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Scientific Highlights: 2015 Asia Pacific conference on cardiometabolic diseases management

Scientific Highlights: 2015 Asia Pacific conference on cardiometabolic diseases management
  • Cardiometabolic
    Endocrinology and metabolism
  • Diabetes
    Thyroid disorder

Resource type



Cardiometabolic diseases
Managing hypertension
Managing diabetes
Managing thyroid disorders
Thyroid Disorder
cardiovascular risk factors
thyroid cancer

2015 Asia-Pacific Conference on Cardiometabolic Diseases Management: the complex management of hypertension, diabetes and thyroid disorders

The conference on cardiometabolic diseases management was held in Mumbai, India, on 4–5 July. It was organised by Stefano Taddei (Italy) and addressed the increasing problem of the complex management of the comorbid diseases, hypertension, diabetes and thyroid disorders. Recent research advancements and the best approaches for clinical management in daily practice in these areas of cardiometabolic medicine were discussed in the form of informative presentations and highly interactive workshops and debate sessions.

Prehypertension should be treated in patients with high cardiovascular risk

Claudio Borghi (Italy) opened the conference examining the risks of prehypertension or ‘high-normal’ blood pressure (BP), which exists in around 25% of the population. Most will go on to develop hypertension and are at increased risk of cardiovascular (CV) morbidity. Patients with additional risk factors, such as diabetes, suffer more. Obstructive sleep apnoea, arterial stiffness, hypercholesterolaemia and hyperuricaemia are associated with progression to overt hypertension; therefore, these metabolic factors should be monitored in patients with prehypertension. Most guidelines recommend just lifestyle changes, whereas Professor Borghi concluded that, ‘prehypertension should be treated in those patients who have BP in the prehypertensive range and associated with pre-existing CV disease to improve clinical outcome in terms of prevention of stroke and major CV events’. Treatment with renin–angiotensin–aldosterone system (RAAS) blockers are effective in reducing development of hypertension, and also in normotensive patients with diabetes, with reduction in progression of microalbuminuria.

Heart rate is a key predictor of cardiovascular risk and hypertension

‘BP measurements should always be associated with measurement of heart rate (HR), because resting HR values independently predict CV morbid or fatal events in several conditions, including hypertension’, Paolo Palatini (Italy) quoted from the ESH/ESC guidelines. Professor Palatini considered that elevated HR is a cause of CV events, rather than an outcome, noting that high HR predates hypertension, obesity, metabolic syndrome and diabetes. The mechanisms involved are complex; HR increases CV risk by being associated with sympathetic overactivity, and also causing mechanical vascular and cardiac damage. Ambulatory HR monitoring may be useful, as night-time increase in HR is a strong predictor of CV events. First-line treatment with beta-blockers is recommended for increased HR, and can be particularly beneficial in patients with other CV conditions such as hypertension, angina, atrial fibrillation and HF. Professor Palatini stressed that beta-1 selectivity of the drug is important for patients with chronic obstructive pulmonary disease (COPD) or asthma, peripheral artery disease, diabetes, dyslipidaemia or erectile dysfunction, with bisoprolol being the most beta-1 selective beta blocker and most effective in reducing HR.

The workshop on the management of HR by Jamshed Dalal (India) echoed what Professor Palatini said in his presentation – that HR control is important in the management of angina and HF to reduce mortality. However, beta-blockers do not work optimally in all cases, and ivabradine (an If inhibitor) is another option, which has been shown to reduce HR and CV mortality; reductions in left ventricular (LV) volumes and improvement of LV ejection fraction have also been seen with ivabradine. Overall, Dr Dalal recommended that HR should not be reduced too far (<50 beats per minute).

