HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events

Study Questions:

In a population free of clinical cardiovascular disease at baseline, what is the association of cholesterol efflux capacity with incident cardiovascular outcomes?

Methods:

This was an analysis of data from the Dallas Heart Study, a multiethnic, population-based cohort study. Participants were free from cardiovascular disease at baseline. Blood was collected from participants at baseline and the high-density lipoprotein (HDL) cholesterol level and HDL particle concentration were measured. Cholesterol efflux capacity was determined by measuring the efflux of fluorescence-labeled cholesterol from J774 macrophages to apolipoprotein B-depleted plasma. The primary endpoint was a composite outcome of first nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or death from cardiovascular causes. Association between cholesterol efflux capacity and the time to a first event was determined with Cox proportional-hazards modeling.

Results:

The analytic sample included 2,416 participants (median age was 42 years). Median follow-up period was 9.4 years. 132 participants had a primary atherosclerotic cardiovascular disease event. While HDL cholesterol level had a strong positive correlation with select traditional cardiovascular risk factors, cholesterol efflux capacity is only modestly associated with these variables. In analyses adjusted for traditional risk factors, HDL cholesterol level, and HDL particle concentration, there was an inverse association between increasing quartiles of cholesterol efflux capacity and the primary endpoint (adjusted hazard ratio for the fourth vs. first quartile of cholesterol efflux capacity, 0.33; 95% confidence interval, 0.19-0.55).

Conclusions:

Cholesterol efflux capacity is inversely associated with incident atherosclerotic cardiovascular disease even after adjustment for traditional cardiovascular risk factors, HDL cholesterol level, and HDL particle concentration.

Perspective:

This is an important analysis that establishes the inverse association between cholesterol efflux capacity (a functional property of HDL) and cardiovascular disease in the Dallas Heart Study, a probability-based population sample. As this association persisted despite adjustment for traditional risk factors, cholesterol efflux capacity may reflect a novel pathophysiologic process. As the authors acknowledge, their cohort was young (median age = 42 years) and experienced a relatively few number of events. Future studies should clarify the role of cholesterol efflux capacity in clinical risk assessment.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins

Keywords: Myocardial Infarction, Stroke, Fluorescence, Atherosclerosis, Macrophages, Risk Factors, Cholesterol, HDL


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