EXCEMED Cardiometabolic Extracts, Fall-Winter 2014

FALL/WINTER 2014 IMPROVING THE PATIENT’S LIFE THROUGH MEDICAL EDUCATION

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CONFERENCE OUTCOMES Asia-Pacific CV Symposium: managing CV risk to prevent CV-related fatalities CONFERENCE OUTCOMES Asia-Pacific Endocrine Conference: optimal management of T2DM and TD CONFERENCE OUTCOMES T2DM and TD in clinical practice: progress and challenges

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HIGHLIGHTS ON EXCEMED ACTIVITIES IN CARDIOMETABOLIC MEDICINE CME TOUR OF AFRICA Enhancing local awareness and capability in diabetes and chronic disease management UPCOMING IN EXCEMED CARDIOMETABOLIC MEDICINE EXCEMED CME events on the horizon YOUR EXCEMED Improving cardiometabolic management through medical education

MEETING REPORT ESH/ISH Annual Meeting

Cardiovascular risk factors – transforming knowledge into practice CONFERENCE OUTCOMES 1-2 MARCH, GUANGZHOU, CHINA Over 130 healthcare professionals who manage hypertension in China, India, the Philippines, Thailand and Vietnam attended this symposium.

Presentations focused on managing CV risk factors to prevent the fatal end of the cardiovascular continuum. Activities were designed to ensure that scientific knowledge could best transform into good clinical practice.

This is a key aim of every EXCEMED CME activity.

The event focused on the clinical management of hypertension, using an evidence-based and guideline-driven approach.

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CVD remains challenging CVD remains the most common cause of mortality and morbidity across Asia-Pacific, and indeed globally, despite increased knowledge and ongoing research.

Treatment of major CVD, including ACS or stroke, presents costly challenges for healthcare systems, without considering the most effective approach for CVD: i.e. prevention. Essential hypertension remains a problem that is often complicated by metabolic disease.

Clinicians should regularly review care for every hypertensive patient to ensure they receive appropriate pharmacological treatment.

Regimens should follow current evidence-based guidelines, focusing on normalisation of BP values.

CME EXCELLENCE Continuing medical education (CME) is our sole focus and our passion.

We pour our energy and expertise into delivering the best for healthcare professionals, with patients as the ultimate beneficiaries. EXCEMED offers many CME activities in cardiometabolic disease management. Educational programmes are developed to suit the needs of healthcare professionals from all over the world who wish to remain up to date with all aspects of cardiometabolic research and patient care.

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CONFERENCE OUTCOMES 1-2 MARCH, GUANGZHOU, CHINA

Hypertension guidelines in the real world Guidelines are a vital tool but are no substitute for the sound judgement of the knowledgeable physician.

Dr Co likened hypertension guidelines to the satellite navigation systems that many people rely on in their vehicles. Both are useful innovative tools for guiding the route to a successful outcome. However, when such tools are used alone, they are not guaranteed to be successful in every situation.

Guidelines need to be regularly updated to ensure their recommendations are based on the latest-available evidence. They should be simple, comprehensive and easy to follow and Free from bias.

At the conference, the majority of delegates used, and were familiar with, the ESC-ESH guidelines.

However, most clinicians used several guidelines. Only 1% of delegates did not follow any guidelines in their daily practice.

Dr Co welcomed the trend towards consensus between guidelines.

Generally, greater emphasis is now placed on: • Out-of-office BP monitoring (both ambulatory and daytime average or home BP) • Global/total CV risk assessment and cardiovascular protection • Combination therapy regimens • Lifestyle modifications

• Target BP levels • Combination treatments and beta blockers as first-line therapy Treatment recommendations Guidelines have two key problems, explained Dr Co: • Disagreement in the definition and preferred treatment regimens for ageing people • Mismatch between chronological and vascular age Guidelines have been influenced by metaanalyses that suggest poorer outcomes with beta-blockers versus other drug classes. This is problematic because most trials use atenolol (which is less selective than newer beta blockers).

Dr Co emphasised that it is important to understand the following when selecting a suitable treatment regimen for people with hypertension: • Pathophysiology/pharmacology of hypertension • Compelling therapeutic indications • Clinical characteristics, risk profile, target organ damage • Clinical trials and guidelines

Dr Marlon T. Co (Chong Hua Hospital, Cebu City, Philippines) summarised the benefits and drawbacks of current hypertension guidelines.

Professor Soetanto Arieska Soenarta (National Heart Centre, Harapan Kita, Jakarta, Indonesia) and Dr Jamshed J Dalal (Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India) debated the role of beta-blockers as first-choice BP treatments

Beta-blockers, hypertension prevention and treatment Beta-blockers are useful in primary and secondary prevention of hypertension (Figure 1), but their value in people already diagnosed with hypertension has come under question, explained Professor Soenarta.

Beta-blockers with high selectivity and low ISA are optimum, but fail to lower CAP (which is responsible for organ damage).

Only two of seven large trials indicate that beta-blockers are inferior to other antihyperintensive agents, he added.

Guidelines generally agree that the BP-lowering benefits of beta-blockers are largely independent of the drug action.

Dr Dalal argued that hypertensive treatment should also prevent vascular degeneration. Beta-blockers do not fulfil this function and in this regard are associated with numerous adverse effects that reduce compliance, he cautioned.

Dr Dalal acknowledged that younger patients have haemodynamic characteristics that are amenable to betablocker use. He said further evidence is needed to establish whether newer betablockers are superior in reducing morbidity and mortality.

