Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study.

BACKGROUND: Multiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians. METHODS: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score--GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure. RESULTS: Of 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m(2) higher BMI (P = 4.5 × 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P(interaction) = 0.014), CADM2 rs13078960 (P(interaction) = 0.037) and GALNT10 rs7715256 (P(interaction) = 0.048) with physical activity, and PTBP2 rs11165643 (P(interaction) = 0.045), HIP1 rs1167827 (P(interaction) = 0.015), C6orf106 rs205262 (P(interaction) = 0.032) and GRID1 rs7899106 (P(interaction) = 0.043) with smoking on BMI. CONCLUSIONS: Most BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity.

Correlation of cardiac troponin I levels (10 folds upper limit of normal) and extent of coronary artery disease in non-ST elevation myocardial infarction.

OBJECTIVE: To determine the correlation of cardiac troponin I (cTnI) 10 folds upper limit of normal (ULN) and extent of coronary artery disease (CAD) in Non-ST-elevation myocardial infarction (NSTEMI). METHODS: A cross-sectional study was conducted on 230 consecutive NSTEMI patients admitted in Tabba Heart Institute, Karachi between April to December 2008. cTnI was measured using MEIA method. All patients underwent coronary angiography in the index hospitalization. Stenosis > or = 70% in any of the three major epicardial vessels was considered significant CAD. Extent of CAD was defined as significant single, two or three vessel CAD. Chi-square test was applied to test the association between cTnI levels and CAD extent. RESULTS: Out of 230 patients, in 111 patients with cTnI levels < or = 10 folds upper limit of normal (ULN), 25 (22.52%) had single vessel, 40 (36%) had two vessel and 34 (30.6%) had three vessel significant CAD, whereas in 119 patients with cTnI levels > 10 folds ULN, 23 (19.3%) had single vessel, 37 (31.1%) had two vessel and 55 (46.2%) had three vessel significant CAD. The results suggest that there was an insignificant association between the cTnI levels and single vessel, two vessel and the overall CAD extent (p = 0.35, p = 0.21 and p= 0.13 respectively), however there was a statistically significant association between the cTnI levels and three vessel CAD (p < 0.04). CONCLUSION: Higher cTnI levels are associated with an increased proportion of severe three vessel CAD involvement. Prompt identification and referral of this patient subset to early revascularization strategies would improve clinical outcomes.

Correlation of thrombolysis in myocardial infarction (TIMI) risk score with extent of coronary artery disease in patients with acute coronary syndrome.

OBJECTIVE: To determine the correlation of thrombolysis in myocardial infarction (TIMI) risk score with extent of coronary artery disease (CAD) in patients with acute coronary syndrome (ACS). METHODS: We conducted a descriptive study among 200 consecutive patients admitted with ACS at Tabba Heart Institute, Karachi from June to December 2008. The TIMI risk score was stratified on seven standard variables. The extent of CAD was evaluated on angiography and significant CAD was defined as > or =70% stenosis in any one of the three major epicardial vessels. RESULTS: The mean age of the sample was 58.53 +/- 10.64 years. Out of 200 patients, there were 142 (71%) patients with TIMI score < or =4 (low and intermediate TIMI risk score) and 58 (29%) patients with TIMI score >4 (high TIMI risk score). Patients with TIMI score >4 were more likely to have significant three vessel CAD (62%) versus those with TIMI risk score <4 (46.2%), (p < 0.04). CONCLUSION: Patients with high TIMI risk score were more likely to have severe multivessel CAD compared with those with low or intermediate TIMI risk score. Hence, patients with TIMI score >4 should be referred for early invasive coronary evaluation to derive clinical benefit.

Role of serum troponin-I in identifying left ventricular ejection fraction of

OBJECTIVE: To determine the serum levels of troponin-I in identifying left ventricular ejection fraction (LVEF) of 63.5 ng/ml predicted LVEF of 87.5 ng/ml predicted LVEF < 40% with a sensitivity of 86% and specificity of 100%. CONCLUSION: Troponin-I concentration of > 63.5 ng/ml and > 87.5 ng/ml can predict LVEF

Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study.

BACKGROUND: Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain. OBJECTIVES: Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF). METHODS: This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls. RESULTS: Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations. CONCLUSIONS: Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions.