Abstract 4992: Cardiovascular Disease Risk Prediction with and without Knowledge of Genetic Variation at Chromosome 9p21.3: The Women’s Genome Health Study

Abstract

Background : While genetic variation at chromosome 9p21.3 is associated with incident cardiovascular disease (CVD), it is unclear whether screening for this polymorphism improves risk prediction. We sought to determine whether knowledge of variation at chromosome 9p21.3 adds to the information provided by traditional risk factors using data from a prospective cohort study of female Caucasian health professionals in the United States. Methods : 22,129 initially healthy participants in the Women’s Genome Health Study were prospectively followed over a median of 10.2 years for incident CVD. We determined genotype for rs10757274 in chromosome 9p21.3 as well as blood pressure, smoking status, diabetes, blood levels of cholesterol, high sensitivity C-reactive protein (hsCRP), and family history of premature myocardial infarction (MI). Models were compared overall using the C-index and for reclassification across commonly used categories of 10-year CVD risk (<5%, 5% to <10%, 10% to <20%, 20+%). Results : Genotype for rs10757274 was associated with an adjusted hazard ratio (HR) for incident CVD of 1.25 (95% CI 1.04 – 1.51) for the AG genotype (present in 49% of the women) and 1.32 (95% CI 1.07 – 1.63) for the GG genotype (present in 24% of the women) compared to the AA genotype. However, the addition of the genotype to traditional CVD risk factors had no effect on the C-index (0.805 to 0.807) with correct reclassification of 526 women (2.4%). When the genotype was added to previously validated prediction models that additionally included hsCRP and family history of premature MI, there was again no effect on the C-index (0.809 to 0.807), and only 214 women (1.0%) were reclassified correctly. Conclusion : In this large prospective cohort of Caucasian women, genetic variation in chromosome 9p21.3 was associated with incident CVD but did not improve discrimination or classification of predicted risk.