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Underappreciated Opportunities for High-Density Lipoprotein Particles in Risk Stratification and Potential Targets of Therapy

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Abstract

The inverse relationship between high-density lipoprotein cholesterol (HDL-C) concentrations and coronary heart disease risk is well established. As a result, in recent years there have been significant resources focused on identifying therapies that raise HDL-C and ultimately reduce cardiovascular events. Unfortunately, a number of trials aimed at increasing HDL-C have failed to show improved outcomes, and hence, have cast doubt on the importance of HDL-C as a therapeutic target. HDL-C, however, is only one measure of HDL. HDL levels can also been estimated by quantifying apolipoprotein A-I (apoA-I) levels using enzyme immunoassay or by measuring HDL particle number (HDL-P) using nuclear magnetic resonance spectroscopy (NMR) or ion mobility. While these surrogate measures are correlated, they are not comparable. Lipoprotein-altering therapies have been shown to have different effects on HDL-C, apoA-I and HDL-P and several studies have demonstrated that HDL-P is a stronger predictor of coronary heart disease risk than HDL-C and/or apoA-I. This paper will review available evidence supporting the use of HDL-P as the biomarker of choice to assess the contribution of HDL to cardiovascular risk and as the primary goal of HDL-raising therapies.

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Authors and Affiliations

  1. Cardiometabolic Disorders Unit Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY, 10029, USA

    Robert S. Rosenson

  2. University of Chicago, 5841 S Maryland Ave, Chicago, IL, 60637, USA

    Michael H. Davidson

  3. Biomarker Core Laboratory Atlanta Research and Education Foundation, 1670 Clairmont Rd - Room 4A186, Decatur, GA, 30033, USA

    Ngoc-Anh Le

  4. Piedmont Heart Institute, 1140 Hammond Drive. Building K. Suite 300, Atlanta, GA, 30328, USA

    Jaime Burkle

  5. LipoScience, Inc, 2500 Sumner Blvd, Raleigh, NC, 27616, USA

    Ray Pourfarzib

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  1. Robert S. Rosenson
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Rosenson, R.S., Davidson, M.H., Le, NA. et al. Underappreciated Opportunities for High-Density Lipoprotein Particles in Risk Stratification and Potential Targets of Therapy. Cardiovasc Drugs Ther 29, 41–50 (2015). https://doi.org/10.1007/s10557-014-6567-0

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