Effect of lipid-modifying therapies on the functional quality of high-density lipoproteins: Implications for drug development

Background: Increasing interest has focused on the development of therapeutic strategies to promote the biological activity of high-density lipoproteins (HDL) to achieve more effective prevention of cardiovascular disease. The highly publicized failure of raising HDL cholesterol with the cholesteryl ester transfer protein inhibitor, torcetrapib, has fueled immense discussion with regard to the potential impact of lipid modifying therapies on the functional quality of HDL particles. Objective/method: To review the literature that has investigated the role of HDL functionality in protection against cardiovascular disease. Conclusion: It remains to be unequivocally demonstrated that therapies that directly target HDL are cardioprotective in humans. Increasing attention on the functional quality of HDL will be essentinal for developing new biomarkers and medical therapies.