be taken to reduce weight gain. The lower BMI in subjects who nap during the day is a novel finding and requires further investigation.

PREVALENCE OF HYPERGLYCAEMIA, OBESITY AND METABOLIC SYNDROME AMONG HOSPITAL PERSONNEL IN THE LITTORAL REGION OF CAMEROON: A PILOT STUDY Ndjebet J*, Kunbuma Tachang G, Choukem S-P, Vincent PK Titanji Department of Internal Medicine, Douala General Hospital, Cameroon; Cardiovascular Center of Bonapriso, Cameroon Introduction: There is evidence worldwide of the high prevalence of obesity, hyperglycaemia and metabolic syndrome in healthcare providers, although very scanty data are available on this in subSaharan Africa.

Subjects and methods: The present study aims to determine the frequency of diabetes, elevated body mass index (BMI) and metabolic syndrome among healthcare workers in some hospitals and clinics in Douala, Cameroon. An observational and cross-sectional study was done for the diagnosis of metabolic syndrome. The 2005 definition of the International Diabetes Federation (IDF) was used for 147 health workers. Data were merged and exported from EpiInfo to Statistical Package for the Social Sciences (SPSS); workers were analysed according to gender and age.

Results: 7.5% of the hospital workers had metabolic syndrome, 71.2% were at high risk of developing metabolic syndrome because of elevated abdominal obesity, 38.4% were obese (BMI ≥30) and 4.8% had elevated blood sugar levels. The prevalence rate increased with age: 2.9% (18–36 years), 9.5% (37–55 years) and 50% for more than 56 years. The definition gave the highest prevalence rate of 7.5% while the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) gave 0.7%.

Interpretation: There is a high prevalence of obesity and metabolic syndrome among healthcare personnel in the Littoral region in Cameroon. It is imperative to implement programmes to screen these risk factors by means of routine medical exams and improving the lifestyle of Cameroonian healthcare workers. These study findings could be the basis for future research among hospital staff and the general population.

PREVENTION, EDUCATION AND CARING FOR THE CARERS HEALTH AFRICA.INFO: A WAY TO PROMOTE THE PREVENTION OF NON-COMMUNICABLE DISEASES IN AFRICA Burgarella F*, Burgarella S

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Heart Friends Around The World, Strada della Boffalora n. 1, 24060 Bianzano (BG), Italy Introduction: Heart Friends Around The World (HFATW) is a worldwide organisation collaborating with the World Health Organization, aiming to promote the prevention and rehabilitation of cardiovascular diseases by involving physicians and patients worldwide, predominantly coming from low- and middle-income countries. To promote the prevention of non-communicable diseases (NCDs) in Africa, HFATW has developed a website called HealthAfrica, offering educational material and networking opportunities.

Subjects and methods: NCDs are the leading global causes of death, but nearly 80% of NCD deaths occur in low- and middleincome countries. Even in African nations, NCDs are rising rapidly and are projected to exceed communicable and nutritional diseases by 2020. HealthAfrica.Info explains how NCDs are preventable through the reduction of their main behavioural risk factors: tobacco use, physical inactivity, harmful use of alcohol and unhealthy diet, overweight and obesity, raised cholesterol and blood pressure. The rapidly growing burden of NCDs is accelerated by the negative effects of globalisations, rapid unplanned urbanisation and increasingly sedentary lives.

Results: On HealthAfrica.Info, a collection of free educational materials is available to download: ‘The School of Cardiology’ is a course on cardiology for African cardiologists; ‘Pinocchio and the sore throat’ is an educational tale for children, to fight rheumatic fever in Africa. The ‘Healthy Farms’ project presented by HealthAfrica.Info involves farms wishing to take an active part in safeguarding health by promoting control of diabetes and obesity, by offering fruit and vegetables, low-cholesterol meat and fish, by organising programmes for physical exercise, by forbidding smoking. An updated networking section of HealthAfrica.Info is dedicated to the information regarding meetings, studies and initiatives taken in African countries with the objective to promote the dissemination of education on NCDs prevention.

Interpretation: Health Africa.Info aims to make new African initiatives against NCDs known, transforming information into education.

CONSORTIUM FOR NCD PREVENTION AND CONTROL IN SUB-SAHARAN AFRICA (CNCD-AFRICA): CONCEPT, EXPERIENCE AND LESSONS Owuor JO*, Amuyunzu-Nyamongo M CNCD-Africa, Nairobi, Kenya

Introduction: CNCD-Africa was established in July 2009 as a result of recognition that the prevalence and burden of non-communicable disease (NCD)-related illness and injury was increasing among low- and middle-income countries. The collective mandates of the Secretariat, Steering Committee and Expert Group were aimed at addressing the objectives of the Consortium comprehensively while building capacity in the region to prevent and control NCDs. Subjects and methods: With financial and technical support from the CDC and IUHPE respectively, the Consortium has utilised health promotion, lobbying and dialogue,and partner platforms to achieve its mission.

Results: The Consortium has excelled in four key areas mainly: convening; knowledge generation and sharing; advocacy; and net-

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working. Some of the challenges so far have been (i) retaining interest of network partners - being a loose and flexible outfit, partners are not tied to specific deliverables; and (ii) resource availability.

Interpretation: A key lesson is that regional platforms can be used to showcase what is being done locally and to share best practices and best buys globally. Partnerships and stakeholder involvement are key in NCD action, and to sustain partnerships, the various partners need incentives to keep them actively involved in NCD action.

This could be achieved through joint inception, project planning, implementation, monitoring and evaluation. Innovative financing for NCD action is possible through establishing and sustaining regional and global partnerships that are robust and respond to country needs.

