Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies

James H O'Keefe; Nathan L Tintle; William S Harris; Evan L O'Keefe; Aleix Sala-Vila; John Attia; G Manohar Garg; Alexis Hure; Christian Sørensen Bork; Erik Berg Schmidt; Stine Krogh Venø; Kuo-Liong Chien; Yun-Yu Amelia Chen; Sarah Egert; Tobias Rudholm Feldreich; Johan Ärnlöv; Lars Lind; Nita G Forouhi; Johanna M Geleijnse; Kamalita Pertiwi; Fumiaki Imamura; Vanessa de Mello Laaksonen; W Matti Uusitupa; Jaakko Tuomilehto; Markku Laakso; Maria Anneli Lankinen; Danielle Laurin; Pierre-Hugues Carmichael; Joan Lindsay; Karin Leander; Federica Laguzzi; Brenton R Swenson; William T Longstreth; JoAnn E Manson; Samia Mora; Nancy R Cook; Matti Marklund; Debora Melo van Lent; Rachel Murphy; Vilmundur Gudnason; Toshihara Ninomiya; Yoichiro Hirakawa; Frank Qian; Qi Sun; Frank Hu; Andres V Ardisson Korat; Ulf Risérus; Iolanda Lázaro; Cecilia Samieri; Mélanie Le Goff; Catherine Helmer; Marinka Steur; Trudy Voortman; M Kamran Ikram; Toshiko Tanaka; Jayanta K Das; Luigi Ferrucci; Stefania Bandinelli; Michael Tsai; Weihua Guan; Parveen Garg; W M Monique Verschuren; Jolanda M A Boer; Anneke Biokstra; Jyrki Virtanen; Michael Wagner; Jason Westra; Luc Albuisson; Kazumasa Yamagishi; David S Siscovick; Rozenn N Lemaitre; Dariush Mozaffarian

doi:10.1161/STROKEAHA.123.044281

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies

James H O'Keefe^*, Nathan L Tintle, William S Harris, Evan L O'Keefe, Aleix Sala-Vila, John Attia, G Manohar Garg, Alexis Hure, Christian Sørensen Bork, Erik Berg Schmidt, Stine Krogh Venø, Kuo-Liong Chien, Yun-Yu Amelia Chen, Sarah Egert, Tobias Rudholm Feldreich, Johan Ärnlöv, Lars Lind, Nita G Forouhi, Johanna M Geleijnse, Kamalita PertiwiFumiaki Imamura, Vanessa de Mello Laaksonen, W Matti Uusitupa, Jaakko Tuomilehto, Markku Laakso, Maria Anneli Lankinen, Danielle Laurin, Pierre-Hugues Carmichael, Joan Lindsay, Karin Leander, Federica Laguzzi, Brenton R Swenson, William T Longstreth, JoAnn E Manson, Samia Mora, Nancy R Cook, Matti Marklund, Debora Melo van Lent, Rachel Murphy, Vilmundur Gudnason, Toshihara Ninomiya, Yoichiro Hirakawa, Frank Qian, Qi Sun, Frank Hu, Andres V Ardisson Korat, Ulf Risérus, Iolanda Lázaro, Cecilia Samieri, Mélanie Le Goff, Catherine Helmer, Marinka Steur, Trudy Voortman, M Kamran Ikram, Toshiko Tanaka, Jayanta K Das, Luigi Ferrucci, Stefania Bandinelli, Michael Tsai, Weihua Guan, Parveen Garg, W M Monique Verschuren, Jolanda M A Boer, Anneke Biokstra, Jyrki Virtanen, Michael Wagner, Jason Westra, Luc Albuisson, Kazumasa Yamagishi, David S Siscovick, Rozenn N Lemaitre, Dariush Mozaffarian

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	50-58
Number of pages	9
Journal	Stroke
Volume	55
Issue number	1
DOIs	https://doi.org/10.1161/STROKEAHA.123.044281
Publication status	Published - Jan 2024

Keywords

Docosahexaenoic Acids
Eicosapentaenoic Acid
Fatty Acids, Omega-3
Hemorrhagic Stroke/epidemiology
Humans
Ischemic Stroke
Prospective Studies
Risk Factors
Stroke/epidemiology

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10.1161/STROKEAHA.123.044281

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O'Keefe, J. H., Tintle, N. L., Harris, W. S., O'Keefe, E. L., Sala-Vila, A., Attia, J., Garg, G. M., Hure, A., Bork, C. S., Schmidt, E. B., Venø, S. K., Chien, K.-L., Chen, Y.-Y. A., Egert, S., Feldreich, T. R., Ärnlöv, J., Lind, L., Forouhi, N. G., Geleijnse, J. M., ... Mozaffarian, D. (2024). Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies. Stroke, 55(1), 50-58. https://doi.org/10.1161/STROKEAHA.123.044281

