Unusual high-density lipoprotein subclass distribution during late pregnancy

Abstract

Plasma lipoprotein distribution during late pregnancy is unusual since high-density lipoprotein (HDL) levels are increased in the presence of hypertriglyceridemia; the latter is usually associated with decreases in HDL levels. To determine whether there is a relationship between late-pregnancy lipid levels and specific HDL subclasses, HDL size distribution was determined by nondenaturing gradient gel electrophoresis (GGE) in a group of 36 women at 35 to 36 weeks of gestation and again at 6 weeks' postpartum, and in a group of 10 nonpregnant women. At 35 to 36 weeks of gesgation, plasma triglyceride (TG) and cholesterol concentrations were significantly increased over postpartum levels (218 ± 62 v 112 ± 69 mg/dL and 234 ± 48 v 197 ± 36 mg/dL, respectively). During late pregnancy, apolipoprotein A-I (apo A-I) and HDL cholesterol concentrations were also increased relative to postpartum levels (211 ± 42 v 168 ± 20 mg/dL and 63 ± 13 v 53 ± 11 mg/dL, respectively). GGE analysis indicated that at 35 to 36 weeks of gestation, 86% of the subjects had a substantial increase of the most buoyant and largest of the HDL species, HDL 2b; postpartum and nonpregnant HDL subclass distribution was characterized by the predominance of HDL 3a, which are smaller, more dense HDL. The shift in the HDL subclass distribution during late pregnancy was associated with significant positive correlations between HDL 2b and apo A-I ( r = .50, P < .05) and HDL cholesterol ( r = .60, P < .001). There were significant elevations in the concentrations of cholesteryl ester transfer protein (CETP) and estrogen during late pregnancy. Within each subject, estrogen was linked ( P < .0001) to changes in HDL 2b; for every 1-ng/mL increase in estrogen level during late pregnancy, there was a 0.94% increase in the percent of HDL 2b mass. We speculate that the shift in HDL subclass distribution during the late pregnancy, where there were substantial increases in HDL 2b, may be accounted for by an increase in CETP activity with a parallel decrease in hepatic lipase activity. The major modulator for both of these activities is likely to be estrogen.