Omega-3脂肪酸与心血管疾病:最新的系统综述。

Ethan M Balk, Gaelen P Adams, Valerie Langberg, Christopher Halladay, Mei Chung, Lin Lin, Sarah Robertson, Agustin Yip, Dale Steele, Bryant T Smith, Joseph Lau, Alice H Lichtenstein, Thomas A Trikalinos
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引用次数: 42

摘要

背景:ω -3脂肪酸(n- 3fa)摄入和生物标志物水平对心血管(CV)临床和中期结局的影响和关联仍然存在争议。我们更新了先前关于n-3 FA与临床和中期心血管疾病(CVD)结局的证据报告。目的:评估n- 3fa对临床和选定的中间CV结局的影响,以及n- 3fa摄入量和生物标志物与CV结局的关系。正在审查的n-3 FA包括二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)、二十二碳五烯酸(DPA)、硬脂酸(SDA)和α亚麻酸(ALA)。数据来源:MEDLINE®、Embase®、Cochrane Central Register of Controlled Trials、Cochrane Database of Systematic Reviews和CAB Abstracts(2000年或2002年至2015年6月8日),以及原始报告和相关现有系统综述中的符合条件的研究。回顾方法:我们纳入了随机对照试验(rct),将任何n- 3fa摄入量与不摄入、低摄入量或其他n- 3fa摄入量进行比较,并对健康成人、有心血管疾病风险者或心血管疾病患者的结果感兴趣。我们还纳入了基线n-3 FA摄入量或生物标志物水平与随访结果之间关系的前瞻性观察性研究。临床结果需要1年或更长时间的随访,中期结果(血压和血脂)需要4周的随访。结果:在11440篇引用(来自电子文献检索和现有系统综述)中,829篇摘要符合基本资格标准;纳入61项随机对照试验和37项纵向观察研究(147篇文章)。大多数随机对照试验和观察性研究很少涉及偏倚风险。总n- 3fa:低强度证据(SoE)表明总n- 3fa摄入与卒中死亡或心肌梗死之间没有关联。其他结果的证据不足。海洋油,总:有中等至高的SoE,较高的海洋油摄入量降低甘油三酯(Tg),提高高密度脂蛋白胆固醇(HDL-c),降低总胆固醇与HDL-c的比率,但提高低密度脂蛋白胆固醇(LDL-c);此外,较高的海洋石油摄入量不会影响主要不良心血管事件、全因死亡、全卒中、心源性猝死、冠状动脉血运重建术、心房颤动或血压。较高的海洋油摄入量与心血管疾病死亡、冠心病、心肌梗死、缺血性中风和充血性心力衰竭风险降低之间的关联程度较低。低SoE与冠心病死亡或出血性中风无关。其他结果的证据不足。单独的海洋油FA: EPA或DHA摄入(单独)与冠心病之间,EPA或DPA与房颤之间,存在低SoE或无关联。低SoE表明EPA生物标志物与房颤之间没有关联,但中等SoE表明补充纯化DHA对血压或LDL-c没有影响。没有足够的证据表明其他特定的海洋石油FA和结果。ALA:摄入ALA对血压、LDL-c、HDL-c或Tg没有影响。ALA摄入量或生物标志物水平与冠心病、冠心病死亡、心房颤动和CHF之间的SoE较低,无相关性。其他结果的证据不足。其他n-3 FA分析:没有足够的证据比较n-3 FA彼此或SDA。亚组分析:22项研究中有19项发现性别对n- 3fa的任何影响没有相互作用。同样,20项研究中有19项发现他汀类药物联合使用没有差异效应。在16项评估糖尿病亚组的研究中,有2项发现n- 3fa在糖尿病患者中有统计学意义的有益作用,而在非糖尿病患者中没有,但没有报道相互作用的测试。结论:61项随机对照试验主要比较了海洋油补充剂与安慰剂在心血管疾病风险人群或患有心血管疾病人群中的心血管疾病结局,而37项观察性研究主要检查了一般健康人群中各种个体n-3脂肪酸与长期心血管疾病事件之间的关系。与之前关于n- 3fa和CVD的报道相比,ALA和临床CV结局的RCT证据更加可靠;此外,通过设计,还增加了n- 3fa生物标志物与CV结果之间关联的新数据。然而,关于n-3脂肪酸摄入对心血管结果的影响或与结果的关联的结论基本保持不变。海洋油在统计学上显著提高HDL-c和LDL-c(≤2 mg/dL),同时以剂量依赖的方式降低Tg,特别是在Tg升高的个体中;它们对血压没有显著影响。ALA对中期结果无显著影响。关于n- 3fa对临床CVD结果影响的随机对照试验数据有限。观察性研究表明,较高的海洋油摄入量(包括食用鱼类)与几种心血管疾病结局的风险较低相关。 在人口、人口统计学特征或联合干预方面,没有明显的效果差异或关联。未来的随机对照试验需要建立足够的证据来证明n- 3fa对心血管疾病结局的影响,或澄清不同人群的差异影响。然而,未来的试验不太可能改变补充n- 3fa对中间心血管结局(血压、LDL-c、HDL-c或Tg)影响的结论。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review.

