Subclinical atherosclerosis in subjects with family history of premature coronary artery disease.

BACKGROUND

First-degree relatives (FDRs) of subjects with early onset of coronary heart disease (CHD) have higher risk of developing cardiovascular disease. We verified early CHD by angiography in index patients and extensively phenotyped their FDRs to investigate the relationship of traditional and nontraditional cardiovascular risk factors to carotid ultrasound measures of subclinical atherosclerosis.

METHODS AND

RESULTS

B-mode carotid ultrasound was used to assess the combined intimamedia thickness and plaque burden in 111 FDRs (65 men, 44.4 +/- 11 and 46 women, 44.7 +/- 13 years old) of 82 index patients (men <50 and women <60 years of age at the time of the event). The biochemical and anthropometrical characteristics of the FDRs were compared with those of healthy controls matched for sex, age, ethnicity, and body mass index. First-degree relatives had increased average total thickness (a combined measure of intimamedia thickness and plaque) compared to controls (0.76 mm, interquartile range [IQR] 0.69-1.01 vs 0.69 mm, IQR 0.60-0.88, P < .001) even after adjusting for age, total cholesterol-to-high-density lipoprotein cholesterol ratio, systolic blood pressure, waist circumference, and smoking (beta = 0.143, P < .05). No differences were observed in average intimamedia thickness measurements alone. Of the nontraditional risk factors, only plasma homocysteine was higher in FDRs then in controls (9.6 mg/L, IQR 8.0-11.1 versus 7.5 mg/L, IQR 6.4-8.7, P < .001), after adjusting for all other confounding variables.

CONCLUSION

First-degree relatives of patients with angiographically confirmed CHD have higher burden of subclinical atherosclerosis even when considered in the context of traditional risk factors. Noninvasive assessment of carotid artery plaques and intimamedia thickness and plasma homocysteine measurements may be useful in such patients.