Abdus Samad

Association of the 9p21.3 Locus With Risk of First-Ever Myocardial Infarction in Pakistanis Case-Control Study in South Asia and Updated Meta-Analysis of Europeans

Objective—To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. Methods and Results—A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10−2) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2×10−3) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1×10−3 for heterogeneity). Meta-analyses of 23 variants, in up to 38 250 cases and 84 820 controls generally yielded higher values in Europeans than in Pakistanis. Conclusion—To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.

Genetic determinants of major blood lipids in Pakistanis compared with Europeans.

Background—Evidence is sparse about the genetic determinants of major lipids in Pakistanis. Methods and Results—Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P<10−13), APOA5/ZNF259 (rs651821; P<10−13) and GCKR (rs1260326; P<10−13) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10−9). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10−4). Conclusions—Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.

Noninvasive therapy for the management of patients with advanced coronary artery disease.

ObjectivesTo determine the efficacy of cardiac shock wave therapy (CSWT) in the management of patients with end-stage coronary artery disease (CAD). IntroductionPatients with end-stage CAD have symptoms such as recurrent angina, breathlessness, and other debilitating conditions. End-stage CAD patients are usually those who have angina pectoris following a coronary artery bypass surgery or a percutaneous coronary intervention. These patients are refractory to optimal medical therapy and not fit for a redo procedure, and are often termed as ‘no option’ patients. MethodsWe carried out a prospective cohort study to examine the effects of CSWT application in patients who had end-stage CAD and were no option patients. Characteristics such as angina class scores and functional status scores among cases (patients with end-stage CAD who received CSWT) and controls (patients with end-stage CAD who did not receive CSWT) were compared at baseline and at 6 months after CSWT therapy. ResultsThere were 43 patients in the case group and 43 patients in the control group. The mean age of the patients was 58.7±9.5 years in the case group and 56.6±11.6 years in the control group. Other characteristics such as the prevalence of diabetes, hypertension, coronary artery bypass graft and percutaneous coronary intervention were similar in both groups. Clinical results showed a significant improvement in exercise time between the cases and the controls 6 months after treatment with CSWT (20.1±15.7 min in cases vs. 10.1±4.2 min in controls; P<0.0001), and symptomatic improvement in the CCS class scores (1.95±0.80 in cases and 2.63±0.69 in controls; P<0.0001) and NYHA class scores (1.95±0.80 in cases vs. 2.48±0.59 in controls; P<0.001). In the control group, there was no improvement in angina class, functional class and exercise time. ConclusionThe present study shows that CSWT application to the ischemic myocardium in patients with refractory angina pectoris improved symptoms and reduced the severity of ischemic areas at 6 months after CSWT treatment compared with the baseline. No side effects were observed with this therapy.