HDL and Cardiovascular Risk: Rethinking the Relationship

Although lower HDL levels are associated with increased cardiovascular risk, therapies to raise HDL levels have failed to reduce cardiovascular events.  In this sub-study of the longitudinal Dallas Heart Study, the authors turn their attention from absolute levels of HDL to reverse cholesterol transport in the shape of HDL efflux capacity.  This efflux capacity is a measure of HDL particles’ ability to accept cholesterol from macrophages.  Using a novel fluorescent cellular assay, HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity were measured in 2924 adults with no history of cardiovascular disease.  The primary end-point was a cardiovascular event, which included a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes over a median of 9.4 years of follow-up.  In this study, cholesterol efflux capacity was inversely associated with future cardiovascular events.  The addition of HDL efflux to a risk-model that included biochemical and traditional risk factors resulted in improved cardiovascular risk discrimination.


Cholesterol efflux capacity appears to be a novel biomarker associated with incident cardiovascular risk.  Furthermore, this study suggests a refined understanding of HDL metabolism and cardiovascular risk may inform drug targets to improve patient outcomes.

Summarized by Hussain Contractor and Steven M. Bradley

Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, Neeland IJ, Yuhanna IS, Rader DR, de Lemos JA, Shaul PW. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med. 2014 Dec 18;371(25):2383-93.