Seven Functional Polymorphisms in the CETP Gene and Myocardial Infarction Risk: A Meta-Analysis and Meta-Regression

Biomarkers in the triage of chest pain: are we making progress?

A prospective study of TaqIB polymorphism in the gene coding for cholesteryl ester transfer protein and risk of myocardial infarction in middle-aged men

Current guideline statements for primary and secondary prevention of cardiovascular disease (CVD) rely on estimates of absolute risk of coronary events. For example, the American Heart Association guidelines on primary prevention state that persons with ≥10% risk over 10 years of myocardial infarction (MI) or coronary death should be considered for antiplatelet therapy with aspirin.1 Similarly, the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines2 state that target low-density lipoprotein level should be based on projected absolute risk of future coronary events rather than on presence or absence of specific risk factors. These guidelines state that patients at high risk of MI and coronary death, defined as an absolute 10-year risk of ≥20%, should have a target low-density lipoprotein level <100 mg/dL and should receive statin therapy if needed to achieve this goal. Stroke, however, is not included as one of the outcomes contributing to these absolute risk levels. Included in the group of patients with elevated risk, moreover, are those who already have ischemic heart disease, as well as patients deemed to be “coronary heart disease (CHD) risk equivalents,” indicating those at the same elevated risk as patients with ischemic heart disease. CHD risk equivalents include patients with diabetes mellitus, those with multiple risk factors that put them at elevated risk based on calculation of their Framingham Score, and patients with “other forms of symptomatic atherosclerotic disease.” The latter group is further defined to include those with peripheral arterial disease (PAD), abdominal aortic aneurysm (AAA), and carotid artery disease. The category of “risk equivalents” in the ATP III guidelines, however, does not include the vast majority (≈80%3) of ischemic stroke patients without carotid artery disease as cause of their stroke. Ischemic stroke is therefore notably excluded from the list of outcomes contributing to …

Common VKORC1 variants are not associated with arterial or venous thrombosis.

Common genomic sequence variation of the prothrombin gene and risk of non-fatal myocardial infarction in white women

Relation of Increased Prebeta-1 High-Density Lipoprotein Levels to Risk of Coronary Heart Disease

Genetic variation in the APOC3 and APOA5 genes has been associated with plasma triglyceride concentrations and may affect the risk of myocardial infarction (MI). To assess whether APOC3/A5 haplotypes are associated with risk of MI, we examined three single-nucleotide polymorphisms (SNPs) in APOC3 (3238C>G, -455T>C, and -482C>T) and six SNPs in the APOA5 gene (-1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, c.553G>T, and c.1259T>C) in incident cases (n = 1,703) of a first nonfatal MI matched for gender, age, and area of residence with population-based controls (n = 1,703). Conditional logistic regression models, adjusted for potential environmental confounders, were used for analysis. The common APOC3*222 haplotype was more frequent in cases than in controls (17.4% and 13.7%, respectively, P < 0.001) and was associated with increased risk of MI [odds ratio (OR) = 1.27; 95% confidence interval (95% CI), 1.09, 1.48] compared with APOC3*111 wild-type haplotype. This association was independent of the APOA5 SNPs. Although the APOC3 3238G, APOA5 -1131C, APOA5 c.-3G, and APOA5 c.1259C alleles were associated with higher triglyceride plasma concentrations, these effects could not explain the associations with MI in this population. In summary, this study supports the hypothesis that haplotypes in the APOC3 gene but not in the APOA5 gene increase susceptibility to MI.

The −629C>A polymorphism in the CETP gene does not explain the association of TaqIB polymorphism with risk and age of myocardial infarction in Icelandic men

Plasma brain-type natriuretic peptide (BNP) and amino-terminal proBNP (NTproBNP) provide prognostic information on cardiovascular morbidity and mortality beyond that provided by standard risk factors. Clinical applications of B-type peptides under ongoing research include their use in diagnosing acute heart failure (HF), in risk stratification in both acute and established HF, in acute coronary syndromes (ACS), in asymptomatic populations at cardiovascular risk (older adults and people with hypertension), and as part of a screening strategy for detection of left ventricular impairment and prediction of cardiovascular risk in the general population.1,2 In this issue of Circulation , Campbell and colleagues3 assess the ability of NTproBNP to predict myocardial infarction (MI) in subjects who have experienced a cerebrovascular event. NTproBNP (reflecting cardiac distension) is compared with C-reactive protein (a systemic marker of inflammation) and renin (a marker of sodium status regulated by renal perfusion and delivery of sodium to the renal glomerulus). See p 110 The nested case-control study is from the 6105 participants in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of converting enzyme inhibitor–based therapy in patients with previous cerebrovascular events.4 Within PROGRESS, 206 subjects incurred an MI during 3.9 years of follow-up. The investigators matched those incurring an MI with control PROGRESS patients avoiding MI from time of randomization to time of case ascertainment. Cases and controls were matched for age, gender, treatment allocation, region, and cerebrovascular qualifying event. The form of matching meant that individual patients may have been controls initially and subsequently became cases on incurring an MI during further follow-up. Matching in this fashion may confuse the interpretation of the nonconditioned analysis of baseline variables. Comparing the 206 cases with 412 controls at randomization, the investigators report that in addition to higher systolic blood pressure, more frequent known coronary disease, …

Purpose of the studyGenome-wide association studies have revealed an association of ADAMTS7 polymorphisms with the risk of cardiovascular diseases. Nonetheless, the role of ADAMTS7 polymorphisms on myocardial infarction (MI) risk...

