Rody G. Sy

Darapladib for Preventing Ischemic Events in Stable Coronary Heart Disease

BACKGROUND Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. METHODS In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). RESULTS During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). CONCLUSIONS In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

An International Atherosclerosis Society Position Paper: Global recommendations for the management of dyslipidemia

An international panel of the International Atherosclerosis Society has developed a new set of recommendations for management of dyslipidemia. The panel identifies non-high density lipoprotein cholesterol (non-HDL-C) as the major atherogenic lipoprotein. Primary and secondary prevention are considered separately. Optimal levels for atherogenic lipoproteins are derived for the two forms of prevention. For primary prevention, the recommendations emphasize lifestyle therapies to reduce atherogenic lipoproteins; drug therapy is reserved for higher risk subjects. Risk assessment is based on estimation of lifetime risk according to differences in baseline population risk in different nations or regions. Secondary prevention emphasizes use of cholesterol-lowering drugs to attain optimal levels of atherogenic lipoproteins.

The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients

Despite current standards of care aimed at achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure and glycaemia, dyslipidaemic patients remain at high residual risk of vascular events. Atherogenic dyslipidaemia, specifically elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease, type 2 diabetes, obesity or metabolic syndrome and is associated with macrovascular and microvascular residual risk. The Residual Risk Reduction Initiative (R3I) was established to address this important issue. This position paper aims to highlight evidence that atherogenic dyslipidaemia contributes to residual macrovascular risk and microvascular complications despite current standards of care for dyslipidaemia and diabetes, and to recommend therapeutic intervention for reducing this, supported by evidence and expert consensus. Lifestyle modification is an important first step. Additionally, pharmacotherapy is often required. Adding niacin, a fibrate or omega-3 fatty acids to statin therapy improves achievement of all lipid risk factors. Outcomes studies are evaluating whether these strategies translate to greater clinical benefit than statin therapy alone. In conclusion, the R3i highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual vascular risk among dyslipidaemic patients who are treated in accordance with current standards of care.

Residual macrovascular risk in 2013: what have we learned?

Cardiovascular disease poses a major challenge for the 21st century, exacerbated by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best standards of care, including high-dose statins, can ameliorate the risk of vascular complications, patients remain at high risk of cardiovascular events. The Residual Risk Reduction Initiative (R3i) has previously highlighted atherogenic dyslipidaemia, defined as the imbalance between proatherogenic triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an important modifiable contributor to lipid-related residual cardiovascular risk, especially in insulin-resistant conditions. As part of its mission to improve awareness and clinical management of atherogenic dyslipidaemia, the R3i has identified three key priorities for action: i) to improve recognition of atherogenic dyslipidaemia in patients at high cardiometabolic risk with or without diabetes; ii) to improve implementation and adherence to guideline-based therapies; and iii) to improve therapeutic strategies for managing atherogenic dyslipidaemia. The R3i believes that monitoring of non-HDL cholesterol provides a simple, practical tool for treatment decisions regarding the management of lipid-related residual cardiovascular risk. Addition of a fibrate, niacin (North and South America), omega-3 fatty acids or ezetimibe are all options for combination with a statin to further reduce non-HDL cholesterol, although lacking in hard evidence for cardiovascular outcome benefits. Several emerging treatments may offer promise. These include the next generation peroxisome proliferator-activated receptorα agonists, cholesteryl ester transfer protein inhibitors and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin type 9. However, long-term outcomes and safety data are clearly needed. In conclusion, the R3i believes that ongoing trials with these novel treatments may help to define the optimal management of atherogenic dyslipidaemia to reduce the clinical and socioeconomic burden of residual cardiovascular risk.

