{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:52:36Z","timestamp":1792047156528,"version":"4.4.0"},"reference-count":45,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"unspecified","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Inger Bendix Foundation for Medical Research"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,5,18]]},"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Rheumatoid arthritis elevates cardiovascular disease risk. Proprotein convertase subtilisin\/kexin type 9 (PCSK9), a regulator of low-density lipoprotein (LDL) metabolism, increases LDL-receptor breakdown in the liver, which elevates LDL-cholesterol levels. In addition, PCSK9 has direct effects on thrombogenesis and atherosclerotic plaque formation.<\/jats:p>\n                  <jats:p>We aimed to investigate (1) the impact of glucocorticoids and biological disease-modifying antirheumatic drug (bDMARD) treatments on PCSK9 and LDL-cholesterol levels, (2) whether this influence is different when autoantibodies are present and (3) the association between PCSK9 and LDL cholesterol.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this post hoc analysis of the NORD-STAR trial, 296 newly diagnosed patients starting methotrexate with glucocorticoids, certolizumab pegol, abatacept or tocilizumab were included. Serum PCSK9 and LDL-cholesterol levels were measured at baseline and 24 weeks. Linear regression models were used to analyse the difference in PCSK9 and LDL cholesterol between glucocorticoid and bDMARD treatments at 24 weeks. In the second analysis, the interactions between the treatment groups and autoantibody status were added to the model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>After 24 weeks, PCSK9 levels were higher in the glucocorticoid group than in the combined bDMARD treatment group (\u2212276.0 (95% CI \u2212468.2 to \u221283.9)). When compared with the bDMARD treatment, these increases were more pronounced in autoantibody-positive patients. Changes in LDL cholesterol exhibited a pattern distinct from PCSK9, as it increased in all treatments.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Glucocorticoid treatment was associated with increased PCSK9 levels after 24 weeks. When compared with the bDMARD treatments, these increases were more pronounced in rheumatoid factor, anticitrullinated protein antibody and antinuclear antibody-positive patients. Our data provide a potential mechanistic link between glucocorticoid treatment and cardiovascular disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>Inger Bendix Foundation for Medical Research.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>EudraCT2011-004720-35, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT01491815\">NCT01491815<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-005129","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T04:05:26Z","timestamp":1749182726000},"page":"e005129","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Glucocorticoid treatment in early rheumatoid arthritis is independently associated with increased PCSK9 levels: data from a randomised controlled trial"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct01491815","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01491815","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01491815","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5037-5546","authenticated-orcid":false,"given":"Kristina","family":"Lend","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centers, Amsterdam, The Netherlands"},{"name":"Division of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos WR","family":"Twisk","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nupur","family":"Kumar","sequence":"additional","affiliation":[{"name":"Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1698-5647","authenticated-orcid":false,"given":"Bas","family":"Dijkshoorn","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centers, Amsterdam, The Netherlands"},{"name":"Amsterdam Rheumatology and immunology Center, Reade, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Lampa","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, Sweden"},{"name":"Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rudin","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4229-6818","authenticated-orcid":false,"given":"Merete Lund","family":"Hetland","sequence":"additional","affiliation":[{"name":"Center for Rheumatology and Spine Diseases, Rigshospitalet Glostrup, Glostrup, Denmark"},{"name":"University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6881-9552","authenticated-orcid":false,"given":"Till","family":"Uhlig","sequence":"additional","affiliation":[{"name":"Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway"},{"name":"University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Nordstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medicine, Helsinki University and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3690-467X","authenticated-orcid":false,"given":"Mikkel","family":"\u00d8stergaard","sequence":"additional","affiliation":[{"name":"University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark"},{"name":"Center for Rheumatology and Spine Diseases, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4631-6505","authenticated-orcid":false,"given":"Bjorn","family":"Gudbjornsson","sequence":"additional","affiliation":[{"name":"Centre for Rheumatology, Centre for Rheumatology Research, University Hospital and Faculty of Medicine, University of Iceland, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuulikki","family":"Sokka-Isler","sequence":"additional","affiliation":[{"name":"University of Eastern Finland, Kuopio, Finland"},{"name":"Wellbeing services county of Central Finland, Jyv\u00e4skyl\u00e4, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerdur","family":"Grondal","sequence":"additional","affiliation":[{"name":"Landspitali University Hospital, Reykjavk, 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