Apolipoprotein E Gene Polymorphism and Subclinical Carotid Atherosclerosis: The Northern Manhattan Study

Background: Apolipoprotein E (APOE) polymorphism has previously been associated with carotid intima-media thickness (cIMT) in predominantly Caucasian populations. We sought to test the strength of the relationship between APOE-ε4 carrier status and subclinical atherosclerosis in a tri-ethnic population with a large Hispanic representation. Methods: We assessed the association between APOE polymorphism and cIMT and plaque burden among 1243 stroke-free individuals (mean age 69 years, 65% Hispanic, 18% black, 17% white) using a sequence of multivariable regression models. Results: After adjusting for demographics, vascular risk factors and plasma low-density lipoprotein (LDL) levels, APOE-ε4 carrier status was positively associated with cIMT (mean difference,.013 mm; 95% confidence interval,.003-.023 mm). The APOE-ε4 association with cIMT appeared to be segment-specific with greater differences in IMT between APOE-ε4 carriers and noncarriers in the common carotid artery (CCA,.014 mm) and bifurcation (.017 mm) than in the internal carotid artery (ICA) IMT (.007 mm). This relationship was not modified by race–ethnicity. Presence of diabetes modified the ε4-cIMT relationship in CCA (P =.045) and ICA (P =.046). APOE-ε4 carrier status was not associated with plaque presence or plaque area. Conclusions: APOE-ε4 carriers had elevated cIMT independent of demographics and vascular risk factors including LDL levels. Diabetes was an effect modifier of the relationship between APOE-ε4 and IMT, such that ε4 carriers with diabetes had greater IMT in the CCA and ICA than those without diabetes. The APOE–IMT relationship was not modified by race–ethnicity.