High-density lipoprotein subfractions as markers of early atherosclerosis

Although the inverse relation between high-density lipoprotein (HDL) cholesterol concentration and the risk of ischemic heart disease is well established, little is known about the relation of HDL subfractions HDL2 and HDL3 or lipoprotein A-I and A-I-A-II to extracoronary disease, particularly at its silent phase before the appearance of clinical lesions. We investigated the potential influence of HDL subfractions as risk markers, among the other main lipid and nonlipid risk factors, by assessing early atherosclerotic plaques detected by 3 ultrasound imaging sites in 181 hypercholesterolemic symptom-free men. No plaques were found in 36% of the patients, but plaques were found at carotid, aortic, and femoral sites in 24%, 40%, and 46% of subjects, respectively. Data were analyzed using univariate comparisons and multiple logistic regression. According to the logistic analysis, plaques were associated (1) with blood pressure (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 HDL3 cholesterol (p = 0.0008) and positively with cigarette smoking (p = 0.004), and age (p = 0.04) in the femoral site. The number of arterial sites affected (0,1,2, and 3) by plaques was inversely associated with HDL3 cholesterol (p = 0.001), and positively associated with smoking (p = 0.002), blood pressure (p = 0.002), LDL cholesterol (p = 0.003), and age (p = 0.006). Using models of multivariate 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 hypercholesterolemic asymptomatic middle-aged men, LDL cholesterol and HDL 3 cholesterol concentrations are 2 specific lipid parameters that strongly influence the development of arterial plaque. A significant increase in the 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 3 subfraction at the early stage of atherosclerosis, and we propose the LDL:HDL 3 ratio as a potential marker of the presence and extent of extracoronary plaques.