Current status and future directions in lipid management: emphasizing low-density lipoproteins, high-density lipoproteins, and triglycerides as targets for therapy

Abstract

Current lipid management guidelines are focused on decreasing low-density lipoprotein (LDL-C) levels as the primary target for reducing coronary heart disease (CHD) risk. Yet, many recent studies suggest that low levels of high-density lipoprotein (HDL-C) are a major independent risk factor for cardiovascular diseases. According to several clinical trials, a 1% increase in HDL-C is associated with a 0.7%-3% decrease in CHD events. The direct link between high levels of triglycerides (TG) and CHD, on the other hand, is less well defined. A large reduction in TG is needed to show a difference in CHD events, especially in men. Evidence for a shift in lipid management toward targeting both LDL-C and HDL-C as primary targets for therapy is presented. Currently, the 3-hydroxy-3-methylgutaryl coenzyme A reductase inhibitors (HMG-CoA reductase inhibitors) have proven to significantly decrease LDL-C levels, reduce CHD morbidity/mortality and improve overall survival. However, improvement of survival with statins may be due to other pleiotropic effects beyond LDL-C lowering. Fibric acid derivatives and niacin are primarily used to increase HDL-C levels, although with side effects. Future therapies targeting HDL-C may have profound results on reducing CHD morbidity and mortality. This article highlights existing and future targets in lipid management and is based on available clinical data. There is an urgent need for new treatments using a combination of drugs targeting both LDL-C and HDL-C. Such treatments are expected to have a superior outcome for dyslipidemia therapy, along with TG management.

Keywords: HDL-C; LDL-C; atherosclerosis; cholesterol; coronary heart diseases; fibric acid; lipid; nicotinic acid; statin; triglycerides.