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We investigated associations to all-cause mortality of the inflammation markers high-sensitivity C-reactive protein (CRP), lactoferrin (neutrophil activation marker), and neopterin (monocyte activation marker). From the population-based Tr\u00f8ndelag Health Study (3rd wave 2006\u20132008), 316 RA patients and 43,579 controls were included. Lactoferrin and neopterin were quantified in a nested cohort (n\u2009=\u2009283 RA patients, n\u2009=\u20093698 controls). Follow-up was until death found by linkage to the Norwegian Cause of Death Registry or 31.12.2018. All-cause mortality was analyzed using Cox regression and Cox regression-based mediation analysis. Having RA (hazard ratio (HR): 1.25, 95%CI: 1.00, 1.56, p\u2009=\u20090.048), and CRP\u2009\u2265\u20093\u00a0mg\/L (HR: 1.50, 95%CI: 1.41, 1.60, p\u2009&lt;\u20090.001) were associated with all-cause mortality. The overall excess relative mortality risk of having RA was 38%. CRP\u2009\u2265\u20093\u00a0mg\/L mediated approximately 1\/4 of this risk (p\u2009&lt;\u20090.001). In the nested cohort, CRP\u2009\u2265\u20093\u00a0mg\/L (HR: 1.51, 95%CI: 1.26, 1.80, p\u2009&lt;\u20090.001) and neopterin (HR: 1.17, 95%CI: 1.01, 1.36, p\u2009=\u20090.031) were associated with all-cause mortality. In conclusion, CRP levels\u2009\u2265\u20093\u00a0mg\/L mediated approximately a quarter of the 38% excess relative all-cause mortality risk associated with RA. Using definitions of RA remission with emphasis both on joint status and the level of general inflammation may help guide the most efficient treatment regimens.<\/jats:p>","DOI":"10.1038\/s41598-022-21977-9","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T14:02:46Z","timestamp":1667484166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inflammation mediates approximately one quarter of excess relative all-cause mortality in persons with rheumatoid arthritis: the Tr\u00f8ndelag Health Study"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1042-3889","authenticated-orcid":false,"given":"Vibeke","family":"Videm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2458-208X","authenticated-orcid":false,"given":"Ingrid S\u00e6ther","family":"Houge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-2032","authenticated-orcid":false,"given":"Marthe Halsan","family":"Liff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9992-8663","authenticated-orcid":false,"given":"Mari","family":"Hoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"21977_CR1","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/S0140-6736(10)60826-4","volume":"376","author":"DL Scott","year":"2010","unstructured":"Scott, D. L., Wolfe, F. & Huizinga, T. W. Rheumatoid arthritis. Lancet 376, 1094\u20131108 (2010).","journal-title":"Lancet"},{"key":"21977_CR2","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1093\/rheumatology\/key013","volume":"57","author":"A Abhishek","year":"2018","unstructured":"Abhishek, A. et al. Rheumatoid arthritis and excess mortality: Down but not out. A primary care cohort study using data from Clinical Practice Research Datalink. Rheumatol. (Oxf.) 57, 977\u2013981 (2018).","journal-title":"Rheumatol. (Oxf.)"},{"key":"21977_CR3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1136\/annrheumdis-2017-212131","volume":"77","author":"M Holmqvist","year":"2018","unstructured":"Holmqvist, M., Ljung, L. & Askling, J. Mortality following new-onset rheumatoid arthritis: Has modern rheumatology had an impact?. Ann. Rheum. Dis. 77, 85\u201391 (2018).","journal-title":"Ann. Rheum. 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H., Hoff, M., Wisloff, U. & Videm, V. Reduced cardiorespiratory fitness is a mediator of excess all-cause mortality in rheumatoid arthritis: The Tr\u00f8ndelag Health Study. RMD Open 7, e001545. https:\/\/doi.org\/10.1136\/rmdopen-2020-001545 (2021).","journal-title":"RMD Open"},{"key":"21977_CR7","doi-asserted-by":"publisher","first-page":"722","DOI":"10.17269\/s41997-021-00476-w","volume":"112","author":"RM Taylor-Gjevre","year":"2021","unstructured":"Taylor-Gjevre, R. M., Nair, B. V., Jin, S. & Quail, J. Higher mortality rates associated with rheumatoid arthritis in Saskatchewan, Canada, 2001\u20132019. Can. J. Public Health. 112, 722\u2013732 (2021).","journal-title":"Can. J. Public Health."},{"key":"21977_CR8","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1093\/rheumatology\/keaa374","volume":"60","author":"BB L\u00f8gstrup","year":"2021","unstructured":"L\u00f8gstrup, B. B. et al. 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