HDL Cholesterol Efflux Capacity a Better Predictor of Cardiovascular Disease Risk Than Measurement of HDL or HDL Cholesterol

A recent paper strengthened the hypothesis that HDL (high-density lipoprotein) function, rather than the absolute concentration of this lipoprotein, is the key factor linking HDL and cardiovascular disease (CVD).

The link between levels of HDL cholesterol and cardiovascular disease (CVD) is well established, but the mechanisms underlying this association had remained elusive. To gain a better understanding of this relationship, investigators at the University of Texas Southwestern Medical Center (Dallas, USA) measured HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity at in 2,924 adults free from cardiovascular disease who were participants in the Dallas Heart Study, a probability-based population sample. Over a median follow-up period of 9.4 years the investigators evaluated the participants for development of atherosclerotic cardiovascular disease, defined as a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes.

Results revealed that cholesterol efflux capacity (cholesterol efflux), which measures HDL cholesterol function, appeared to be a superior indicator of cardiovascular risk and a better target for therapeutic treatments than standard measurements of HDL. In a fully adjusted model that included traditional risk factors, HDL cholesterol level, and HDL particle concentration, there was a 67% reduction in cardiovascular risk in participants with the highest quarter of cholesterol efflux capacity versus those with the lowest quarter.

“HDL is very dynamic. It has many functions that are not fully captured by the measurement of static cholesterol levels,” said first author Dr. Rohatgi, assistant professor of internal medicine at the University of Texas Southwestern Medical Center. “The hypothesis has changed from an HDL-cholesterol hypothesis to an HDL-function hypothesis to better capture cardiovascular risk and provide a better target for therapy to reduce that risk. We drew on the strengths of the Dallas Heart Study to thoroughly investigate the relationship between HDL function and cardiovascular disease What we found was a strong, graded, protective relationship between cholesterol efflux and incidence of cardiovascular events among people who were free from heart disease at baseline testing.”

The study was published in the November 18, 2014, online edition of the New England Journal of Medicine.

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University of Texas Southwestern Medical Center