Current guidelines for high-density lipoprotein cholesterol in therapy and future directions

Area of Science:

• Cardiology
• Biochemistry
• Pharmacology

Background:

• Low high-density lipoprotein cholesterol (HDL-C) is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD).
• Therapeutic strategies aimed at increasing HDL-C levels have been pursued, with some agents showing modest HDL-C increases and ASCVD event reduction in the past.
• Recent clinical trials have questioned the direct correlation between elevated HDL-C levels and cardiovascular benefits, leading to controversy surrounding the HDL hypothesis.

Purpose of the Study:

• To review current therapeutic approaches targeting HDL-C for ASCVD.
• To explore emerging and novel strategies for HDL therapeutics that focus on HDL's structure and function.
• To discuss future directions in the development of agents that mimic or enhance HDL's cardioprotective properties.

Main Methods:

• Literature review of clinical trials and therapeutic strategies related to HDL-C.
• Analysis of findings from randomized trials involving niacin and cholesteryl ester transfer protein inhibitors.
• Discussion of novel therapeutic approaches in early-phase development.

Main Results:

• Past therapies like fibrates and niacin showed modest HDL-C increases and some ASCVD event reduction.
• Recent randomized trials have challenged the assumption that higher HDL-C levels uniformly lead to ASCVD benefits.
• Current guidelines lack clear direction for targeting HDL-C due to insufficient outcome data for HDL-specific therapies.

Conclusions:

• The direct benefit of quantitatively increasing HDL-C for ASCVD prevention is now debated.
• Novel therapeutic strategies are being developed to mimic HDL structure or enhance its functions beyond cholesterol transport.
• Future HDL therapeutics may involve approaches like HDL infusions, Apo A-I mimetics, and gene therapy, pending early-phase trial results.