HIGH-DENSITY-LIPOPROTEIN SUBFRACTIONS AS MARKERS OF EARLY ATHEROSCLEROSIS

Although the inverse relation between high-density lipoprotein (HDL) c holesterol concentration and the risk of ischemic heart disease is wel l established, little is known about the relation of HDL subfractions HDL(2) and HDL(3) or lipoprotein A-I and A-I-A-II to extracoronary dis ease, particularly at its silent phase before the appearance of clinic al lesions. We investigated the potential influence of HDL subfraction s as risk markers, among the other main lipid and nonlipid risk factor s, early atherosclerotic plaques detected by imaging sites in 181 hype rcholesterolemic symptom-free men. No plaques were found in 36% of the patients, but plaques were found at carotid, aortic, and femoral site s in 24%, 40%, and 46% of subjects, respectively. Data were analyzed u sing univariate comparisons and multiple logistic regression. Accordin g to the logistic analysis, plaques were associated (1) with blood pre ssure (p = 0.008) and low-density lipoprotein (LDL) cholesterol (p = 0 .02) in the carotid arteries; (2) with age (p = 0.0005), triglycerides (p = 0.002), and cigarette smoking (p = 0.02) at the aortic site; and (3) inversely with HDL(3) cholesterol (p = 0.0008) and positively wit h cigarette smoking (p = 0.004), and age (p = 0.04) in the femoral sit e. The number of arterial sites affected (0, 1, 2, and 3) by plaques w as inversely associated with HDL, cholesterol (p = 0.001), and positiv ely associated with smoking = (p = 0.002), blood pressure (p = 0.002), LDL cholesterol (p = 0.003), and age (p = 0.006). Using models of mul tivariate analysis, we showed that HDL(2) and HDL(3) subfractions were better predictors of plaque at the femoral site and of the number of affected segments than total HDL cholesterol. Thus, in hypercholestero lemic asymptomatic middle-aged men, LDL cholesterol and HDL(3) cholest erol concentrations are 2 specific lipid parameters that strongly infl uence the development of arterial plaque. A significant increase in th e LDL:HDL(3) ratio was associated with the presence of plaque at each site, and also with the number of diseased sites. Our data support the hypothesis of a specific protective effect of HDL, subfraction at the early stage of atherosclerosis, and we propose the LDL:HDL, ratio as a potential marker of the presence and extent of extracoronary plaques .