Deepa Mohan1, Andrew Mente2,3, Mahshid Dehghan2, Sumathy Rangarajan2, Martin O'Donnell4,5, Weihong Hu2, Gilles Dagenais6, Andreas Wielgosz7, Scott Lear8, Li Wei9, Rafael Diaz10, Alvaro Avezum11, Patricio Lopez-Jaramillo12, Fernando Lanas13, Sumathi Swaminathan14, Manmeet Kaur15, K Vijayakumar16, Viswanathan Mohan1, Rajeev Gupta17, Andrzej Szuba18, Romaina Iqbal19, Rita Yusuf20, Noushin Mohammadifard21, Rasha Khatib22,23, Khalid Yusoff24, Sadi Gulec25, Annika Rosengren26, Afzalhussein Yusufali27, Edelweiss Wentzel-Viljoen28, Jephat Chifamba29, Antonio Dans30, Khalid F Alhabib31, Karen Yeates32, Koon Teo2,3,4, Hertzel C Gerstein2,3,4, Salim Yusuf2,3,4. 1. Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, Chennai, India. 2. Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada. 3. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada. 4. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 5. HRB-Clinical Research Facility, NUI Galway, Ireland. 6. Université Laval Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada, G1V 4G5. 7. Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. 8. Faculty of Health Sciences, and Department of Biomedical Physiology & Kinesiology, Simon Fraser University, Vancouver, British Columbia, Canada. 9. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. 10. Estudios Clinicos Latinoamerica ECLA, Rosario, Santa Fe, Argentina. 11. International Research Centre, Hospital Alemao Oswaldo Cruz, Sao Paulo, Brazil, Universidade Santo Amaro (UNISA), Sao Paulo, SP Brazil. 12. Masira Research Institute, Medical School, Santander University (UDES), Colombia. 13. Universidad de La Frontera, Francisco Salazar, Temuco, Chile. 14. St John's Research Institute, Koramangala, Bangalore, India. 15. School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 16. Health Action by People, Amrita Institute of Medical Sciences, Trivandrum, Kerala, India. 17. Eternal Heart Care Centre and Research Institute, Rajasthan University of Health Sciences, Jaipur, India. 18. Wroclaw Medical University, Department of Internal Medicine, 4th Military Hospital, Wroclaw, Poland. 19. Department of Community Health Sciences and Medicine, Aga Khan University, Karachi Pakistan. 20. Independent University, Bangladesh, Bashundhara, Dhaka, Bangladesh. 21. Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran. 22. Institute for Community and Public Health, Birzeit University, Birzeit, Palestine. 23. Advocate Research Institute, Advocate Health Care, Chicago, Illinois. 24. Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia, UCSI University, Cheras, Selangor, Malaysia. 25. Cardiology Department, Ankara University Medical School, Ankara, Turkey. 26. Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra Hospital, Gothenburg, Sweden. 27. Hatta Hospital, Dubai Health Authority, Dubai Medical University, Dubai, United Arab Emirates. 28. Centre of Excellence for Nutrition, Faculty of Health Sciences, Potchefstroom, South Africa. 29. Physiology Department, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe. 30. University of the Philippines, Ermita, Manila, Philippines. 31. Department of Cardiac Sciences, King Fahad Cardiac Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia. 32. Department of Medicine, Etherington Hall, Queen's University, Kingston, Ontario, Canada.
Abstract
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.
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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