BACKGROUND: Parental history is a widely accepted risk factor for offspring cardiovascular events, although the mechanisms remain unclear. We examined the contribution of conventional and novel risk factors in explaining the excess risk of cardiovascular events in offspring with positive parental history (PH+).
METHODS AND RESULTS: We collected conventional (blood pressure, cholesterol, adiposity), lifestyle, and novel (C-reactive protein, CRP) risk factors at baseline in participants from the Scottish Health Surveys (n = 5946, 44.5% men, aged 53.6 +/- 12.4 years), who were followed up over an average of 7.1 years for cardiovascular disease (CVD) events (a composite of fatal and nonfatal events incorporating acute myocardial infarction, coronary artery bypass surgery, percutaneous coronary angioplasty, stroke, heart failure). Younger PH+ participants (<65 years) were at higher risk of incident CVD events [age-adjusted and sex-adjusted hazard ratio = 1.91, 95% confidence interval (CI) 1.21-3.00] compared with PH-. Despite an association of PH+ with blood pressure, total and high-density lipoprotein cholesterol, CRP, and physical activity, less than 15% of the excess risk was explained through conventional and novel risk factors. However, the greatest risk of CVD was observed in PH+ participants with elevated CRP (> or =3 mg/l) (hazard ratio = 2.99, 95% CI 2.15-4.16) or hypertension (hazard ratio = 2.87, 95% CI 2.07-3.99).
CONCLUSION: Only a small amount of the excess CVD risk associated with PH+ is accounted for by conventional and novel mechanisms. However, the combination of elevated CRP or hypertension with PH+ substantially increases the risk of CVD.
