Apolipoprotein E polymorphism affects carotid artery atherosclerosis in smoking hypertensive men

Objective Smoking is a risk factor for increased carotid artery intima-media thickness (IMT). The apolipoprotein E (apoE) epsilon4 allele has been associated with cardiovascular diseases, but the role of apoE in regard to intima-media thickness (IMT) has remained controversial. The objective was to investigate whether there is some gene-environment interaction between smoking and apoE polymorphism. Design Cross-sectional case-control study. Methods IMTs of 511 hypertensive and control men were measured ultrasonographically and the apoE genotypes were determined. Genotypes with the epsilon4 allele were pooled into one group and the genotypes without it into another. Results A significant interaction between the epsilon4 allele and smoking affecting IMT was observed among the hypertensive smokers, as assessed by analysis of covariance. The mean carotid IMT was significantly greater (1.01 versus 0.90 mm, P= 0.003) in the epsilon4 carriers than in the subjects without epsilon4 among the hypertensive smokers. The number of plaques was also significantly higher. No differences were found in the other subjects (hypertensive non-smokers or controls). Linear regression analysis indicated that the epsilon4 allele was an independent determinant of IMT in the hypertensive smokers but not in the other subjects. The estimated average effect of the 4 allele on the mean IMT in the hypertensive smokers was 0.088 mm (P < 0.001). In the oldest age group, the interaction of smoking and epsilon4 was also seen in the control subjects. Conclusion The findings suggest that the epsilon4 carriers are particularly susceptible to the atherogenic effects of smoking. This interaction is particularly clear in hypertensive subjects. J Hypertens 20:2371-2378. (C) 2002 Lippincott Williams Wilkins.