Age-dependent association of apolipoprotein E genotype with coronary and aortic atherosclerosis in middle-aged men - An autopsy study

Background-Apolipoprotein E (apoE) polymorphism is one of the genetic deter minants of serum cholesterol values, The apoE epsilon 4 allele has been ass ociated with advanced coronary heart disease (CHD) diagnosed by angiography , but the role of the apoE genotype in atherosclerosis has not been confirm ed at vessel-wall level, nor is any age-dependent effect of the apoE genoty pe on the development of CHD known. Methods and Results-The right and left anterior descending coronary arterie s (RCA and LAD) and the aorta from 700 male autopsy cases (Helsinki Sudden Death Study) in 1981-1982 and 1991-1992 (average age 53 years, range 33 to 70 years) were stained for fat, and all areas covered with fatty streaks, f ibrotic plaques, and complicated lesions were measured, In the RCA and LAD, the apoE genotype was significantly associated with the area of total athe rosclerotic lesions in men <53 years old but not with that in older men (P = 0.0085 and P=0.041, respectively, fir age-by-genotype interaction). Men < 53 years old with the E4/3 genotype showed 61% larger total atherosclerotic lesion area in the RCA (P=0.0027) and 26% larger area in the LAD (P=0.12) than did men with the epsilon 3/3. The apoE epsilon 4/3 was also associated with atherosclerotic lesions in the abdominal (P=0.014) and thoracic (P=0. 12) aorta, but this effect, unlike that of the coronary arteries, was not a ge-related. Conclusions-In men, the apoE epsilon 4 allele is a significant genetic risk factor for coronary atherosclerosis in early middle age. This suggests tha t at older age, other known risk factors of CHD play a more important role in the atherosclerotic process than apoE polymorphisms.