The aim of the present study was to investigate the high-density lipoprotein (HDL) structural characteristics and metabolism in hyperalphalipoproteinemic (HALP) patients (HDL-cholesterol [HDL-C], 92 +/- 14 mg/dL) with combined elevated low-density lipoprotein-cholesterol (LDL-C) levels (LDL-C, 181 +/- 33 mg/dL). Patients were subjected to a complete cardiovascular examination, including ultrasonographic investigation of carotid arteries. Two HALP profiles were identified according to the HDL2/HDL3 ratio. HALP profile A was characterized in 28 patients by increased HDL2/HDL3 ratio, HDL2b, and lipoprotein (Lp)A-I levels compared with normolipidemic subjects, and HALP profile B, including the 12 remaining patients, was characterized by a HDL2/HDL3 ratio within the normal range and by the increase of all HDL subclasses (HDL(2b,2a,3a,3b,3c)), LpA-I, and LpA-I:A-II levels. With regard to the exploration of carotid arteries, in HALP profile A, 20 patients were free from lesions and eight had only intimal wall thickening. In HALP profile B, only one patient was free from lesions, four had intimal wall thickening, and seven displayed plaques, but none had stenosis. Taking into account the number of patients with plaques within each group, HALP profile A was associated with a low prevalence of atherosclerotic lesions, whereas HALP profile B was less cardioprotective (odds ratio, 77.7 [95% confidence interval, 3.7 to 1,569.7]; P < .0001). For both HALP profiles, cholesteryl ester transfer protein (CETP) deficiency was discarded and activities of phospholipid transfer protein (PLTP) and lipoprotein lipase (LPL) were normal. However, hepatic lipase (HL) activity was significantly decreased in HALP profile A, but within the normal range for HALP profile B. In conclusion, an HALP profile A with a low prevalence of atherosclerosis was characterized by an increased HDL2/HDL3 ratio, HDL2b, and LpA-I levels associated with decreased HL activity.
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