ArticleAnnals of the rheumatic diseases2021
Investigating changes in disease activity as a mediator of cardiovascular risk reduction with methotrexate use in rheumatoid arthritis.
Article in Annals of the rheumatic diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 45 citations in OpenAlex.
- Metabolic Complications in Autoimmune and Autoinflammatory Diseases: Pathophysiology, Clinical Implications, and Therapeutic Perspectives.Journal of clinical medicine · 2026Review
- The evolving comorbidity landscape of rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Performance of the Predicting Risk of Cardiovascular Disease Events Calculator in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- [Consensus statement of the Austrian Society for Rheumatology and Rehabilitation on the management of increased cardiovascular risk in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis].Wiener klinische Wochenschrift · 2026Article
- Heart Failure in Rheumatoid Arthritis: Epidemiology, Pathogenesis, Diagnosis, Treatment, and Emerging Insights-A Comprehensive Review.Medicina (Kaunas, Lithuania) · 2026Review
- Observational
- A multimodal vision knowledge graph of cardiovascular disease.Nature cardiovascular research · 2026Article
- A controlled comparative study of the effects of methotrexate and pharmacogenetic factors on arterial blood pressure and arterial stiffness in patients with rheumatoid arthritis.Annals of medicine · 2025Article
- Citrullinated and Malondialdehyde-Acetaldehyde-Modified Fibrinogen Activates Macrophages and Promotes Coronary Endothelial Cell Inflammation.Current issues in molecular biology · 2025Article
- Risk and temporal trends of heart failure subtypes in rheumatoid arthritis.Seminars in arthritis and rheumatism · 2025Article
- From joints to vessels: How rheumatoid arthritis therapy alters the fate of the heart.World journal of cardiology · 2025Review
- Characteristics Associated With Detectable High-Sensitivity Cardiac Troponin in Patients With Rheumatoid Arthritis at Low-Intermediate Cardiac Risk.ACR open rheumatology · 2025Article
- Trends of Large for Gestational Age and Macrosomia and Their Mediating Effect on the Association Between Diabetes Mellitus and Obstetric Hemorrhage.Maternal & child nutrition · 2025Article
- Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Methotrexate associates with ischemic cardiovascular risk reduction in males but not females: a transatlantic cardiovascular consortium for people with rheumatoid arthritis observational study.Rheumatology international · 2025Observational
- The Veterans Affairs Rheumatoid Arthritis Registry: A unique population in rheumatoid arthritis research.Seminars in arthritis and rheumatism · 2025Review
- The Effects of Disease-Modifying Antirheumatic Drugs on Cardiovascular Risk in Inflammatory Joint Diseases: Current Evidence and Uncertainties.Vascular health and risk management · 2025Review
- Trends in stroke occurrence in rheumatoid arthritis: a retrospective cohort study from Western Norway, 1972 through 2020.Frontiers in medicine · 2025Article
- 2024 Guidelines of the Taiwan Society of Cardiology on the Primary Prevention of Atherosclerotic Cardiovascular Disease --- Part I.Acta Cardiologica Sinica · 2024Article
- Cardio-rheumatology: the cardiovascular, pharmacological, and surgical risks associated with rheumatological diseases in women.Canadian journal of physiology and pharmacology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
objectiveExamine the association of methotrexate (MTX) use with cardiovascular disease (CVD) in rheumatoid arthritis (RA) using marginal structural models (MSM) and determine if CVD risk is mediated through modification of disease activity.
methodsWe identified incident CVD events (coronary artery disease (CAD), stroke, heart failure (HF) hospitalisation, CVD death) within a multicentre, prospective cohort of US Veterans with RA. A 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) was collected at regular visits and medication exposures were determined by linking to pharmacy dispensing data. MSMs were used to estimate the treatment effect of MTX on risk of incident CVD, accounting for time-varying confounders between receiving MTX and CVD events. A mediation analysis was performed to estimate the indirect effects of methotrexate on CVD risk through modification of RA disease activity.
resultsAmong 2044 RA patients (90% male, mean age 63.9 years, baseline DAS28-CRP 3.6), there were 378 incident CVD events. Using MSM, MTX use was associated with a 24% reduced risk of composite CVD events (HR 0.76, 95% CI 0.58 to 0.99) including a 57% reduction in HF hospitalisations (HR 0.43, 95% CI 0.24 to 0.77). Individual associations with CAD, stroke and CVD death were not statistically significant. In mediation analyses, there was no evidence of indirect effects of MTX on CVD risk through disease activity modification (HR 1.03, 95% CI 0.80 to 1.32).
conclusionsMTX use in RA was associated with a reduced risk of CVD events, particularly HF-related hospitalisations. These associations were not mediated through reductions in RA disease activity, suggesting alternative MTX-related mechanisms may modify CVD risk in this population.
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Registered trials
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