ω-3 多不饱和脂肪酸生物标志物与冠心病：19 项队列研究的汇总项目。
ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.
机构信息
Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California.
Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom.
出版信息
JAMA Intern Med. 2016 Aug 1;176(8):1155-66. doi: 10.1001/jamainternmed.2016.2925.
IMPORTANCE
The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers.
OBJECTIVE
To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD.
DATA SOURCES
A global consortium of 19 studies identified by November 2014.
STUDY SELECTION
Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD.
DATA EXTRACTION AND SYNTHESIS
Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes.
MAIN OUTCOMES AND MEASURES
Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI).
RESULTS
The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses.
CONCLUSIONS AND RELEVANCE
On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.
重要性
ω-3 多不饱和脂肪酸在冠心病（CHD）一级预防中的作用仍存在争议。大多数先前的纵向研究评估了自我报告的消耗，而不是生物标志物。
目的
评估来源于海鲜的二十碳五烯酸（EPA；20:5ω-3）、二十二碳五烯酸（DPA；22:5ω-3）和二十二碳六烯酸（DHA；22:6ω-3）以及植物源性 α-亚麻酸（ALA；18:3ω-3）的生物标志物与冠心病发病的关系。
数据来源
2014 年 11 月前确定的全球 19 项研究的联合体。
研究选择
具有循环或组织ω-3 生物标志物和确定冠心病的前瞻性（队列、嵌套病例对照）或回顾性研究。
数据提取和综合
每项研究均采用标准化、个体水平分析，使用协调一致的模型、暴露、结局和协变量。采用随机效应荟萃分析集中汇总发现。通过年龄、性别、种族、糖尿病、他汀类药物、阿司匹林、ω-6 水平和 FADS 去饱和酶基因来检验异质性。
主要结局和测量指标
总冠心病、致死性冠心病和非致死性心肌梗死（MI）。
结果
这 19 项研究来自 16 个国家，涵盖了 45637 名个体，共发生 7973 例总冠心病、2781 例致死性冠心病和 7157 例非致死性 MI。总血浆、磷脂、胆固醇酯和脂肪组织中均测量了 ω-3 生物标志物。基线时的中位年龄为 59 岁（范围，18-97 岁），28660 名（62.8%）为男性。多变量调整分析表明，ALA、DPA 和 DHA 这三种 ω-3 生物标志物与致死性冠心病的风险降低相关，其相对风险（RR）分别为 0.91（95%CI，0.84-0.98）、0.90（95%CI，0.85-0.96）和 0.90（95%CI，0.84-0.96）。尽管 DPA 与总冠心病（RR，0.94；95%CI，0.90-0.99）风险降低相关，但 ALA（RR，1.00；95%CI，0.95-1.05）、EPA（RR，0.94；95%CI，0.87-1.02）和 DHA（RR，0.95；95%CI，0.91-1.00）并无此关联。非致死性 MI 也未显示出明显的关联。在磷脂和总血浆中，关联似乎更强。受限三次样条分析并未发现剂量反应呈非线性的证据。
结论和相关性
基于全球自由生活人群的现有研究，海鲜和植物源性 ω-3 脂肪酸的生物标志物浓度与致死性冠心病的发病率略有降低相关。
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