High-density lipoprotein cholesterol: current perspective for clinicians

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Lipid Metabolism

Background:

• High-density lipoproteins (HDL) are traditionally considered cardioprotective, but their role is complex.
• High-density lipoprotein cholesterol (HDL-C) is a key clinical marker, though its direct impact on cardiovascular risk is debated.
• A significant portion of patients do not achieve sufficient cardiovascular benefit from statin therapy alone.

Purpose of the Study:

• To review the role of high-density lipoproteins in cardiovascular risk.
• To evaluate the efficacy and tolerability of medications that increase HDL-C.
• To explore the potential of HDL-C modulation in patients unresponsive to statins.

Main Methods:

• Review of clinical literature and medication trial data concerning HDL-C.
• Analysis of therapeutic strategies aimed at increasing HDL-C levels.
• Consideration of patient tolerability and adverse events associated with HDL-C-raising drugs.

Main Results:

• Nicotinic acid effectively raises HDL-C, potentially reducing cardiovascular risk, but flushing is a common side effect.
• Laropiprant mitigates nicotinic acid-induced flushing and is approved in Europe.
• Cholesteryl ester transfer protein (CETP) inhibitors are potent HDL-C elevators; early agents like torcetrapib were withdrawn due to safety concerns, while newer ones like anacetrapib show potential.

Conclusions:

• Elevating HDL-C may offer significant cardiovascular benefits, especially for the 60% of patients not fully benefiting from statins.
• Nicotinic acid and CETP inhibitors represent viable therapeutic options for increasing HDL-C, pending further safety and efficacy data.
• Future research should focus on the clinical utility of HDL-C modulation in diverse patient populations.