Treatment options for low high-density lipoproteins

Abstract

To examine the current and future therapeutic option of HDL-based therapies. The inverse association between plasma level of high-density lipoprotein cholesterol (HDL-C) is strong and coherent across the population studied. In-vitro and in-vivo studies show the strong biological plausibility for HDL as a therapeutic target. Mendelian randomization does not support HDL-C as a causal (protective) cardiovascular risk factor, and clinical data does not support the concept that raising HDL-cholesterol mass alters the outcomes. Better biomarkers of HDL function are being examined in the clinical trials. These include cellular cholesterol efflux, antioxidant and anti-inflammatory effects, effects on vascular endothelial cells (inflammation and nitric oxide release) and endothelial progenitor cells. Novel therapeutic agents that alter HDL function are in advanced phase 3 trials and in early preclinical trials. These include inhibitors of cholesteryl ester transfer protein, reconstituted proteoliposomes, apolipoprotein A-I and HDL mimetic peptides and small molecules that increase apo A-I production rate. Targeting HDL-C has, to date, not led to changes in the cardiovascular outcomes. Novel therapeutic advances target the HDL function. In keeping with the recent 2013 American College of Cardiology/American Heart Association Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults, the major focus of prevention lies with LDL-cholesterol reduction.