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OBJECTIVE: Circulating levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides are recognized risk factors for cardiovascular disease. We tested the hypothesis that the cumulative effects of common genetic variants for lipids are collectively associated with subclinical atherosclerosis and incident coronary heart disease. APPROACH AND RESULTS: Participants were drawn from the Erasmus Rucphen Family Study (n=2269) and the Rotterdam Study (n=8130). Linear regression and Cox proportional hazards models were applied to assess the influence of 4 risk scores derived from common genetic variants for lipids (total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglycerides) on carotid plaque, intima-media thickness, incident myocardial infarction, and coronary heart disease. Adjusted for age and sex, all 4 risk scores were associated with carotid plaque. This relationship was the strongest for the LDL-C score, which increased plaque score by 0.102 per SD increase in genetic risk score (P=3.2 × 10(-8)). The LDL-C score was also nominally associated with intima-media thickness, which increased 0.006 mm per SD increase in score (P=0.05). Both the total cholesterol and LDL-C scores were associated with incident myocardial infarction and coronary heart disease with hazard ratios between 1.10 and 1.13 per SD increase in score. Inclusion of additional risk factors as covariates minimally affected these results. CONCLUSIONS: Common genetic variants with small effects on lipid levels are, in combination, significantly associated with subclinical and clinical cardiovascular outcomes. As knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events.

Original publication

DOI

10.1161/atvbaha.113.301236

Type

Journal article

Journal

Arteriosclerosis, thrombosis, and vascular biology

Publication Date

09/2013

Volume

33

Pages

2233 - 2239

Addresses

Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. a.isaacs@erasmusmc.nl

Keywords

Humans, Carotid Artery Diseases, Coronary Disease, Myocardial Infarction, Genetic Predisposition to Disease, Cholesterol, Lipids, Triglycerides, Biological Markers, Prognosis, Incidence, Linear Models, Proportional Hazards Models, Risk Assessment, Risk Factors, Gene Frequency, Phenotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Netherlands, Female, Male, Cholesterol, LDL, Cholesterol, HDL, Asymptomatic Diseases, Carotid Intima-Media Thickness