Evidence mapPaperPMID 41766719Full record

ArticleGlobal heart2026

Association of Disease-Modifying Antirheumatic Drugs (DMARDs) with Cardiovascular Diseases: Evidence from a Drug Target Mendelian Randomization Study.

Chengui Zhuo, Lei Chen, Xiangjie Sun, Ting Chen, Haipeng Cai, Xiaosheng Hu

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Article in Global heart, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Chengui ZhuoDepartment of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.ORCID 0009-0003-5447-6661
Lei ChenDepartment of Cardiology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.
Xiangjie SunDepartment of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Ting ChenDepartment of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.ORCID 0000-0002-9723-9020
Haipeng CaiDepartment of Cardiology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.
Xiaosheng HuDepartment of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.ORCID 0000-0002-4025-7068

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objectives: Cardiovascular diseases (CVDs) still represent a major cause of mortality, with inflammation playing a key role in their pathogenesis. Thus, elucidating the possible effects of disease-modifying antirheumatic drugs (DMARDs) on CVD risk in the general population may hold considerable clinical implications. Methods: Genetic instruments were employed to proxy the pharmacological effects of seven DMARD classes, including sulfasalazine, cyclosporine, leflunomide, IL-6 inhibitors, TNF-alpha inhibitors, abatacept, rituximab, and JAK inhibitors. To investigate their potential causal associations with 11 CVD outcomes, a comprehensive framework incorporating two-sample Mendelian randomization (TSMR), summary-data-based MR (SMR), and colocalization analysis was developed. Lastly, several sensitivity analyses were undertaken to verify the robustness of our findings. Results: In the primary TSMR results, sulfasalazine targeting PLA2G1B was linked to reduced risks of heart failure (OR: 0.86, 95% CI: 0.80-0.94), total cholesterol (OR: 0.89, 95% CI: 0.83-0.95), high-density lipoprotein cholesterol (OR: 0.88, 95% CI: 0.82-0.94), and aortic stenosis (OR: 0.72, 95% CI: 0.62-0.84). Sulfasalazine targeting RELB exhibited similar protective associations, whereas RELA exhibited the opposite associations. Moreover, IL-6R was robustly associated with increased risks of atrial fibrillation (OR: 1.29, 95% CI: 1.16-1.44), coronary artery disease (OR: 1.38, 95% CI: 1.23-1.56), myocardial infarction (OR: 1.27, 95% CI: 1.11-1.44), ischemic stroke (OR: 1.34, 95% CI: 1.22-1.48), and aortic stenosis (OR: 1.75, 95% CI: 1.46-2.09). Genetically higher IL-6R expression was associated with increased CVD risk, suggesting that IL-6 inhibition may confer cardiovascular benefit. SMR analysis further validated the associations of RELA, CD80, and IL-6R with one or more cardiovascular phenotypes. Finally, colocalization analyses for IL-6R and RELB provided strong evidence supporting their involvement in multiple CVDs. Conclusion: Overall, this study presents evidence supporting a causal association between DMARDs and several CVDs. Nevertheless, further clinical investigations are necessary to validate our findings.

Indexed as

Antirheumatic AgentsCardiovascular DiseasesMendelian Randomization AnalysisHumansAntirheumatic Agentscardiovascular diseasescolocalization analysesDMARD target genessummary-data-based MRtwo-sample Mendelian randomization

Identifiers

PMID41766719
PMCPMC12947826

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.