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QUARTERLY FOCUS ISSUE: PREVENTION/OUTCOME: STATE-OF-THE-ART PAPER

High-Density Lipoprotein and Coronary Heart Disease

Current and Future Therapies

Pradeep Natarajan, MD^_*, Kausik K. Ray, MD and Christopher P. Cannon, MD^_*,,_*

^_* Department of Medicine, Cardiovascular Division, Brigham & Women's Hospital/Harvard Medical School, Boston, Massachusetts
TIMI Study Group, Cardiovascular Division, Brigham & Women's Hospital/Harvard Medical School, Boston, Massachusetts
Department of Public Health and Primary Care, University of Cambridge, Cambridge, England

Manuscript received November 25, 2009; revised manuscript received January 4, 2010, accepted January 4, 2010.

^_* Reprint requests and correspondence: Dr. Christopher P. Cannon, Brigham and Women's Hospital, Cardiovascular Division, TIMI Study, 350 Longwood Avenue, First Floor Office, Boston, Massachusetts 02115 (Email: cpcannon{at}partners.org).

Coronary heart disease remains a major cause of worldwide morbidity and mortality despite therapeutic advances that control many risk factors such as low-density lipoprotein cholesterol to levels lower than previously possible. Population studies have consistently demonstrated an inverse association between high-density lipoprotein cholesterol (HDL-C) levels with the risk of coronary heart disease. As a result, HDL-C is gaining increasing interest as a therapeutic target. In this review, we explore the protective mechanisms of HDL and how current and future therapies harness these beneficial properties. We offer a biological framework to understand treatment strategies as well as their resultant successes and failures to guide management and future directions. At present, raising HDL-C level holds great promise, on the basis of epidemiology and initial trials, but we await the outcomes of the many large clinical outcomes trials currently under way to define the clinical role of older and novel therapies to raise HDL-C level.

Key Words: high-density lipoprotein • coronary artery disease • prognosis • prevention

Abbreviations and Acronyms   ABC = ATP-binding cassette transporter   ACAT = acyl-coenzyme A cholesterol acyltransferase   ATP = adenosine triphosphate   CETP = cholesterol ester transfer protein   CHD = coronary heart disease   HDL-C = high-density lipoprotein cholesterol   LCAT = lecithin-cholesterol acyltransferase   LDL-C = low-density lipoprotein cholesterol   PPAR = peroxisome proliferator-activated receptor   VLDL = very low-density lipoprotein

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