{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T10:13:15Z","timestamp":1772705595547,"version":"3.50.1"},"reference-count":36,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"unspecified","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["249944"],"award-info":[{"award-number":["249944"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Liaison Committee for Education, Research and Innovation","award":["2016\/29014"],"award-info":[{"award-number":["2016\/29014"]}]},{"name":"The Liaison Committee for Education, Research and Innovation","award":["5056\/46051000"],"award-info":[{"award-number":["5056\/46051000"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2023,7,21]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Inflammation and reduced cardiorespiratory fitness (CRF) are associated with increased mortality rates in rheumatoid arthritis (RA). We aimed at directly comparing the relative importance of inflammation and reduced CRF as mediators of all-cause mortality in persons with RA compared with controls, quantifying direct and indirect (mediated) effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Persons with (n=223, cases) and without (n=31 684, controls) RA from the third survey of the Tr\u00f8ndelag Health Study (HUNT3, 2006\u20132008) were included. Inflammation was quantified using C reactive protein (CRP) and estimated CRF (eCRF) was calculated using published formulae. All-cause mortality was found by linkage to the Norwegian Cause of Death Registry, with follow-up from inclusion in HUNT3 until death or 31 December 2018. Data were analysed using standardised equation modelling, permitting complex correlations among variables.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Persons with RA had increased all-cause mortality rates (24.1% vs 9.9%, p&lt;0.001). Both eCRF (p&lt;0.001) and CRP \u22653\u2009mg\/L (p&lt;0.001) were mediators of this excess mortality, rendering the direct effect of RA non-significant (p=0.19). The indirect effect of RA mediated by eCRF (standardised coefficient 0.006) was approximately three times higher than the indirect effect mediated by CRP (standardised coefficient 0.002) in a model adjusted for other mortality risk factors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Even with CRP concentrations &lt;3\u2009mg\/L in all patients with RA, excess mortality mediated by low CRF would still play an important role. Improved inflammation control in RA does not necessarily lead to better CRF. Therefore, our study strongly supports recommendations for development and implementation of exercise programmes aimed at improving CRF in persons with RA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2023-003194","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T11:21:23Z","timestamp":1691493683000},"page":"e003194","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Relative importance of inflammation and cardiorespiratory fitness for all-cause mortality risk in persons with rheumatoid arthritis: the population-based Tr\u00f8ndelag Health Study"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1042-3889","authenticated-orcid":false,"given":"Vibeke","family":"Videm","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine, NTNU\u2013Norwegian University of Science and Technology, Trondheim, Norway"},{"name":"Department of Immunology and Transfusion Medicine, St Olavs University Hospital, Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-2032","authenticated-orcid":false,"given":"Marthe Halsan","family":"Liff","sequence":"additional","affiliation":[{"name":"Clinic of Rehabilitation, St Olavs University Hospital, Trondheim, Norway"},{"name":"Department of Rheumatology, St Olavs University Hospital, Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9992-8663","authenticated-orcid":false,"given":"Mari","family":"Hoff","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, St Olavs University Hospital, Trondheim, Norway"},{"name":"Department of Neuromedicine and Movement Science, NTNU\u2013Norwegian University of Science and Technology, Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"2025090313481065000_9.3.e003194.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60826-4"},{"key":"2025090313481065000_9.3.e003194.2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210602"},{"key":"2025090313481065000_9.3.e003194.3","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220249"},{"key":"2025090313481065000_9.3.e003194.4","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2019-001084","article-title":"Management of fatigue in rheumatoid arthritis","volume":"6","author":"Pope","year":"2020","journal-title":"RMD Open"},{"key":"2025090313481065000_9.3.e003194.5","doi-asserted-by":"crossref","DOI":"10.1016\/j.autrev.2021.102776","article-title":"Rheumatoid arthritis: extra-articular manifestations and comorbidities","volume":"20","author":"Figus","year":"2021","journal-title":"Autoimmun Rev"},{"key":"2025090313481065000_9.3.e003194.6","doi-asserted-by":"crossref","DOI":"10.3390\/jcm10030509","article-title":"The key comorbidities in patients with rheumatoid arthritis: A narrative review.","volume":"10","author":"Taylor","year":"2021","journal-title":"J Clin Med"},{"key":"2025090313481065000_9.3.e003194.7","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1093\/rheumatology\/key013","article-title":"Rheumatoid arthritis and excess mortality: down but not out. A primary care cohort study using data from Clinical Practice Research Datalink","volume":"57","author":"Abhishek","year":"2018","journal-title":"Rheumatology (Oxford)"},{"key":"2025090313481065000_9.3.e003194.8","first-page":"636","article-title":"Cause-specific mortality in a large population-based cohort of patients with rheumatoid arthritis in Italy","volume":"36","author":"Ometto","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"2025090313481065000_9.3.e003194.9","doi-asserted-by":"crossref","DOI":"10.1177\/2235042X19853484","article-title":"Morbidity and mortality in patients with rheumatoid arthritis compared with an age- and sex-matched control population: A nationwide register study","volume":"9","author":"L\u00f8ppenthin","year":"2019","journal-title":"J Comorb"},{"key":"2025090313481065000_9.3.e003194.10","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph182312338","article-title":"Mortality in inflammatory rheumatic diseases: Lithuanian national registry data and systematic review","volume":"18","author":"Dadonien\u0117","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"2025090313481065000_9.3.e003194.11","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/1756-185X.14058","article-title":"Excess mortality persists in patients with rheumatoid