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The unresolved mystery of high-density lipoprotein: time for a paradigm shift?

  • Byambaa Enkhmaa
    Affiliations
    Department of Internal Medicine, School of Medicine, University of California, Davis, Calif, USA
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  • Erdembileg Anuurad
    Affiliations
    Department of Internal Medicine, School of Medicine, University of California, Davis, Calif, USA
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  • Lars Berglund
    Correspondence
    Reprint requests: Lars Berglund, Department of Medicine, University of California, Davis UC Davis Medical Center, CTSC 2921 Stockton Blvd, Suite 1400, Sacramento, CA 95817
    Affiliations
    Department of Internal Medicine, School of Medicine, University of California, Davis, Calif, USA

    Veterans Affairs Northern California Health Care System, Sacramento, Calif, USA
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Published:March 14, 2016DOI:https://doi.org/10.1016/j.trsl.2016.03.004
      Despite a declining trend of mortality seen over the last decades, cardiovascular disease (CVD) remains the leading cause of death in the United States. Over the years, advances in science and technology have facilitated the gain of new knowledge and discoveries leading to substantial improvement in our understanding of the underlying disease-causing mechanisms. As a result, CVD is established as a chronic disease caused by a complex interplay between multiple factors where genetic and environmental influences play vital roles in shaping its ultimate outcome. Among the many disease-causing factors, dyslipidemia characterized by elevated levels of atherogenic lipids and lipoproteins (low-density lipoprotein [LDL] cholesterol, small dense LDL particles, triglycerides, remnant lipoproteins, and so forth) and low levels of antiatherogenic lipoproteins (high-density lipoprotein [HDL] cholesterol) have garnered considerable attention and been a subject of a long-standing investigation by a large number of biomedical researchers. Among these various lipid/lipoprotein abnormalities, a low level of HDL cholesterol is the most commonly observed type in patients with premature CVD,
      • Genest Jr., J.J.
      • Martin-Munley S.S.
      • McNamara J.R.
      • et al.
      Familial lipoprotein disorders in patients with premature coronary artery disease.
      and it has been shown to be a strong, consistent, and independent predictor of incident cardiovascular events
      • Ridker P.M.
      • Stampfer M.J.
      • Rifai N.
      Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease.
      • van der Steeg W.A.
      • Holme I.
      • Boekholdt S.M.
      • et al.
      High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies.
      • Yeh P.S.
      • Yang C.M.
      • Lin S.H.
      • et al.
      Low levels of high-density lipoprotein cholesterol in patients with atherosclerotic stroke: a prospective cohort study.
      and in some cases, a superior predictor of CVD risk when compared to an elevated level of LDL cholesterol.
      • Yusuf S.
      • Hawken S.
      • Ounpuu S.
      • et al.
      Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
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