Singh Inder M, Shishehbor Mehdi H, Ansell Benjamin J
Department of Cardiovascular Medicine, Krannert Institute of Cardiology, Indiana University Medical Center, Indianapolis, USA.
JAMA. 2007 Aug 15;298(7):786-98. doi: 10.1001/jama.298.7.786.
High-density lipoprotein cholesterol (HDL-C) is a cardiovascular risk factor that is gaining substantial interest as a therapeutic target.
To review the current and emerging strategies that modify high-density lipoproteins (HDLs).
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 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.
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.
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.
高密度脂蛋白胆固醇（HDL-C）是一种心血管危险因素，作为治疗靶点正受到广泛关注。
综述当前及新出现的改善高密度脂蛋白（HDL）的策略。
在MEDLINE和Cochrane数据库中系统检索1965年至2007年5月的英文文献，使用关键词HDL-C和载脂蛋白A-I以及副标题逆向胆固醇转运、心血管疾病（CVD）预防与控制、药物治疗和疗法；回顾2003年至2007年主要心血管会议上的报告；以及回顾ClinicalTrials.gov上正在进行的试验和主要心血管学会的现行指南。
研究选择优先考虑随机对照试验而非荟萃分析和机制研究；确定的研究还包括概念验证研究以及新型药物的关键1期至3期试验。由2位作者评估研究的合格性；分歧通过与第三位作者达成共识来解决。
在识别出的754项研究中，31项随机对照试验符合纳入标准。目前可用的治疗和生活方式策略在优化后可使HDL-C水平提高20%至30%。虽然基础研究和小型试点研究显示出前景，但证明提高HDL-C水平能在不依赖低密度脂蛋白胆固醇或甘油三酯水平变化的情况下降低主要心血管结局的证据却更难获得。人体研究中的一些新型治疗药物似乎能有效提高HDL-C水平，而其他针对HDL代谢或功能的新策略可能对HDL-C水平影响甚微。
目前仅有适度证据支持在仅通过生活方式改善所达到的基础上积极提高HDL-C水平。针对HDL代谢特定途径的正在进行的临床试验可能有助于扩大心血管治疗选择。
