ω-3 Fatty acids, atherosclerosis progression and cardiovascular outcomes in recent trials: new pieces in a complex puzzle
Open accessAbstract
The cardiovascular effects of seafood-derived n-3 polyunsaturated fatty acids (n-3 PUFA) have been examined in a diverse and continually expanding array of studies ranging from in vitro molecular experiments to large randomised controlled trials. In contrast to earlier trials, recent clinical trials have not observed significant effects of n-3 PUFA supplementation on cardiovascular disease (CVD) events.1 ,2 These mixed findings have stimulated renewed debate and interest about the role of n-3 PUFA for CVD prevention and treatment. Sekikawa and colleagues investigated whether circulating n-3 PUFA levels were associated with differences in new-onset of coronary artery calcification (CAC) between middle-aged men in Japan and the USA.3 Measurement of CAC by electron beam CT provides an estimate of overall coronary atherosclerotic burden. While CAC does not necessarily identify with plaque morphology or propensity for rupture, overall CAC burden does predict future risk of clinical CVD events. In this case, investigating the association of circulating n-3 PUFA with serial measures of CAC addresses the interesting hypothesis that these fats might slow atherosclerosis progression, providing mechanistic insight that would be complimentary to studies of clinical endpoints. In this investigation, Japanese men had substantially (∼150%) higher circulating n-3 PUFA than did US men, consistent with much higher levels of seafood consumption in Japan. Japanese men also had a substantially lower incidence of new CAC (rate ratio=0.26, 95%CI=0.09 to 0.73), compared with US men, which was not explained by adjustment for conventional CVD risk factors including age, systolic blood pressure, cholesterol, triglycerides, BMI, diabetes, smoking and hypertension medication. In contrast, the association between country (Japan vs USA) and incident CAC was attenuated following adjustment for serum n-3 PUFA. The authors concluded that n-3 PUFA may have antiatherosclerotic effects at levels observed in Japan. While this analysis has several strengths, including use of objective …
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More recent omega-3 therapy outcome studies conducted in the presence of statins have been less encouraging, but evaluated nonhypertriglyceridemic patient populations and administered low doses of long-chain omega-3 fatty acids.
“Other more recent omega‐3 therapy outcome studies conducted in the presence of statins have been less encouraging, but these studies were characterized by evaluating nonhypertriglyceridemic patient populations (eg, TG <200 mg/dL) and administering low doses of long‐chain omega‐3 fatty acids (eg, eicosapentaenoic acid [EPA] and/or docosoahexaenoic acid [DHA]).19, 20, 21, 22, 23, 24”
From Rationale and design of <scp>REDUCE‐IT</scp> : Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (2017) · cites this paper as [19]
The main text (page not available in our copy) reports that all six more recent trials failed to show significant effects, that background lipid-lowering medication use was very high, and that supplementation was modest (for example, 1 g/day). It does not establish that those trials enrolled nonhypertriglyceridemic populations or had triglyceride levels below 200 mg/dL. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEven among omega-3 fatty acid studies, there are marked differences with respect to the relatively low doses of omega-3 administered and the ratio of EPA to DHA.
“Even among omega‐3 fatty acid studies, there are marked differences with respect to the relatively low doses of omega‐3 administered and the ratio of EPA to DHA.16, 17, 18, 19, 20, 21, 22, 23, 24”
From Rationale and design of <scp>REDUCE‐IT</scp> : Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (2017) · cites this paper as [19]
In the main text (page unavailable), the paper describes supplementation in recent trials as modest (for example, 1 g/day) and calls for trials of higher doses. That supports the low-dose aspect, but our copy does not discuss differences between studies in the EPA-to-DHA ratio. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn cohort-harmonized, stratified analyses, there was little evidence of effect modification by statin or aspirin use.
“In cohort-harmonized, stratified analyses, we found little evidence of effect modification by statin or aspirin use, which have been hypothesized to reduce benefits of ω-3 fattyacids.54”
From ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies (2016) · cites this paper as [54]
In meta-analyses of multiple controlled interventions, fish and omega-3 consumption improve major physiologic risk factors including BP, heart rate, endothelial function, triglycerides, and adiponectin.
“Notably, in meta-analyses of multiple controlled interventions, fish and omega-3 consumption improve major physiologic risk factors including BP, heart rate, endothelial function, triglycerides, and adiponectin.201, 205”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [205]
Omega-3's reduce inflammatory biomarkers, reduce myocardial oxygen utilization, and enhance cardiac function.
“Omega-3's also reduce inflammatory biomarkers, reduce myocardial oxygen utilization, and enhance cardiac function.201, 205”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [205]
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“reduce inflammatory biomarkers, reduce myocardial oxygen use, and enhance cardiac function.(201,205) Overall, although the”
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- Authors
- Wu, J. H. Y., & Mozaffarian, D.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Wu, Jason H Y
- Venue
- Heart
- Publisher
- BMJ
- Published
- 2014-01-23
- Volume
- 100
- Issue
- 7
- Pages
- 530-533
- ISSN
- 1355-6037 (ISSN-L)
- 1468-201X
- PMC
- PMC6269084
- OpenAlex
- W1974775396
- Cited by
- 47
- References
- 32
- Citations by year
- 2023: 1 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 7 · 2016: 13 · 2015: 6 · 2014: 4
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Heart (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL085710)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Aquaculture Nutrition and Growth
- Keywords
- omega-3 fatty acids, atherosclerosis progression, coronary artery calcification, cardiovascular disease prevention, seafood consumption, cardiovascular outcomes, Japanese men, cross-national comparison
- MeSH terms
- Cardiovascular Diseases, Humans, Fatty Acids, Omega-3, Disease Progression, Atherosclerosis
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