The complexity of HDL

Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with coronary artery disease risk in large epidemiologic studies. This rule, however, has many exceptions in individual patients, and evidence suggests that other facets of high-density lipoprotein particle biology not captured by measuring HDL-C levels are responsible for HDL's effects in vivo. This article reviews the evidence for the protective nature of HDL, current evidence from animal and human studies regarding HDL-based therapies, the major steps in HDL particle formation and metabolism, alterations leading to dysfunctional HDL in diabetes and inflammatory states, and potential alternatives to HDL-C to measure HDL function and predict its protective value clinically.

Research Highlights
► High-density lipoproteins are widely held to protect against atherosclerosis, and a large number of protective actions of HDL have been discovered.
► Despite this, no clinical trial in humans has yet proven that specifically raising HDL-cholesterol reduces cardiovascular events.
► The purpose of this article was to review the evidence suggesting a protective role for HDL against atherosclerosis, the steps involved in HDL particle formation and metabolism, and changes that occur in HDL in diabetes and inflammation.
► Potential new assays to assess HDL function clinically are also proposed.