Pharmacologic Management of Isolated Low High-Density Lipoprotein Syndrome

High-density lipoprotein (HDL) cholesterol is a heterogeneous group of lipoproteins exhibitinga variety of properties like prostacyclin production stimulation, decrease in platelet aggregation,endothelial cell apoptosis inhibition, and low-density lipoprotein oxidation blockade. Epidemiologicstudies have shown an inverse relation between HDL cholesterol levels and cardiovascular risk. LowHDL cholesterol is associated with increased risk for myocardial infarction, stroke, sudden death,peripheral artery disease, and postangioplasty restenosis. In contrast, high HDL levels are associatedwith longevity and protection against atherosclerotic disease development. Given the evolvingepidemic of obesity, diabetes mellitus, and metabolic syndrome, the prevalence of low HDL willcontinue to rise. In the United States, low HDL is present in 35% of men, 15% of women, andapproximately 63% of patients with coronary artery disease. Data extracted from the Framinghamstudy highlight that 1-mg increase in HDL levels decreases by 2% to 3% the risk of cardiovasculardisease. There is no doubt regarding clinical importance about isolated low HDL, but relatively fewclinicians consider a direct therapeutic intervention of this dyslipidemia. In this sense, lifestylemeasures should be the first-line strategy to manage low HDL levels. On the other hand,pharmacologic options include niacin, fibrates, and statins. Fibrates appear to reduce riskpreferentially in patients with low HDL with metabolic syndrome, whereas statins reduce riskacross all levels of HDL. Torcetrapib, a cholesteryl esters transfer protein inhibitor, representeda hope to raise this lipoprotein; however, all clinical trials on this drug had ceased afterILLUMINATE, RADIANCE and ERASE trials had recorded an increase in mortality, rates ofmyocardial infarction, angina, and heart failure. In the near future, drugs as b-glucans, Apo-A1mimetic peptides, and ACAT inhibitors, are the new promises to treat this condition.Keywords: dyslipidemia, HDLc, cholesterol, reverse cholesterol transport, atherosclerosis, coronaryartery disease