Hypertension is the biggest contributor to coronary artery disease

There are several risk factors for coronary artery disease (CAD), hypertension being the most important, said Professor Borghi, though dyslipidaemia, diabetes and obesity are also significant. Most patients are asymptomatic until they experience a major CV event; therefore, all patients with high CV risk should be examined for CAD. Control of BP is key to the management of CAD and a BP reduction of 10 mmHg systolic blood pressure (SBP) or 5 mmHg diastolic blood pressure (DBP) results in a reduction in the rate of CAD and stroke by up to 24% and 46%, respectively. However, Professor Borghi pointed out that the target BP needs to be carefully considered, as there is a trend for J-shaped response for CV events, and the effect is different in the elderly. Overall, the evidence has led to guidelines recommending BP be reduced to <140/90 mmHg, with slightly higher SBP targets in the elderly. As well as lifestyle changes, beta-blockers seem to offer the greatest benefit for patients with hypertension and CAD, in particular after myocardial infarction (MI) and in angina, in which RAAS blockade (with angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin II receptor blockers [ARBs]) or calcium-channel blockers, respectively, are also indicated.

This was reiterated in the workshop by Piyamitr Sritara (Thailand). He added that the choice of diagnostic methods is important in CAD, and that, whereas coronary computed tomography angiogram is highly sensitive and specific for CAD, it does not improve clinical outcomes, compared with functional testing. As for treatment, medical vs. invasive approach in moderate ischaemia is still controversial, and percutaneous coronary intervention or coronary artery bypass graft is indicated in more severe disease. However, moderate to high intensity statin treatment is mandatory, along with a cardioselective beta-blocker.

Hypertension is a major risk factor for heart failure

Brian Tomlinson (Hong Kong) described how hypertension is a major risk factor for HF and contributes to CAD, MI, arterial stiffening and cardiac hypertrophy. Seventy-five percent of HF cases have hypertension; the risk increases with increasing BP and age, and race also plays a part. Recent data show that HF with either reduced or preserved ejection fraction (HFrEF or HFpEF, respectively) carries a high mortality rate of 10% and 30% within 1 month and 1 year, respectively, after being hospitalised for acute decompensated HF. ‘It is important to distinguish between HFrEF and HFpEF in order to find the underlying causes of HF and to guide medical therapy’, Professor Tomlinson said, a point he reiterated in the workshop on HF management. He recommended also to look out for pericardial effusion, which occurs in 20% of patients with HF and is an indicator of poor prognosis. B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are key biomarkers for HF; additional tests include pulmonary function tests, HR, stress testing, stress imaging and cardiac magnetic resonance imaging or computed tomography. Guidelines recommend that patients with HFrEF (or systolic HF) will need combination therapy, comprising RAAS blockade and beta-blockers, with addition of loop or thiazide diuretics and mineralocorticoid receptor antagonists, as necessary. Evidence for treating HFpEF (or diastolic HF) is not so clear and the underlying cause should be treated if possible.

It is likely that a patient with systemic hypertension, end-organ damage, dyslipidaemia and obesity – a patient with high CV risk and meeting criteria for metabolic syndrome – would need combination therapy to control BP, said Shirish Hiremath (India) in the workshop on hypertension management. Individualised therapy comprising one or more of thiazides, ACEI or ARB, calcium-channel blocker and beta-blocker, on top of CV-risk-reducing diet and exercise, is important.

High rate of comorbidities in heart failure

Stefano Taddei (Italy) expanded on the comorbidities frequently seen in HF: chronic renal failure, anaemia and COPD. Renal dysfunction occurs in 60% of patients with HF, presenting under the guise of cardiorenal syndrome; it is often unclear which disease comes first. As estimated glomerular filtration rate reduces, there is an increased risk of CV events and all-cause mortality. Professor Taddei noted that BNP and NT-proBNP should not be used as markers of HF in patients with renal failure, as they have higher levels anyway due to reduced renal clearance. There is a lack of evidence-based guidelines for treatment of patients with HF and renal failure, but loop diuretics are the preferred treatment, and RAAS blockade is also important; Professor Taddei stressed that it is important not to stop RAAS blockade, even if there is high plasma creatinine or there are high potassium levels, as the CV benefits outweigh the risks. Anaemia in HF is often concomitant to renal dysfunction; intravenous iron or darbepoetin alfa improve outcomes. Up to 52% of patients with HF also have COPD, although often only one of the conditions is diagnosed, because symptoms of one condition can mask the other. A low-dose, cardioselective beta-blocker, e.g., bisoprolol, is a useful treatment for patients with concomitant HF and COPD to avoid respiratory complications.

