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Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3.

ABSTRACT: BACKGROUND:Although genetic variation at chromosome 9p21.3 is associated with incident cardiovascular disease, it is unclear whether screening for this polymorphism improves risk prediction. OBJECTIVE:To determine whether knowledge of variation at chromosome 9p21.3 provides predictive information beyond that from other readily available risk factors. DESIGN:Prospective cohort study. SETTING:United States. PATIENTS:22 129 female white health professionals participating in the Women's Genome Health Study, initially without any major chronic disease, who were prospectively followed over a median of 10.2 years for incident cardiovascular disease. MEASUREMENTS:Polymorphism at rs10757274 in chromosome 9p21.3 and additional cardiovascular disease risk factors (blood pressure, smoking status, diabetes, blood levels of cholesterol, high-sensitivity C-reactive protein, and family history of premature myocardial infarction). RESULTS:Polymorphism at rs10757274 was associated with an adjusted hazard ratio for incident cardiovascular disease of 1.25 (95% CI, 1.04 to 1.51) for the AG genotype and 1.32 (CI, 1.07 to 1.63) for the GG genotype. However, the addition of the genotype to a prediction model based on traditional risk factors, high-sensitivity C-reactive protein, and family history of premature myocardial infarction had no effect on model discrimination as measured by the c-index (0.807 to 0.809) and did not improve the Net Reclassification Improvement score (-0.2%; P = 0.59) or the Integrated Discrimination Improvement score (0.0; P = 0.18). LIMITATION:Study participants were all white women. CONCLUSION:In this large prospective cohort of white women, genetic variation in chromosome 9p21.3 was associated with incident cardiovascular disease but did not improve on the discrimination or classification of predicted risk achieved with traditional risk factors, high-sensitivity C-reactive protein, and family history of premature myocardial infarction.

SUBMITTER: Paynter NP

PROVIDER: S-EPMC2629586 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3.

Paynter Nina P NP Chasman Daniel I DI Buring Julie E JE Shiffman Dov D Cook Nancy R NR Ridker Paul M PM

Annals of internal medicine 20090101 2

<h4>Background</h4>Although genetic variation at chromosome 9p21.3 is associated with incident cardiovascular disease, it is unclear whether screening for this polymorphism improves risk prediction.<h4>Objective</h4>To determine whether knowledge of variation at chromosome 9p21.3 provides predictive information beyond that from other readily available risk factors.<h4>Design</h4>Prospective cohort study.<h4>Setting</h4>United States.<h4>Patients</h4>22 129 female white health professionals parti ...[more]

PMID: 19153409

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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.

Dataset Information

Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3.

Publications

Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3.

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