Figure 1: Beta-blockers can intervene at many points in the cardiovascular continuum Adapted from; Willenheimer R & Erdmann E. Eur Heart J Suppl 2009;11:A1-A2.

Key differences between guidelines include: • ‘Normal’ BP definitions • Definitions of/recommendations for ageing people 2

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Abbreviations are defined in the Glossary, page 19

CONFERENCE OUTCOMES 1-2 MARCH, GUANGZHOU, CHINA

Treating hypertension optimally in the clinic Practical steps to reduce pollution are needed

Professor Piyamitr Sritara

Professor Stefano Taddei

(Mahidol University, Bangkok, Thailand) described the burden of cardiometabolic diseases in Asian people

(University of Pisa, Pisa, Italy) discussed whether a first-choice treatment exists for hypertension.

He also reviewed the link between pollution and CVD

Focus on Asia-Pacific In Asian people, lifestyle modification gives major benefits to patient outcome.

The first 10% reduction in body weight reduces visceral fat by 30–40%.

Rates of MS and T2DM are rapidly increasing among Asian populations, due to the abandonment of traditional lifestyles. Women of low socio-economic status are at particular risk, said Professor Sritara.

He added that that in Thailand, central or abdominal obesity is a good predictor of CV risk. (Figure 3) In a study of potentially modifiable risk factors associated with MI (undertaken in 52 countries), abdominal obesity was a greater predictor of CVD than BMI.

In clinical practice, choice of antihypertensive regimen should be informed by careful evaluation of the patients’ clinical characteristics. This should be balanced with knowledge of the specific pharmacological and therapeutic characteristics of the available drugs.

Selecting a first-choice antihypertensive regimen depends on many factors including patient age, comorbidities, adherence likelihood, explained Professor Taddei.

As monotherapy can only normalise BP in ~30% of hypertensive patients, combination therapy is usually necessary (Figure 2), he added.

Figure 2: To achieve target BP, combination antihypertensive regimens are usually required

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Guidelines differ regarding first-choice therapy for BP normalisation, but suitable first-choice therapies include diuretics, beta-blockers, calcium antagonists, ACEi and ARBs. There are strong associations between CVD incidence and high rates of pollution.

Professor Taddei highlighted that, in 2012, pollution caused 52.8 million deaths (760,000 in China).

Short-term exposure to pollution is as serious as long-term exposure, with a strong association between pollution and CV hospitalisation, mortality and MI. Improvements in air quality have a positive effect, and practical steps to reduce pollution are needed, added Professor Taddei. He described the key sources of pollution that have a detrimental effect on health are traffic (60%), industry (16%) and indoor heating (7%).

Figure 3: Reducing abdominal obesity helps to improve CHD risk

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CONFERENCE OUTCOMES 1-2 MARCH, GUANGZHOU, CHINA

Individualising hypertension treatment

Waist measurement is important to assess risk of cardiometabolic disease. With support, health benefits through lifestyle modification can be achieved

Professor Brian Tomlinson

Professor Hung-Fat Tse

Professor Bambang Budi Siswanto

(The Chinese University of Hong Kong, Hong Kong SAR, China) summarised the differences in responsiveness to antihypertensive drugs

(The University of Hong Kong, Hong Kong SAR, China) summarised the treatment of concomitant T2DM and hypertension

(National Heart Center Harapan Kita, Jakarta Barat, Indonesia) described the management of a young male with acute MI

To achieve personalised medicine in patients with (or at risk of) hypertension, factors that affect drug responsiveness (including age, genetic profile and physiology) must be identified.

Hypertension management in special populations

Personalised medicine Criteria useful for identifying subpopulations of hypertensive patients who will respond similarly to drugs are uncertain, although Professor Tomlinson suggested that the following could be beneficial: • Demographics – age (Figure 4), sex, ethnicity • Physiological phenotype – renin profiling, salt sensitivity • Pharmacogenetics – pharmacokinetics, pharmacodynamics Guidelines suggest that factors affecting responsiveness to antihypertensives include age and ethnicity, but supporting evidence is limited, he added.

European guidelines recommend combination treatments because additive and synergistic effects occur. The move to combination regimens should therefore make the choice of first-line therapy less critical, explained Professor Tomlinson.

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Professor Tse presented a hypothetical case of an elderly man with hypertension and T2DM, to show how a clinical approach that aggressively lowers BP does not benefit older people with these concomitant health problems.

Professor Tse discussed how to balance the needs of glycaemic and BP control, including how to set individualised physiological targets, and how to select appropriate combination therapy.

He reminded delegates that, in the diabetic population, hypertension prevalence is 60%–80%, with a particularly strong correlation in males.

Another case, presented by Professor Bambang Budi Siswanto, emphasized that altering body fat distribution is vital in younger people with CVD. Lowering the percentage of body fat should be part of the therapeutic management, in addition

to selecting appropriate combination treatment.

Professor Sisiwanto stressed the need to consider the patient’s waist measurement. Evidence indicates that waist circumference predicts risk of cardiovascular complications. The combination of waist circumference and BMI are superior to using either parameter separately in the assessment of MS and CVD risk.

Treating hypertension in obese people requires lifestyle management, focusing on weight loss and risk reduction.

Treatment objectives should: • Substantially reduce the risk of CVD • Substantially reduced the risk of obesity-related metabolic disease • Minimise the need for medications • Optimise the effects of any drugs that are administered.

