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Emerging Strategies and Agents to Lower Cardiovascular Risk by Increasing High Density Lipoprotein Cholesterol Levels

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For decades, the focus of therapy to mitigate cardiovascular risk has been to lower low density lipoprotein cholesterol (LDL-C), so called “bad cholesterol”. Widespread use of statins has resulted in a large body of clinical experience, which indicates that lower LDL-C levels do indeed correlate with decreased risk of cardiovascular and coronary artery diseases (CVD and CAD). Given these findings, recommended targets for LDL-C levels are continually being revised lower. Interestingly, however, even at low LDL-C levels there remains a substantial residual risk of CVD and CAD, particularly in patients with additional contributing factors.

Recent post-hoc analyses of several large lipid modulation trials specifically assessing high density lipoprotein cholesterol (HDL-C) have revealed that increased HDL-C levels confer additional benefit against risk of CVD and CAD, even when LDL-C levels are already low. Human clinical outcomes trials that specifically target increasing HDL-C have not yet been conducted. However, the strong epidemiological inverse correlation between HDL-C and CVD risk remains. Discovery efforts aimed at increasing circulating levels of HDL-C have increased dramatically in recent years. This review will cover recent efforts and agents being developed such as cholesterol ester transfer protein inhibitors and nicotinic acid receptor agonists among other potential strategies.
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Keywords: CETP; Cardiovascular disease; FXR; GPR109A; LXR; RXR; high density lipoprotein

Document Type: Research Article

Affiliations: Schering Plough Research Institute, 2015 Galloping Hill Rd. MS-1600, Kenilworth, NJ 07033, USA.

Publication date: 2009-01-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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