Controversies on HDL: should it be a target biomarker in patients with lipid disorders?

Area of Science:

• Cardiovascular Medicine
• Lipid Metabolism
• Pharmacotherapy

Background:

• Statins significantly reduce cardiovascular (CV) events by lowering low-density lipoprotein (LDL) cholesterol, establishing them as a cornerstone of CV risk reduction.
• Residual CV risk persists even after effective LDL cholesterol lowering, highlighting the need for novel therapeutic strategies beyond statin therapy.

Purpose of the Study:

• To review the potential benefits of targeting high-density lipoproteins (HDL) for cardiovascular disease (CVD) prevention.
• To discuss the challenges and controversies surrounding the development of HDL-targeted therapies in light of recent clinical trial outcomes.

Main Methods:

• Review of existing scientific literature and clinical trial data related to HDL cholesterol, genetics, and cardiovascular outcomes.
• Analysis of evidence supporting and refuting the therapeutic utility of targeting HDL for CV risk reduction.

Main Results:

• Recent studies on HDL genetics and raising agents have yielded disappointing results, leading to debate regarding the clinical efficacy of HDL-targeting strategies.
• Despite the potential protective properties of HDL, attempts to therapeutically raise HDL levels or function have not consistently translated into reduced clinical events.

Conclusions:

• The clinical benefit of targeting HDL for cardiovascular prevention remains uncertain, necessitating a critical evaluation of current approaches.
• Further research is required to overcome the challenges in developing effective HDL-targeted therapies and to clarify their role in comprehensive CV risk management.