Figure 4: Evolution of hypertension with age

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Abbreviations are defined in the Glossary, page 19

CONFERENCE OUTCOMES 1-2 MARCH, GUANGZHOU, CHINA

Optimising beta-blocker use in CVD

Observations suggest that patients of Chinese origin are more sensitive to propanolol than white Caucasians

Professor Brian Tomlinson

Professor Gao Pinjin

Professor Aniruddha Dharmadhikari

(The Chinese University of Hong Kong, Hong Kong SAR, China) summarised how betablockers slow heart rate in Asian patients with hypertension

(Ruinjin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China) presented preliminary evidence that some beta-blockers have dissimilar effects on arterial distensibility and compliance in hypertensive people

(Shree Saibaba Heart Institute and Research Centre, Nasik, India) compared metoprolol succinate and bisoprolol in the treatment of stage-1 hypertension

Modifications in treatment choice may be necessary in people with CVD who are candidates for betablocker treatment. Several presentations at the EXCEMED conference discussed the characteristics of specific betablockers in different treatment populations.

Genetic factors?

More research required Early studies of propanolol revealed that patients of African descent responded less well to beta-blockers than other patients. Empirical observations suggest that patients of Chinese origin are more sensitive to propanolol than white Caucasian patients.

Professor Tomlinson stated that genetic factors may influence responsiveness, with polymorphisms affecting the metabolism of propanolol.

Having the ability to predict the effects of a beta-blocker in advance of prescribing would be advantageous, However, he cautioned, current data are insufficient to support genotyping for polymorphisms before selecting or initiating beta-blocker treatment.

Professor Tomlinson commented that studies are needed to clarify the situation.

Findings of a small-scale study indicate that different betablockers have different effects on arterial distensibility. In addition, compliance rates are not the same for each type of beta-blocker. These findings are preliminary, but may be important when considering treatment choice.

The results of this single-centre study of bisoprolol versus atenolol use in hypertensive patients in China justify an extension of the work to cover multiple centres, explained Dr Pinjin.

Dr Pinjin commenting that brachial BP in the two groups was significantly (and similarly) reduced after beta-blocker treatment. However, the decrease in aortic-SBP and aortic-PP was significantly higher in the bisoprolol group compared with the atenolol group.

This finding suggests that bisoprolol may have a better effect on CAP than atenolol, he explained.

There was little difference in heart rate variability or RHR between the two groups – RHR decreased significantly and almost identically from the baseline with each drug.

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Although bisoprolol and metoprolol are commonly used for prophylaxis and treatment in people with hypertension, bisoprolol appears to be the more selective of the two agents, and may have a theoretical advantage.

However, their effects are similar.

Different effects observed with different beta-blockers Professor Dharmadhikari suggested this in his presentation of an ABPM study in Indian patients. Both types of beta-blocker had similar efficacy; few patients required additional amlodipine.

Nighttime, systolic and diastolic BP were equivalently well controlled. Overall, the global efficacy and tolerability scores were equivalent.

Sympathetic nervous activity and CAP differ, depending on beta-blocker choice

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CONFERENCE OUTCOMES 1-2 MARCH, GUANGZHOU, CHINA

Sympathetic nervous system and hypertension

Professor Guido Grassi

HEART FAILURE – NEUROENDOCRINE DISEASE Professor Roberto Ferrari Professor Roberto Ferrari (University Hospital of Ferrara, Ferrara, Italy) summarised the management of CAD

Heart failure is now being considered a neuroendocrine disease. Guidelines advise ACEi and beta-blockers use soon as possible after diagnosis, to achieve better action on remodelling and greater reduction in rates of sudden death.

Professor Ferrari emphasised that beta-blockers are useful in HFrEF but may not be being used correctly. It is more important to monitor the target effect rather than the target dose and to use a dose sufficient to reduce heart rate to 70 beats per minute.

Unmet needs in HfrEF include prevention (control of risk factors and comorbidities) and therapy (no specific therapy available).

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Hypertension and AF

Professor Claudio Borghi

(San Gerardo dei Tintori Hospital, Monza, Italy and Milano-Bicocca University, Milan, Italy) reviewed the role of the sympathetic nervous system in hypertension

(San Gerardo dei Tintori Hospital, Monza, Italy and Milano-Bicocca University, Milan, Italy) said that hypertension may be a reversible risk factor for AF

The sympathetic nervous system is both a direct and indirect promoter of hypertension (Figure 5).

Research is currently investigating the optimum methods for measuring sympathetic activity.

AF is probably the most common arrhythmia observed globally, particularly in those with hypertension. The incidence of AF has increased substantially over the last 20 years (Figure 6).

The ideal antihypertensive agent would lower BP, control 24 hour BP and also possess ancillary properties, such as the ability to favour regression of target organ damage or reduce sympathetic activation.

Although such an agent does not appear to exist at present, research into links between the sympathetic nervous system and hypertension are helping to develop new approaches.

Professor Grassi explained that central sympatholytic agents (e.g. clonidine) reduce central and peripheral sympathetic overdrive. In contrast, betablockers reduce cardiac and central sympathetic overdrive.

A drug which increases sympathetic activity may have unfavourable effects, such as causing an increase in heart rate, myocardial oxygen demand and possibly an increase in BP variability. Full-scale clinical research will be important for investigating safety features in great detail.

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Professor Borghi pointed out that hypertension is probably a reversible risk factor for AF – if BP is effectively reduced and this achieves regression of LVH, AF will be greatly reduced.

