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Lack of association of chromosome 9p21.3 genotype with cardiovascular structure and function in persons with stable coronary artery disease: The Heart and Soul Study.

ABSTRACT: Recent large-scale genome-wide association studies have identified a novel susceptibility locus on chromosome 9p21.3 that contributes a significant attributable risk for myocardial infarction. The phenotypic significance of this locus in patients with established coronary artery disease is unknown. We sought to compare cardiovascular structure and function in carriers and non-carriers of the risk haplotype in a cross-sectional study.We genotyped the rs1333049 single-nucleotide polymorphism in 593 Caucasian individuals with stable coronary artery disease recruited in the Heart and Soul Study. All study subjects underwent resting and stress echocardiography. Linear and logistic regression models were used to examine the association between the rs1333049 polymorphism and echocardiographic parameters of cardiovascular structure and function.There was no association between rs1333049 genotype and echocardiographic phenotype (left ventricular hypertrophy, systolic dysfunction, diastolic dysfunction, inducible ischemia, exercise capacity, mitral annular calcification, and aortic plaque).In a cross-sectional study of individuals with stable coronary artery disease, there was no association of chromosome 9p21.3 genotype with cardiovascular structure and function.

SUBMITTER: Farzaneh-Far R

PROVIDER: S-EPMC2717182 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Lack of association of chromosome 9p21.3 genotype with cardiovascular structure and function in persons with stable coronary artery disease: The Heart and Soul Study.

Farzaneh-Far Ramin R Na Beeya B Schiller Nelson B NB Whooley Mary A MA

Atherosclerosis 20081230 2

<h4>Objective</h4>Recent large-scale genome-wide association studies have identified a novel susceptibility locus on chromosome 9p21.3 that contributes a significant attributable risk for myocardial infarction. The phenotypic significance of this locus in patients with established coronary artery disease is unknown. We sought to compare cardiovascular structure and function in carriers and non-carriers of the risk haplotype in a cross-sectional study.<h4>Methods</h4>We genotyped the rs1333049 si ...[more]

PMID: 19171343

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Project description:The aim of the present study was to investigate the susceptibility of two coronary artery disease (CAD)-associated single nucleotide polymorphisms on 9p21 (rs1333049 and rs10757278) to myocardial infarction (MI) in a primary (stratification of high risk group for MI) and secondary prevention setting. The prospective observational study included 500 patients with MI [411 males (82.2%) and 89 females (17.8%)] under 65 years. The risk of MI for carriers of the homozygous CC genotype of rs1333049 and homozygous GG genotype of rs10757278 was 1.77 [95% confidence interval (CI): 1.36-2.37], and 1.70 (95% CI: 1.24-2.32) respectively. The risk of MI for heterozygous allele carriers was slightly lower. Specifically, the risk of MI was 1.58 (95% CI: 1.18-2.11) for both heterozygous and homozygous carriers of the rs1333049 C allele, and 1.36 (95% CI: 1.01-1.83) for the carriers of the rs10757278 G allele. A logistic regression model including sex, age, presence of excess weight or obesity, abdominal obesity, diabetes mellitus, arterial hypertension, hypercholesterolemia, positive family history and smoking status parameters revealed that rs1333049 CC genotype was an independent predictive factor of myocardial infraction [OR=1.71 (95% CI: 1.16-2.52), P=0.006]. Patients who underwent percutaneous coronary intervention (PCI) during index hospitalization and patients who did not receive PCI were followed up for two years after discharge. Compared with patients with MI who underwent PCI, the risk of recurrent acute coronary syndrome (re-ACS) was higher among rs1333049 C allele carriers who did not receive PCI during index hospitalization. One year after MI, the OR of re-ACS was 4.91 (95% CI: 1.45-16.66), while two years after MI, OR was 3.77 (95% CI: 1.50-9.52) in those patients who did not receive PCI during index hospitalization. There was no statistically significant association between polymorphic variants of rs1333049 and MI follow-up outcomes in patients who underwent PCI. The present study indicated clinical utility of 9p21.3 genotyping to predict the outcomes for patients with MI without PCI. Due to the small sample size, this association study forms basis for larger, nationwide studies investigating clinical applications of genetic data.

Project description:BackgroundGrowth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers.MethodsA prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death.ResultsBaseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years.ConclusionsHigher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Dataset Information

Lack of association of chromosome 9p21.3 genotype with cardiovascular structure and function in persons with stable coronary artery disease: The Heart and Soul Study.

Publications

Lack of association of chromosome 9p21.3 genotype with cardiovascular structure and function in persons with stable coronary artery disease: The Heart and Soul Study.

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