Can We Make High-Density Lipoproteins Great Again?

1833 Elevated levels of circulating high-density lipoprotein cholesterol (HDL-C) have long been thought to be associated with reduced coronary artery disease (CAD) risk. This concept has led to the HDL hypothesis: increasing HDL-C would be a key addendum in the prevention of CAD, in addition to reducing circulating low-density lipoprotein cholesterol levels. In theory, increasing HDL-C should improve the antiatherosclerotic process of reverse cholesterol transport (RCT). However, repeated attempts to increase HDL-C pharmacologically have shown no changes to the risk of CAD. Although discouraging, the concept of HDL functionality, or its ability to efflux cholesterol from extrahepatic tissues during the RCT process, was shown to be a negative correlate of CAD. Thus, studies of interventions that attempt to target HDL functionality are highly desirable.