甲氨蝶呤与男性缺血性心血管疾病风险降低相关，但与女性无关：一项针对类风湿关节炎患者的跨大西洋心血管联盟观察性研究。

Methotrexate associates with ischemic cardiovascular risk reduction in males but not females: a transatlantic cardiovascular consortium for people with rheumatoid arthritis observational study.

作者信息

Karpouzas George A, Ormseth Sarah R, Van Riel Piet, Myasoedova Elena, Gonzalez-Gay Miguel A, Corrales Alfonso, Rantapaa-Dahlqvist Solbritt, Sfikakis Petros, Dessein Patrick, Hitchon Carol A, Pascual-Ramos Virginia, Yanez Irazu Contreras, Colunga-Pedraza Iris Jazmín, Galarza-Delgado Dionicio Angel, Azpiri-Lopez Jose, Semb Anne Grete, Misra Durga Prasanna, Kitas George D, Hauge Ellen M

机构信息

Department of Rheumatology, Harbor-UCLA Medical Center, 1124 West Carson Street, Building E4- R17, 90502, Torrance, California, USA.

Radboud University Medical Centre, Nijmegen, the Netherlands.

出版信息

Rheumatol Int. 2025 Apr 18;45(5):106. doi: 10.1007/s00296-025-05838-y.

DOI:10.1007/s00296-025-05838-y

PMID:40249410

Abstract

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.

摘要

目的

类风湿关节炎（RA）患者心血管风险较高。甲氨蝶呤可能会降低这种风险，尽管尚不清楚男性和女性是否同样受益。我们探讨了性别对甲氨蝶呤用于RA患者心血管风险影响的作用。

方法

从一个国际RA心血管联盟纳入了4362例无心血管疾病的患者组成观察队列，其中3223例（73.9%）为女性。结局指标为：（a）主要不良心血管事件（MACE），包括心血管死亡、心肌梗死或中风；（b）任何缺血性心血管事件（iCVE），包括MACE、心绞痛、血运重建、短暂性脑缺血发作和外周动脉疾病。采用多变量Cox回归模型评估性别、入组时甲氨蝶呤的使用情况及其相互作用对MACE和iCVE的影响，报告校正风险比（HR）和95%置信区间（CI）。

结果

发生237例首次MACE和358例首次iCVE。甲氨蝶呤与性别的相互作用对MACE（p = 0.005）和iCVE（p = 0.006）具有显著意义，表明甲氨蝶呤用于心血管风险的影响在男性和女性中有所不同。在男性中，使用甲氨蝶呤与较低的MACE风险（HR 0.32，[95%CI 0.12 - 0.83]）和iCVE风险（HR 0.43 [95%CI 0.21 - 0.85]）相关。在女性中，使用甲氨蝶呤与MACE（p = 0.267）或iCVE（p = 0.407）无关。在敏感性分析中，采用治疗权重逆概率模型和额外调整炎症因素的模型得出了相似的结果。