HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events

Authors: ROSENSON, ROBERT S. - Mount Sinai School Of Medicine; BREWER JR., H. BRYAN - Medstar Research Institute; CHAPMAN, M. JOHN - Paris Hospital; FAZIO, SERGIO - Vanderbilt University; HUSSAIN, M. MAHMOOD - State University Of New York (SUNY); KONUSH, ANATOL - Paris Hospital; KRAUSS, RONALD M. - Children'S Hospital Oakland Research Institute; OTVOS, JAMES D. - Liposcience; REMALEY, ALAN T. - National Heart, Lung And Blood Institute(NHLBI, NIH); SCHAEFER, ERNST J. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Clinical Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2010
Publication Date: 3/1/2012
Citation: Rosenson, R., Brewer Jr., H., Chapman, M., Fazio, S., Hussain, M., Konush, A., Krauss, R., Otvos, J., Remaley, A., Schaefer, E. 2012. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clinical Chemistry. 57(3):392-410.

Interpretive Summary: Low levels of high density lipoprotein (HDL) cholesterol have been associated with an increased risk of heart disease in many studies. Data indicates that looking at different HDL particles in a variety of ways may provide more information about risk than the measurement of HDL cholesterol. HDL cholesterol is measured after removing non HDL particles from the plasma or serum. HDL particles can also be analyzed by separating them using various forms of ultracentrifugation, by either gradient or vertical rotor methods. Different HDL particles can be distinguished by the unique signals based on nuclear magnetic resonance imaging. In addition HDL particles can be imaged and analyzed by one and two dimensional gel electrophoresis. In general all of the methods identify five major HDL particles ranging from very small to small to medium, to large, and finally to very large HDL particles. This type of nomenclature provides the field with some common ground for identifying and discussing these different HDL particles. This report is of interest to people working in the field of heart disease prevention.

Technical Abstract: A growing body of evidence from epidemiological data, animal studies, and clinical trials supports HDL as the next target to reduce residual cardiovascular risk in statin-treated, high-risk patients. For more than 3 decades, HDL cholesterol has been employed as the principal clinical measure of HDL and cardiovascular risk associated with low HDL-cholesterol concentrations. The physicochemical and functional heterogeneity of HDL present important challenges to investigators in the cardiovascular field who are seeking to identify more effective laboratory and clinical methods to develop a measurement method to quantify HDL that has predictive value in assessing cardiovascular risk. In this report, we critically evaluate the diverse physical and chemical methods that have been employed to characterize plasma HDL. To facilitate future characterization of HDL subfractions, we propose the development of a new nomenclature based on physical properties for the subfractions of HDL that includes very large HDL particles (VL-HDL), large HDL particles (L-HDL), medium HDL particles (M-HDL), small HDL particles (S-HDL), and very-small HDL particles (VS-HDL). This nomenclature also includes an entry for the pre-Beta-1 HDL subclass that participates in macrophage cholesterol efflux. We anticipate that adoption of a uniform nomenclature system for HDL subfractions that integrates terminology from several methods will enhance our ability not only to compare findings with different approaches for HDL fractionation, but also to assess the clinical effects of different agents that modulate HDL particle structure, metabolism, and function, and in turn, cardiovascular risk prediction within these HDL subfractions.