The investigators, recognizing that coronary artery disease (CAD), including acute myocardial infarction (MI), is the leading cause of death worldwide, carried out a genome-wide associational study on Icelandic patients with MI. Initially more than 300,000 single nucleotide polymorphisms (SNPs) were examined for any association with MI. Ultimately, the study enrolled 4587 cases and 12,769 controls. The strongest association with MI was noted with 3 correlated SNPs, all located within a 190-kb linkage disequilibrium block on chromosome 9p21. The association with MI was replicated in case-control sample sets of persons of European descent from 3 US cities. The identified variant was adjacent to the tumor suppressor genes CDKN2A and CDKN2B. It was associated with MI at a high level of significance (P = 1.2 × 10−20). The proteins encoded by these genes have a key role in regulating cell proliferation, cell senescence, and apoptosis—all important features of atherogenesis.
Approximately 21% of individuals in the study population are homozygous for the variant, and it is estimated that their risk of having MI is 1.64-fold greater than for noncarriers. The risk is 2.02-fold greater for early-onset cases. The population-attributable risk was estimated as 21% for MI in general and 31% for early-onset cases. This is the first common variant found to consistently confer a substantial risk of MI, defined as an odds ratio exceeding 1.20, in multiple case-control groups of European descent. The variant poses a substantial risk from a public health viewpoint, but it explains only a small part of familial clustering of the disease and would not yield high linkage scores. The implication is that other susceptibility variants are as yet unidentified. In addition to MI, there is reason to believe that the present variant might increase the risk of CAD in general. Just how genetic variants influence the pathogenesis of MI remains to be clarified.

A common variant on chromosome 9p21 affects the risk of myocardial infarction

Structure, function, and genetics of lipoprotein (a)

South Asia is home to one of the largest population of people with metabolic syndrome (MetS). The prevalence of MetS in South Asians varies according to region, extent of urbanization, lifestyle patterns, and socioeconomic/cultural factors. Recent data show that about one-third of the urban population in large cities in India has the MetS. All classical risk factors comprising the MetS are prevalent in Asian Indians residing in India. The higher risk in this ethnic population necessitated a lowering of the cut-off values of the risk factors to identify and intervene for the MetS to prevent diabetes and cardiovascular disease. Some pharmacological and nonpharmacological interventions are underway in MetS to assess the efficacy in preventing the diabetes and cardiovascular disease in this ethnic population.

Metabolic syndrome in South Asians.

Dyslipidaemia is frequently present in obesity, metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). The predominant features of dyslipidaemia in these disorders include increased flux of free fatty acids (FFA), raised triglyceride (TG) and low high density lipoprotein cholesterol (HDL-C) levels, a predominance of small, dense (atherogenic) low density lipoprotein cholesterol (LDL) particles and raised apolipoprotein (apo) B values Posprandial hyperlipidaemia may also be present. Insulin resistance (IR) appears to play an important role in the pathogenesis of dyslipidaemia in obesity, MetS and T2DM. The cornerstone of treatment of this IR-related dyslipidaemia is lifestyle changes and in diabetic patients, tight glycaemic control. In addition to these measures, recent clinical trials showed benefit with statin treatment. Nevertheless, a substantial percentage of patients treated with statins still experience vascular events. This residual vascular risk needs to be addressed. This review summarizes the effects of hypolipidaemic drug combinations (including statins with cholesterol ester protein inhibitors, niacin, fibrates or fish oil, as well as fibrate-ezetimibe combination) on the residual vascular risk in patients with obesity, MetS or T2DM.

/pdf/dyslipidaemia-of-obesity-metabolic-syndrome-and-type-2-69rkuwqoc8.pdf

Dyslipidaemia of Obesity, Metabolic Syndrome and Type 2 Diabetes Mellitus: the Case for Residual Risk Reduction After Statin Treatment

Objectives
1. To determine the prevalence of Metabolic Syndrome in adults aged 18 years and above in Chandigarh, India. 2. To determine the socio-demographic factors associated with MS. 3. To determine the agreement between IDF (International Diabetes federation definition) and ATP-III (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults criteria).

/pdf/metabolic-syndrome-a-challenging-health-issue-in-highly-11idgbn8tg.pdf

Metabolic syndrome: a challenging health issue in highly urbanized Union Territory of north India.

Asian Indians have a high predisposition to metabolic syndrome (MS) and coronary artery disease (CAD). The present study aimed to estimate MS prevalence in 531 Asian Indian families comprising of 2318 individuals. Anthropometrics and lipid profile were assessed. MS prevalence was estimated using standard Adult Treatment Panel III (ATP-III) and World Health Organisation (WHO) criteria and modified definitions which included lowered cut-offs for waist circumference (WC) (≥90 cm for men and ≥80 cm for women], body mass index (BMI) (≥23 kg/m2) and impaired fasting glucose (IFG) levels. ATP-III criteria identified a significantly higher proportion of people with MS (N = 933; 40.3%) compared with WHO (N = 708; 30.6%; p < 0.0001) while modified ATP-III showed maximum gain in percent prevalence among the revised criteria (17.3%; p = 0.0056). The IDF criteria identified similar proportion of subjects with MS (N = 809; 34.9%) as the revised WHO criteria (N = 792; 34.2%). The number of MS subjects was highest in the 50–59 years age group. MS was diagnosed a decade earlier in unaffected subjects compared with those with CAD/diabetes using the modified MS criteria. WC correlated significantly with BMI and waist–hip ratio (WHR) (p = 0.000). Among MS components, high density lipoprotein cholesterol and BMI contributed significantly in males (71.4% and 85.9%) and females (86.8% and 88.8%), respectively. The higher percentage contribution of WC among males and WHR among females indicates the influence of gynecoid/android pelvis on WHR measures. In conclusion, the revision of definition criteria for MS with lowered cut-offs for WC and BMI is critical for the accurate assessment of MS among Asian Indians.

