The Role of High-Density Lipoprotein Cholesterol in 2022

Purpose of the Review High-density lipoproteins (HDL) are responsible for the transport in plasma of a large fraction of circulating lipids, in part from tissue mobilization. The evaluation of HDL-associated cholesterol (HDL-C) has provided a standard method for assessing cardiovascular (CV) risk, as supported by many contributions on the mechanism of this arterial benefit. The present review article will attempt to investigate novel findings on the role and mechanism of HDL in CV risk determination. Recent Findings The most recent research has been aimed to the understanding of how a raised functional capacity of HDL, rather than elevated levels per se, may be responsible for the postulated CV protection. Markedly elevated HDL-C levels appear instead to be associated to a raised coronary risk, indicative of a U-shaped relationship. While HDL-C reduction is definitely related to a raised CV risk, HDL-C elevations may be linked to non-vascular diseases, such as age-related macular disease. The description of anti-inflammatory, anti-oxidative and anti-infectious properties has indicated potential newer areas for diagnostic and therapeutic approaches. In the last two decades inconclusive data have arisen from clinical trials attempting to increase HDL-C pharmacologically or by way of recombinant protein infusions (most frequently with the mutant A-I (Milano)); prevention of stent occlusion or heart failure treatment have shown instead significant promise. Targeted clinical studies are still ongoing.