Treatment that could prevent AF development in hypertension should be based on some of all of the following factors: • Systemic BP control • Central (aortic) BP control • Persistent heart rate control • Improved arterial stiffness • Protection against target-organ damage • Effective regression of LVH • Effective blockade of RAS/SNS • New oral anticoagulants • (Possibly) antioxidant treatment

Abbreviations are defined in the Glossary, page 19

CONFERENCE OUTCOMES 1-2 MARCH, GUANGZHOU, CHINA

CAD, a disease of the monocyte and/or the endothelium?

Professor Roberto Ferrari

Figure 5: Mechanisms that may be responsible for sympathetic activation in hypertension.

(University Hospital of Ferrara, Ferrara, Italy) summarised current knowledge of CAD pathophysiology and management

CAD could be a disease of the myocyte, the endothelium or both. In addition, it is unclear whether CAD is initially a disease of the coronary artery endothelium, which then then becomes a disease of the myocyte.

Figure 6: Incidence of AF rose substantially between 1990 and 2010

Professor Ferrari reviewed the various treatment options for CAD, including statin and ACEi therapy.

Guidelines for patients with hypertension and CAD recommend aspirin, statins and ACEi for preventing events, beta-blockers or CCBs for firstline and a broader range of agents for second-line treatment.

The benefits of beta-blockers are related to the extent of heart rate reduction – better reduction means better survivability.

Beta-blocker therapy influences two risk factors – BP and heart rate (Figure 7) – which improve atherosclerosis and lead to specific effects in patients with CAD, MI and heart failure, said Professor Ferrari.

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Figure 7: Beta-blocker benefit related to extent of heart rate reduction

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CONFERENCE OUTCOMES 7–8 JUNE, MANILA, PHILIPPINES

Optimising T2DM and TD management T2DM: urgent public health issue for AsiaPacific

Health professionals from all over the world attended this educational conference. The broad programme was organised

by Professor George J. Kahaly (Germany) and Professor Roberto Mirasol (Philippines); it included four plenary sessions (two each on T2DM and TD), together with workshops involving participants in interactive case presentations. Learning was assessed before, during, and after the meeting to determine delegates’ personal progression.

First- and second-line therapies for T2DM

Professor Roberto Mirasol

Professor Mohamed Mafauzy Dr Nanny N M Soetedjo

(St Luke’s Medical Centre, Quezon City, The Philippines) presented alarming statistics on the growing number of people with T2DM in the region. (Figure 8)

(Universiti Sains Malaysia, Kelantan, Malaysia) (Padjadjaran University, Padjadjaran, Indonesia) summarised first- and second-line therapies for T2DM

The number of people living with T2DM is staggering; almost half of all patients are undiagnosed. Figure 8 provides an overview of the worldwide T2DM epidemic.

The decision as to what constitutes optimum therapy for T2DM should be tailored to each patient according to the ABCDHH criteria. Always consider that a too-aggressive treatment approach may cause hypoglycaemia, weight gain and (in some cases) may increase the risk of CV events and mortality.

Figure 8: A snapshot of the worldwide T2DM epidemic

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Treatment and monitoring of T2DM must be individualised

Metformin remains the first-line medical option for T2DM management when diet control alone is not sufficient.

Metformin treatment may reduce hyperglycaemia and body weight; it is associated with a low risk of hypoglycaemic episodes.

In addition, metformin also reduces CV morbidity and mortality in people with T2DM by decreasing the risk of cancer incidence, progression and mortality, stated Dr Mafauzy.

Dr Soetedjo reviewed second-line medical therapies for T2DM. These include pharmacological agents such as the TZDs, sulfonylureas, DPP4 inhibitors and GLP1 agonists, in addition to insulin therapy. The use of these agents should be considered on an individualised basis, according to ABCDHH criteria, but all second-line treatments are associated with reductions in HbA1c and body weight. They also carry a low risk of hypoglycaemia, have few side-effects and are rarely linked to CV events.

Hypoglycaemia is a risk associated with many antiglycaemic treatments and in itself is linked to an increase in CV-related mortality. Both speakers emphasised the importance of managing the care of people with T2DM very carefully because of the importance of balancing treatment needs with hypoglycaemic risk.

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CONFERENCE OUTCOMES 7–8 JUNE, MANILA, PHILIPPINES

Tools for improving adherence in T2DM

Dr Iris Thiele Isip Tan (University of the Philippines, College of Medicine, Manila, Philippines) outlined how mobile health devices may improve adherence in T2DM patients

Poor adherence to treatment, health monitoring and lifestyle interventions have become global challenges in T2DM management, although innovative ways are being developed to improve them.

Mobile health management is rapidly developing

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Mobile health management, using apps, is becoming important in T2DM care

Mobile health management is a rapidly developing sector in health care. It describes the technology, largely provided by smartphones or specifically tailored devices, which help to support and educate patients.

Mobile health management devices monitor and measure an individual’s health state; these devices store data and may increase the efficiency of both selfand health care professional management of chronic diseases.

Dr Tan emphasised that many ‘apps’ are available to suit different smartphones and other devices. These apps are easy to use, free to access, and are approved by health care systems.

Mobile health apps covering the field of T2DM include diet schemes, exercise programmes, body weight control, therapy guidance, glucose level monitoring, and also provide clinical and

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medical information. Most of the apps are designed for patient use rather than physician education/support.

Dr Tan explored the problem of poor adherence to treatment in T2DM in the context of how mobile health management may, in future, help to improve adherence.

