{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:45:16Z","timestamp":1782819916268,"version":"3.54.5"},"reference-count":40,"publisher":"Ubiquity Press, Ltd.","issue":"1","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFC3606500"],"award-info":[{"award-number":["2023YFC3606500"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82470428"],"award-info":[{"award-number":["82470428"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["gh"],"abstract":"<jats:p>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.\nMethods: 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.\nResults: In the primary TSMR results, sulfasalazine targeting PLA2G1B was linked to reduced risks of heart failure (OR: 0.86, 95% CI: 0.80\u20130.94), total cholesterol (OR: 0.89, 95% CI: 0.83\u20130.95), high-density lipoprotein cholesterol (OR: 0.88, 95% CI: 0.82\u20130.94), and aortic stenosis (OR: 0.72, 95% CI: 0.62\u20130.84). 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\u20131.44), coronary artery disease (OR: 1.38, 95% CI: 1.23\u20131.56), myocardial infarction (OR: 1.27, 95% CI: 1.11\u20131.44), ischemic stroke (OR: 1.34, 95% CI: 1.22\u20131.48), and aortic stenosis (OR: 1.75, 95% CI: 1.46\u20132.09). 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.\nConclusion: Overall, this study presents evidence supporting a causal association between DMARDs and several CVDs. Nevertheless, further clinical investigations are necessary to validate our findings.<\/jats:p>","DOI":"10.5334\/gh.1526","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T09:44:37Z","timestamp":1772099077000},"page":"15","source":"Crossref","is-referenced-by-count":0,"title":["Association of Disease-Modifying Antirheumatic Drugs (DMARDs) with Cardiovascular Diseases: Evidence from a Drug Target Mendelian Randomization Study"],"prefix":"10.5334","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5447-6661","authenticated-orcid":false,"given":"Chengui","family":"Zhuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjie","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-9020","authenticated-orcid":false,"given":"Ting","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4025-7068","authenticated-orcid":false,"given":"Xiaosheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3285","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"key20260226094430_B1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update From the GBD 2019 Study","volume":"76","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"key20260226094430_B2","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1002\/art.24836","article-title":"Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? 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