Population-based studies show that a low concentration of HDL cholesterol is a risk factor for cardiovascular disease. The purpose of this review was to summarize the reported evidence that supports the HDL cholesterol hypothesis which is based on the fact that HDL protects against atherosclerosis. In agreement with the HDL hypothesis, HDL has been reported to display many anti-atherogenic properties through its role in reverse cholesterol transport and its anti-inflammatory, oxidative and thrombotic functions. Despite a considerable and diverse body of evidence that supports the HDL hypothesis, direct evidence from human studies is almost absent. Results from clinical trials to determine whether raising plasma HDL levels will reduce the risk of atherosclerosis remains inconclusive until now. Therefore, more research to identify possible drug targets related to HDL pathways are essential to demonstrate the HDL hypothesis.
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