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Annals of Clinical & Laboratory Science 32:123-136 (2002)
© 2002 Association of Clinical Scientists

High Density- and Beta-Lipoprotein Screening for Risk of Coronary Artery Disease in the Context of New Findings on Reverse Cholesterol Transport

Stanley S. Levinson
Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, and Laboratory Service, Department of Veterans Affairs Medical Center, Louisville, Kentucky

Address correspondence to Stanley S. Levinson, Ph.D., Laboratory Service, VAMC, 800 Zorn Avenue, Louisville, KY 40206, USA; tel 502 895 3401 ext 5565 or 5572; fax 502 894 6265; e-mail levinson{at}louisville.edu.

This article considers how high density lipoproteins (HDL) act as anti-arteriosclerotic agents, examines the usefulness of HDL indexes alone and in conjunction with other markers of coronary artery disease (CAD), and discusses how HDL markers compare with what one might expect from known metabolic mechanisms. This is accomplished by: (i) an overview of mechanisms associated with CAD, especially new findings regarding reverse cholesterol transport; (ii) a brief review of the clinical literature on biochemical markers for automated use; and (iii) analysis of data for persons with or without angiographically documented CAD. Based on these considerations, the ratio of optimized apo A-I/apo B appears superior to lipoprotein lipid markers for predicting the risk of CAD. Yet the ratio shows poor diagnostic accuracy by itself; it yields poorer diagnostic accuracy than would be expected from assessing the metabolic pathways. Discrimination is improved by using the ratio in conjunction with risk factors defined by the National Cholesterol Education Program (NCEP). Based on receiver-operator characteristic (ROC) curve data, this approach increases the accuracy by 13–14% above that obtained with current lipid markers; it improves discrimination more than the use of inflammatory markers. Apolipoprotein testing is better related to the mechanisms of cholesterol transport, is widely available, and requires only two tests, compared to three, to improve discrimination. However, inclusion of inflammatory markers may need to be considered in the future, when more information is available about their functions and clinical value.

Keywords: apolipoproteins, arteriosclerosis, C-reactive protein, reverse cholesterol transport




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