Enhancing cardiovascular disease risk reduction: raising high-density lipoprotein levels

PURPOSE OF REVIEW: Despite optimally reducing low-density lipoprotein cholesterol (LDL-C) levels to recommended targets using intensive statin therapy, the risk of cardiovascular disease (CVD) remains significant. Low levels of high-density lipoprotein cholesterol (HDL-C; <1.03 mmol/l or <40 mg/dl) are an independent risk factor for CVD, and raising levels of HDL-C is a major treatment strategy for regressing atherosclerosis and enhancing CVD risk reduction. This can be achieved by both nonpharmacological lifestyle measures and pharmacological treatment strategies. RECENT FINDINGS: This article will focus on the currently available and emerging pharmacological treatment strategies for raising HDL-C. Extended-release nicotinic acid (or Niacin) remains the most effective pharmacological treatment currently available for elevating HDL-C, having recently been combined with simvastatin (as Simcor) and laropripant (as Cordaptive, to reduce flushing). Other HDL-C-raising agents in current clinical use or in clinical development are fibrates, peroxisome proliferator-activated receptor agonists, cholesteryl ester transfer protein inhibitors, and HDL-C mimetics. Novel pharmacological targets for raising HDL-C also include the nuclear liver X and farnesoid X receptors and endothelial lipase. SUMMARY: Novel well tolerated and efficacious treatment strategies for raising HDL-C are required to target atherosclerosis and enhance CVD risk reduction.