Abstract 1259: The Contribution of C-reactive Protein, a KIF6 Variant, and a 9p21 Variant to the Prediction of Myocardial Infarction in the Cardiovascular Health Study
Background: Genetic and non-genetic risk markers might improve prediction of coronary events. A gene variant of KIF6 and several chromosome 9p21 variants were associated with increased risk of coronary heart disease (CHD) or myocardial infarction (MI) in large prospective studies. We asked if addition of genetic information (KIF6, Trp719Arg or 9p21, rs10757274) or a well-established non-genetic risk marker (C-reactive protein [CRP]), can improve risk prediction by the Framingham Risk Score (FRS) in the Cardiovascular Health Study (CHS), a prospective observational study of cardiovascular disease in men and women aged 65 years or older.
Methods: The predicted 10-year risk for MI of white participants of CHS was calculated by using FRS covariates in Cox models of incident MI for men (n=1495) and women (n=2156) separately. The coefficients for the FRS covariates were estimated using CHS data. Two methods were used to assess whether additional risk markers improved risk prediction: change in the area under the receiver operator characteristic curve (AUC) and net reclassification improvement (NRI), i.e., using incident event information to determine if individuals were reclassified to more appropriate risk categories.
Results: Among white participants, addition of plasma CRP level to the FRS did not improve the AUC (P>0.15) or NRI (P>0.19) in men or women (Table⇓). Similarly, addition of 9p21 information did not improve the AUC (P>0.35) or NRI (P>0.39). Addition of KIF6 719Arg carrier status to FRS improved the AUC in men (P=0.03) but not women (P=0.57); the NRI was not improved (P>0.32). Adding both CRP and KIF6 carrier status to the FRS improved both AUC (P=0.02) and NRI (P=0.008) in men but not women (P>0.24). Adding both CRP and 9p21 did not improve AUC or NRI (P>0.09 in men P>0.40 in women).
Conclusion: While none of these risk markers individually or in combination improved risk prediction in women, KIF6 carrier status and CRP levels improved risk prediction among older men.