This Article  • Full text  • PDF  • Video  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (55)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Topic Collections  • Lipids and Lipid Disorders  • Review  • Cardiovascular Disease/ Myocardial Infarction  • Alert me on articles by topic  Social Bookmarking   What's this?

A Systematic Review

Inder M. Singh, MD, MS; Mehdi H. Shishehbor, DO, MPH; Benjamin J. Ansell, MD

JAMA. 2007;298:786-798.

Context  High-density lipoprotein cholesterol (HDL-C) is a cardiovascular risk factor that is gaining substantial interest as a therapeutic target.

Objectives  To review the current and emerging strategies that modify high-density lipoproteins (HDLs).

Data Sources  Systematic search of English-language literature (1965-May 2007) in MEDLINE and the Cochrane database, using the key words HDL-C and apolipoprotein A-I and the subheadings reverse cholesterol transport, CVD [cardiovascular disease] prevention and control, drug therapy, and therapy; review of presentations made at major cardiovascular meetings from 2003-2007; and review of ongoing trials from ClinicalTrials.gov and current guidelines from major cardiovascular societies.

Study Selection and Data Extraction  Study selection was prioritized to identify randomized controlled trials over meta-analyses over mechanistic studies; identified studies also included proof-of-concept studies and key phase 1 through 3 trials of novel agents. Study eligibility was assessed by 2 authors; disagreements were resolved by consensus with the third.

Data Synthesis  Of 754 studies identified, 31 randomized controlled trials met the inclusion criteria. Currently available therapeutic and lifestyle strategies, when optimized, increase HDL-C levels by 20% to 30%. While basic and small pilot studies have shown promise, proof that increasing HDL-C levels confers a reduction in major cardiovascular outcomes independent of changes in levels of low-density lipoprotein cholesterol or triglycerides has been more elusive. Some novel therapeutic agents in human studies appear to effectively increase HDL-C levels, whereas other novel strategies that target HDL metabolism or function may have minimal effect on HDL-C levels.

Conclusions  At present there is modest evidence to support aggressively increasing HDL-C levels in addition to what is achieved by lifestyle modification alone. Ongoing clinical trials that target specific pathways in HDL metabolism may help expand cardiovascular treatment options.

Author Affiliations: Department of Cardiovascular Medicine, Krannert Institute of Cardiology, Indiana University Medical Center, Indianapolis (Dr Singh); Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio (Dr Shishehbor); and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California (Dr Ansell).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Assessing niacin as an atherosclerosis therapeutic agent valuable insights provided by high-resolution vascular magnetic resonance imaging.
Jaffer
J Am Coll Cardiol 2009;54:1795-1796.
FULL TEXT  

Evaluating the Incremental Benefits of Raising High-Density Lipoprotein Cholesterol Levels During Lipid Therapy After Adjustment for the Reductions in Other Blood Lipid Levels
Grover et al.
Arch Intern Med 2009;169:1775-1780.
ABSTRACT | FULL TEXT  

Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors
Chapman et al.
Eur Heart J 2009;0:ehp399v1-ehp399.
ABSTRACT | FULL TEXT  

Four additional mouse crosses improve the lipid QTL landscape and identify Lipg as a QTL gene
Su et al.
J. Lipid Res. 2009;50:2083-2094.
ABSTRACT | FULL TEXT  

Advanced Lipoprotein Testing and Subfractionation Are Not (Yet) Ready for Routine Clinical Use
Mora
Circulation 2009;119:2396-2404.
FULL TEXT  

Effects of Aspirin When Added to the Prostaglandin D2 Receptor Antagonist Laropiprant on Niacin-Induced Flushing Symptoms
Dishy et al.
J Clin Pharmacol 2009;49:416-422.
ABSTRACT | FULL TEXT  

Vascular-Protective Effects of High-Density Lipoprotein Include the Downregulation of the Angiotensin II Type 1 Receptor
Van Linthout et al.
Hypertension 2009;53:682-687.
ABSTRACT | FULL TEXT  

Lipoprotein Particle Profiles by Nuclear Magnetic Resonance Compared With Standard Lipids and Apolipoproteins in Predicting Incident Cardiovascular Disease in Women
Mora et al.
Circulation 2009;119:931-939.
ABSTRACT | FULL TEXT  

Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis
Briel et al.
BMJ 2009;338:b92-b92.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes--2009
American Diabetes Association
Diabetes Care 2009;32:S13-S61.
FULL TEXT  

HDL-cholesterol levels and cardiovascular risk: acCETPing the context
Lange and Lindsey
Eur Heart J 2008;29:2708-2709.
FULL TEXT  

Niacin Increases HDL by Reducing Hepatic Expression and Plasma Levels of Cholesteryl Ester Transfer Protein in APOE*3Leiden.CETP Mice
van der Hoorn et al.
Arterioscler. Thromb. Vasc. Bio. 2008;28:2016-2022.
ABSTRACT | FULL TEXT  

Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk
Thompson et al.
JAMA 2008;299:2777-2788.
ABSTRACT | FULL TEXT  

The Specific Amino Acid Sequence between Helices 7 and 8 Influences the Binding Specificity of Human Apolipoprotein A-I for High Density Lipoprotein (HDL) Subclasses: A POTENTIAL FOR HDL PREFERENTIAL GENERATION
Carnemolla et al.
J. Biol. Chem. 2008;283:15779-15788.
ABSTRACT | FULL TEXT  

Lipoprotein Management in Patients With Cardiometabolic Risk: Consensus Conference Report From the American Diabetes Association and the American College of Cardiology Foundation
Brunzell et al.
J Am Coll Cardiol 2008;51:1512-1524.
FULL TEXT  

Lipoprotein Management in Patients With Cardiometabolic Risk: Consensus statement from the American Diabetes Association and the American College of Cardiology Foundation
Brunzell et al.
Diabetes Care 2008;31:811-822.
FULL TEXT  

Association Between Cardiovascular Risk Profiles and the Presence and Extent of Different Types of Coronary Atherosclerotic Plaque as Detected by Multidetector Computed Tomography
Bamberg et al.
Arterioscler. Thromb. Vasc. Bio. 2008;28:568-574.
ABSTRACT | FULL TEXT  

Standards of Medical Care in Diabetes--2008
American Diabetes Association
Diabetes Care 2008;31:S12-S54.
FULL TEXT  

Effects of Torcetrapib in Patients at High Risk for Coronary Events
Barter et al.
NEJM 2007;357:2109-2122.
ABSTRACT | FULL TEXT  

High-Density Lipoprotein and Dietary Fatty Acids
Kim
JAMA 2007;298:2263-2264.
FULL TEXT  

DEBATING CARDIOVASCULAR GOALS
Pokrywka
DOC News 2007;4:5-5.
FULL TEXT