Kristina Lend, Jos Wr Twisk, Nupur Kumar, Bas Dijkshoorn, Jon Lampa, Anna Rudin, Merete Lund Hetland, Till Uhlig, Dan Nordström, Mikkel Østergaard, Bjorn Gudbjornsson, Tuulikki Sokka-Isler, Gerdur Grondal, Kim Hørslev-Petersen, Michael T Nurmohamed, Johan Frostegård, Ronald F van Vollenhoven
{"title":"糖皮质激素治疗早期类风湿性关节炎与PCSK9水平升高独立相关：来自一项随机对照试验的数据","authors":"Kristina Lend, Jos Wr Twisk, Nupur Kumar, Bas Dijkshoorn, Jon Lampa, Anna Rudin, Merete Lund Hetland, Till Uhlig, Dan Nordström, Mikkel Østergaard, Bjorn Gudbjornsson, Tuulikki Sokka-Isler, Gerdur Grondal, Kim Hørslev-Petersen, Michael T Nurmohamed, Johan Frostegård, Ronald F van Vollenhoven","doi":"10.1136/rmdopen-2024-005129","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>After 24 weeks, PCSK9 levels were higher in the glucocorticoid group than in the combined bDMARD treatment group (-276.0 (95% CI -468.2 to -83.9)). 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Funding: </strong>Inger Bendix Foundation for Medical Research.</p><p><strong>Trial registration number: </strong>EudraCT2011-004720-35, NCT01491815.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 2","pages":""},"PeriodicalIF":4.7000,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161332/pdf/","citationCount":"0","resultStr":"{\"title\":\"Glucocorticoid treatment in early rheumatoid arthritis is independently associated with increased PCSK9 levels: data from a randomised controlled trial.\",\"authors\":\"Kristina Lend, Jos Wr Twisk, Nupur Kumar, Bas Dijkshoorn, Jon Lampa, Anna Rudin, Merete Lund Hetland, Till Uhlig, Dan Nordström, Mikkel Østergaard, Bjorn Gudbjornsson, Tuulikki Sokka-Isler, Gerdur Grondal, Kim Hørslev-Petersen, Michael T Nurmohamed, Johan Frostegård, Ronald F van Vollenhoven\",\"doi\":\"10.1136/rmdopen-2024-005129\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>After 24 weeks, PCSK9 levels were higher in the glucocorticoid group than in the combined bDMARD treatment group (-276.0 (95% CI -468.2 to -83.9)). 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Funding: </strong>Inger Bendix Foundation for Medical Research.</p><p><strong>Trial registration number: </strong>EudraCT2011-004720-35, NCT01491815.</p>\",\"PeriodicalId\":21396,\"journal\":{\"name\":\"RMD Open\",\"volume\":\"11 2\",\"pages\":\"\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-06-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161332/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"RMD Open\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/rmdopen-2024-005129\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"RMD Open","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/rmdopen-2024-005129","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：类风湿关节炎增加心血管疾病的风险。蛋白转化酶枯草杆菌素/酮素9型（PCSK9）是低密度脂蛋白（LDL）代谢的调节因子，可增加肝脏中LDL受体的分解，从而提高LDL-胆固醇水平。此外，PCSK9对血栓形成和动脉粥样硬化斑块形成有直接影响。我们的目的是研究(1)糖皮质激素和生物疾病缓解抗风湿药物（bDMARD）治疗对PCSK9和LDL-胆固醇水平的影响，(2)当自身抗体存在时，这种影响是否不同，(3)PCSK9和LDL-胆固醇之间的关联。方法：在这项NORD-STAR试验的事后分析中，纳入了296名新诊断的开始使用甲氨蝶呤治疗糖皮质激素、certolizumab pegol、abataccept或tocilizumab的患者。在基线和24周时测定血清PCSK9和ldl -胆固醇水平。采用线性回归模型分析糖皮质激素和bDMARD治疗24周时PCSK9和LDL胆固醇的差异。在第二次分析中，将治疗组与自身抗体状态之间的相互作用添加到模型中。结果：24周后，糖皮质激素组的PCSK9水平高于bDMARD联合治疗组（-276.0 (95% CI -468.2至-83.9)）。与bDMARD治疗相比，这些增加在自身抗体阳性患者中更为明显。LDL胆固醇的变化表现出与PCSK9不同的模式，因为它在所有治疗中都有所增加。结论：糖皮质激素治疗与24周后PCSK9水平升高相关。与bDMARD治疗相比，这些增加在类风湿因子、抗纤氨酸化蛋白抗体和抗核抗体阳性患者中更为明显。我们的数据提供了糖皮质激素治疗与心血管疾病之间潜在的机制联系。资助：英格·本迪克斯医学研究基金会。试验注册号：EudraCT2011-004720-35， NCT01491815。
Glucocorticoid treatment in early rheumatoid arthritis is independently associated with increased PCSK9 levels: data from a randomised controlled trial.
Background: 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.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.
Methods: 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.
Results: After 24 weeks, PCSK9 levels were higher in the glucocorticoid group than in the combined bDMARD treatment group (-276.0 (95% CI -468.2 to -83.9)). 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.
Conclusion: 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.
Funding: Inger Bendix Foundation for Medical Research.
期刊介绍：
RMD Open publishes high quality peer-reviewed original research covering the full spectrum of musculoskeletal disorders, rheumatism and connective tissue diseases, including osteoporosis, spine and rehabilitation. Clinical and epidemiological research, basic and translational medicine, interesting clinical cases, and smaller studies that add to the literature are all considered.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