Currently, poor adherence affects the majority of patients with T2DM and may often explain the frequent therapy failures that are seen. Poor adherence is also likely associated with the onset and progression of T2DM-related complications and increased health care costs, especially in the developed world.

Abbreviations are defined in the Glossary, page 19

CONFERENCE OUTCOMES 7–8 JUNE, MANILA, PHILIPPINES

Iodine crucial for neurocognitive development

Professor Nemencio A Nicodemus Jr (University of the Philippines, College of Medicine, Manila, Philippines) reviewed the important role of iodine in neurocognitive development and function

Iodine and derived thyroid hormones are crucial for brain and neurocognitive development and function. This critical relationship stretches from the beginning of life - in utero to adolescence - by inducing neuron cell differentiation, maturation, migration and synapsis formation, said Professor Nicodemus.

In utero, iodine passes from mother to fetus via the placental circulation.

Following birth, breast feeding supports brain organogenesis and thyroid function.

Consequently, adequate dietary iodine intake is critical for women of childbearing age and potential (Table 1), to help facilitate proper neurological development in their children.

However, iodine intake in individuals is low, particularly in many developing countries (Figure 9). This is a critical issue

IN BRIEF: CARDIOVASCULAR IMPLICATIONS OF TD Professor George Kahaly (Gutenberg University Medical Centre, Mainz, Germany) emphasised the cardiovascular consequences of TD

that must be corrected through public health initiatives.

The European Food Safety Authority recently advised that there is a cause and effect relationship between dietary iodine intake and normal cognitive development.

Even mild iodine deficiency during pregnancy may have long-term effects on fetal neurocognition. Such effects, said Professor Nicodemus, are not ameliorated by iodine sufficiency in childhood.

Consequently, programmes of iodine supplementation are now being followed in many countries, with iodine levels being carefully monitored at a population level.

Iodine and derived thyroid hormones are crucial for brain and neurocognitive development

Hyperthyroidism and hypothyroidism both increase risk of CVD Thyroid hormones can have a deep impact on the cardiovascular system due to their direct and indirect effects on heart and vessels, said Professor Kahaly. Such effects have possible repercussions in terms of heightening the morbidity and mortality rates. Consequently, patients with or at risk of TD should be adequately monitored.

Hyperthyroidism, even when subclinical, increases CV-associated morbidity and mortality. This increases the risk of cardiac arrhythmias (e.g. AF and thromboembolism with stroke) but also induces LVH and cardiac valve degeneration.

In addition, hypothyroidism increases the risk of CHD, due to increased atherosclerosis and plaque formation.

Figure 9: Degree of iodine insufficiency in school-age children by WHI region (2011)

Table 1: Recommended iodine intakes in women

Population Nonpregnant adults Pregnant women Breast-feeding woman

RDA, μg 150 220–250 250-290

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CONFERENCE OUTCOMES 7–8 JUNE, MANILA, PHILIPPINES

Workshop: Managing GDM – from diagnosis to insulin therapy To avoid complications in women with GDM, a close collaboration between diabetologists and obstetricians/ gynaecologists is essential.

In women with GDM, a close collaboration between diabetologists and gynecologists is needed to establish appropriate care and avoid complications associated with pregnancy for women and metabolic disorders in their children

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Dr Patricia Gatbonton (Our Lady of Lourdes Hospital, Manila, Philippines) looked at the prevalence of GDM and discussed its treatment

It is critical to manage GDM using an expert, multidisciplinary approach, because good glucose control is the best way to optimize outcomes for both the mother and infant.

Dr Gatbonton gave a detailed presentation, in which she described GDM as an increasing problem in many countries. Prevalence rates range between 7.5 and 14%.

The cornerstones of therapy are medical nutrition therapy, exercise, frequent SMBG and pharmacologic therapy (including insulin when other approaches are inadequate).

Dr Gatbonton recommended that health care professionals look at countryspecific guidelines as a first-line approach to checking appropriate management.

Guidelines that cover screening, diagnosis and the different treatment approaches have been ratified in many countries.

However, since country specific guidelines do not exist or are unavailable, Dr Gatbonton suggested that materials provided by international groups such as the ADA, EndoDoc, IDF, AACE and NICE would be of benefit.

Interactive discussions of cases led participants through issues with diagnosis, risk factors, testing, weight management and exercise, treatment, monitoring and glycaemic targets and issues during labour.

GDM is an increasing problem: Prevalence rates are 7.5 - 14%

Abbreviations are defined in the Glossary, page 19

CONFERENCE OUTCOMES 21 JUNE, ROME, ITALY

T2DM and TD – progress and challenges

Healthcare professionals from a range of countries attended this dynamic conference on T2DM and TD. Workshop and didactic sessions addressed the many clinical challenges associated with these highly prevalent, chronic conditions.

Managing pre-T2DM – lifestyle first but drugs work

Nonsurgical interventions in thyroid nodular disease

Professor David Leslie | Dr Lelio Morviducci

Professor Laszlo Hegedüs

(St Bartholomew’s Hospital and The Blizard Institute, London, UK) (San Camillo Hospital, Rome, Italy) debated whether to treat pre-T2DM with a dietary or drug-focused approach

(Odense University Hospital/University of Southern Denmark, Denmark) described how medical therapy and ultrasound-guided interventions have simplified management of symptomatic benign thyroid nodules

Although lifestyle modification remains the best way to help prevent T2DM development, drugtreatment strategies are crucial when lifestyle interventions fail.

