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HDL cholesterol and ASCVD risk stratification: A debate

  • Philip Barter
    Affiliations
    Lipid Research Group, School of Medical Sciences, The University of New South Wales Kensington, NSW, Australia
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  • Jacques Genest
    Correspondence
    Corresponding author. McGill University Health Center/Royal Victoria Hospital, 1001 boul. Decarie Bloc E, EM12212, Montréal, Québec, H4A 3J1, Canada.
    Affiliations
    McGill University Health Center/Royal Victoria Hospital Montréal, Québec, H4A 3J1, Canada
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      Highlights

      • HDL-C is a strong, graded and coherent biomarker of cardiovascular health.
      • A very high HDL-C is not necessarily protective against ASCVD.
      • Mendelian randomization does not support HDL-C as a causal cardiovascular risk factor.
      • The clinical trial data does not support raising HDL-C pharmacologically to decrease outcomes.
      • HDL function (e.g. cellular cholesterol efflux) may be the way forward.

      Abstract

      This debate is designed to review the usefulness of the cholesterol mass within high-density lipoproteins (HDL-C) to predict the risk of atherosclerotic cardiovascular disease (ASCVD).

      Pro

      There is much current confusion regarding the role of high density lipoproteins (HDLs) in atherosclerotic cardiovascular disease (ASCVD). While it is an established fact that the concentration of HDL cholesterol is a robust, independent, inverse predictor of the risk of having an ASCVD event, recent studies have questioned whether HDLs actually protect against ASCVD. But this in no way challenges that fact that the concentration of HDL cholesterol is a powerful tool to be used in risk stratification of ASCVD.

      Con

      The measurement of HDL-C in the 1970 heralded a new area of promising and exciting research in cardiovascular disease. The measurement of HDL-C has been part of cardiovascular risk stratification for the past three decades. HDL have pleotropic beneficial effects on the arterial vasculature and promote the removal of excess cholesterol from lipid laden macrophages. These effects are only weakly correlated with HDL-C levels. While HDL-C is associated with atherosclerotic cardiovascular disease, the epidemiological relationship falters at the extremes of measurement. Mendelian randomization does not support a link of causality and to date, attempts to raise HDL-C pharmacologically have not yielded the expected outcomes. The time has come to consider abandoning HDL-C for cardiovascular risk prediction and clinical decision making and to double efforts to develop better biomarkers of HDL function.
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