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Here, we examined associations of circulating PUFA profiles and PUFA supplementation with AF prevalence and incidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We analysed 483 372 individuals from the UK Biobank (8503 prevalent AF; 32 671 incident AF) with nuclear magnetic resonance (NMR) metabolomics, combining systematic deconfounding, an explainable supervised classifier and generalized structural equation modelling (GSEM).<\/jats:p>\n                    <jats:p>Anthropometric, demographic and genetic risk factors were stronger correlates of AF prevalence and incidence than lipidomic profiles. NMR analysis indicated lower plasma PUFA concentrations in AF, atrial cardiomyopathy (AtCM) and in HFpEF, most pronounced with cholesterol-lowering medication (CLM) use and partially attenuated in participants reporting PUFA supplementation. Higher \u03c9-6 concentrations were associated with lower AF prevalence and incidence; for AF incidence, \u03b2 = \u22120.083 (95% CI \u22120.097 to \u22120.069; P &amp;lt; .001), higher \u03c9-3 with lower AF incidence (\u03b2 = \u22120.093, 95% CI \u22120.122 to \u22120.065; P &amp;lt; .001), and higher DHA with higher incidence (\u03b2 = 0.058, 95% CI 0.031 to 0.085; P &amp;lt; .001), an association not evident in women. Supplementation was associated with higher circulating PUFAs and lower AF prevalence (\u03b2 = \u22120.096, 95% CI \u22120.145 to \u22120.047; P &amp;lt; .001), strongest among CLM users and women. Subgroup findings in HFpEF were directionally similar.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Circulating PUFAs were lower in AF, AtCM and HFpEF. Lipid profiles indicated favourable associations for circulating \u03c9-3 and \u03c9-6, with a modest adverse signal for DHA. After adjustment for established risk factors, PUFA supplementation was associated with lower AF prevalence, including in patients with CLM and those with HFpEF. Formulations that substantially increase plasma DHA levels warrant careful evaluation given the observed association with AF incidence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejhf\/xuag238","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T11:37:22Z","timestamp":1784979442000},"source":"Crossref","is-referenced-by-count":1,"title":["The role of circulating polyunsaturated fatty acids in atrial fibrillation and atrial cardiomyopathy a machine learning-informed structural modelling approach"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6179-1014","authenticated-orcid":false,"given":"Jakob","family":"Versnjak","sequence":"first","affiliation":[{"name":"Institute of Computer-Assisted Cardiovascular Medicine, Deutsches Herzzentrum der Charit\u00e9 , Augustenburger Platz 1, Berlin 13353 ,","place":["Germany"]},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Charit\u00e9platz 1, Berlin 10117 ,","place":["Germany"]},{"name":"BIFOLD\u2014Berlin Institute for the Foundations of Learning and Data , Technische Universit\u00e4t Berlin, Franklinstr. 28\/29, Berlin 10587 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5558-3112","authenticated-orcid":false,"given":"Giuseppe","family":"Trimarchi","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Charit\u00e9platz 1, Berlin 10117 ,","place":["Germany"]},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Institute of Pharmacology , Hessische Str. 3-4, Berlin 10115 ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Potsdamer Str. 58, Berlin 10785 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