To determine whether hyperalphalipoproteinemia modifies carotid intima-media thickness (cIMT) and/or influences the relationship of clinical and biochemical parameters with cIMT. This study was conducted on 169 asymptomatic individuals, classified as hyperalphalipoproteinemic (Hyper-A) (Hyper-A, n = 71, HDL-C > or =68 mg/dL) and controls (CTL) (CTL, n = 98, HDL-C >32 and <68 mg/dL). Enzymatic, nephelometric and ultracentrifugation methods were used for biochemical determinations. Hepatic lipase (HL), lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and phospholipids transfer protein (PLTP) activities were measured by radiometric exogenous methods. The prevalence of dyslipidemia, hypertension, smoking, sedentariness, postmenopausal women, coronary artery disease (CAD) and familial history of CAD were determined. High resolution beta-mode carotid ultrassonography was performed. The Hyper-A group was older and had higher frequencies of hypercholesterolemia (40%), hypertension (31%), sedentariness (37%) and postmenopausal women (1%). In Hyper-A individuals, the mean cIMT after adjustment for age and gender was similar between the groups (0.85 +/- 0.24 mm Hyper-A versus 0.69 +/- 0.17 mm CTL). In multivariate models, age was a significant predictor of cIMT in Hyper-A (R (2) = 0.04, p < or = 0.001), independently of other clinical or biochemical factors. In contrast to CTL, where age (R (2) = 0.63 p < or = 0.001), male sex (R (2) = 0.03, p < or = 0.001), blood pressure (R (2) = 0.006, p < or = 0.001) and HDL-C (R (2) = 0.02, p < 0.022) accounted for the cIMT variations. Despite an increased prevalence of cardiovascular risk factors in Hyper-A and resistance of carotid thickness to modulation by metabolic and anthropometric factors (except age), the similarity in cIMT between Hyper-A and healthy individuals emphasizes the atheroprotective effects of HDL.