Treatment options for low high-density lipoproteins

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Biochemistry

Background:

• High-density lipoprotein cholesterol (HDL-C) is inversely associated with cardiovascular risk.
• In vitro and in vivo studies suggest HDL is a plausible therapeutic target.
• Genetic studies (Mendelian randomization) challenge HDL-C as a causal protective factor.

Purpose of the Study:

• To review current and future therapeutic strategies targeting HDL.
• To evaluate the efficacy of raising HDL-C mass versus improving HDL function.

Main Methods:

• Review of in vitro, in vivo, Mendelian randomization, and clinical trial data.
• Examination of novel biomarkers for HDL function (e.g., cholesterol efflux, anti-inflammatory effects).
• Analysis of emerging therapeutic agents targeting HDL function.

Main Results:

• Clinical data do not support that increasing HDL-C mass improves cardiovascular outcomes.
• Biomarkers of HDL function are under investigation in ongoing clinical trials.
• Novel therapies targeting HDL function, including CETP inhibitors and HDL mimetics, are in development.

Conclusions:

• Therapeutic strategies targeting HDL-C mass have not improved cardiovascular outcomes.
• Future HDL-based therapies aim to enhance HDL function.
• Current guidelines emphasize LDL-cholesterol reduction for cardiovascular risk management.