Medical therapy and ultrasound-guided interventions are good alternatives to standard surgery for patients with benign thyroid nodular disease. Several minimally-invasive strategies have been developed, with treatment selection based on the type of nodule.

Both speakers emphasised the importance for the clinical team of preventing T2DM – large-scale trials have investigated the optimum approach for preventing onset in high-risk people.

Lifestyle modification (‘healthy eating’ diets and physical activity) are most effective in reducing the risk of developing T2DM, but are challenging. (Figure 10)

Figure 10: Relative risk reduction (%) of new-onset T2DM in randomised, controlled clinical prevention trials

Excellent results have been obtained with PEI as a nonsurgical strategy for cystic nodule management; it is an outpatient procedure with no safety concerns.

For solid nodules, UGILT can be performed in outpatient centres with favourable safety, cost and efficacy. Recurrence rates are high (≥30%) but treatment is easily repeatable.

RA also shows safety and efficacy in patients with functioning and nonfunctioning benign thyroid nodules, but Professor Hegedüs cautioned that it is only available in selected centres and its long-term efficacy is unproven.

Da Qing (Pan et al, T2DM Care 1997); Finnish T2DM Prevention Study, Tuomilehto et al, N Engl J Med 2001; DPP, T2DM prevention programme (Ratner et al, et al Endocrin Pract, 2006) STOP-NIDDM, Study to Prevent Non-Insulin-Dependent T2DM Mellitus (Chiasson, Endocrin Pract, 2006); DREAM (Gerstein, Lancet, 2006); TRIPOD, XENDOS, RAS Blockade (Chiasson, Endocrinol 2005)

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CONFERENCE OUTCOMES 21 JUNE, ROME, ITALY

CVD and T2DM: close association requires investigation Professor Standl reminded clinicians to be alert for insulin resistance and metabolic syndrome in patients with several key risk factors, including high BP and fat intake, HbA1c, obesity and low physical activity

Professor Eberhard Standl (Munich T2DM Research Group, Helmholtz Centre, Munich, Germany) characterised the association between CVD and the altered metabolic function seen in T2DM

The close relationship between CVD and T2DM means patients with one condition should be routinely screened for the other, said Dr Standl.

Prompt identification of problems facilitates rapid treatment.

Closely controlling glycaemia, lipid and BP levels helps to prevent coronary ischaemic disease and reduce stroke incidence. Professor Standl highlighted the risks and how to screen for them: • T2DM patients are at very high/high risk of CVD depending on concomitant risk factors and target organ damage • Urinary albumin excretion rate should be estimated when performing risk stratification • Screening for silent myocardial ischaemia may be considered in selected high-risk patients

Hyperglycaemia is common and often undiagnosed (Figure 11).

T2DM is closely linked with CVD development due to associated metabolic alterations including hyperglycaemia, dislipidaemia, hypertension, endothelial dysfunction, prothrombotic state, chronic inflammation, autonomic dysfunction and accelerated atherosclerosis.

Figure 11: Hyperglycaemia is often undiagnosed in patients with CVD

Hyperglycaemia is common and often undiagnosed

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Abbreviations are defined in the Glossary, page 19

CONFERENCE OUTCOMES 21 JUNE, ROME, ITALY

Treating subclinical hypothyroidism

Managing T2DM in pregnancy

Professor Bernadette Biondi and Dr Salman Razvi

Workshops led by Professor Osama Hamdy

(Università Federico II di Napoli, Naples, Italy) debated the advantages and disadvantages of treating subclinical hypothyroidism

(Joslin T2DM Centre, Boston, USA) Harvard Medical School focused on the diagnosis and treatment of T2DM in pregnancy

Subclinical hypothyroidism is associated with increased occurrence of cardiovascular events. Some clinicians believe it should be treated, especially in certain patient groups (such as the elderly).

GDM requires prompt, accurate diagnosis and treatment to reduce rates of serious perinatal complications and improve maternal health-related quality of life.

Treating subclinical hypothyroidism may prevent the onset of further cardiovascular complications, said Dr Razvi.

Treatment may ‘medicalise’ normal conditions or neglect other causes of symptoms (e.g. fatigue, weight gain), argued Professor Biondi.

If treatment of subclinical hypothyroidism is considered, absolute values of TSH should be evaluated.

Dr Razvi emphasised that age-specific reference ranges for serum TSH should be used, according to international recommendations.

GDM treatment (diet and exercise regimens) begins immediately upon diagnosis

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GDM treatment begins immediately upon diagnosis

No international consensus exists on the criteria for GDM screening and diagnosis – further research is needed to establish a uniform approach to this, explained Professor Hamdy.

Two procedures can be used at 24-28 weeks’ gestation to diagnose GDM in women not previously diagnosed with T2DM: • One-step approach (IADPSG): 75g OGTT • Two-step approach (NIH consensus): 50g non-fasting glucose test GDM treatment (diet and exercise regimens) begins immediately upon diagnosis.

Specialist referral is necessary because as pregnancy progresses, treatment with metformin, selected sulphonylureas, or insulin may be required.

Combining measurement of Hb1Ac with frequent SMBG, or continuous glucose monitoring, helps women achieve target glucose levels safely, added Professor Hamdy. SMBG alone can miss certain high glucose values.

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MEETING REPORT 13–16 JUNE, ATHENS, GREECE

Hypertension and cardiovascular protection – clinical perspectives from ESH and ISH The joint ESH and ISH meeting gathered thousands of healthcare professionals to hear the latest research and clinical perspectives in hypertension and cardiovascular protection.

