Therapeutic Approaches to Raising Plasma HDL-cholesterol Levels

MM Thompson; SC Reed; GW Cockerill

Disclosures

Nat Clin Pract Cardiovasc Med. 2004;1(2) 

In This Article

Summary and Introduction

Epidemiologic data from the Framingham and Prospective Cardiovascular Munster studies, demonstrating an inverse correlation between the plasma concentration of HDLs and the incidence of cardiovascular disease, have driven research to explore precisely how HDLs confer this cardioprotective effect. HDLs are anti-inflammatory, antithrombogenic and have vasoactive effects, as well as being efficient cholesterol acceptors enabling the removal of cholesterol from peripheral tissues, all functions that are likely to protect the vasculature. The first part of this article will review the clinical evidence in support of the pleiotropic effects of HDLs, along with laboratory-based investigations of the molecular mechanisms of action. As the evidence of clinical benefits of raising plasma HDL concentration has increased, so has the number of strategies currently being considered to achieve this goal. The second part of this article will review three current strategies: infusion of HDL-like products, comparing physicopharmacologic characteristics of the two commercial products currently under trial; the use of fibrates to raise plasma HDLs (although fibrates primarily reduce triglyceride levels, certain derivatives are able to induce significant increases in plasma HDLs); and the use of drugs that inhibit cholesterol ester transfer protein (these drugs increase plasma HDL concentration either alone or as an adjunct therapy with statins). The clinical efficacy and mechanism of action of fibrates and inhibitors of cholesterol ester transfer protein will be reviewed.

Epidemiologic data have demonstrated an inverse correlation between the plasma concentration of HDLs and the incidence of cardiovascular disease. Such findings have provided the main stimulus for research into how HDLs afford a protective effect. In addition to the ability of HDLs to act as efficient acceptors of cholesterol, they have anti-inflammatory, antithrombogenic and vasoactive effects. All these functions can have beneficial effects on the vasculature.

Clearly, pathologies with complex multifactorial etiologies, such as acute coronary syndrome, stroke and metabolic syndrome, call for pleiotropic therapies. Therapeutically raising plasma HDL concentration may offer a pleiotropic treatment for cardiovascular disease.

As evidence of the clinical benefits of raising plasma HDL concentrations has increased, various strategies to therapeutically raise plasma HDL have been proposed. In this article we review the clinical efficacy and mechanism of action of three current therapeutic interventions; administration of HDL-like products; the use of fibrates to raise plasma HDLs; and the use of drugs that inhibit cholesterol ester transfer protein (CETP).

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