Piyamitr Sritara

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.).

A Risk Score for Predicting Incident Diabetes in the Thai Population

OBJECTIVE—The objective of this study was to develop and evaluate a risk score to predict people at high risk of diabetes in Thailand. RESEARCH DESIGN AND METHODS—A Thai cohort of 2,677 individuals, aged 35–55 years, without diabetes at baseline, was resurveyed after 12 years. Logistic regression models were used to identify baseline risk factors that predicted the incidence of diabetes; a simple model that included only those risk factors as significant (P < 0.05) when adjusted for each other was developed. The coefficients from this model were transformed into components of a diabetes score. This score was tested in a Thai validation cohort of a different 2,420 individuals. RESULTS—A total of 361 individuals developed type 2 diabetes in the exploratory cohort during the follow-up period. The significant predictive variables in the simple model were age, BMI, waist circumference, hypertension, and history of diabetes in parents or siblings A cutoff score of 6 of 17 produced the optimal sum of sensitivity (77%) and specificity (60%). The area under the receiver-operating characteristic curve (AUC) was 0.74. Adding impaired fasting glucose or impaired glucose tolerance status to the model slightly increased the AUC to 0.78; adding low HDL cholesterol and/or high triglycerides barely improved the model. The validation cohort demonstrated similar results. CONCLUSIONS—A simple diabetes risk score, based on a set of variables not requiring laboratory tests, can be used for early intervention to delay or prevent the disease in Thailand. Adding impaired fasting glucose or impaired glucose tolerance or triglyceride and HDL cholesterol status to this model only modestly improves the predictive ability.

Risk Factors for Development of Decreased Kidney Function in a Southeast Asian Population: A 12-Year Cohort Study

End-stage kidney disease has become an increasing burden in all regions of the world. However, limited epidemiologic data on chronic kidney disease in Southeast Asian populations are available. Therefore, a cohort study over a period of 12 yr (1985 to 1997) in 3499 employees of the Electric Generation Authority of Thailand, aged 35 to 55 yr, was conducted to determine the prevalence of decreased kidney function and risk factors associated with future development of decreased kidney function. The prevalence of decreased kidney function (GFR <60 ml/min) increased from 1.7% (95% confidence interval [CI], 1.3 to 2.1) in 1985 to 6.8% (95% CI, 5.7 to 7.9) in 1997, and the prevalence of elevated serum creatinine was 6.1% (95% CI, 5.3 to 6.9) and 16.9% (95% CI, 15.3 to 18.5) in 1985 and 1997 surveys, respectively. The adjusted odds ratio for future development of decreased kidney function was 2.57 (1.0 to 6.81) for systolic hypertension (>159 mmHg), 1.82 (1.12 to 2.98) for hyperuricemia (>6.29 mg/dl), 1.68 (1.02 to 2.77) for elevated body mass index (>24.9 kg/m(2)) compared with subjects with systolic BP <140 mmHg, serum uric acid <4.5 mg/dl, and body mass index 20.8 to 22.8 kg/m(2). The rising prevalence of decreased kidney function in this population resulted mainly from the increasing prevalence of the risk factors in the population. Screening to detect decreased kidney function and early intervention to modify the associated risk factors should be considered in otherwise healthy individuals. Future studies are also necessary to determine whether implementation of these measures results in a reduction of ESRD incidence in the population.

Cardiovascular risk prediction tools for populations in Asia

Background: Cardiovascular risk equations are traditionally derived from the Framingham Study. The accuracy of this approach in Asian populations, where resources for risk factor measurement may be limited, is unclear. Objective: To compare “low-information” equations (derived using only age, systolic blood pressure, total cholesterol and smoking status) derived from the Framingham Study with those derived from the Asian cohorts, on the accuracy of cardiovascular risk prediction. Design: Separate equations to predict the 8-year risk of a cardiovascular event were derived from Asian and Framingham cohorts. The performance of these equations, and a subsequently “recalibrated” Framingham equation, were evaluated among participants from independent Chinese cohorts. Setting: Six cohort studies from Japan, Korea and Singapore (Asian cohorts); six cohort studies from China; the Framingham Study from the US. Participants: 172 077 participants from the Asian cohorts; 25 682 participants from Chinese cohorts and 6053 participants from the Framingham Study. Main results: In the Chinese cohorts, 542 cardiovascular events occurred during 8 years of follow-up. Both the Asian cohorts and the Framingham equations discriminated cardiovascular risk well in the Chinese cohorts; the area under the receiver–operator characteristic curve was at least 0.75 for men and women. However, the Framingham risk equation systematically overestimated risk in the Chinese cohorts by an average of 276% among men and 102% among women. The corresponding average overestimation using the Asian cohorts equation was 11% and 10%, respectively. Recalibrating the Framingham risk equation using cardiovascular disease incidence from the non-Chinese Asian cohorts led to an overestimation of risk by an average of 4% in women and underestimation of risk by an average of 2% in men. Interpretation: A low-information Framingham cardiovascular risk prediction tool, which, when recalibrated with contemporary data, is likely to estimate future cardiovascular risk with similar accuracy in Asian populations as tools developed from data on local cohorts.

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.

Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry

AIMS Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. METHODS Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. RESULTS A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72-0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73-0.96; P = 0.01). CONCLUSION Among patients with PAD in the REACH registry, statin use was associated with an ∼18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD.

The impact of different GFR estimating equations on the prevalence of CKD and risk groups in a Southeast Asian cohort using the new KDIGO guidelines

BackgroundRecently, the Kidney Disease: Improving Global Outcomes (KDIGO) group recommended that patients with CKD should be assigned to stages and composite relative risk groups according to GFR (G) and proteinuria (A) criteria. Asians have among the highest rates of ESRD in the world, but establishing the prevalence and prognosis CKD is a problem for Asian populations since there is no consensus on the best GFR estimating (eGFR) equation. We studied the effects of the choice of new Asian and Caucasian eGFR equations on CKD prevalence, stage distribution, and risk categorization using the new KDIGO classification.MethodsThe prevalence of CKD and composite relative risk groups defined by eGFR from with Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI); standard (S) or Chinese(C) MDRD; Japanese CKD-EPI (J-EPI), Thai GFR (T-GFR) equations were compared in a Thai cohort (n = 5526)ResultsThere was a 7 fold difference in CKD3-5 prevalence between J-EPI and the other Asian eGFR formulae. CKD3-5 prevalence with S-MDRD and CKD-EPI were 2 - 3 folds higher than T-GFR or C-MDRD. The concordance with CKD-EPI to diagnose CKD3-5 was over 90% for T-GFR or C-MDRD, but they only assigned the same CKD stage in 50% of the time. The choice of equation also caused large variations in each composite risk groups especially those with mildly increased risks. Different equations can lead to a reversal of male: female ratios. The variability of different equations is most apparent in older subjects. Stage G3aA1 increased with age and accounted for a large proportion of the differences in CKD3-5 between CKD-EPI, S-MDRD and C-MDRD.ConclusionsCKD prevalence, sex ratios, and KDIGO composite risk groupings varied widely depending on the equation used. More studies are needed to define the best equation for Asian populations.

Prevalence of the G1691A mutation in the factor V gene (factor V Leiden) and the G20210A prothrombin gene mutation in the Thai population

We investigated the prevalence of a genetic variation in the factor V gene (G1691A Leiden mutation) and the prothrombin gene (G20210A) using polymerase chain reaction techniques in samples from 500 normal Thai population and among 50 unselected Thai patients with an objectively confirmed history of deep venous thrombosis. The prevalence of factor V Leiden and the prothrombin G20210A gene mutation in a group of 500 healthy controls was 0.2% in both groups (allele frequency of 0.1%). Of the 50 adult patients studied, none was a carrier of factor V Leiden or the prothrombin G20210A gene mutation. Our findings confirm that the prevalence of factor V Leiden and prothrombin G20210A gene mutation is lower among Asians than Caucasians and that the distribution of factor V Leiden is similar to that of the prothrombin G20210A variant. The low prevalence of these two mutations can, at least in part, account for the lower frequency of deep venous thrombosis reported in the Thai population. Screening for factor V Leiden and prothrombin gene mutation is of limited benefit and may not be cost‐effective in Thai patients with the first episode of deep venous thrombosis. Am. J. Hematol. 65:119–122, 2000.

A reduced serum level of total osteocalcin in men predicts the development of diabetes in a long‐term follow‐up cohort

Background  Osteocalcin (OC), an osteoblast‐specific protein, has been demonstrated to affect glucose metabolism in both animals and humans. Studies in animals have shown an effect of undercarboxylated OC (ucOC) on beta‐cell proliferation and insulin resistance. It remains unclear whether OC is associated with the future development of diabetes in humans, as well as the relative importance of ucOC vs OC.

Changes in prevalence, awareness, treatment and control of hypertension in Thai population, 2004-2009: Thai National Health Examination Survey III-IV.

Objective: To determine the changes in prevalence, awareness, treatment and control of hypertension and their metabolic risk factors in Thai population between 2004 and 2009. Methods: The Thai National Health Examination Survey (NHES) in 2004 and 2009 data were used. Blood pressure and anthropometric measurements were performed. Prevalence, awareness, treatment and control of hypertension of Thai population aged at least 15 years were calculated. Analyses were weighted to the probability of sampling. Results: The prevalence of hypertension in 2004 and 2009 were relatively stable at approximately 21.0%. There was improvement in awareness of hypertension, from 18.2% for men and 33.0% for women in 2004 to 39.5 and 59.4% in 2009, respectively. The high blood pressure control rates improved from 4.8 to 14.4% for men and from 10.8 to 27.2% for women, respectively (all P < 0.05). The improvement in awareness, treatment and control of hypertension was also observed in individuals with diabetes, obesity and hypercholesterolemia. However, among hypertensive individuals, there were increases in proportions of obesity (BMI ≥ 25 kg/m2) between two surveys: from 39.1 to 47.5% in men and from 54.6 to 62.9% in women, respectively (all P < 0.05). Conclusion: Despite improvement in awareness and control of hypertension in Thai population, a large proportion of hypertensive individuals remained suboptimally controlled. Strengthening measures to control high blood pressure and metabolic risk factors, especially obesity and hypercholesterolemia, in individuals with hypertension are needed.