All-round management is required to manage heart failure in diabetes

‘Diabetes is a more serious risk factor for HF than CAD, left ventricular hypertrophy or renal dysfunction’, said Saifuddin Bandukwala (India). Around 20–25% of patients with HF have type 2 diabetes (T2DM), and women with diabetes are at greater risk than men. Glycaemic control is crucial: just a 1% rise in HbA1c can increase risk of HF by 25%. It is likely that T2DM has a direct effect in the development of HF via complex metabolic disturbances contributing to cardiac dysfunction, and comorbid conditions such as hypertension and dyslipidaemia further contribute. ‘Echocardiography is the gold standard for diagnosing HF in diabetes patients’, said Dr Bandukwala, with BNP or NT-proBNP helping confirm HF. There is controversy in the benefits of tight glycaemic control for preventing HF in diabetes – meta-analyses have failed to show a definitive advantage of intensive control vs. standard control, and HbA1c of <7% offers a worse CV prognosis. The choice of antihyperglycaemic treatment is also important; there is mounting evidence that metformin is beneficial for HF, whereas thiazolidinediones are thought to increase risk of HF. Newer treatments for diabetes, such as dipeptidylpeptidase-4 inhibitors, sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 agonists, are still being studied in large prospective CV outcome trials, but data from pivotal studies show mixed effects on HF. The effect of insulin on HF is also not clear. Depending on the stage of HF, ACEIs or ARBs are the recommended first-line treatment for HF in patients with diabetes. Beta-blockers may be added but only a few are recommended in patients with T2DM, which are bisoprolol, carvedilol and metoprolol.

Optimal diabetes treatment should be evidence-based and tailored to the individual

Mafauzy Mohamed (Malaysia) expressed concern that, ‘despite the plethora of evidence that diabetes complications can be prevented or delayed, optimal management is not reaching many patients’. Reasons include the complexity and diversity of the disease and its standards of care, with resources varying widely between and within countries. The International Diabetes Federation (IDF) clinical guidelines are sensitive to resource and cost-effectiveness issues worldwide, and state that, ‘no person should be denied any element of effective diabetes care’. Hence, they outline different levels of care depending on resources available. For example, HbA1c tests are not available everywhere and treatment recommendations are based on costs; they do not recommend the newer, more expensive antihyperglycaemic drugs as first- or second-line. The American Diabetes Association (ADA) adopts an evidence-based approach, and stresses that an individualised patient approach should be taken based not only on the evidence available but also on the patient’s characteristics. Dr Mohamed suggested that, as the ADA guidelines are based on US standards and resources, they should be followed if your country has similar resources, as they offer a wide choice of medications and regimens to suit different patient characteristics. He noted, however, that evidence is not available in some patient groups and so guidelines may not be applicable to all (e.g., the elderly or those with comorbidities) and physicians must use their own clinical experience and discretion.

‘Should prediabetes be treated?’ was the question debated by Sanjiv Shah (India) and Patricia Gatbonton (Philippines). It is estimated that there are as many people with prediabetes as there are with T2DM and as 35% of prediabetes cases will lead to T2DM, preventing progression to T2DM is important. Both presenters agreed that lifestyle modification should undoubtedly be undertaken to help prevent or slow progression to T2DM. Dr Shah said that an approximately 50% reduction in development of T2DM is seen with lifestyle modification alone, with additional benefits of weight loss, reduced stress and increase in physical activity, which confer additional health benefits – especially CV. Even a small change in weight loss will result in significant benefit in CV health. He argued that with continued self-management education, support and motivation (e.g., with new technologies), lifestyle modification alone can be very successful.

