O'Keefe JH, Tintle NL, Harris WS, O'Keefe EL, Sala-Vila A, Attia J, Garg GM, Hure A, Bork CS, Schmidt EB, Venø SK, Chien KL, Chen YA, Egert S, Feldreich TR, Ärnlöv J, Lind L, Forouhi NG, Geleijnse JM, Pertiwi K, Imamura F, de Mello Laaksonen V, Uusitupa WM, Tuomilehto J, Laakso M, Lankinen MA, Laurin D, Carmichael PH, Lindsay J, Leander K, Laguzzi F, Swenson BR, Longstreth WT, Manson JE, Mora S, Cook NR, Marklund M, Melo van Lent D, Murphy R, Gudnason V, Ninomiya T, Hirakawa Y, Qian F, Sun Q, Hu F, Ardisson Korat AV, Risérus U, Lázaro I, Samieri C, Le Goff M, Helmer C, Steur M, Voortman T, Ikram MK, Tanaka T, Das JK, Ferrucci L, Bandinelli S, Tsai M, Guan W, Garg P, Verschuren WMM, Boer JMA, Biokstra A, Virtanen J, Wagner M, Westra J, Albuisson L, Yamagishi K, Siscovick DS, Lemaitre RN, and Mozaffarian D
Background: The effect of marine omega-3 PUFAs on risk of stroke remains unclear., Methods: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome., Results: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P <0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P <0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P =0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P =0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD., Conclusions: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke., Competing Interests: Disclosures Dr O’Keefe reports major ownership interest in Cardiotabs. Dr Harris reports minor ownership interest in Omegaquant Analytics, LLC. Dr Sala-Vila reports travel and grant support from California Walnut Commission. Dr Mora reports compensation for consultant services from Quest Diagnostics. Dr Murphy reports compensation from Pharmavite for consultant services. Dr Bork reports grants from Karen Elise Jensens Fond. Dr Ärnlöv reports compensation from Astellas Pharma for other services; compensation from Boehringer Ingelheim for consultant services; compensation from AstraZeneca for other services; and compensation from Novartis for other services. Dr Geleijnse reports grants from National Institutes of Health to other; grants from Upfield Europe BV to other; and grants from The Dutch Heart Foundation to other. Dr Manson reports grants from National Institutes of Health and compensation from National Institutes of Health for other services. Dr Mora reports compensation from Pfizer for consultant services; employment by Brigham and Women’s Hospital; grants from National Institute of Diabetes and Digestive and Kidney Diseases; and grants from National Heart, Lung, and Blood Institute. Dr Melo van Lent reports grants from National Institutes of Health and grants from Alzheimer’s Association. Dr Mozaffarian reports grants from Rockefeller Foundation; compensation from Beren Therapeutics for other services; stock holdings in HumanCo; compensation from January Inc. for other services; compensation from Filtricine for other services; compensation from Perfect Day for other services; compensation from Tiny Organics for other services; grants from Bill and Melinda Gates Foundation; compensation from Calibrate for other services; grants from Vail Innovative Global Research; grants from Kaiser Permanente Fund at East Bay Community Foundation; compensation from DayTwo for other services; compensation from Instacart health for other services; compensation from Season Health for other services; grants from National Institutes of Health; compensation from Barilla for consultant services; stock holdings in Calibrate; compensation from Kaiser Permanente Fund for other services; compensation from HumanCo for other services