High-density lipoprotein as a therapeutic target: a systematic review - PubMed (original) (raw)
Review
. 2007 Aug 15;298(7):786-98.
doi: 10.1001/jama.298.7.786.
Affiliations
- PMID: 17699012
- DOI: 10.1001/jama.298.7.786
Review
High-density lipoprotein as a therapeutic target: a systematic review
Inder M Singh et al. JAMA. 2007.
Erratum in
- JAMA. 2007 Oct 3;298(13):1516
Abstract
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.
Comment in
- High-density lipoprotein and dietary fatty acids.
Kim DH. Kim DH. JAMA. 2007 Nov 21;298(19):2263-4; author reply 2264. doi: 10.1001/jama.298.19.2263-c. JAMA. 2007. PMID: 18029828 No abstract available.
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