Dr Gatbonton argued that there is a large failure rate with lifestyle modification strategies, which require a huge amount of effort and cost on the part of the patient and healthcare team. She added that diagnosis of prediabetes presents healthcare providers with an opportunity to implement interventions to delay or prevent T2DM and its complications, since prediabetic individuals already manifest all of the pathophysiological abnormalities present in overt T2DM, such as loss of beta-cell mass or presence of microvascular complications. Medications approved for obesity, e.g., orlistat, as well as metformin, acarbose and pioglitazone have proven effective in slowing progression to T2DM. Further medication to treat risk factors for CVD is also recommended.

The hazards of cardiometabolic diseases during pregnancy

Hyperglycaemia during pregnancy has serious implications for both mother and child, said Bipin Sethi (India). Diet and exercise are often sufficient treatment for many patients and they need to be followed up regularly to monitor glucose levels. Insulin is required when lifestyle modifications are not adequate, however. Metformin is only recommended if diet and exercise fail and patients cannot use insulin, and should only be used after the first trimester. Dr Sethi noted that its safety in pregnancy is not entirely established and there is no evidence for preventing abortion due to gestational diabetes. Gestational diabetes that develops during or just before labour also needs to be treated to prevent neonatal hypoglycaemia. Dr Sethi ended by saying that, ‘whilst managing gestational diabetes poses challenges during pregnancy, it does provide opportunities to better manage the patient’s ongoing health and hopefully prevent long-term development of T2DM’.

The most common complication in pregnancy is hypertension, which can cause maternal and perinatal morbidity and mortality and is a risk of future CVD, said Jamshed Dalal (India). He added that hypertension is more common in very young (<18 years) or older (>35 years) mothers or in twin births, and that the prevalence is likely to increase as the obstetric population becomes older and more obese. Of all pregnant women, 1–5% have pre-existing hypertension, and gestational hypertension occurs in 5–6% of pregnancies, being usually mild, developing after 20 weeks’ gestation and resolving postpartum. Pre-eclampsia is a more serious gestational hypertension and is associated with proteinuria and poor organ perfusion. Dr Dalal said that treatment of hypertension in pregnancy should be considered when SBP ≥150 mmHg or DBP ≥100 mmHg, but ensuring that the drugs are also safe. It was previously thought that over-treating hypertension would cause fetal damage by reduced utero-placental perfusion; however, the CHIPS trial (N Engl J Med 2015;372:407-17) concluded that tight control of BP (DBP <85 mmHg) was safe for the baby. The preferred drugs are methyldopa, nifedipine, labetalol and hydralazine, whereas diuretics are best avoided first-line. ACEIs and ARBs must be avoided, and women being treated with these prepregnancy must be switched. In patients with pre-eclampsia (including HELLP syndrome), early delivery is recommended. If hypertension persists postpartum, methyldopa, hydralazine or beta-blockers are considered safe when breastfeeding, but again, ACEIs and ARBs are contraindicated. Follow-up is important to avoid future complications, as hypertensive pregnant women have a worse CVD risk profile years after the pregnancy compared with those with normotensive pregnancies; low-dose aspirin is recommended.

Dr Mohamed said that hypo- and hyperthyroidism during pregnancy can lead to several serious adverse outcomes for both fetus and mother. The thyroid gland expands during pregnancy, with 50% increased production of T3 and T4 and iodine requirements, whereas thyroid stimulating hormone (TSH) decreases. Of all healthy non-pregnant women, 2–3% have subclinical hypothyroidism (SCH), so it is important to be aware of this risk. Normalising TSH is important and careful dose adjustment of L-thyroxine (L-T4) is required to maintain TSH levels to meet the increasing demand as pregnancy progresses. Patients who are hypothyroid prepregnancy will require an approximate 25–30% increase in L-T4 dose during pregnancy.

Hyperthyroidism during pregnancy is mainly due to Graves’ disease or gestational (transient) hyperthyroidism. Management of Graves' disease during pregnancy is more complex and antithyroid drug treatment is necessary, though surgery may be required in some women. Gestational (transient) hyperthyroidism occurs in 1–3% of pregnancies and is often related to hyperemesis gravidarum. It is usually limited to the first half of pregnancy; antithyroid drugs are not always indicated, since T4 usually returns to normal; however, short courses of antithyroid drugs may be necessary.