START YOUNG, PREVENTION IS BETTER THAN CURE: THE USE OF VIDEOS TO PREVENT CHRONIC DISEASES OF LIFESTYLE IN SOWETO Lamont KT, Pretorius S, Albertyn Z, Nicholson L, Sliwa K NIH Millennium Leadership Programme for Chronic Diseases, Soweto Cardiovascular Unit, University of the Witwatersrand, Johannesburg, South Africa Introduction: Goal 2 of the South African Millenium Goals is to achieve universal education and to ensure that, by 2015, children everywhere, boys and girls alike, will be able to complete a full course of primary schooling. For South Africa, poor education and poverty has given many learners the misconception that healthy foods are too expensive. A pilot study was performed in Soweto (Ibhongo Secondary School).

Subjects and methods: The aim was to address poor diet of learners from disadvantaged backgrounds and to determine their interest in health information via technological interventions. A health questionnaire was administered to 66 pupils. The questionnaire was explained to the pupils by postgraduates students. A healthy eating demonstration was given by a dietician. Thereafter 3 short clips that were developed by the Hatter Institute, in conjuction with Soweto Cardiovascular Unit were shown.

Results: Starch intake was excessive with maize meal and bread as the staple diet for many; 35% of learners ate ‘pap’ daily and 33% consumed bread. Processed foods were eaten a minimum of 3 times a week; 28% of learners consumed confectionery daily. Over 50% of the learners added extra salt to their meals. Green leafy vegetables were consumed by 12% of learners who ate vegetables <3 times a week. When protein intake was assessed, only 20% of the learners ate either chicken or meat daily. Frozen fish was perceived to be more expensive and 3% of learners ate fish <3 times a week. Tinned fish was popular among the learners with over 30% consuming tinned fish at least once a week or more. The use of IT as an educational tool to coach learners on how to eat healthily for

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less was remarkable: 61% of the leaners were interested in accessing information via the internet, 35% were interested in receiving health messages, and 84% preferred the healthy videos that were screened.

Interpretation: Health education has become the foundation for preventing chronic diseases. The use of technological interventions such as fluid, flexible solutions for the dissemination of health information to all, in the form of health videos can be used to address the poor diet of learners from disadvantaged backgrounds.

A STUDY OF AWARENESS OF THE WARNING AGAINST SMOKING, PERCEPTION OF TOBACCO USE AND TOBACCO CONTROL MEASURES AMONG RESIDENTS OF ABIA STATE, SOUTH EAST NIGERIA Ogah OS*, Onyeonoro UU, Madukwe OO, Chukwuonye II, Akhimien M, Ukaegbu A Department of Medicine, University College Hospital, Ibadan, Nigeria Introduction: As part of global efforts to control tobacco use, in Nigeria tobacco control is primarily through health education on the harmful effects of tobacco, disseminated primarily through the media and cigarette packs. The goal of the health education is to influence perceptions of tobacco use, thereby discouraging smokers and would-be smokers from smoking. This study is aimed at ascertaining the level of awareness of the warning against smoking, perception of tobacco use and tobacco control measures among residents of Abia State, south east Nigeria.

Subjects and methods: It is a cross-sectional, population-based survey of 2 983 respondents (aged 18 years and above) selected by multistaged sampling technique. Responses were elicited using an interviewer-administered questionnaire on sociodemographic characteristics, awareness of warning against tobacco use, sources of information, perception of harmful effecs of tobacco and tobacco control measures.

Results: About 88% of the respondents were aware of warnings against tobacco use; the most common source of information was media adverts (50.7%). Awareness of warning against tobacco use was found to be associated with sociodemographic characteristics, history of smoking, exposure to smoke at home and in public places, and perception of tobacco use. Similarly, more than 90% of subjects believed that smoking is harmful to health and also expressed their support for the law banning smoking in public places.

Interpretation: The study revealed a high level of awareness of the warnings against tobacco use, positive perceptions about the harmful effects tobacco and tobacco control measures among the study population, thereby presenting an opportunity for initiating more robust policies, programmes and interventions for tobacco control in the state.

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For your patients with type 2 diabetes on monotherapy when HbA1c levels begin to rise above 7 %1,2,3

References: 1. DeFronzo RA, et al. Diabetes Care 2009;32:1649–55. 2. Chacra AR, et al. Int J Clin Pract 2009;63(9):1395–406. 3. Hollander P, et al. J Clin Endocrinol Metab 2009;94(12):4810–9.

S3 ONGLYZA® 2.5 (Tablet). Each ONGLYZA® 2.5 tablet contains saxagliptin hydrochloride equivalent to 2.5 mg saxagliptin free base. S3 ONGLYZA® 5 (Tablet). Each ONGLYZA® 5 tablet contains saxagliptin hydrochloride equivalent to 5 mg saxagliptin free base. PHARMACOLOGICAL CLASSIFICATION: A.21.2 Oral hypoglycaemics. Reg. No. ONGLYZA ® 2.5 : 43/21.2/0608. Reg. No. ONGLYZA® 5 : 43/21.2/0609. Ref: Reg. No. ONGLYZA® - EPI (28/07/11). ONGLYZA® is a registered trademark of Bristol-Myers Squibb. For full details relating to any information mentioned above please refer to the package insert. Bristol-Myers Squibb (Pty) Limited. Reg. No. 1956/001115/07. 47 van Buuren Road, Bedfordview, 2008, South Africa. Tel: (011) 456 6400. Fax: (011) 4566579/80. www.Bms.com. Date compiled: December 2011