{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T13:02:24Z","timestamp":1773406944335,"version":"3.50.1"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K01 HL122394 and R03 HL146875"],"award-info":[{"award-number":["K01 HL122394 and R03 HL146875"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169"],"award-info":[{"award-number":["75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420"],"award-info":[{"award-number":["UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006260","name":"Rheumatology Research Foundation","doi-asserted-by":"publisher","award":["K Bridge"],"award-info":[{"award-number":["K Bridge"]}],"id":[{"id":"10.13039\/100006260","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K24 DK110427"],"award-info":[{"award-number":["K24 DK110427"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL104047"],"award-info":[{"award-number":["R01 HL104047"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Antibodies to citrullinated protein antigens have been linked to altered left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA). Serum reactivity to several citrullinated protein\/peptide antigens has been identified in RA, which are detectable years before RA onset and in individuals who may never develop RA. Among community-living individuals without heart failure (HF) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated associations between serum reactivity to citrullinated protein\/peptide antigens, LV mass, LV ejection fraction (LVEF), and incident HF.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Among 1232 MESA participants, we measured serum reactivity to 28 different citrullinated proteins\/peptides using a multiplex bead-based array. Each antibody was defined as having extremely high reactivity (EHR) if &gt;95<jats:sup>th<\/jats:sup> percentile cut-off in MESA. Number of EHR antibody responses to citrullinated protein\/peptide antigens were summed for each participant (range 0\u201328). LV mass(g) and LVEF(%) were measured on cardiac MRI. Associations between EHR antibodies and LV mass and LVEF were evaluated using linear regression. Cox proportional hazards models were used to evaluate associations between EHR antibodies and incident HF during 11 years of follow-up, adjusting for age, gender, race\/ethnicity, smoking status, systolic blood pressure, use of anti-hypertensive medications, self-reported arthritis, IL-6, body surface area, and estimated glomerular filtration rate.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Mean age was 65\u00b110, 50% were female, 40% were White, 21% were Black, 26% were Hispanic\/Latino, and 14% were Chinese. Twenty-seven percent of MESA participants had extremely high reactivity to \u2265 1 citrullinated protein\/peptide antigen. In fully adjusted analysis, every additional EHR antibody was significantly associated with 0.1% lower LVEF (95% CI: -0.17%, -0.02%). No association was observed with LV mass (\u03b2 per additional EHR antibody) = 0.13\u00b10.15 (p = 0.37)). Neither the presence nor number of EHR antibodies was associated with incident HF during follow-up (HR per additional EHR antibody = 1.008 (95% CI: 0.97, 1.05)).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Greater number of extremely highly reactive antibodies was associated with lower LVEF, but not with LV mass or incident HF. Thus, serum reactivity to citrullinated protein\/peptide antigens was associated with subtle subclinical changes in myocardial contractility, but the significance in relation to clinically apparent HF is uncertain.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0291967","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T17:23:01Z","timestamp":1698168181000},"page":"e0291967","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum reactivity to citrullinated protein\/peptide antigens and left ventricular structure and function in the Multi-Ethnic Study of Atherosclerosis (MESA)"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7255-274X","authenticated-orcid":true,"given":"Jan M.","family":"Hughes-Austin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronit","family":"Katz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darcy S.","family":"Majka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael H.","family":"Criqui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William H.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary S.","family":"Firestein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. Gregory","family":"Hundley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim H.","family":"Ix","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"issue":"2","key":"pone.0291967.ref001","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/art.20855","article-title":"The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years","volume":"52","author":"PJ Nicola","year":"2005","journal-title":"Arthritis Rheum"},{"issue":"10","key":"pone.0291967.ref002","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1002\/art.21349","article-title":"How much of the increased incidence of heart failure in rheumatoid arthritis is attributable to traditional cardiovascular risk factors and ischemic heart disease?","volume":"52","author":"CS Crowson","year":"2005","journal-title":"Arthritis Rheum"},{"issue":"5","key":"pone.0291967.ref003","doi-asserted-by":"crossref","first-page":"e12915","DOI":"10.1111\/eci.12915","article-title":"Development of heart failure in patients with rheumatoid arthritis: A Danish population-based study","volume":"48","author":"BB Logstrup","year":"2018","journal-title":"Eur J Clin Invest"},{"issue":"10","key":"pone.0291967.ref004","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/j.jacc.2016.12.033","article-title":"Association Between Rheumatoid Arthritis and Risk of Ischemic and Nonischemic Heart Failure","volume":"69","author":"A Mantel","year":"2017","journal-title":"J Am Coll Cardiol"},{"issue":"8","key":"pone.0291967.ref005","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.3899\/jrheum.100979","article-title":"The influence of rheumatoid arthritis disease characteristics on heart failure","volume":"38","author":"E Myasoedova","year":"2011","journal-title":"J Rheumatol"},{"issue":"10","key":"pone.0291967.ref006","doi-asserted-by":"crossref","first-page":"e014661","DOI":"10.1161\/JAHA.119.014661","article-title":"Heart Failure Risk Associated With Rheumatoid Arthritis-Related Chronic Inflammation","volume":"9","author":"MJ Ahlers","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"pone.0291967.ref007","unstructured":"Hughes-Austin JM, Young KA, Deane KD, Weisman MH, Buckner JH, Mikuls TR, et al., editors. 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