@article{ee48f09663794ae2ac8eb457f9545097,

title = "Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies",

abstract = "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.",

keywords = "Docosahexaenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Hemorrhagic Stroke/epidemiology, Humans, Ischemic Stroke, Prospective Studies, Risk Factors, Stroke/epidemiology",

author = "O'Keefe, {James H} and Tintle, {Nathan L} and Harris, {William S} and O'Keefe, {Evan L} and Aleix Sala-Vila and John Attia and Garg, {G Manohar} and Alexis Hure and Bork, {Christian S{\o}rensen} and Schmidt, {Erik Berg} and Ven{\o}, {Stine Krogh} and Kuo-Liong Chien and Chen, {Yun-Yu Amelia} and Sarah Egert and Feldreich, {Tobias Rudholm} and Johan {\"A}rnl{\"o}v and Lars Lind and Forouhi, {Nita G} and Geleijnse, {Johanna M} and Kamalita Pertiwi and Fumiaki Imamura and {de Mello Laaksonen}, Vanessa and Uusitupa, {W Matti} and Jaakko Tuomilehto and Markku Laakso and Lankinen, {Maria Anneli} and Danielle Laurin and Pierre-Hugues Carmichael and Joan Lindsay and Karin Leander and Federica Laguzzi and Swenson, {Brenton R} and Longstreth, {William T} and Manson, {JoAnn E} and Samia Mora and Cook, {Nancy R} and Matti Marklund and {Melo van Lent}, Debora and Rachel Murphy and Vilmundur Gudnason and Toshihara Ninomiya and Yoichiro Hirakawa and Frank Qian and Qi Sun and Frank Hu and {Ardisson Korat}, {Andres V} and Ulf Ris{\'e}rus and Iolanda L{\'a}zaro and Cecilia Samieri and {Le Goff}, M{\'e}lanie and Catherine Helmer and Marinka Steur and Trudy Voortman and Ikram, {M Kamran} and Toshiko Tanaka and Das, {Jayanta K} and Luigi Ferrucci and Stefania Bandinelli and Michael Tsai and Weihua Guan and Parveen Garg and Verschuren, {W M Monique} and Boer, {Jolanda M A} and Anneke Biokstra and Jyrki Virtanen and Michael Wagner and Jason Westra and Luc Albuisson and Kazumasa Yamagishi and Siscovick, {David S} and Lemaitre, {Rozenn N} and Dariush Mozaffarian",

year = "2024",

month = jan,

doi = "10.1161/STROKEAHA.123.044281",

language = "English",

volume = "55",

pages = "50--58",

journal = "Stroke",

issn = "0039-2499",

publisher = "Lippincott Williams & Wilkins",

number = "1",

}

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, K-L, Chen, Y-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, P-H, 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 & Mozaffarian, D 2024, 'Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies', Stroke, vol. 55, no. 1, pp. 50-58. https://doi.org/10.1161/STROKEAHA.123.044281

TY - JOUR

T1 - Omega-3 Blood Levels and Stroke Risk

T2 - A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies

AU - O'Keefe, James H

AU - Tintle, Nathan L

AU - Harris, William S

AU - O'Keefe, Evan L

AU - Sala-Vila, Aleix

AU - Attia, John

AU - Garg, G Manohar

AU - Hure, Alexis

AU - Bork, Christian Sørensen

AU - Schmidt, Erik Berg

AU - Venø, Stine Krogh

AU - Chien, Kuo-Liong

AU - Chen, Yun-Yu Amelia

AU - Egert, Sarah

AU - Feldreich, Tobias Rudholm

AU - Ärnlöv, Johan

AU - Lind, Lars

AU - Forouhi, Nita G

AU - Geleijnse, Johanna M

AU - Pertiwi, Kamalita

AU - Imamura, Fumiaki

AU - de Mello Laaksonen, Vanessa

AU - Uusitupa, W Matti

AU - Tuomilehto, Jaakko

AU - Laakso, Markku

AU - Lankinen, Maria Anneli

AU - Laurin, Danielle

AU - Carmichael, Pierre-Hugues

AU - Lindsay, Joan

AU - Leander, Karin

AU - Laguzzi, Federica

AU - Swenson, Brenton R

AU - Longstreth, William T

AU - Manson, JoAnn E

AU - Mora, Samia

AU - Cook, Nancy R

AU - Marklund, Matti

AU - Melo van Lent, Debora

AU - Murphy, Rachel

AU - Gudnason, Vilmundur

AU - Ninomiya, Toshihara

AU - Hirakawa, Yoichiro

AU - Qian, Frank

AU - Sun, Qi

AU - Hu, Frank

AU - Ardisson Korat, Andres V

AU - Risérus, Ulf

AU - Lázaro, Iolanda

AU - Samieri, Cecilia

AU - Le Goff, Mélanie

AU - Helmer, Catherine

AU - Steur, Marinka

AU - Voortman, Trudy

AU - Ikram, M Kamran

AU - Tanaka, Toshiko

AU - Das, Jayanta K

AU - Ferrucci, Luigi

AU - Bandinelli, Stefania

AU - Tsai, Michael

AU - Guan, Weihua

AU - Garg, Parveen

AU - Verschuren, W M Monique

AU - Boer, Jolanda M A

AU - Biokstra, Anneke

AU - Virtanen, Jyrki

AU - Wagner, Michael

AU - Westra, Jason

AU - Albuisson, Luc

AU - Yamagishi, Kazumasa

AU - Siscovick, David S

AU - Lemaitre, Rozenn N

AU - Mozaffarian, Dariush

PY - 2024/1

Y1 - 2024/1

N2 - 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.

AB - 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.

KW - Docosahexaenoic Acids

KW - Eicosapentaenoic Acid

KW - Fatty Acids, Omega-3

KW - Hemorrhagic Stroke/epidemiology

KW - Humans

KW - Ischemic Stroke

KW - Prospective Studies

KW - Risk Factors

KW - Stroke/epidemiology

UR - http://www.scopus.com/inward/record.url?scp=85180982660&partnerID=8YFLogxK

U2 - 10.1161/STROKEAHA.123.044281

DO - 10.1161/STROKEAHA.123.044281

M3 - Article

C2 - 38134264

SN - 0039-2499

VL - 55

SP - 50

EP - 58

JO - Stroke

JF - Stroke

IS - 1

ER -

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies

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