arthritis","volume":"24","author":"Lee","year":"2021","journal-title":"Int J Rheum Dis"},{"key":"2025090313481065000_9.3.e003194.12","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00296-016-3638-5","article-title":"Mortality in patients with rheumatoid arthritis: a 15-year prospective cohort study","volume":"37","author":"van den Hoek","year":"2017","journal-title":"Rheumatol Int"},{"key":"2025090313481065000_9.3.e003194.13","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1002\/acr.23548","article-title":"Causes of death in rheumatoid arthritis: how do they compare to the general population","volume":"70","author":"Widdifield","year":"2018","journal-title":"Arthritis Care Res"},{"key":"2025090313481065000_9.3.e003194.14","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2021-001694","article-title":"All-cause mortality in systemic rheumatic diseases under treatment compared with the general population, 2015-2019","volume":"7","author":"Bournia","year":"2021","journal-title":"RMD Open"},{"key":"2025090313481065000_9.3.e003194.15","doi-asserted-by":"crossref","first-page":"722","DOI":"10.17269\/s41997-021-00476-w","article-title":"Higher mortality rates associated with rheumatoid arthritis in Saskatchewan, Canada, 2001-2019","volume":"112","author":"Taylor-Gjevre","year":"2021","journal-title":"Can J Public Health"},{"key":"2025090313481065000_9.3.e003194.16","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00019.2016"},{"key":"2025090313481065000_9.3.e003194.17","doi-asserted-by":"crossref","first-page":"14","DOI":"10.31189\/2165-6193-4.1.14","article-title":"Exercise as medicine in rheumatoid arthritis: effects on function, body composition, and cardiovascular disease risk","volume":"4","author":"Metsios","year":"2015","journal-title":"J Clin Exercise Physiol"},{"key":"2025090313481065000_9.3.e003194.18","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-21977-9","article-title":"Inflammation mediates approximately one quarter of excess relative all-cause mortality in persons with rheumatoid arthritis \u2013 the Tr\u00f8ndelag Health Study","volume":"12","author":"Videm","year":"2022","journal-title":"Sci Rep"},{"key":"2025090313481065000_9.3.e003194.19","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2020-001545","article-title":"Reduced cardiorespiratory fitness is a mediator of excess all-cause mortality in rheumatoid arthritis: the Tr\u00f8ndelag Health Study","volume":"7","author":"Liff","year":"2021","journal-title":"RMD Open"},{"key":"2025090313481065000_9.3.e003194.20","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys095"},{"key":"2025090313481065000_9.3.e003194.21","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.138461"},{"key":"2025090313481065000_9.3.e003194.22","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.161396"},{"key":"2025090313481065000_9.3.e003194.23","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1249\/MSS.0000000000002250","article-title":"An estimation model for cardiorespiratory fitness in adults with rheumatoid arthritis","volume":"52","author":"Liff","year":"2020","journal-title":"Med Sci Sports Exerc"},{"key":"2025090313481065000_9.3.e003194.24","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e31821d3f6f"},{"key":"2025090313481065000_9.3.e003194.25","unstructured":"Mehmetoglu M , Jakobsen TG . Applied statistics using Stata. A guide for the social sciences. London: Sage Publications, 2017: 270\u2013322."},{"key":"2025090313481065000_9.3.e003194.26","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-60621-2","article-title":"Mortality is increased in patients with rheumatoid arthritis or diabetes compared to the general population - the Nord-Tr\u00f8ndelag Health Study","volume":"10","author":"Houge","year":"2020","journal-title":"Sci Rep"},{"key":"2025090313481065000_9.3.e003194.27","doi-asserted-by":"crossref","DOI":"10.4061\/2011\/681640","article-title":"Benefits of exercise in rheumatoid arthritis","volume":"2011","author":"Cooney","year":"2011","journal-title":"J Aging Res"},{"key":"2025090313481065000_9.3.e003194.28","doi-asserted-by":"crossref","DOI":"10.1186\/1479-5868-7-38","article-title":"Physical activity and functional limitations in older adults: a systematic review related to Canada\u2019s Physical Activity Guidelines","volume":"7","author":"Paterson","year":"2010","journal-title":"Int J Behav Nutr Phys Act"},{"key":"2025090313481065000_9.3.e003194.29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2004.52454.x"},{"key":"2025090313481065000_9.3.e003194.30","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1586\/1744666X.2015.1067606","article-title":"The role of exercise in the management of rheumatoid arthritis","volume":"11","author":"Metsios","year":"2015","journal-title":"Expert Rev Clin Immunol"},{"key":"2025090313481065000_9.3.e003194.31","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1007\/s10067-020-04937-4","article-title":"Benefits of exercise in patients with rheumatoid arthritis: a randomized controlled trial of a patient-specific exercise programme","volume":"39","author":"Azeez","year":"2020","journal-title":"Clin Rheumatol"},{"key":"2025090313481065000_9.3.e003194.32","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0b013e3181d14633"},{"key":"2025090313481065000_9.3.e003194.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.03.008"},{"key":"2025090313481065000_9.3.e003194.34","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2019-000912","article-title":"Cardiorespiratory fitness in patients with rheumatoid arthritis is associated with the patient global assessment but not with objective measurements of disease activity","volume":"5","author":"Liff","year":"2019","journal-title":"RMD Open"},{"key":"2025090313481065000_9.3.e003194.35","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000461"},{"key":"2025090313481065000_9.3.e003194.36","doi-asserted-by":"crossref","unstructured":"Moholdt T , Skarpsno ES , Moe B , et al . It is never too late to start: adherence to physical activity recommendations for 11-22 years and risk of all-cause and cardiovascular disease mortality. Br J Sports Med 2020:bjsports-2020-102350. doi:10.1136\/bjsports-2020-102350","DOI":"10.1136\/bjsports-2020-102350"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2023-003194","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T20:48:20Z","timestamp":1756932500000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2023-003194"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,8,8]]},"published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1136\/rmdopen-2023-003194"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2023-003194","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8]]}}}