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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Article info
Publication history
Published online: January 16, 2019
Accepted:
January 10,
2019
Received in revised form:
December 29,
2018
Received:
October 2,
2018
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
