{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T03:21:31Z","timestamp":1781320891940,"version":"3.54.1"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Randomized trials of pharmacologic strength omega\u20103 fatty acid (n3\u2010FA)\u2013based therapies suggest a dose\u2010dependent cardiovascular benefit. Whether blood n3\u2010FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3\u2010FA levels would be associated with incident bleeding and AF events in MESA (Multi\u2010Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We examined the association between baseline plasma n3\u2010FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization\n              <jats:italic>International Classification of Diseases, Ninth Revision<\/jats:italic>\n              (\n              <jats:italic>ICD\u20109<\/jats:italic>\n              ), and\n              <jats:italic>International Classification of Diseases, Tenth Revision<\/jats:italic>\n              (\n              <jats:italic>ICD\u201010<\/jats:italic>\n              ), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3\u2010FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1\u00a0years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">In MESA, higher plasma levels of n3\u2010FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.021431","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T09:37:05Z","timestamp":1622108225000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Association Between Omega\u20103 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA"],"prefix":"10.1161","volume":"10","author":[{"given":"Karan","family":"Kapoor","sequence":"first","affiliation":[{"name":"Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2801-7624","authenticated-orcid":false,"given":"Abdulhamied","family":"Alfaddagh","sequence":"additional","affiliation":[{"name":"Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6933-790X","authenticated-orcid":false,"given":"Mahmoud","family":"Al Rifai","sequence":"additional","affiliation":[{"name":"Section of Cardiology Baylor College of Medicine Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":false,"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's HospitalHarvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9616-1946","authenticated-orcid":false,"given":"Matthew J.","family":"Budoff","sequence":"additional","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center Torrance CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5376-2269","authenticated-orcid":false,"given":"Khurram","family":"Nasir","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Prevention and Wellness Houston Methodist DeBakey Heart and Vascular Center Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Maryland Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0091-406X","authenticated-orcid":false,"given":"Francine K.","family":"Welty","sequence":"additional","affiliation":[{"name":"Division of Cardiology Beth Israel Deaconess Medical Center Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6530-5479","authenticated-orcid":false,"given":"J. William","family":"McEvoy","sequence":"additional","affiliation":[{"name":"Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Department of Cardiology National University of Ireland Galway (NUIG) Galway Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeina","family":"Dardari","sequence":"additional","affiliation":[{"name":"Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9071-3287","authenticated-orcid":false,"given":"Michael D.","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Section on Cardiovascular Medicine Wake Forest University School of Medicine Winston Salem NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1910-3168","authenticated-orcid":false,"given":"Roger S.","family":"Blumenthal","sequence":"additional","affiliation":[{"name":"Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7553-3408","authenticated-orcid":false,"given":"Michael Y.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine &amp; Pathology University of Minnesota Minneapolis MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5138-9683","authenticated-orcid":false,"given":"Michael J.","family":"Blaha","sequence":"additional","affiliation":[{"name":"Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812792"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60527-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(78)91505-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/S000711451300425X"},{"key":"e_1_3_2_6_2","first-page":"1","article-title":"Effect of omega\u20103 dosage on cardiovascular outcomes: an updated meta\u2010analysis and meta\u2010regression of interventional trials","volume":"96","author":"Bernasconi AA","year":"2020","unstructured":"Bernasconi AA, Wiest MM, Lavie CJ, Milani RV, Laukkanen JA. Effect of omega\u20103 dosage on cardiovascular outcomes: an updated meta\u2010analysis and meta\u2010regression of interventional trials. Mayo Clin Proc. 2020;96:1\u201310. 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