Contribution of major cardiovascular risk factors to familial premature coronary artery disease: the GENECARD project.

OBJECTIVES This study was designed to assess the prevalence of major cardiovascular risk factors in familial premature coronary artery disease (P-CAD), affecting two or more siblings within one sibship. BACKGROUND Premature CAD has a genetic component. It remains to be established whether familial P-CAD is due to genes acting independently from major cardiovascular risk factors. METHODS We recruited 213 P-CAD survivors from 103 sibships diagnosed before age <or=50 (men) or <or=55 (women) years old. Hypertension, hypercholesterolemia, obesity, and smoking were documented at the time of the event in 163 patients (145 men and 18 women). Each patient was compared with two individuals of the same age and gender, diagnosed with sporadic (nonfamilial) P-CAD, and three individuals randomly sampled from the general population. RESULTS Compared with the general population, patients with sporadic P-CAD had a higher prevalence of hypertension (29% vs. 14%, p < 0.001), hypercholesterolemia (54% vs. 33%, p < 0.001), obesity (20% vs. 13%, p < 0.01), and smoking (76% vs. 39%, p < 0.001). These risk factors were equally or even more prevalent in patients with familial P-CAD (43% [p < 0.05 vs. sporadic P-CAD], 58% [p = 0.07], 21% and 72%, respectively). Overall, only 7 (4%) of 163 of patients with familial P-CAD and 22 (7%) of 326 of patients with sporadic P-CAD had none of these conditions, as compared with 167 (34%) of 489 patients in the general population. CONCLUSIONS Classic, remediable risk factors are highly prevalent in patients with familial P-CAD. Accordingly, a major contribution of genes acting in the absence of these risk factors is unlikely.