In vivo metabolism of HDL, apo A-I, and lp A-I, and function of HDL--a clinical perspective.

Abstract

Serum levels of high density lipoprotein cholesterol (HDL-C) are inversely correlated with coronary heart disease (CHD). Kinetic studies indicate that the mechanism for the variation in HDL levels associated with various pathophysiologic states includes changes in the fractional catabolic rate (FCR) and/or the synthesis rate of HDL and its major proteins apolipoprotein (apo) A-I and apo A-II. The antiatherogenic effects of HDL are thought to be mainly due to its role in reverse cholesterol transport. HDL is an assembly of heterogeneous particles. HDL enlarges when it takes up cellular cholesterol, and shrinks when HDL cholesterol ester (CE) is transfered to low density lipoprotein (LDL) and very low density lipoprotein (VLDL) particles. The functional ability of HDL (to remove cellular cholesterol) has drawn considerable attention. The fractional esterification rate of cholesterol in HDL (FER(HDL)) has been established as a functional assay of HDL, and reflects the size of HDL particles. We investigated the clinical significance of FER(HDL) and its relationship to the quantity of HDL. FER(HDL) values were inversely correlated with levels of HDL-C and large lipoprotein containing apo A-I (LpA-I). The association between FER(HDL) and CHD changed with serum HDL-C levels: increased FER(HDL) values significantly increased the risk of CHD when serum HDL-C levels were low, while there was no such relationship when HDL-C levels were high. We concluded that the combination of HDL-C levels and FER(HDL) is a stronger indicator of CHD than either the HDL-C level (quantitative measure of HDL) or FER(HDL) (functional measure of HDL) alone.