Omega-3 fatty acid biomarkers and incident atrial fibrillation: an individual participant level pooled analysis of 17 international prospective studies

Authors: QIAN, FRANK - Beth Israel Deaconess Medical Center; TINTLE, NATHAN - Dordt University; JENSEN, PAUL - University Of Washington; LEMAITRE, ROZENN - University Of Washington; IMAMURA, FUMIAKI - University Of Cambridge; FELDREICH, TOBIAS - Dalarna University; NOMURA, SARAH - University Of Minnesota; GUAN, WEIHUA - University Of Minnesota; LAGUZZI, FEDRICA - Karolinska Institute; KIM, EUNJUNG - Brigham & Women'S Hospital; VIRTANEN, JYRKI - University Of Eastern Finland; STEUR, MARINKA - Erasmus Medical Center; BORK, CHRISTIAN - Aalborg University Hospital; HIRAKAWA, YOICHIRO - Kyushu University; O'DONOGHUE, MICHELLE - Brigham & Women'S Hospital; SALA-VILA, ALEIX - Fatty Acid Research Institute; ARDISSON KORAT, ANDRES - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SUN, QI - Harvard School Of Public Health; RIMM, EIRC - Harvard School Of Public Health; PSATY, BRUCE - University Of Washington; HECKBERT, SUSAN - University Of Washington; FOROUHI, NITA - University Of Cambridge; WAREHAM, NICHOLAS - University Of Cambridge; MARKLUND, MATTI - The George Institute For Global Health; RISERUS, ULF - Uppsala University; LIND, LARS - Uppsala University; ARNLOV, JOHAN - Karolinska Institute; GARG, PARVEEN - University Of Southern California; TSAI, MICHAEL - University Of Minnesota; PANKOW, JAMES - University Of Minnesota; MISIALEK, JEFFREY - University Of Minnesota; GIGANTE, BRUNA - Karolinska Institute; LEANDER, KARIN - Karolinska Institute; PESTER, JULIE - Brigham & Women'S Hospital; ALBERT, CHRISTINE - Cedars-Sinai Medical Center; KAVOUSI, MARYAM - Erasmus Medical Center; IKRAM, ARFAN - Erasmus Medical Center; VOORTMAN, TRUDY - Erasmus Medical Center; SCHMIDT, ERIK - Aalborg University; NINOMIYA, TOSHIHARU - Kyushu University; MORROW, DAVID - Brigham & Women'S Hospital; BAYES-GENIS, ANTONI - University Hospital - “germans Trias I Pujol”; O'KEEFE, JAMES - University Of Missouri; ONG, KWOK LEUNG - University Of New South Wales; WU, JASON - University Of New South Wales; MOZAFFARIAN, DARIUSH - Tufts University; HARRIS, WILLIAM - Fatty Acid Research Institute; SISCOVICK, DAVID - New York Academy Of Medicine

Submitted to: Journal of the American College of Cardiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/9/2023
Publication Date: 7/1/2023
Citation: Qian, F., Tintle, N., Jensen, P.R., Lemaitre, R.N., Imamura, F., Feldreich, T.R., Nomura, S.O., Guan, W., Laguzzi, F., Kim, E., Virtanen, J.K., Steur, M., Bork, C.S., Hirakawa, Y., O'Donoghue, M., Sala-Vila, A., Ardisson Korat, A., Sun, Q., Rimm, E.B., Psaty, B.M., Heckbert, S.R., Forouhi, N.G., Wareham, N.J., Marklund, M., Riserus, U., Lind, L., Arnlov, J., Garg, P., Tsai, M.Y., Pankow, J., Misialek, J.R., Gigante, B., Leander, K., Pester, J.A., Albert, C.M., Kavousi, M., Ikram, A., Voortman, T., Schmidt, E., Ninomiya, T., Morrow, D.A., Bayes-Genis, A., O'Keefe, J.H., Ong, K., Wu, J.H., Mozaffarian, D., Harris, W.S., Siscovick, D.S. 2023. Omega-3 fatty acid biomarkers and incident atrial fibrillation: An individual participant level pooled analysis of 17 international prospective studies. Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2023.05.024.
DOI: https://doi.org/10.1016/j.jacc.2023.05.024

Interpretive Summary: The role of omega-3 polyunsaturated fatty acid intake in the development of atrial fibrillation is unclear. We evaluated the relationship between circulating and tissue markers of omega-3 fatty acid levels and incident atrial fibrillation in a global pooled analysis of multiple cohorts that included ~55,000 participants without history of atrial fibrillation 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 circulating or tissue levels of docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were associated with lower risk of atrial fibrillation. However, levels of eicosapentaenoic acid (EPA) alone were not associated with risk of atrial fibrillation. Our study found that biomarker levels of omega-3 fatty acid intake were associated with lower risk of atrial fibrillation, which suggest a potential benefit of omega-3 fatty acid intake in the prevention of atrial fibrillation.

Technical Abstract: Importance: While observational studies of self-reported fish and omega-3 fatty acid intake suggest benefits in the prevention of atrial fibrillation (AF), recent randomized controlled trials (RCTs) of omega-3 treatments suggest harm. The relationship of objective levels of omega-3 fatty acids with incident AF is not well established. Objective: To prospectively evaluate circulating and adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and the sum of EPA and DHA, with respect to incident AF. Design: We used participant-level data from a global consortium of 17 prospective cohort studies with measurements of EPA, DPA, or DHA in adults aged 18 years or older identified through March 2021. Participating studies conducted de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. Data analysis was conducted from October 2021 to April 2022. Setting: Seventeen prospective cohort studies from 21 nations Participants: Adults aged 18 years or older who did not have prevalent or a history of AF Exposures: Blood or adipose tissue levels of EPA, DPA, DHA, and EPA+DHA Main Outcome and Measure: Atrial fibrillation Results: Among 54,799 participants, 7,720 incident cases of AF were ascertained, with median follow-up ranging from 0.9 to 29.1 years (weighted median: 13.3 years). In multivariable analysis, per interquintile range (difference between the 10th and 90th percentiles for each fatty acid), DPA, DHA, and EPA plus DHA were associated with lower incidence of AF, with RR (95%CI) of 0.89 (0.83, 0.95), 0.90 (0.85, 0.96), and 0.93 (0.87, 0.99), respectively. EPA levels were not associated with incident AF, 1.00 (0.95, 1.05). Heterogeneity as measured using I2 was 52.2% for EPA, 0% for DPA, 47.5% for DHA, and 60.7% for EPA plus DHA. Associations were broadly consistent across subgroups of age, sex, baseline cardiovascular risk, global region, and lipid compartment. Conclusions and Relevance: Biomarkers of omega-3 fatty acids including DPA, DHA, and EPA plus DHA demonstrated an inverse association with incident AF. In the absence of RCTs examining long-term dietary omega-3 intake and AF, our results suggest that biomarkers of dietary intakes of these fatty acids are associated with lower risk of incident AF.