Curr Atheroscler Rep (2014) 16:398 DOI 10.1007/s11883-014-0398-0


HDL Hypothesis: Where Do We Stand Now? Sayed M. Tariq & Mandeep S. Sidhu & Peter P. Toth & William E. Boden

# Springer Science+Business Media New York (outside the USA) 2014

Abstract There is robust epidemiological evidence dating back to the original Framingham Heart Study from 1977 that indicates an important inverse relationship between highdensity lipoprotein cholesterol (HDL-C) and risk of incident coronary artery disease (CAD). Despite this body of scientific information demonstrating that low levels of HDL-C are an independent predictor of subsequent CAD events, multiple therapeutic attempts to raise HDL-C levels have failed to demonstrate a consistent reduction in prognostically important endpoints such as death, myocardial infarction (MI), and stroke. Recently, several major randomized trials using different therapeutic interventions have raised appropriate concerns about our basic understanding of HDL-C and whether the “HDL hypothesis” of lowering cardiovascular events through therapeutic interventions directed at raising HDL-C is a scientifically viable one. While two recent randomized controlled trials (AIM-HIGH and HPS2-THRIVE) failed to show a reduction in cardiovascular events in patients treated to optimally low levels of low-density lipoprotein cholesterol (LDL-C) at baseline with extended-release niacin on a

background of simvastatin, these clinical trials studied specific populations of stable ischemic heart disease patients. The data from these two contemporary trials cannot be extrapolated to all patient populations, such as those with acute coronary syndromes or myocardial infarction or those with significant residual mixed dyslipidemia not treated with optimal doses of intensive statin therapy, as these patients were excluded by trial design in both studies. Therefore, at the present time, there is insufficient evidence from clinical trials to recommend HDL-targeted therapy for additional event reduction in CAD patients. However, we will review the relevant data from recent major trials (AIM-HIGH, HPS2-THRIVE, ILLUMINATE, and dal-OUTCOMES) and highlight the potential clinical implications of these trials in modern pharmacotherapy as it relates to HDL-C raising and potential cardiovascular event reduction. Keywords HDL . Niacin . Atherosclerosis . Coronary artery disease . AIM-HIGH . HPS2-THRIVE

Introduction This article is part of Topical Collection on Nonstatin Drugs S. M. Tariq Department of Medicine, Albany Medical Center, Albany Medical College, Albany, NY, USA e-mail: [email protected] M. S. Sidhu : W. E. Boden (*) Department of Medicine, Albany Stratton VA Medical Center and Albany Medical Center, Albany Medical College, 113 Holland Avenue, Albany, NY 12208, USA e-mail: [email protected] M. S. Sidhu e-mail: [email protected] P. P. Toth Department of Family and Community Medicine, University of Illinois School of Medicine, and CGH Medical Center, Sterling, IL, USA e-mail: [email protected]

The National Cholesterol Education Program recommended that optimal treatment for high-risk cardiac patients include both lowering LDL-C and non-HDL-C to risk-stratified levels and that raising HDL-C levels should be considered for HDLC

HDL hypothesis: where do we stand now?

There is robust epidemiological evidence dating back to the original Framingham Heart Study from 1977 that indicates an important inverse relationship...
3MB Sizes 2 Downloads 4 Views