Interaction of body mass index and Framingham Risk Score in predicting incident coronary disease in families

Background-Siblings of individuals with premature coronary heart disease (CHD) have a marked excess risk of CHD risk factors and premature CHD. The impact of body mass index (BMI) on incident CHD in these families and the extent to which it may be mediated by associated risk factors are unknown. The aim of this study was to examine the effect of high BMI on incident CHD in white and black families with premature CHD and to estimate the heritability of BMI. Methods and Results-Risk factors, BMI, and Framingham Risk Score (FRS) were assessed at baseline and incident CHD was determined prospectively in 827 apparently healthy siblings of probands with premature CHD aged <60 years. During a mean follow-up of 8.7 years, 13.3% of siblings had incident CHD events. Event rates were higher in obese and overweight siblings than in those with normal weight (15.3% and 16.0% versus 8.1%, respectively; P=0.01). Multivariable Cox proportional hazards analyses demonstrated the independent prognostic value of BMI when added to FRS (P=0.02). A marked interaction between obesity (BMI >= 30 kg/m(2)) and high FRS (>20%) was seen for incident CHD (P for interaction=0.008), with an adjusted hazard ratio compared with low-FRS/normal-weight siblings of 14.63 (95% CI, 6.40 to 33.44; P<0.0001). BMI heritability (h(2)) was moderate for whites and low for blacks (52% and 29%, respectively). Conclusions-High BMI contributed independently and significantly to incident CHD, beginning in the overweight range, and was most notable for obese siblings with a high-risk FRS.