(PHILADELPHIA) – The discovery that high levels of high-density lipoprotein (HDL) cholesterol (the “good cholesterol”) is associated with reduced risk of cardiovascular disease has fostered intensive research to modify HDL levels for therapeutic gain. However, recent findings have called into question the notion that pharmacologic increases in HDL cholesterol levels are necessarily beneficial to patients.  Now, a new study from researchers at the University of Pennsylvania School of Medicine shows that a different metric, a measure of HDL function called cholesterol efflux capacity, is more closely associated with protection against heart disease than HDL cholesterol levels themselves. Findings from the study could lead to new therapeutic interventions in the fight against heart disease. The new research will be published in the January 13 issue of the New England Journal of Medicine.

Atherosclerosis, a component of heart disease, occurs with a build-up along the artery wall of fatty materials such as cholesterol.  Cholesterol efflux capacity, an integrated measure of HDL function, is a direct measure of the efficiency by which a person's HDL removes cholesterol from cholesterol-loaded macrophages (a type of white blood cell), the sort that accumulate in arterial plaque.

"Recent scientific findings have directed increasing interest toward the concept that measures of the function of HDL, rather than simply its level in the blood, might be more important to assessing cardiovascular risk and evaluating new HDL-targeted therapies,” said Daniel J. Rader, MD, director, Preventive Cardiology at Penn. “Our study is the first to relate a measure of HDL function--its ability to remove cholesterol from macrophages--to measures of cardiovascular disease in a large number of people.”

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