The Decanucleotide Insertion/Deletion Polymorphism in the Promoter Region of the Coagulation Factor VII Gene and the Risk of Familial Myocardial Infarction

This meta-analysis was undertaken in an attempt to understand the relationships of functional polymorphisms in the SELE and SELP genes to myocardial infarction (MI) risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before March 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios with 95 % confidence intervals were calculated. The effect of SELE and SELP genetic polymorphisms on the pathogenesis of MI was investigated in this meta-analysis with a total of ten case–control studies, including 2,696 MI patients and 4,724 healthy subjects. Eight single nucleotide polymorphisms were assessed, including polymorphisms 98G/T, 128S/R and 561A/C in the SELE gene, and polymorphisms 715T/P, 599V/L, 290S/N, 562N/D and 2123G/C in the SELP gene. The results of our meta-analysis suggested that SELE genetic polymorphisms might be correlated with an increased risk of MI, especially for 128S/R and 561A/C polymorphisms. A subgroup analysis by ethnicity was conducted to investigate its effects on susceptibility to MI. The results revealed positive significant correlations between SELE genetic polymorphisms and the risk of MI among Asians, but not among Caucasians (all P > 0.05). Nevertheless, no significantly correlations were found between SELP genetic polymorphisms and MI risk (all P > 0.05). In the subgroup analysis by ethnicity, we also did not observe significant associations between SELP genetic polymorphisms and MI risks among both Asians and Caucasians (all P > 0.05). The current meta-analysis suggests that SELE genetic polymorphisms may contribute to the development of MI, especially for the 128S/R and 561A/C polymorphisms among Asians. However, SELP genetic polymorphisms may not be important risk factors in MI.

This meta-analysis was undertaken in an attempt to understand the relationships of functional polymorphisms in the SELE and SELP genes to myocardial infarction (MI) risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before March 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios with 95 % confidence intervals were calculated. The effect of SELE and SELP genetic polymorphisms on the pathogenesis of MI was investigated in this meta-analysis with a total of ten case-control studies, including 2,696 MI patients and 4,724 healthy subjects. Eight single nucleotide polymorphisms were assessed, including polymorphisms 98G/T, 128S/R and 561A/C in the SELE gene, and polymorphisms 715T/P, 599V/L, 290S/N, 562N/D and 2123G/C in the SELP gene. The results of our meta-analysis suggested that SELE genetic polymorphisms might be correlated with an increased risk of MI, especially for 128S/R and 561A/C polymorphisms. A subgroup analysis by ethnicity was conducted to investigate its effects on susceptibility to MI. The results revealed positive significant correlations between SELE genetic polymorphisms and the risk of MI among Asians, but not among Caucasians (all P > 0.05). Nevertheless, no significantly correlations were found between SELP genetic polymorphisms and MI risk (all P > 0.05). In the subgroup analysis by ethnicity, we also did not observe significant associations between SELP genetic polymorphisms and MI risks among both Asians and Caucasians (all P > 0.05). The current meta-analysis suggests that SELE genetic polymorphisms may contribute to the development of MI, especially for the 128S/R and 561A/C polymorphisms among Asians. However, SELP genetic polymorphisms may not be important risk factors in MI.

BackgroundGenetic variation at 1p13 modulates serum lipid levels and the risk of coronary heart disease through the regulation of serum lipid levels. Here we investigate if the interaction between genetic variants at 1p13 and serum lipid levels affects the risk of non-fatal myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP), a large population based case control study.MethodsIn the present study only non fatal MI cases (n = 1213, men/women: 852/361) and controls (n = 1516, men/women =1054/507) matched by age, sex and residential area, were included. Three SNPs 12740374 G/T, rs599839A/G and rs646776T/C mapping at 1p13 were analysed for association with serum lipid levels and the risk of MI by a weighted least square regression and logistic regression analyses, respectively. To analyse the effect of the interaction between genetic variants and serum lipid levels on the risk of MI, we applied the biological model of interaction that estimates the difference in risk, expressed as OR (95%CI), observed in the presence and in the absence of both exposures. One derived measure is the Synergy index (S) and 95%CI, where S > 1 indicates synergy and S < 1 antagonism between the two interaction terms.ResultsRs12740374G/T and rs646776T/C were in strong linkage disequilibrium (LD) (r2 = 0.99), therefore only rs599839A/G and rs646776 were included in the analysis. Consistently with published data, presence of the rare genotypes was associated with reduced total-, LDL-cholesterol and ApoB serum levels (all p < 0.05) as compared to the reference genotype, but was not associated with the risk of MI.However, the increased risk of MI observed in individual exposed to high (≥75th percentile) serum lipid levels was offset in subjects carrying the rare alleles G and C. In particular, the risk of MI associated with high ApoB serum levels OR (95%CI) 2.27 (1.86-2.77) was reduced to 1.76 (1.33-2.34) in the presence of the G allele at rs599839 with an S of 0.47 (0.20-0.90).ConclusionsThese results indicate that an antagonism between ApoB serum levels and genetic variants at 1p13 contributes to reduce the risk of non-fatal MI in the presence of high ApoB serum levels.

From Creatine Kinase-MB to Troponin