Metabolic syndrome in the Philippine general population: prevalence and risk for atherosclerotic cardiovascular disease and diabetes mellitus

The objectives of this study were to determine the prevalence of metabolic syndrome (MS) and its component risk factors among Filipinos using three sets of criteria and to evaluate the association between MS and atherosclerotic cardiovascular disease and diabetes mellitus. The study utilised a multi-staged cluster sampling design. The prevalence of MS was found to be 11.9% by National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) criteria, 14.5% by International Diabetes Federation (IDF) criteria and 18.6% by NCEP/ATP III criteria modified by the American Heart Association/National Heart, Lung and Blood Institute (NCEP/ATP III-AHA/NHLBI) criteria. Low levels of high-density lipoprotein cholesterol (HDL-C) occurred in 60.2% of men and 80.9% of women. Abdominal obesity was noted in 17.7% of men and 35.1% of women. Blood pressure (BP) ≥ 130/85 mmHg was seen in 33.3%, hypertriglyceridaemia in 20.6% and fasting blood sugar ≥ 100 mg/dL (5.55 mmol/L) in 7.1%. Age-adjusted odds ratios showed that MS, by all three definitions, predisposed an individual to diabetes mellitus (DM) and stroke while MS by the IDF definition predisposed an individual to myocardial infarction (MI). Individuals with MS did not have a significant predisposition to angina and peripheral artery disease (PAD). Thus, the metabolic syndrome is common in Filipinos, with low HDL-C as the most prevalent component. The metabolic syndrome predisposes to diabetes mellitus and stroke, with a tendency to MI using the IDF criteria.

The incidence of type 2 diabetes mellitus in the Philippines: A 9-year cohort study

AIMS Currently, there are no available data on the incidence of type 2 diabetes mellitus (T2DM) in the Philippines. A cohort derived from a national study population (FNRI-NNS, 1998) was revisited after 9 years to yield valuable data on glucose homeostasis among Filipinos. METHODS Six out of 13 national regions were included in the cohort. There were 1749 out of 2122 respondents (82.4%). 1386 (95.9%) consented to a fasting blood glucose (FBG) test, and 1275 (88.2%) completed the 2h post-glucose (2HPG) load determination using whole blood capillary samples. RESULTS We observed a significant increase of mean FBGs (91.5mg/dL to 103.3mg/dL) from 1998 to 2007. The 9-year incidence of T2DM was 16.3%. The prevalence of T2DM was 28.0%. The prevalence of pre-diabetes, i.e., combined impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) was 31.3%; IFG was 17.5% and IGT was 23.9%. CONCLUSIONS The study shows the alarming growth of diabetes, IFG, and IGT in our country that warrants early aggressive intervention for prevention and management. We encourage the use of 2h post-glucose load aside from FBG in screening for true diabetics, IFGs, and IGTs.

Serum cholesterol and coronary artery disease in populations with low cholesterol levels: The Indian paradox

OBJECTIVE To examine the relation between serum cholesterol and coronary artery disease prevalence below the range of cholesterol values generally observed in developed countries. DESIGN AND SETTING Cross-sectional survey of two randomly selected villages from Moradabad district and 20 randomly selected streets in the city of Moradabad. SUBJECTS AND METHODS 3575 Indians, aged 25-64 years including 1769 rural (894 men, 875 women) and 1806 urban (904 men, 902 women) subjects. The survey methods were questionnaires, physical examination and electrocardiography. RESULTS The overall prevalences of coronary artery disease were 9.0% in urban and 3.3% in rural subjects and the prevalences were significantly (P<0.001) higher in men compared to women in both urban (11.0 vs. 6.9%) and rural subjects (3.9 vs. 2.6%). The average serum cholesterol concentrations were 4.91 mmol/l in urban and 4.22 mmol/l in rural subjects without any sex differences. The prevalences of coronary artery disease were significantly higher among subjects with low and high serum cholesterol concentration compared to subjects with very low cholesterol and showed a positive relation with serum cholesterol within the range of serum cholesterol level studied in both rural and urban in both sexes. Among subjects with low serum cholesterol, there was a higher prevalence of coronary risk factors, hypertension, diabetes, obesity and sedentary lifestyle. Serum cholesterol level showed a significant positive relation with low density lipoprotein cholesterol and triglycerides in all the four subgroups. Logistic regression analysis after pooling of data from both rural and urban, with adjustment of age showed that low serum cholesterol level (odds ratio: men 0.96, women 0.91) had a positive strong relation with coronary artery disease and there was no evidence of any threshold. Diabetes mellitus (men 0.73, women 0.74) and sedentary lifestyle (men 0.86, women 0.74) were significant risk factors of coronary disease in both sexes. Hypertension (men 0.82, women 0.64) and smoking (men 0.81, women 0.52) were weakly associated with coronary disease in men but not in women. CONCLUSION Serum cholesterol level was directly related to prevalence of coronary artery disease even in those with low cholesterol concentration (<5.18 mmol/l). It is possible that some Indian populations may benefit by increased physical activity and decline in serum cholesterol below the range of desired serum cholesterol in developed countries.

Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease

Assess the risk of ischaemic events associated with psychosocial stress in patients with stable coronary heart disease (CHD).

Efficacy and tolerability of amlodipine in the general practice treatment of essential hypertension in an asian multinational population.

AbstractObjective: To evaluate the efficacy and tolerability of once-daily amlodipine (Pfizer Pharmaceuticals Inc.) alone or in combination with other antihypertensive drugs in an Asian population with essential hypertension. Patients: An open study was undertaken in 165 male and 158 female patients with uncomplicated hypertension (diastolic blood pressure 95 to 115mm Hg). Patients were recruited from 41 general practices in seven Asian countries and received amlodipine 5mg daily for 4 weeks and then 10mg once daily for a further 4 weeks if the target diastolic blood pressure of ≤90mm Hg or a reduction from baseline by ≥10mm Hg had not been achieved. This one-step dose-adjustment period was followed by a 4-week maintenance period on a constant dose. Amlodipine was the sole medication in 284 patients and was added to other antihypertensive drugs in 39 patients uncontrolled on previous medication. Results: 263 patients, including 131 males, were evaluated for efficacy at the final treatment visit. 166 (63%) patients achieved the target reduction in diastolic blood pressure with amlodipine 5mg once daily, while 84 patients achieved the target reduction with 10mg once daily. Systolic and diastolic blood pressure reductions were similar irrespective of gender or age, and there were no significant changes in resting heart rate in any subgroup. In 68 patients who underwent ambulatory monitoring, the systolic and diastolic blood pressures were reduced by once-daily amlodipine throughout the 24-hour period without change in the intrinsic circadian pattern. Amlodipine was well tolerated in all patient subgroups; adverse events accounted for less than 1% of treatment discontinuations, and there were no hospitalisations or deaths during the study. Investigators rated both the antihypertensive efficacy and tolerability of amlodipine as excellent or good in 93% of patients. Conclusion: In 263 Asian patients with uncomplicated essential hypertension treated in general practice, once-daily amlodipine in a dose of 5 or 10mg provided significant antihypertensive efficacy either as monotherapy or in combination with other antihypertensive drugs while maintaining a favourable tolerability profile regardless of gender or age.

Cohort Profile: LIFE course study in CARdiovascular disease Epidemiology (LIFECARE)

Cohort Profile: LIFE course study in CARdiovascular disease Epidemiology (LIFECARE) Mahham Shafiq, Alan Yean Yip Fong, E Shyong Tai, Ei Ei Khaing Nang, Hwee Lin Wee, John Adam, Mark Woodward, Piyamitr Sritara, Richie Poulton, Rody Sy and Kavita Venkataraman* Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Clinical Research Centre (CRC), Sarawak General Hospital, Kuching, Malaysia, Department of Cardiology, Sarawak General Hospital Heart Centre, Kota, Samarahan, Malaysia, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Department of Internal Medicine, Jaury Jusuf Putera Hospital, Makassar, Indonesia, Faculty of Medicine, University of Hasanuddin, Makassar, Indonesia, Professorial Advisory Unit, George Institute for Global Health and Faculty of Medicine, University of New South Wales, Sydney, Australia, Medical Sciences Division, University of Oxford, Oxford, UK, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, Department of Psychology, University of Otago, Otago, New Zealand and Department of Internal Medicine, College of Medicine, University of the Philippines, Quezon City, Philippines