Association between apolipoprotein E genotype and carotid intima-media thickness may suggest a specific effect on large artery atherothrombotic stroke

BACKGROUND AND PURPOSE: Apolipoprotein E genotype (APOE) influences cholesterol levels and ischemic heart disease. Although there is no convincing overall association with ischemic stroke, APOE may influence large artery (atherothrombotic) stroke, for which carotid intima-media thickness (CIMT) is an informative intermediate phenotype. We therefore performed a systematic review and meta-analysis of the association between APOE and CIMT. METHODS: We sought all published studies assessing the association between APOE and CIMT. From each study, we extracted available data on study methods, subjects' characteristics, and mean (and standard deviation) CIMT for each genotype or genotype group. We calculated study-specific and random effects pooled differences in mean CIMT between genotype groups, and assessed heterogeneity between studies and predefined subgroups using I(2) and chi(2) statistics. RESULTS: Meta-analysis of 22 published studies (30,879 subjects) showed a significant association between APOE and CIMT (pooled mean difference epsilon 4- versus epsilon 2-allele containing genotypes 46 microm, 95% CI 29 to 62, P1000 subjects (pooled mean difference 17 microm, 95% CI 12 to 23, P