HDL therapy: the next big step in the treatment of atherosclerosis?
Karam M Kostner1, Edmund Cauza
1University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Qld. 4102, Australia.
Insights
New treatments targeting high-density lipoprotein (HDL) cholesterol are needed because current therapies leave many cardiovascular events preventable. Enhancing HDL or apolipoproteins offers promising therapeutic strategies.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Pharmacology
Background:
- Cardiovascular disease remains a leading cause of mortality despite statin therapy.
- Current treatments for lowering low-density lipoprotein cholesterol (LDL-C) are insufficient to prevent approximately two-thirds of cardiovascular events.
- There is a critical need for novel therapeutic strategies beyond LDL-C reduction.
Purpose of the Study:
- To review current and emerging therapeutic interventions aimed at increasing high-density lipoprotein (HDL) cholesterol levels.
- To explore novel approaches targeting HDL apolipoproteins and reverse cholesterol transport.
- To discuss the potential of combination therapies and novel strategies for cardiovascular risk reduction.
Main Methods:
- Review of existing literature on HDL-raising therapies.
- Analysis of novel approaches including HDL-like particle infusion and CETP inhibition.
- Discussion of established drugs (fibrates, nicotinic acid) and future directions (plasma delipidation, recombinant apoAI).
Main Results:
- Lifestyle interventions and certain drugs (fibrates, nicotinic acid) offer modest increases in HDL.
- Direct infusion of HDL-like particles and inhibition of cholesteryl ester transfer protein (CETP) show significant effects on atherosclerosis and HDL cholesterol.
- Emerging therapies demonstrate potential for dramatic improvements in cardiovascular outcomes.
Conclusions:
- Targeting HDL cholesterol and enhancing reverse cholesterol transport represent a promising frontier in cardiovascular disease prevention.
- Novel therapeutic strategies, including HDL-based therapies and CETP inhibitors, hold significant potential to complement existing treatments.
- Future research should focus on optimizing HDL-raising therapies and combination strategies for comprehensive cardiovascular risk management.
Abstract:
Despite significant reductions in mortality with statins and increasingly lower targets of low-density-lipoprotein cholesterol, two thirds of cardiovascular events cannot be prevented with current treatments. Therefore, a clear need for additional therapeutic interventions to complement the results of low-density lipoprotien lowering, exists. One prime target for new interventions is high-density lipoprotein (HDL) and/or its apolipoproteins. While lifestyle interventions and well-established drugs, such as fibrates and nicotinic acid, modestly increase HDL, the most promising current approaches are direct infusion of HDL-like particles (e.g., apolipoprotein AI Milano-phospholipid complexes) and inhibition of one of the key enzymes in HDL metabolism, cholesterol ester transfer protein. These methods have been shown to have dramatic effects on the incidence of atherosclerosis and/or HDL cholesterol. This review will focus on treatments that raise HDL cholesterol or enhance reverse cholesterol transport. Old and new drugs will be discussed as well as combination therapy and novel approaches such as plasma delipidation and recombinant apolipoprotein AI.
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