RELATIONSHIP OF THE APOLIPOPROTEIN-E POLYMORPHISM WITH CAROTID-ARTERYATHEROSCLEROSIS

From the cohort taking part in the Atherosclerosis Risk in Communities (ARIC) study, a multicenter investigation of atherosclerosis and its sequelae in women and men ages 45-64 years, a sample of 145 subjects w ith significant carotid artery atherosclerosis but without clinically recognized coronary heart disease was identified along with 224 group- matched control subjects. The aim of this paper is to measure the asso ciation of the apolipoprotein (ape) E polymorphism with the prevalence of significant carotid artery atherosclerotic disease (CAAD) after co nsidering the contribution of established risk factor variables. The f irst model used a stepwise selection procedure to define a group of si gnificant physical and lifestyle characteristics and a group of signif icant plasma lipid, lipoprotein, and apolipoprotein variables that wer e predictive of CAAD status in this sample. Those variables selected i ncluded age (years), body mass index (BMI; kg/m(2)), consumption of ci garettes (CigYears; number of cigarettes/d x the number of smoking yea rs), hypertension status, high-density lipoprotein (HDL)-cholesterol ( mg/dl), total cholesterol (mg/dl), and Lp[a] (mu g/ml). The second mod el was built by forcing into the equation an a priori set of demograph ic, anthropometric, and lipoprotein variables, which were age, BMI, Ci gYears, hypertensive status, LDL-cholesterol, and HDL-cholesterol. In both models, the apo E genotype epsilon 2/3 was related to CAAD status . For both models, the estimated odds ratio of being a CAAD case assoc iated with the apo E genotype epsilon 2/3 was >2:1. The mechanism of t he observed association between the epsilon 2/3 genotype and carotid a therosclerosis is unknown, but it is likely due to the known effects o f the E2 isoform in causing delayed clearance of triglyceride-rich lip oproteins.