Abstract

Although family history of premature coronary artery disease (CAD) confers increased risk of CAD, the magnitude of this increase beyond that expected from the risk factors incorporated in the Framingham Risk Equation (FRE) remains unknown. We prospectively determined the accuracy of the FRE 10-year incident CAD events prediction in initially healthy siblings of patients with documented premature CAD. We recruited 784 siblings (30 to 59 years) of 449 patients hospitalized with CAD <60 years of age (1983 to 1995). We compared the estimated 10-year incidence of total CAD events by the gender-specific FREs at baseline, to the observed incidence at 10 years of follow-up. In men, the 10-year actual CAD event rate was 20%, only half of which was predicted by the FRE (12% vs 20%, p <0.001). In women, the observed CAD event rate was 7.1% (p <0.001 vs men), modestly but not significantly greater than the 6.3% predicted by the FRE (p = 0.34). Thus, there was a significant 66.6% excess risk in men, and a nonsignificant 12.7% excess risk in women beyond the risk predicted by the FRE for total CAD events. The FRE and its known classic risk factor profile failed to accurately predict total incident 10-year CAD events in individuals with a sibling history of premature CAD, most particularly in men. In conclusion, in families with a history of premature CAD, the excess risk observed cannot be attributed to traditional risk factors, suggesting a major role for as yet undetermined genetic and other susceptibility factors.