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Original Investigation
March 8, 2021

Associations of Fish Consumption With Risk of Cardiovascular Disease and Mortality Among Individuals With or Without Vascular Disease From 58 Countries

Author Affiliations
  • 1Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialities Centre, Chennai, India
  • 2Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada
  • 3Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
  • 4Department of Medicine, McMaster University, Hamilton, Ontario, Canada;
  • 5HRB-Clinical Research Facility, NUI Galway, Ireland
  • 6Université Laval Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada, G1V 4G5
  • 7Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  • 8Faculty of Health Sciences, and Department of Biomedical Physiology & Kinesiology, Simon Fraser University, Vancouver, British Columbia, Canada
  • 9State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
  • 10Estudios Clinicos Latinoamerica ECLA, Rosario, Santa Fe, Argentina
  • 11International Research Centre, Hospital Alemao Oswaldo Cruz, Sao Paulo, Brazil, Universidade Santo Amaro (UNISA), Sao Paulo, SP Brazil
  • 12Masira Research Institute, Medical School, Santander University (UDES), Colombia
  • 13Universidad de La Frontera, Francisco Salazar, Temuco, Chile
  • 14St John’s Research Institute, Koramangala, Bangalore, India
  • 15School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India
  • 16Health Action by People, Amrita Institute of Medical Sciences, Trivandrum, Kerala, India
  • 17Eternal Heart Care Centre and Research Institute, Rajasthan University of Health Sciences, Jaipur, India
  • 18Wroclaw Medical University, Department of Internal Medicine, 4th Military Hospital, Wroclaw, Poland
  • 19Department of Community Health Sciences and Medicine, Aga Khan University, Karachi Pakistan
  • 20Independent University, Bangladesh, Bashundhara, Dhaka, Bangladesh
  • 21Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
  • 22Institute for Community and Public Health, Birzeit University, Birzeit, Palestine
  • 23Advocate Research Institute, Advocate Health Care, Chicago, Illinois
  • 24Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia, UCSI University, Cheras, Selangor, Malaysia
  • 25Cardiology Department, Ankara University Medical School, Ankara, Turkey
  • 26Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra Hospital, Gothenburg, Sweden
  • 27Hatta Hospital, Dubai Health Authority, Dubai Medical University, Dubai, United Arab Emirates
  • 28Centre of Excellence for Nutrition, Faculty of Health Sciences, Potchefstroom, South Africa
  • 29Physiology Department, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe
  • 30University of the Philippines, Ermita, Manila, Philippines
  • 31Department of Cardiac Sciences, King Fahad Cardiac Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  • 32Department of Medicine, Etherington Hall, Queen's University, Kingston, Ontario, Canada
JAMA Intern Med. 2021;181(5):631-649. doi:10.1001/jamainternmed.2021.0036
Key Points

Question  Is there a difference in the association of fish consumption with risk of cardiovascular disease (CVD) or of mortality between individuals with and individuals without vascular disease?

Findings  In this analysis of 4 international cohort studies of 191 558 people from 58 countries on 6 continents, a lower risk of major CVD and total mortality was associated with higher fish intake of at least 175 g (2 servings) weekly among high-risk individuals or patients with vascular disease, but not in general populations without vascular disease; a similar pattern of results was observed for sudden cardiac death. Oily fish but not other types of fish were associated with greater benefits.

Meaning  Study findings suggest that fish intake of at least 175 g (2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD, but not in the general population.


Importance  Cohort studies report inconsistent associations between fish consumption, a major source of long-chain ω-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown.

Objective  To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease.

Design, Setting, and Participants  This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies—147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. This analysis was conducted from January to June 2020.

Exposures  Fish consumption was recorded using validated food frequency questionnaires. In 1 of the cohorts with vascular disease, a separate qualitative food frequency questionnaire was used to assess intake of individual types of fish.

Main Outcomes and Measures  Mortality and major CVD events (including myocardial infarction, stroke, congestive heart failure, or sudden death).

Results  Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] male) were included in the present analysis. During 9.1 years of follow-up in PURE, compared with little or no fish intake (≤50 g/mo), an intake of 350 g/wk or more was not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 0.88-1.05). By contrast, in the 3 cohorts of patients with vascular disease, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/wk (or approximately 2 servings/wk) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher. Fish with higher amounts of ω-3 fatty acids were strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other fish were neutral (collected in 1 cohort of patients with vascular disease). The association between fish intake and each outcome varied by CVD status, with a lower risk found among patients with vascular disease but not in general populations (for major CVD, I2 = 82.6 [P = .02]; for death, I2 = 90.8 [P = .001]).

Conclusions and Relevance  Findings of this pooled analysis of 4 cohort studies indicated that a minimal fish intake of 175 g (approximately 2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease.

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    1 Comment for this article
    Fish consumption and cardiovascular disease risk
    Tomoyuki Kawada, MD | Nippon Medical School
    Mohan et al. examined the associations of fish consumption with risk of cardiovascular disease (CVD) or of mortality, stratified by the existence of vascular disease (1). Fish is a major source of long-chain omega-3 fatty acids, and a minimal fish intake of 175 g weekly was significantly associated with lower risk of major CVD and mortality among patients with prior CVD. But the significance disappeared in general populations. I have a comment about their study with special reference to dose-response relationship.

    There was no linear dose-response relationship in their study. Is there an optimal amount of fish intake? Exercise
    also interacts with food intake (2), and causes of statistical discrepancy between subjects with and without vascular disease might be complicated. Although nutritional information is important for preventing CVD events, patients with vascular disease might have a higher prevalence of undesired lifestyles including poor fish consumption. In addition, higher amount of fish consumption would relate to overdose of food consumption. I suppose that ethnic difference would also have an effect on the association, because Mohan et al. analyzed data from many countries.

    There is a meta-analysis of randomized controlled trials. Hu et al. reported that marine omega-3 supplementation lowered the risk for myocardial infarction, coronary heart disease (CHD) death, total CHD, CVD death, and total CVD, and risk reductions were linearly related to marine omega-3 dose (3). In any case, further prospective/intervention studies are needed to verify the dose-response relationship.

    1. Mohan D, Mente A, Dehghan M, et al. Associations of Fish Consumption With Risk of Cardiovascular Disease and Mortality Among Individuals With or Without Vascular Disease From 58 Countries. JAMA Intern Med 2021 doi: 10.1001/jamainternmed.2021.0036. Epub ahead of print
    2. Clifton PM. Diet, exercise and weight loss and dyslipidaemia. Pathology 2019;51(2):222-226.
    3. Hu Y, Hu FB, Manson JE. Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants. J Am Heart Assoc 2019;8(19):e013543.