George A Karpouzas, Sarah R Ormseth, Piet Van Riel, Elena Myasoedova, Miguel A Gonzalez-Gay, Alfonso Corrales, Solbritt Rantapaa-Dahlqvist, Petros Sfikakis, Patrick Dessein, Carol A Hitchon, Virginia Pascual-Ramos, Irazu Contreras Yanez, Iris Jazmín Colunga-Pedraza, Dionicio Angel Galarza-Delgado, Jose Azpiri-Lopez, Anne Grete Semb, Durga Prasanna Misra, George D Kitas, Ellen M Hauge
{"title":"甲氨蝶呤与男性缺血性心血管风险降低相关，但与女性无关：类风湿关节炎患者的跨大西洋心血管联盟观察性研究","authors":"George A Karpouzas, Sarah R Ormseth, Piet Van Riel, Elena Myasoedova, Miguel A Gonzalez-Gay, Alfonso Corrales, Solbritt Rantapaa-Dahlqvist, Petros Sfikakis, Patrick Dessein, Carol A Hitchon, Virginia Pascual-Ramos, Irazu Contreras Yanez, Iris Jazmín Colunga-Pedraza, Dionicio Angel Galarza-Delgado, Jose Azpiri-Lopez, Anne Grete Semb, Durga Prasanna Misra, George D Kitas, Ellen M Hauge","doi":"10.1007/s00296-025-05838-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Patients with rheumatoid arthritis (RA) experience higher cardiovascular risk. Methotrexate may decrease this risk, although it is unclear whether males and females similarly benefit. We explored the influence of sex on the effect of methotrexate use on cardiovascular risk in RA.</p><p><strong>Methods: </strong>An observational cohort of 4362 patients, 3223 (73.9%) females, without cardiovascular disease were included from an international cardiovascular consortium for RA. Outcomes were (a) major adverse cardiovascular events (MACE) including cardiovascular death, myocardial infarction, or stroke and (b) any ischemic cardiovascular events (iCVE) including MACE, angina, revascularization, transient ischemic attack, and peripheral arterial disease. The effects of sex, prevalent methotrexate use at enrollment visit and their interaction on MACE and iCVE were assessed with multivariable Cox regression models, reporting adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>There were 237 first MACE and 358 first iCVE. The sex by methotrexate interaction was significant for MACE (p = 0.005) and iCVE (p = 0.006), suggesting the effect of methotrexate use on cardiovascular risk differed among males and females. In males, methotrexate use associated with lower risk of MACE (HR 0.32, [95% CI 0.12-0.83]) and iCVE (HR 0.43 [95% CI 0.21-0.85]). In females, methotrexate use was not associated with MACE (p = 0.267) or iCVE (p = 0.407). In sensitivity analyses, models with inverse probability of treatment weighting and models additionally adjusting for inflammation yielded similar results.</p><p><strong>Conclusion: </strong>Methotrexate use associated with cardiovascular benefit in males but not females with RA and the effect was independent of inflammation.</p>","PeriodicalId":21322,"journal":{"name":"Rheumatology International","volume":"45 5","pages":"106"},"PeriodicalIF":3.2000,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Methotrexate associates with ischemic cardiovascular risk reduction in males but not females: a transatlantic cardiovascular consortium for people with rheumatoid arthritis observational study.\",\"authors\":\"George A Karpouzas, Sarah R Ormseth, Piet Van Riel, Elena Myasoedova, Miguel A Gonzalez-Gay, Alfonso Corrales, Solbritt Rantapaa-Dahlqvist, Petros Sfikakis, Patrick Dessein, Carol A Hitchon, Virginia Pascual-Ramos, Irazu Contreras Yanez, Iris Jazmín Colunga-Pedraza, Dionicio Angel Galarza-Delgado, Jose Azpiri-Lopez, Anne Grete Semb, Durga Prasanna Misra, George D Kitas, Ellen M Hauge\",\"doi\":\"10.1007/s00296-025-05838-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Patients with rheumatoid arthritis (RA) experience higher cardiovascular risk. Methotrexate may decrease this risk, although it is unclear whether males and females similarly benefit. We explored the influence of sex on the effect of methotrexate use on cardiovascular risk in RA.</p><p><strong>Methods: </strong>An observational cohort of 4362 patients, 3223 (73.9%) females, without cardiovascular disease were included from an international cardiovascular consortium for RA. Outcomes were (a) major adverse cardiovascular events (MACE) including cardiovascular death, myocardial infarction, or stroke and (b) any ischemic cardiovascular events (iCVE) including MACE, angina, revascularization, transient ischemic attack, and peripheral arterial disease. The effects of sex, prevalent methotrexate use at enrollment visit and their interaction on MACE and iCVE were assessed with multivariable Cox regression models, reporting adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>There were 237 first MACE and 358 first iCVE. The sex by methotrexate interaction was significant for MACE (p = 0.005) and iCVE (p = 0.006), suggesting the effect of methotrexate use on cardiovascular risk differed among males and females. In males, methotrexate use associated with lower risk of MACE (HR 0.32, [95% CI 0.12-0.83]) and iCVE (HR 0.43 [95% CI 0.21-0.85]). In females, methotrexate use was not associated with MACE (p = 0.267) or iCVE (p = 0.407). In sensitivity analyses, models with inverse probability of treatment weighting and models additionally adjusting for inflammation yielded similar results.</p><p><strong>Conclusion: </strong>Methotrexate use associated with cardiovascular benefit in males but not females with RA and the effect was independent of inflammation.</p>\",\"PeriodicalId\":21322,\"journal\":{\"name\":\"Rheumatology International\",\"volume\":\"45 5\",\"pages\":\"106\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-04-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Rheumatology International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00296-025-05838-y\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Rheumatology International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00296-025-05838-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Methotrexate associates with ischemic cardiovascular risk reduction in males but not females: a transatlantic cardiovascular consortium for people with rheumatoid arthritis observational study.
Objective: Patients with rheumatoid arthritis (RA) experience higher cardiovascular risk. Methotrexate may decrease this risk, although it is unclear whether males and females similarly benefit. We explored the influence of sex on the effect of methotrexate use on cardiovascular risk in RA.
Methods: An observational cohort of 4362 patients, 3223 (73.9%) females, without cardiovascular disease were included from an international cardiovascular consortium for RA. Outcomes were (a) major adverse cardiovascular events (MACE) including cardiovascular death, myocardial infarction, or stroke and (b) any ischemic cardiovascular events (iCVE) including MACE, angina, revascularization, transient ischemic attack, and peripheral arterial disease. The effects of sex, prevalent methotrexate use at enrollment visit and their interaction on MACE and iCVE were assessed with multivariable Cox regression models, reporting adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: There were 237 first MACE and 358 first iCVE. The sex by methotrexate interaction was significant for MACE (p = 0.005) and iCVE (p = 0.006), suggesting the effect of methotrexate use on cardiovascular risk differed among males and females. In males, methotrexate use associated with lower risk of MACE (HR 0.32, [95% CI 0.12-0.83]) and iCVE (HR 0.43 [95% CI 0.21-0.85]). In females, methotrexate use was not associated with MACE (p = 0.267) or iCVE (p = 0.407). In sensitivity analyses, models with inverse probability of treatment weighting and models additionally adjusting for inflammation yielded similar results.
Conclusion: Methotrexate use associated with cardiovascular benefit in males but not females with RA and the effect was independent of inflammation.
期刊介绍：
RHEUMATOLOGY INTERNATIONAL is an independent journal reflecting world-wide progress in the research, diagnosis and treatment of the various rheumatic diseases. It is designed to serve researchers and clinicians in the field of rheumatology.
RHEUMATOLOGY INTERNATIONAL will cover all modern trends in clinical research as well as in the management of rheumatic diseases. Special emphasis will be given to public health issues related to rheumatic diseases, applying rheumatology research to clinical practice, epidemiology of rheumatic diseases, diagnostic tests for rheumatic diseases, patient reported outcomes (PROs) in rheumatology and evidence on education of rheumatology. Contributions to these topics will appear in the form of original publications, short communications, editorials, and reviews. "Letters to the editor" will be welcome as an enhancement to discussion. Basic science research, including in vitro or animal studies, is discouraged to submit, as we will only review studies on humans with an epidemological or clinical perspective. Case reports without a proper review of the literatura (Case-based Reviews) will not be published. Every effort will be made to ensure speed of publication while maintaining a high standard of contents and production.
Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.
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