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

Haraki T, Takegoshi T, Kitoh C, Wakasugi T, Saga T, Hirai J‐I, Aoyama T, Inazu A, Mabuchi H (Fukui Prefectural Hospital, Fukui; Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan). Carotid artery intima‐media thickness and brachial artery flow‐ mediated vasodilation in asymptomatic Japanese male subjects amongst apolipoprotein E phenotypes. J Intern Med 2002; 252: 114–120. 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.