SMALL LOW-DENSITY LIPOPROTEINS AND VASCULAR CELL-ADHESION MOLECULE-1 ARE INCREASED IN ASSOCIATION WITH HYPERLIPIDEMIA IN PREECLAMPSIA

The pregnancy disorder preeclampsia is characterized by endothelial ce ll dysfunction that may be promoted by abnormal increases in circulati ng lipids, particularly triglycerides and free fatty acids. Serum trig lyceride concentration is a major regulatory determinant of low-densit y lipoprotein (LDL) size and density distribution. Smaller, denser LDL particles have several intrinsic properties capable of inducing endot helial dysfunction. The present nested, case-control study of gestatio nally matched preeclamptic and normal pregnant women tested the hypoth esis that hypertriglyceridemia in preeclampsia is accompanied by decre ases in LDL peak particle diameter (predominant LDL size). Plasma LDL peak particle diameter was determined by nondenaturing 2% to 16% polya crylamide gel electrophoresis. Correlations of LDL diameter with the c oncentration of serum triglycerides, free fatty acids, total cholester ol, LDL-cholesterol, and apolipoprotein B (apo B) were determined. In the same individuals, we measured serum concentrations of a marker of vascular dysfunction previously reported to be increased in preeclamps ia, soluble vascular cell adhesion molecule-1 (VCAM-1), and examined t he association of VCAM-1 with LDL diameter and serum lipids. LDL peak particle diameter was decreased in preeclampsia relative to normal pre gnancy (P < .01). The LDL-cholesterol:apo B ratio, which frequently de creases with decreasing LDL diameter, was also decreased (P < .04). Tr iglyceride concentrations were increased in preeclampsia (P < .0002), and there was a significant inverse relationship between LDL peak part icle diameter and triglycerides (r = -.55, P < .02). Serum soluble VCA M-1 concentrations were markedly increased in preeclampsia (P < .0003) . Apo B (P < .004), free fatty acids (P < .01), total cholesterol (P < .01), and LDL-cholesterol (P < .02) were also increased. VCAM-1 corre lated with apo B (r = .50, P < .03) and LDL-cholesterol (r = .50, P < .03), but showed no relationship with the LDL diameter, LDL-cholestero l:apo B ratio, or other lipids. We conclude that the predominance of s maller, denser LDL, a potential contributor to endothelial cell dysfun ction, is a feature of preeclampsia. However, the serum VCAM-1 level,o ne indicator of endothelial involvement, may be influenced more by qua ntitative lipoprotein changes (serum apo B or LDL-cholesterol) than by LDL particle size. Copyright (C) 1998 by W.B. Saunders Company.