Fixed-dose combination monotherapy may improve treatment adherence in hypertension

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Hypertension management now involves a broad spectrum of agents capable of dissecting the different pathophysiological aspects with limited contraindications.

The concept of ‘sub-maximal dose’ combination therapy has been established with respect to ‘maximal dose’ monotherapy, which achieves questionable BP control, and has side-effects.

Current international guidelines recommend blocking the RAS system as a first-line therapy and eventually adding a CCB, diuretic, or beta-blocker to improve BP. Single tablet, fixed-dose combination treatment may improve treatment adherence in hypertension : poor adherence affects >50% of patients in some studies, representing the major cardiovascular risk factor, together with comorbidities.

Preventing or reducing end-organ damage from high BP is a major objective of hypertensive treatment. Drugs should therefore be chosen that limit cardiovascular morbidity and mortality, especially in predisposed patients Consequently, early target-organ damage assessment is crucial.

Measuring serum creatinine, urine albumin excretion and electrocardiographic left ventricular mass in hypertensive patients is highly recommended. In addition, measuring

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echocardiographic left ventricular mass, ultrasonic carotid wall thickness, aortic pulse wave velocity and anklebrachial index increases the prognostic value of investigations and helps block progression in the CVD continuum. This allows for tailored interventions and prevention plans.

Management of hypertension is particularly challenging when comorbidities and cardiovascular risk factors are present. However, BP should not be lowered too much in elderly people.

Controlling hypertension and the underlying atherosclerosis are major factors in preventing cerebral and cardiovascular events in dyslipidaemia.

T2DM is a complex interplay of complications, and BP values merit specific and tighter control than usual, without increasing side effects or collateral injuries.

Chronic kidney disease deserves special attention to avoid progression to dialysis – lowering BP can help preserve renal function and reduce cardiovascular risk.

Controlling hypertension over heart rhythm and rate is crucial to reducing the risk of stroke and embolism in AT.

Abbreviations are defined in the Glossary, page 19

IN BRIEF

CME TOUR OF AFRICA OVERVIEW

Enhancing clinical diabetes management in Africa

Medical education within reach Can’t join us for the live events? No problem.

Subsequent online learning opportunities and takeaway messages will be available on a free educational platform, www.managediabetesonline.org.

This has been developed by EXCEMED so that professionals unable to attend the live CME Tour of Africa can still benefit from its valuable educational events.

EXCEMED launched its first CME Tour of Africa in 2013 to enhance local awareness and capability in diabetes and chronic disease management.

Diabetes and related conditions are a growing problem on the African continent, alongside changes in diet and lifestyle.

The 2014 CME Tour of Africa, in brief • When: September-November 2014 • Where: Angola, Ghana, Kenya, Mozambique, Namibia, Tanzania and Uganda and online CME courses for those who cannot attend the live events, at www. managediabetesonline.org • Who: Medical students, pharmacy students, general practitioners • Why: Enhance local awareness and capability in diabetes and chronic disease management

If the purpose of medical research, education and practice are to enhance the quality of life for people across the planet, the EXCEMED CME Tour of Africa is not only timely, but essential.

This initiative is farreaching, powerful and cost-effective - is there a better way to make a difference?

The tour is being repeated in 2014. It is engaging three African universities and many local scientific societies, reaching over 400 general practitioners, medical students and pharmacists. The workshops are tailored to local needs and present evidence-based data and novel diabetes management approaches through interactive clinical case studies.

The EXCEMED 2014 CME Tour of Africa is run in partnership with diabetes expert Dr Jonathan Levy from the Oxford Centre of Diabetes, Churchill Hospital, Oxford, UK and will touch down in Angola, Ghana Kenya, Mozambique, Namibia, Tanzania and Uganda.

For the 2013 tour, participant feedback was outstanding: 97% of attendees believed the training would benefit patient care and 96% were ‘satisfied’ or ‘very satisfied’ with the education offered.

The education offered to physicians during the CME Tour of Africa aligns with the standards of the European Accreditation Council for Continuing Medical Education (EACCME).

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Tour 1: Kenya, Uganda • What to expect online: A CMEaccredited online course (Kenya) and online video lectures (Uganda) • Target audiences: medical students, general practitioners, pharmacists Tour 2: Namibia, Mozambique, Angola • What to expect online: video lectures (Namibia), video lectures in Portuguese with English subtitles (Mozambique, Angola) • Target audiences: medical students, general practitioners Tour 3: Ghana, Tanzania • What to expect online: video lectures • Target audiences: medical students, general practitioners, pharmacists

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UPCOMING ACTIVITIES IN EXCEMED CARDIOMETABOLIC MEDICINE

EXCEMED is offering innovative live educational events in the coming months. Please visit www.excemed.org to see the latest news on the cardiometabolic educational programme

Practical course on the management of cardiology from cell to patient: The experience of the Centre for Prevention and Care of Cardiovascular Diseases of the University of Ferrara

Advances and challenges in the management of T2DM and thyroid disorders SAO PAULO, BRAZIL 10-11 OCTOBER, 2014 SCIENTIFIC ORGANISERS H GRAF, BRAZIL AND M TAMBASCIA, BRAZIL

