HDL FUNCTIONALITY AS A NEW POSSIBLE CLINICAL BIOMARKER

Several epidemiological studies define HDL as the most powerful plasmatic factor with atheroprotective activity in humans. Some post hoc analyses from randomized controlled trials also suggest that raising HDL-C beneficially affects the risk of CVD. However, the clinical efficacy of raising plasma HDL-C levels to achieve cardiovascular risk reduction has been difficult to prove. Published outcome trials involving the addition of niacin or dalcetrapib to standard low-density lipoprotein cholesterol reduction therapy failed to demonstrate clinical benefit despite increases in HDL-C concentration. Furthermore, genetic variants associated with increased HDL-C, thus conferring lifelong exposure to higher circulating levels, are not consistently associated with improved vascular outcomes. These findings have reinforced the idea that changes in HDL-C levels are an inadequate surrogate for therapeutic use. Therefore, an emerging concept is that of quality of HDL, which are heterogeneous in terms of size, charge and lipid content and display functional differences, such as cell cholesterol efflux promotion. Cholesterol efflux from peripheral tissues is a key function of HDL particles, and the first step of reverse cholesterol transport to the liver for biliary secretion. Recent studies have shown that cholesterol efflux capacity (CEC), as a measure of HDL functionality in humans, is inversely associated with prevalent ASCVD and incident cardiovascular events in a population-based cohort without cardiovascular disease at baseline. These associations were independent of HDL-C and traditional cardiovascular risk factors, which suggested that the HDL-C level is only a modest biomarker of HDL function, and that CEC may be more closely correlated with cardiovascular outcomes. This review of different published results could help to better understand that HDL CEC might provide an alternative mechanism for therapeutic modulation of the HDL pathway beyond HDL cholesterol concentration to help reduce risk of coronary heart disease.