Implications of reverse cholesterol transport: recent studies.

INTRODUCTION

There is a strong epidemiological relationship between high density lipoproteins and atherosclerotic coronary vascular disease (ASCVD). The process of reverse cholesterol transport (RCT) has been hypothesized to help explain this relationship. The corollary that raising HDL should reduce ASCVD is also drawn from this relationship. In recent years, the metabolism of HDL has become better understood. A hypothetical process for explaining RCT has been superimposed on the currently understood HDL metabolic pathways.

METHODS

Outline of HDL metabolism and the superimposed RCT process. Literature review of studies of persons with genetic defects, HDL cholesterol raising clinical trials, Mendelian randomization studies and treatments with molecules that mimic HDL.

CONCLUSIONS

Mutation studies of ABCA1, LCAT and SR-B1 genes in humans showed expected variations in HDLC but little association with ASCVD and there was no significant association between HDLC and ASCVD in Mendelian randomization studies. Elevations in HDLC due to treatment with niacin and cholesteryl ester transport protein inhibitors in randomized trials raised HDLC but did not significantly reduce risk of ASCVD. Treatment with molecules that mimic HDL did not seem to reduce ASCVD. Thus, recent evidence does not seem to support RCT as currently proposed. This hypothesis seems to need substantial revision.