Low density lipoproteins (LDL) and high density lipoproteins (HDL) are independent risk factors for coronary heart disease
(CHD); decreasing LDL-cholesterol (LDL-C) levels with statin therapy represents the primary goal in the management of cardiovascular
disease. However, despite the efficacy of statins in reducing cardiovascular morbidity and mortality, a significant residual risk has been
observed even after reaching the LDL-C target, suggesting that other risk factors beyond LDL-C should be addressed, including low levels
of HDL-cholesterol (HDL-C). Several clinical trials have shown an inverse relationship between HDL-C levels and cardiovascular
risk, and 1 mg/dl increment in HDL-C is associated in epidemiological studies with a 2-3% decrease in cardiovascular risk, suggesting
that raising HDL-C levels might have beneficial effects to reduce cardiovascular disease.
However, several lines of evidence indicate that the functional properties of HDL may be relevant as well. In patient with CAD and normal
HDL-C levels, HDL exhibit significantly reduced protective functions, and rather appear to be pro-atherogenic; on the other hand
some genetic mutations causing low levels of HDL-C are not associated with increased atherosclerosis. Furthermore, although niacin significantly
increased HDL-C levels, no further clinical benefit was observed from the addition of niacin to statin therapy, suggesting that
increasing HDL-C levels is not sufficient and perhaps functional properties of HDL must be considered when choosing a therapeutic
strategy to reduce the residual cardiovascular risk.