{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:40:33Z","timestamp":1787017233372,"version":"build-2736575974"},"reference-count":50,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"unspecified","delay-in-days":32,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["68633259"],"award-info":[{"award-number":["68633259"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2026,1,13]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Female sex and anticitrullinated protein antibodies (ACPA) are associated with higher disease activity in rheumatoid arthritis (RA). Since disease-related inflammation is linked to cardiovascular risk, we explored whether sex and ACPA influenced the association between disease activity at study entry and cardiovascular risk in established RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated 4008 patients with prevalent RA from an international observational cohort enrolled between 1985 and 2012. Outcomes included major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction and stroke) and ischaemic cardiovascular events (iCVE: MACE, angina, revascularisation, transient ischaemic attack and peripheral arterial disease). Follow-up accrued from enrolment until the first event or censoring. Multivariable Cox models stratified by centre risk evaluated disease activity, sex, ACPA and their interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We documented 193 MACE and 299 iCVE. Disease activity and sex were associated with MACE (all p\u22640.017) and iCVE (p\u22640.005) but ACPA was only associated with MACE (p=0.043). A three-way interaction on MACE (p=0.034) but not iCVE was noted. Among ACPA-negative patients, disease activity was associated with MACE in males (HR 1.57 (95% CI 1.14 to 2.16)) but not females (p-for-interaction=0.022). Among ACPA-positive patients, neither the disease activity x sex interaction (p=0.929), nor main effect of disease activity on MACE (p=0.124) was significant, but male sex was (HR 1.61 (95% CI 1.15 to 2.27)). Among females, neither disease activity x ACPA interaction (p=0.523) nor disease activity (p=0.319) was significant for MACE, but ACPA was (HR 1.57 (95% CI 1.02 to 2.42)).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The effect of disease activity at enrolment on cardiovascular risk in prevalent RA varies across patient groups with different sex and ACPA characteristics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-006420","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T16:25:42Z","timestamp":1770049542000},"page":"e006420","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Sex and anticitrullinated protein antibodies modify the relationship between inflammation and cardiovascular risk in rheumatoid arthritis"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-1563","authenticated-orcid":false,"given":"George A","family":"Karpouzas","sequence":"first","affiliation":[{"name":"Harbor-UCLA Medical Center, Torrance, California, USA"},{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7368-498X","authenticated-orcid":false,"given":"Virginia","family":"Pascual-Ramos","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-7406","authenticated-orcid":false,"given":"Miguel A","family":"Gonzalez-Gay","sequence":"additional","affiliation":[{"name":"University of Cantabria, Santander, Spain"},{"name":"IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-7396","authenticated-orcid":false,"given":"Durga P","family":"Misra","sequence":"additional","affiliation":[{"name":"Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2006-1436","authenticated-orcid":false,"given":"Elena","family":"Myasoedova","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8259-3863","authenticated-orcid":false,"given":"Solbritt","family":"Rantap\u00e4\u00e4-Dahlqvist","sequence":"additional","affiliation":[{"name":"Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Sfikakis","sequence":"additional","affiliation":[{"name":"Laiko Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3092-9474","authenticated-orcid":false,"given":"Patrick","family":"Dessein","sequence":"additional","affiliation":[{"name":"University of Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A","family":"Hitchon","sequence":"additional","affiliation":[{"name":"University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9714-2109","authenticated-orcid":false,"given":"Dionicio","family":"Galarza-Delgado","sequence":"additional","affiliation":[{"name":"Hospital Universitario \"Dr. Jos\u00e9 E. 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