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Omega-3 Fatty Acids and Cardiovascular Disease
Evidence Reports/Technology Assessments, No. 223
Investigators: Ethan M Balk, MD, MPH, Gaelen P Adam, MLIS, Valerie Langberg, ScM, Christopher Halladay, BA, ScM, Mei Chung, MPH, PhD, Lin Lin, MA, ScM, Sarah Robertson, BS, Agustin Yip, MD, Dale Steele, MD, Bryant T Smith, MPH, CPH, Joseph Lau, MD, Alice H Lichtenstein, DSc, and Thomas A Trikalinos, MD, PhD.
Author Information and AffiliationsStructured Abstract
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).
Contents
- Preface
- Technical Expert Panel
- Peer Reviewers
- Executive Summary
- Introduction
- Methods
- Results
- Summary of Studies
- Study Risk of Bias
- Major Adverse Cardiovascular Events
- CVD Death (Including Stroke)
- Cardiac Death
- Coronary Heart Disease Death
- Myocardial Infarction Death
- Congestive Heart Failure Death
- Stroke Death, Total (Ischemic and Hemorrhagic)
- Ischemic Stroke Death
- Hemorrhagic Stroke Death
- Death, All-Cause
- Coronary Heart Disease, Incident
- Myocardial Infarction, Total (Fatal and Nonfatal)
- Revascularization
- Acute Coronary Syndrome
- Angina Pectoris
- Stroke, Total (Ischemic and Hemorrhagic, Fatal and Nonfatal)
- Stroke, Ischemic (Fatal and Nonfatal)
- Stroke, Hemorrhagic (Fatal and Nonfatal)
- Sudden Cardiac Death
- Atrial Fibrillation
- Ventricular Arrhythmia
- Congestive Heart Failure
- Hypertension, Incident
- Blood Pressure, Systolic and Diastolic
- Mean Arterial Pressure
- Low Density Lipoprotein Cholesterol
- High Density Lipoprotein Cholesterol
- Triglycerides
- Total Cholesterol to HDL-c Ratio
- LDL-c to HDL-c Ratio
- Adverse Events
- Summary by n-3 FA
- Subgroup Analyses Summary
- Summary by Key Question
- Discussion
- References
- Abbreviations
- Appendix A. Search Strategy
- Appendix B. Excluded Studies
- Appendix C. Risk of Bias Assessment
- Appendix D. Baseline Characteristics
- Appendix E. Study Design
- Appendix F. Observational results
- Appendix G. Causality Tables
Suggested citation:
Balk EM, Adam GP, Langberg V, Halladay C, Chung M, Lin L, Robertson S, Yip A, Steele D, Smith BT, Lau J, Lichtenstein AH, Trikalinos TA. Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review. Evidence Report/Technology Assessment No. 223. (Prepared by the Brown Evidence-based Practice Center under Contract No. 290-2012-00012-I.) AHRQ Publication No. 16-E002-EF. Rockville, MD: Agency for Healthcare Research and Quality; August 2016. www.effectivehealthcare.ahrq.gov/reports/final.cfm. DOI: https://doi.org/10.23970/AHRQEPCERTA223.
This report is based on research conducted by the Brown Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2012-00012-I). The report is sponsored by the National Institutes of Health Office of Dietary Supplements (NIH/ODS). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ or NIH/ODS. Therefore, no statement in this report should be construed as an official position of AHRQ, NIH/ODS, or the U.S. Department of Health and Human Services.
None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.
The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.
AHRQ or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.
This report may periodically be assessed for the currency of conclusions. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program Web site at www.effectivehealthcare.ahrq.gov. Search on the title of the report.
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- Omega-3 Fatty Acids and Cardiovascular DiseaseOmega-3 Fatty Acids and Cardiovascular Disease
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- LIMK1 LIM domain kinase 1 [Gallus gallus]LIMK1 LIM domain kinase 1 [Gallus gallus]Gene ID:373922Gene
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