Background: The effect and association of omega-3 fatty acids (n-3 FA) intake and biomarker levels with cardiovascular (CV) clinical and intermediate outcomes remains controversial. We update prior Evidence Reports of n-3 FA and clinical and intermediate CV disease (CVD) outcomes.

Objectives: Evaluate the effect of n-3 FA on clinical and selected intermediate CV outcomes and the association of n-3 FA intake and biomarkers with CV outcomes. The n-3 FA under review include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), stearidonic acid (SDA), and alphalinolenic acid (ALA).

Data sources: MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CAB Abstracts from 2000 or 2002 to June 8, 2015, and eligible studies from the original reports and relevant existing systematic reviews.

Review methods: We included randomized controlled trials (RCTs) of any n-3 FA intake compared to no, lower, or other n-3 FA intake with an outcome of interest conducted in healthy adults, those at risk for CVD, or those with CVD. We also included prospective observational studies of the association between baseline n-3 FA intake or biomarker level and followup outcomes. We required 1 year or more of followup for clinical outcomes and 4 weeks for intermediate outcomes (blood pressure [BP] and lipids).

Results: From 11,440 citations (from electronic literature searches and existing systematic reviews), 829 abstracts met basic eligibility criteria; 61 RCTs and 37 longitudinal observational studies (in 147 articles) were included. Most RCTs and observational studies had few risk-of-bias concerns.

Total n-3 FA: There is low strength of evidence (SoE) of no association between total n-3 FA intake and stroke death or myocardial infarction. There is insufficient evidence for other outcomes.

Marine oils, total: There is moderate to high SoE that higher marine oil intake lowers triglycerides (Tg), raises high density lipoprotein cholesterol (HDL-c), and lowers the ratio of total cholesterol to HDL-c but raises low density lipoprotein cholesterol (LDL-c); also that higher marine oil intake does not affect major adverse CV events, all-cause death, total stroke, sudden cardiac death, coronary revascularization, atrial fibrillation, or BP. There is low SoE of associations between higher marine oil intake and decreased risk of CVD death, coronary heart disease (CHD), myocardial infarction, ischemic stroke, and congestive heart failure (CHF). There is low SoE of no association with CHD death or hemorrhagic stroke. There is insufficient evidence for other outcomes.

Marine oil FA individually: There is low SoE of no associations between EPA or DHA intake (separately) and CHD, and between EPA or DPA and atrial fibrillation. There is low SoE of no association between EPA biomarkers and atrial fibrillation, but moderate SoE of no effect of purified DHA supplementation on BP or LDL-c. There is insufficient evidence for other specific marine oil FA and outcomes.

ALA: There is moderate SoE of no effect of ALA intake on BP, LDL-c, HDL-c, or Tg. There is low SoE of no association between ALA intake or biomarker level and CHD, CHD death, atrial fibrillation, and CHF. There is insufficient evidence for other outcomes.

Other n-3 FA analyses: There is insufficient evidence comparing n-3 FA with each other or for SDA.

Subgroup analyses: Nineteen of 22 studies found no interaction of sex on any effect of n-3 FA. Likewise, 19 of 20 studies found no differential effect by statin co-use. Within 16 studies evaluating diabetes subgroups, 2 found statistically significant beneficial effects of n-3 FA in those with diabetes but not in those without diabetes, but no test of interaction was reported.

Conclusions: The 61 RCTs mostly compared marine oil supplements with placebo on CVD outcomes in populations at risk for CVD or with CVD, while the 37 observational studies mostly examined associations between various individual n-3 FA and long-term CVD events in generally healthy populations. Compared with the prior report on n-3 FA and CVD, there is more robust RCT evidence on ALA and on clinical CV outcomes; also, by design there are newly added data on associations between n-3 FA biomarkers and CV outcomes. However, conclusions regarding the effect of n-3 FA intake on CV outcomes or associations with outcomes remain substantially unchanged. Marine oils statistically significantly raise HDL-c and LDL-c by similar amounts (≤2 mg/dL), while lowering Tg in a dose-dependent manner, particularly in individuals with elevated Tg; they have no significant effect on BP. ALA has no significant effect on intermediate outcomes. Limited data were available from RCTs on the effect of n-3 FA on clinical CVD outcomes. Observational studies suggest that higher marine oil intake (including from dietary fish) is associated with lower risk of several CVD outcomes. No clear differences in effects or associations were evident based on population, demographic features, or cointerventions. Future RCTs would be needed to establish adequate evidence of the effect of n-3 FA on CVD outcomes or to clarify differential effects in different groups of people. However, future trials are unlikely to alter conclusions about the effects of n-3 FA supplementation on intermediate cardiovascular outcomes (BP, LDL-c, HDL-c, or Tg).

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