DISTRIBUTION OF SUBCLASSES OF HDL CONTAINING APOA-I WITHOUT APOA-II (LPA-I) IN NORMOLIPIDEMIC MEN AND WOMEN

Women have significantly higher plasma concentrations of high-density lipoprotein (HDL) and apolipoprotein (ape) A-I than men. Human HDL consists of two major species of apoA-I-containing lipoproteins: LpA-I (lipoprotein containing apoA-I but not apoA-II) and LpA-I:A-II (lipoprotein containing both apoA-I and apoA-II). LpA-I is itself heterogeneous and contains several subclasses of different size and composition. We analyzed LpA-I subclasses in 12 male and 12 female healthy normolipidemic adults. LpA-I concentrations were significantly higher in women (72.4 +/- 5.6 mg/dL) than in men (50.2 +/- 2.2 mg/dL) (P < .05). LpA-I was preparatively isolated from fasting plasma by immunoaffinity chromatography. Gel filtration chromatography was then used to isolate LpA-I subclasses based on size. Three major subclasses were eluted: large, medium, and small LpA-I. No differences between men and women in the size or composition of individual LpA-I subclasses were observed. In contrast, the distribution and plasma concentration of LpA-I subclasses were significantly different between men and women. As a fraction of total LpA-I, the large LpA-I was significantly higher (68.0% to 48.4%) and the medium LpA-I was significantly lower (26.4% to 44.9%) in women than in men. The fraction of small LpA-I was not significantly different. Plasma concentrations of large LpA-I in women (49.2 mg/dL) were twice that in men (24.3 mg/dL), whereas plasma concentrations of medium LpA-I (19.1 mg/dL versus 22.5 mg/dL) and small LpA-I (4.0 mg/dL versus 3.0 mg/dL) were similar in women and men. The activities and distribution of lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) were similar between women and men. The majority of plasma LCAT and CETP were associated with large LpA-I. In conclusion, the higher HDL cholesterol and apoA-I levels in normolipidemic women compared with men are primarily associated with elevation in a specific subclass, the large LpA-I particles. This suggests that large LpA-I may be a more specific marker for risk of premature coronary heart disease.