Abstract
OBJECTIVE: To investigate which history of cardiovascular disease [coronary heart disease (CHD), stroke, or peripheral arterial disease] in a first-degree family member predicts cardiovascular mortality. METHODS: We studied a prospective cohort (the Lipid Research Clinics Prevalence Study) from ten primary care centers across North America. The primary outcome was cardiovascular mortality, assessed using Cox survival models. RESULTS: There were 8,646 participants (mean age: 47.4 ± 12.1 years, 46% women, 52% of participants with hyperlipidemia) who were followed up for a mean duration of 19.4 ± 4.9 years. There were 1,851 deaths (21%), including 852 cardiovascular deaths. A paternal, maternal or sibling history of premature CHD (before 60 years) was present in 26% of participants, of stroke in 27% of participants, and of peripheral arterial disease in 24% of participants. After adjusting for risk factors (age, sex, systolic blood pressure, diastolic blood pressure, body mass index, smoking, fasting glucose, low-density lipoprotein cholesterol and triglycerides), only a paternal history of premature or any CHD, a maternal history of diabetes mellitus or premature or any CHD, and a sibling history of premature CHD, hypertension, or hyperlipidemia were individually predictive of cardiovascular mortality. After adjusting for risk factors and the mentioned familial factors, only paternal and maternal histories of CHD, especially before 60 years, remained predictive of cardiovascular mortality, with a somewhat higher association for a maternal history [adjusted hazard ratio (aHR) = 1.99, 95% CI: 1.36-2.92,P < 0.001 for maternal history of premature CHD; aHR = 1.52, 95% CI: 1.10-2.10, P = 0.011 for paternal history of premature CHD]. Family history of stroke or peripheral arterial disease did not predict cardiovascular mortality. Parental history of premature CHD predicted cardiovascular mortality independently of baseline age (< 60 years and ≥ 60 years), hypertension, or hyperlipidemia and carried more important prognostic value in men rather than women. CONCLUSIONS: In this study, a parental history of CHD, especially before 60 years, best predicted cardiovascular mortality. This finding could help more accurately identify high-risk patients who would benefit from preventive strategies.