/pdf/prevalence-and-component-analysis-of-metabolic-syndrome-an-3lkblqxeps.pdf

Prevalence and component analysis of metabolic syndrome: An Indian atherosclerosis research study perspective

Diabetes (DM), hypertension (HTN), and metabolic syndrome (MS) are established cardiovascular risk factors with a complex etiology. The aim of the present study was to estimate the rates of concordance for the above coronary risk factors between siblings in Asian Indian families with premature coronary artery disease (CAD). Spouse concordance rates were used to evaluate the relative contribution of shared genes and lifestyle towards these traits. A total of 508 families comprising of 1250 sib-pairs and 463 corresponding spouse-pairs were analyzed. Concordance rates were manually determined. Plasma lipids were estimated by standard enzymatic assay. The concordance rates among sib-pairs for DM, HTN, and MS was 11% (N = 136), 14% (N = 174), and 23% (N = 287), while the corresponding concordance for spouse-pairs was 2.8% (N = 13), 6.3% (N = 29), and 28.1% (N = 130), respectively. Employing Chi-square test, sib-pairs showed significantly higher concordance for diabetes (p ≤ 0.0001) and hypertension (p < 0.0001) while spouse-pairs had higher concordance for metabolic syndrome (p = 0.033) in our study. These findings suggest a probable dominant genetic component in the causation of DM and HTN and a predominantly nongenetic component for metabolic syndrome among Asian Indians.

Adult nontwin sib concordance rates for type 2 diabetes, hypertension and metabolic syndrome among Asian Indians: The Indian Atherosclerosis Research Study

Coronary artery disease (CAD) is a multifactorial disease, and family history is the best available tool to assess gene-environment interaction. This study addressed the heritability of quantitative traits, namely lipid, coagulation/fibrinolysis and pro-inflammatory markers in the ongoing family-based Indian Atherosclerosis Research Study and assessed the effect of the type/lineage of CAD family history on inheritance patterns in the high-risk Indian population. A total of 518 families comprising 2,305 individuals were recruited in phase I of the IARS; of these, 1,195 individuals from 220 families were included in the heritability analysis. With the exception of leptin, all phenotypes exhibited significant age- and sex-adjusted heritability (p < 0.0001). Amongst all the phenotypes analysed after adjustment for confounding factors, the significantly higher heritability estimates of triglycerides (0.53, p < 0.0001), lipoprotein (a) (0.83, p < 0.0001) and interleukin-6 (0.46, p < 0.0001) with low spouse pair correlations identifies them as possible CAD risk factors. Families with parental history of CAD had onset of CAD symptoms at much younger ages with significantly higher heritability of proinflammatory markers, whereas in families with sibling history of CAD, more risk factors were present at significantly higher levels. Triglycerides, lipoprotein (a) and interleukin-6 appear to be promising atherothrombotic candidate phenotypes in this population. Genes controlling these phenotypes are possible candidate genes linked with CAD. An informed understanding and incorporation of 'family history' as a screening tool may help in the prevention and pre-emption of CAD.

Genetic contribution to variation in atherothrombotic phenotypes in the Asian Indian population - the Indian atherosclerosis research study.

Introduction: Metabolic syndrome (MS) and its co-morbidities including coronary artery disease (CAD) are highly prevalent among Asian Indians and share common risk factors. The aim of this study was to look for an association of atherothrombotic biomarkers with MS among Asian Indian families with premature CAD. Material and methods: MS subjects were identified employing standard and adapted definitions. Lipids were measured on an auto-analyzer while the non- lipid markers were assayed by the ELISA method. Standard and modified MS definitions were applied to 2316 individuals from 531 families. Results: The ATP III criteria identified a significantly larger proportion of people with MS (N=933, P<0.0001) as compared to WHO (N=708) while maximum gain was seen in the modified MS criteria group (MSmod, N=1333), which included a lowered cut-off for waist circumference (WC) and body mass index (BMI) (P=0.0056). Atherothrombotic blood phenotypes, namely TC, TG, Ox-LDL, ApoB100, fibrinogen, FVII.c, PAI-1, IL-6, hsCRP, P-selectin, sICAM and leptin, were significantly elevated, while HDL-c and adiponectin were lower in the MSmod group (P<0.01). All the above phenotypes correlated significantly with WC and BMI but not with waist-hip ratio. Conlusions: In conclusion, an association of the atherothrombotic blood phenotypes with MS indicates the propensity of people with MS to develop CAD, thereby emphasizing the need for early and precise diagnosis of MS among Asian Indians.

/pdf/association-of-metabolic-syndrome-with-atherothrombotic-1aizrn6v3v.pdf

Association of metabolic syndrome with atherothrombotic blood phenotypes in Asian Indian families with premature coronary artery disease

https://www.termedia.pl/Journal/-19/pdf-10665-1?filename=association of metabolic.pdf

Clinical research Association of metabolic syndrome with atherothrombotic blood phenotypes in Asian Indian families with premature coronary artery disease

Saikat Kanjilal

Papers

Prevalence and component analysis of metabolic syndrome: An Indian atherosclerosis research study perspective

Adult nontwin sib concordance rates for type 2 diabetes, hypertension and metabolic syndrome among Asian Indians: The Indian Atherosclerosis Research Study

Genetic contribution to variation in atherothrombotic phenotypes in the Asian Indian population - the Indian atherosclerosis research study.

Association of metabolic syndrome with atherothrombotic blood phenotypes in Asian Indian families with premature coronary artery disease

Clinical research Association of metabolic syndrome with atherothrombotic blood phenotypes in Asian Indian families with premature coronary artery disease