Carotid artery intima-media thickness and brachial artery flow-mediated vasodilation in asymptomatic Japanese male subjects amongst apolipoprotein E phenotypes

Background. Epidemiological studies suggest that apolipoprotein E (apoE) polymorphism influences plasma lipoprotein levels and the development of cardiovascular disease. Objective. To clarify the role of apoE polymorphism as a risk factor for early atherosclerosis. Design. Using a high-resolution ultrasound method, we investigated the association between apoE phenotypes, carotid intima-media thickness (CCA-IMT), and flow-mediated dilation in the brachial artery (brachial-FMD) in 96 healthy asymptomatic Japanese men (mean +/- SD age, 50 +/- 8 years). Results. Serum cholesterol and LDL-cholesterol levels in subjects with E3E4 were highest and those with E2E3 were lowest (P < 0.05 and P < 0.05, respectively). The CCA-IMT in E3E4 subjects (0.76 +/- 0.17 mm) was greater than that in E2E3 and E3E3 (0.61 +/- 0.15 and 0.64 +/- 0.14 mm, respectively; P < 0.01). In contrast, there was no difference between brachial-FMD and apoE phenotypes (P =0.15). By univariate analysis, CCA-IMT was positively correlated with age (r =0.51, P < 0.01), LDL-chol/HDL-chol ratio (r =0.37, P < 0.01), triglycerides (r =0.23, P < 0.05), and negatively correlated with HDL-cholesterol (r =-0.31, P < 0.01). An association between CCA-IMT and the presence of E4 allele was also found (P < 0.05). Logistic regression analysis revealed that the presence of E4 allele was a higher risk for increased IMT (relative risk of 4.4, 95% CI 1.5-12.5), even after adjustment for age, LDL-cholesterol, blood pressure and other known risk factors. A negative correlation between brachial-FMD and CCA-IMT was also found in all subjects (r =-0.21, P < 0.05), being most apparent in the E3E4 subjects (r =-0.53, P < 0.02). Conclusion. ApoE4 phenotype was independently associated with an increased risk of carotid atherosclerosis and elevated LDL-cholesterol levels in asymptomatic middle-aged Japanese men.