FERRARA, ITALY 11–13 SEPTEMBER, 2014 SCIENTIFIC ORGANISER R FERRARI, ITALY AIM this educational activity will offer the opportunity to learn from and interact with a recognised, experienced multidisciplinary team lead by Professor Ferrari, providing participants with knowledge and information on diagnosis and managing patients with hypertension thus improving the skills in clinical practice and ultimately patient care KEY TOPICS history and unknown aspects of heart rate, role of beta-blockers in cardiovascular treatment in 2014, FASC projects and EHC, the different hypertension guidelines on beta-blockers TARGET AUDIENCE cardiologists and internists FORMAT lectures, and discussions/demonstrations of a number of sub-specialities sessions

AIM this live educational conference will review the most significant achievements of research in T2DM and thyroid disorders and will share best practice for the clinical management of such diseases KEY TOPICS ‘diabesity’ in Latin America, comparison of international and local guidelines for diabetic management, role of pharmacological therapy in the management of pre-T2DM, treating T2DM and improving outcomes., improving adherence to treatment, complications and comorbidities of T2DM, consequences of iodine deficiency in Latin America, Graves’ disease and its complications, managing thyroid nodules and thyroid cancers TARGET AUDIENCE Latin American diabetologists, endocrinologists, general practitioners and all healthcare professionals involved in managing T2DM or TDs FORMAT lectures, case study presentations, roundtable discussions, interactive workshops (with clinical case presentations)

www.excemed.org EXCEMED is a non-profit organization dedicated to providing CME to healthcare professionals. This newsletter is intended for healthcare professionals and provides a brief summary of a selection of previous educational events. EXCEMED will make reasonable efforts to include accurate and current information, wherever possible, but makes no warranties or representations as to its accuracy or completeness. This information is provided “as is” without warranty of any kind, either express or implied, including but not limited to implied warranty of fitness for particular purpose. EXCEMED has implemented and maintains a Quality Management System which fulfils the requirements of the ISO 9001:2008 standard for the activity of design and provision of training events in the healthcare sector. © EXCEMED, 2014. All rights reserved.

EXCEMED Excellence in Medical Education, Salita di S. Nicola da Tolentino, 1/b, 00187 Rome, Italy.

Editorial development: Ray Ashton, Linda Edmondson, Dorina Monaco,Michèle Piraux, Emma Wadland

© Copyright 2014 EXCEMED. All rights reserved.

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Design: katehouben.com Photos on pages 1, 4, 5, 6, 7, 9, 10, 12, 14, 15, 16 and 17. courtesy of www.bigstockphoto.com

Abbreviations are defined in the Glossary, page 19

GLOSSARY

YOUR EXCEMED

EXCEMED: improving cardiometabolic management through medical education EXCEMED – Excellence in Medical Education – is the new name of Serono Symposia International Foundation (SSIF). Our new name marks an exciting point in our evolution, but our focus on education in cardiometabolic disease management remains paramount.

The Foundation has provided world-class education to thousands of healthcare professionals over the past four decades.

During this time, over 1500 international scientific congresses have been organised, with more than 500 proceedings published in leading international journals.

EXCEMED has pioneered online CME courses since 2000; the organisation oversees an expanding portfolio of e-learning activities including video lectures, CME-accredited online courses and symposia. These digital ventures reach over 12,500 people per month via the EXCEMED website or through e-newsletters.

As a non-profit global organisation, EXCEMED is dedicated to improving the patient’s life through the provision of independent, high-impact CME to scientists, physicians, nurses, pharmacists and other healthcare professionals.

Upcoming EXCEMED events of relevance to specialists in cardiometabolic medicine are summarised on Page 19 of this publication.

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EXCEMED has an innovative educational programme in cardiometabolic medicine

ABCDHH, age, body weight, complications, duration of T2DM, hypoglycemia, HbA1c ABPM, ambulatory blood pressure monitoring ACEi, angiotensin-converting enzyme inhibitors ACS, acute coronary syndrome ARB, angiotensin receptor blocker AF, atrial fibrillation BMI, body mass index BP, blood pressure CAD, coronary arterial disease CAP, central aortic pressure CCB, calcium channel blockers CHD, coronary heart disease CVD, cardiovascular disease DDP4, dipeptidyl peptidase-4 EHC, European Heart for Children ESC-ESH, European Societies of Hypertension and Cardiology FASC, Fondazione Anna Maria Sechi per il Cuore GDM, gestational T2DM mellitus GLP-1, glucagon-like peptide-1 HbA1c, glycated haemoglobin HfrEF, heart failure with reduced ejection fraction ISA, intrinsic sympathomimetic activity ISH, International Society of Hypertension IADPSG, International Association of T2DM and Pregnancy Study Group LVH, left ventricular hypertrophy MS, metabolic syndrome MI, myocardial infarction NIH, National Institutes of Health OGTT, oral glucose tolerance test PEI, percutaneous ethanol injection PP, pulse pressure RA, radiofrequency ablation RAS, renin-angiotensin system RHR, resting heart rate SBP, systolic blood pressure SMBG, self-monitoring of blood glucose SNS, sympathetic nervous system T2DM, type 2 T2DM mellitus TD, thyroid disease TSH, thyroid stimulating hormone TZD, thiazolidinedione UGILT, ultrasound-guided interstitial laser therapy

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EXCEMED at your fingertips IMPROVING THE PATIENT’S LIFE THROUGH MEDICAL EDUCATION

> > >

www.excemed.org It’s active in here

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Six specialty micro sites, including cardiometabolic medicine Accessible and accredited e-learning packages A world-class repository of CME knowledge and learning materials Monthly updates about our events and resources in cardiometabolic Register with us online and access it all – free

Better outcomes for patients start here. With over 40 years of experience, EXCEMED has been delivering continuing medical education (CME) longer than any other provider.