Omega-3 levels and stroke risk: a pooled and harmonized analysis of 183,291 participants from 29 prospective studies

Authors: O'KEEFE, JAMES - University Of Missouri; TINTLE, NATHAN - Fatty Acid Research Institute; HARRIS, WILLIAM - Fatty Acid Research Institute; O'KEEF, EVAN - Tulane University; SALA-VILA, ALEIX - Fatty Acid Research Institute; ATTIA, JOHN - University Of Newcastle; GARG, MANOHAR - University Of Newcastle; BORK, CHRISTIAN - Aalborg University Hospital; SCHMIDT, ERIK - Aalborg University Hospital; VENOE, STINE - Aalborg University Hospital; HURE, ALEXIS - University Of Newcastle; CHIEN, KUO-LIONG - National Taiwan University; EGERT, SARAH - University Of Bonn; FELDREICH, TOBIAS - Dalarna University; ARNLOV, JOHAN - Karolinska Institute; LIND, LARS - Uppsala University; FOROUHI, NITA - University Of Cambridge; GELEIJNSE, JOHANNA - Wageningen University; PERTIWI, KARMALITA - Wageningen University; IMAMURA, FUMIAKI - University Of Cambridge; LAAKSONEN, VANESSA - University Of Eastern Finland; UUSITUPA, MATTI - University Of Eastern Finland; TOUMILEHTO, JAAKKO - University For Continuing Education Krems; LAAKSO, MARKKU - University Of Kuopio; LANKINEN, MARIA - University Of Eastern Finland; LAURIN, DANIELLE - Laval University; CARMICHAEL, PIERRE-HUGUES - Vitam; LINDSAY, JOAN - University Of Ottawa; LEANDER, KARIN - Karolinska Institute; LAGUZZI, FREDERICA - Karolinska Institute; SWENSON, BRENTON - University Of Washington; LONGSTRETH, JR., W.T. - University Of Washington; MANSON, JOANN - Brigham & Women'S Hospital; MORA, SAMIA - Harvard Medical School; COOK, NANCY - Brigham & Women'S Hospital; MARKLAND, MATTI - The George Institute For Global Health; MELO VAN LENT, DEBORA - University Of Texas; MURPHY, RACHEL - University Of British Columbia; GUDNASON, VILMUNDUR - Icelandic Heart Association; NINOMIYA, TOSHIHARU - Kyushu University; HIRAKAWA, Y - Kyushu University; QIAN, FRANK - Beth Israel Deaconess Medical Center; SUN, QI - Brigham & Women'S Hospital; HU, FRANK - Harvard School Of Public Health; ARDISSON KORAT, ANDRES - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RISERUS, ULF - Uppsala University; LAZARA, IOLANDA - Hospital Del Mar Medical Research Institute; SAMIERI, CECILIA - Bordeaux University; LE GOFF, MELANIE - University Of Bordeaux; HELMER, CATHERINE - Institut National De La Sante Et De La Recherche Medicale (INSERM); STEUR, MARINKA - University Medical Center Rotterdam; VOORTMAN, TRUDY - Erasmus Medical Center; KAMRAN IKRAM, M. - Erasmus Medical Center; TANAKA, TOSHIKO - National Institute On Aging (NIA, NIH); DAS, JAYANTA - The Tata Institute Of Fundamental Research; FERRUCCI, LUIGI - National Institute On Aging (NIA, NIH); TSAI, MICHAEL - University Of Minnesota; GUAN, WEIHUA - University Of Minnesota; GARG, PARVEEN - University Of Southern California; VERSCHUREN, W.M. - National Institute For Public Health And The Environment (RIVM); BOER, JOLANDA - National Institute For Public Health And The Environment (RIVM); BLOKSTRA, ANNEKE - National Institute For Public Health And The Environment (RIVM); VIRTANEN, JYRKI - University Of Eastern Finland; WAGNER, MICHAEL - University Hospital Zurich; YAMAGISHI, KAZUMASA - University Of Tsukuba; SISCOVICK, DAVID - New York Academy Of Medicine; ROZENN, LAMAITRE - University Of Washington; MOZAFFARIAN, DARIUSH - Tufts University

Submitted to: Stroke
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/30/2023
Publication Date: 1/1/2024
Citation: O'Keefe, J., Tintle, N., Harris, W., O'Keefe, E., Sala-Vila, A., Attia, J., Garg, M., Bork, C., Schmidt, E., Venoe, S., Hure, A., Chien, K., Egert, S., Feldreich, T., Arnlov, J., Lind, L., Forouhi, N.G., Geleijnse, J., Pertiwi, K., Imamura, F., Laaksonen, V., Uusitupa, M., Toumilehto, J., Laakso, M., Lankinen, M., Laurin, D., Carmichael, P., Lindsay, J., Leander, K., Laguzzi, F., Swenson, B., Longstreth, Jr., W., Manson, J., Mora, S., Cook, N., Markland, M., Melo Van Lent, D., Murphy, R., Gudnason, V., Ninomiya, T., Hirakawa, Y., Qian, F., Sun, Q., Hu, F., Ardisson Korat, A., Riserus, U., Lazara, I., Samieri, C., Le Goff, M., Helmer, C., Steur, M., Voortman, T., Kamran Ikram, M., Tanaka, T., Das, J., Ferrucci, L., Tsai, M., Guan, W., Garg, P., Verschuren, W.M., Boer, J., Blokstra, A., Virtanen, J., Wagner, M., Yamagishi, K., Siscovick, D., Rozenn, L., Mozaffarian, D. 2024. Omega-3 levels and stroke risk: a pooled and harmonized analysis of 183,291 participants from 29 prospective studies. Stroke. https://doi.org/10.1161/STROKEAHA.123.044281.
DOI: https://doi.org/10.1161/STROKEAHA.123.044281

Interpretive Summary: The role of omega-3 polyunsaturated fatty acid intake in the development of stroke remains unclear. We evaluated the relationship between circulating and tissue markers of omega-3 fatty acid levels and incident stroke in a global pooled analysis of 29 cohorts that included ~183,000 participants without history of stroke at study enrollment. Each participating study measured omega-3 fatty acid levels from blood samples or adipose tissue provided by participants at study enrollment. Our study found that higher biomarker levels of omega-3 levels are associated with lower risks of total and ischemic stroke, which suggest a potential benefit of omega-3 fatty acid intake in the prevention of stroke.

Technical Abstract: Background: The effect of marine omega-3 polyunsaturated fatty acids (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 pre-specified analytical protocol with defined exposures, covariates, analytical methods and outcomes; the harmonized data from the 29 studies were then centrally pooled. Multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI) 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 (EPA), comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (0.83, CI 0.76-0.91; P<0.0001), and ischemic stroke was 18% lower (0.82, CI 0.74-0.91; P<0.0001). For docosahexaenoic acid (DHA), comparing Q5 with Q1, there was a 12% lower incidence of total stroke (0.88, CI 0.82-0.94; P=0.0001) and a 14% lower incidence of ischemic stroke (0.86, CI 0.79-0.94; P=0.0001). Neither EPA nor DHA was associated with risk for hemorrhagic stroke. These associations were not modified by either baseline history of atrial fibrillation (AF) or prevalent cardiovascular (CV) disease (CVD). Conclusion: Higher omega-3 levels are associated with lower risks of total and ischemic stroke, but not with hemorrhagic stroke.