The latest from guidelines on thyroid nodules and cancer

The prevalence of thyroid nodules varies widely across the globe, depending on populations and detection methods, said Nemecio Nicodemus (Philippines), with prevalence of up to 65% in the USA when detected by autopsy. Detection by palpation is less accurate, with nearly 80% of nodules being missed, and nearly 70% being over-diagnosed. For this reason, most international thyroid nodule guidelines recommend thyroid ultrasonography (US) be performed in all patients with known or suspected thyroid nodules, depending on patient risk factors, e.g., family history. Malignancy of thyroid nodules is independent of their size, therefore detection of even the smallest nodules is important. US provides a classification of the nodules, with the most accurate estimate of a malignant nodule being ‘taller than wide’. Elasticity of the nodule can be examined by real-time US elastography, which has a very high negative-predictive value for tumours; for example, a completely soft nodule (elasticity score of 1) is very likely to be benign. Therefore, in these patients, invasive fine-needle aspiration can be avoided.

‘Management of thyroid nodules has been revolutionised in the 21st century by the presence of laser ablation therapies (LAT),’ Dr Nicodemus said. A single LAT can result in significant nodule volume reduction, which persists long term. Radiofrequency ablation is the most effective in reducing thyroid nodule volume and has the greatest effect in those with smaller nodules. Additionally, there are no major complications after either of these minimally invasive techniques, which are also better than the more traditional L-T4 therapy. There is little chance of a benign tumour becoming malignant, so they are removed for symptom relief and/or cosmetic reasons.

Shashank Joshi (India) provided a thorough examination of the ATA 2009 guidelines on management of thyroid cancer. The four main types of thyroid cancer are papillary (PTC), follicular, medullary (MTC) and anaplastic (ATC). The B-RAF gene is a positive predictor of thyroid cancer, especially PTC, and it is important to consider genetic counselling for relatives of patients with genetic familial cancer subtypes who may be at increased risk of developing the disease. Dr Joshi strongly emphasised that thyroid cancer should be treated the same worldwide, by complete thyroidectomy, then radioactive iodine ablation, followed by TSH suppression using L-T4 for life (without inducing thyrotoxicosis) and regular follow-up examinations.

Whether or not to treat SCH was debated by Roberto Mirasol (Philippines) and Manoj Chadha (India). SCH can exist in 4–10% of apparently healthy people, who are at increased risk of CVD and mortality, atherosclerosis and ischaemic heart disease. Professor Mirasol argued that treatment is necessary with L-T4, which has been shown to significantly reduce CV events and mortality, as well as lipids, cognitive function and other psychological and neurological disorders; it has also been shown to prevent progression to overt hypothyroidism. Consensus guidelines recommend treating patients with TSH ≥10 mIU/L, and with 4.5–10 mIU/L only if they have additional risk factors. Women with SCH who are pregnant or planning pregnancy must be treated.

Dr Chadha agreed that treatment should not be started in every patient with SCH, because progression to overt hypothyroidism is very slow (5% of patients/year) and there are conflicting data on the effects on CV health of patients with and without SCH. He cautioned that there are many common symptoms, such as weight gain, lethargy, irregular menstrual cycles, etc, that could be mistaken for hypothyroidism, and so a certain diagnosis is key. Obesity, in particular, is associated with slightly elevated TSH, so this needs to be distinguished from actual SCH. Many people are treated unnecessarily, receive increasing doses of L-T4 with little benefit and end up with iatrogenic thyrotoxicosis. TSH levels also increase naturally with age, and with approximately 5–20% of men and women >55 years having elevated TSH, it is not practical or cost-effective to treat all these people. Dr Chadha advised, ‘don’t be in a rush to treat a number – be sure of what you are trying to treat’. Selected patients do need treatment but he advocated waiting and monitoring the patients instead.

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International conference
Mumbai, India
Jul 4 - 5, 2015
Target audience
General practitioners, junior cardiologists, internists, Healthcare professionals
by Excemed
Cardiometabolic, Endocrinology and metabolism