{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:42:09Z","timestamp":1780393329952,"version":"3.54.1"},"reference-count":102,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease which predominantly affects joints, but it can also lead to significant extra-articular complications, particularly cardiovascular disease (CVD). Chronic systemic inflammation promotes endothelial dysfunction and accelerates atherosclerosis, increasing cardiovascular risk. Methods: Current data were analyzed to explore the mechanisms between RA and CVD, focusing on systemic inflammation, pro-inflammatory cytokine patways (IL-1, IL-6, TNF, and JAK-STAT), and their interactions with traditional cardiovascular risk factors. Recent studies and clinical guidelines were reviewed to highlight gaps and advances in risk assessment and management. Results: Persistent disease activity and the presence of autoantibodies significantly increase cardiovascular risk in RA contributing to atherosclerosis and major cardiovascular events. Data also suggest that anti-inflammatory treatments, including methotrexate and biologic agents, may lower this risk. Conclusion: This review highlights the pathophysiological mechanisms between RA and CVD, and the need for early diagnosis and active monitoring to identify and assess cardiovascular risk. A multidisciplinary approach, involving rheumatologists and cardiologists is essential for optimizing cardiovascular risk management and improving patient outcomes. Optimization of cardiovascular risk management strategies in patients with RA should be an essential component of current medical practice, with the main goal of reducing morbidity and mortality from cardiovascular complications.<\/jats:p>","DOI":"10.3390\/life15040629","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T08:46:20Z","timestamp":1744274780000},"page":"629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["From Joints to the Heart: An Integrated Perspective on Systemic Inflammation"],"prefix":"10.3390","volume":"15","author":[{"given":"Diana Elena","family":"Cos\u0103u","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina Iuliana","family":"Costache Enache","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"\u201cSt. Spiridon\u201d Emergency County Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8544-9904","authenticated-orcid":false,"given":"Alexandru Dan","family":"Costache","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4956-2595","authenticated-orcid":false,"given":"Ionu\u021b","family":"Tudorancea","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"\u201cSt. Spiridon\u201d Emergency County Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-8121","authenticated-orcid":false,"given":"Codrina","family":"Ancu\u021ba","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragomir Nicolae","family":"\u0218erban","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8942-1909","authenticated-orcid":false,"given":"Codru\u021ba Minerva","family":"B\u0103descu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"\u201cSt. Spiridon\u201d Emergency County Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u0103t\u0103lin","family":"Loghin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology Division, University of Texas Health Science Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ionela L\u0103cr\u0103mioara","family":"\u0218erban","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lin, Y.J., Anzaghe, M., and Sch\u00fclke, S. (2020). Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis. Cells, 9.","DOI":"10.3390\/cells9040880"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wu, D., Luo, Y., Li, T., Zhao, X., Lv, T., Fang, G., Ou, P., Li, H., Luo, X., and Huang, A. (2022). Systemic complications of rheumatoid arthritis: Focus on pathogenesis and treatment. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1051082"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1136\/annrheumdis-2019-216694","article-title":"Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985\u20132014","volume":"79","author":"Myasoedova","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Radu, A.F., and Bungau, S.G. (2021). Management of Rheumatoid Arthritis: An Overview. Cells, 10.","DOI":"10.3390\/cells10112857"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102776","DOI":"10.1016\/j.autrev.2021.102776","article-title":"Rheumatoid arthritis: Extra-articular manifestations and comorbidities","volume":"20","author":"Figus","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1093\/rheumatology\/keu224","article-title":"Cardiovascular risk in rheumatoid arthritis: Recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment","volume":"53","author":"Choy","year":"2014","journal-title":"Rheumatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1161\/01.CIR.0000054612.26458.B2","article-title":"Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis","volume":"107","author":"Solomon","year":"2003","journal-title":"Circulation"},{"key":"ref_8","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? A prospective study","volume":"61","author":"Peters","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1136\/ard.2010.143396","article-title":"The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: A Danish nationwide cohort study","volume":"70","author":"Lindhardsen","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1016\/j.amjmed.2008.06.011","article-title":"Cardiovascular morbidity and mortality in rheumatoid arthritis","volume":"121","author":"Gabriel","year":"2008","journal-title":"Am. J. Med."},{"key":"ref_11","first-page":"435","article-title":"Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis","volume":"32","author":"Dessein","year":"2005","journal-title":"J. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jbspin.2010.07.016","article-title":"Traditional cardiovascular risk factors in rheumatoid arthritis: A meta-analysis","volume":"78","author":"Boyer","year":"2011","journal-title":"Jt. Bone Spine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1136\/ard.2009.113696","article-title":"EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis","volume":"69","author":"Peters","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1253\/circj.CJ-09-0274","article-title":"Rheumatoid arthritis: Model of systemic inflammation driving atherosclerosis","volume":"73","author":"Ku","year":"2009","journal-title":"Circ. J."},{"key":"ref_15","first-page":"S1","article-title":"RAPID: Rheumatoid arthritis","volume":"56","author":"Weinblatt","year":"2007","journal-title":"J. Fam. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1136\/ard.56.6.341","article-title":"Dyslipidemia and rheumatoid arthritis","volume":"56","author":"Situnayake","year":"1997","journal-title":"Ann. Rheum. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1002\/1529-0131(200112)44:12<2737::AID-ART460>3.0.CO;2-#","article-title":"High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors","volume":"44","author":"Williams","year":"2001","journal-title":"Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/01.bor.0000158150.57154.f9","article-title":"Vascular comorbidity in rheumatoid arthritis: Potential mechanisms and solutions","volume":"17","author":"Sattar","year":"2005","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation, 106, 3143\u20133421.","DOI":"10.1161\/circ.106.25.3143"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1136\/ard.2010.135871","article-title":"Lipid paradox in rheumatoid arthritis: The impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease","volume":"70","author":"Myasoedova","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e19241","DOI":"10.1016\/j.heliyon.2023.e19241","article-title":"Protocol for rheumatoid arthritis complicated with cardiovascular damage treated with Guanxining tablet with a randomized controlled trial","volume":"9","author":"Yu","year":"2023","journal-title":"Heliyon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41584-020-0428-y","article-title":"Atherosclerotic cardiovascular disease prevention in rheumatoid arthritis","volume":"16","author":"Semb","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_23","first-page":"e47416","article-title":"Role of Cardiac Biomarkers in the Evaluation of Rheumatoid Arthritis: A Systematic Review","volume":"15","author":"Borra","year":"2023","journal-title":"Cureus"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Erre, G.L., Chessa, I., Bassu, S., Cavagna, L., Carru, C., Pintus, G., Giordo, R., Mangoni, A.A., Damiano Sanna, G., and Zinellu, A. (2024). Association between ischemia-modified albumin (IMA) and peripheral endothelial dysfunction in rheumatoid arthritis patients. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-54641-5"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6548715","DOI":"10.1155\/2018\/6548715","article-title":"Prevalence and Determinants of Peripheral Microvascular Endothelial Dysfunction in Rheumatoid Arthritis Patients: A Multicenter Cross-Sectional Study","volume":"2018","author":"Erre","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/art.22482","article-title":"HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis","volume":"57","author":"Ollier","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"R71","DOI":"10.1186\/ar2989","article-title":"A1298C polymorphism in the MTHFR gene predisposes to cardiovascular risk in rheumatoid arthritis","volume":"12","author":"Rodriguez","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"R133","DOI":"10.1186\/ar3444","article-title":"CCR5\u039432 variant and cardiovascular disease in patients with rheumatoid arthritis: A cohort study","volume":"13","author":"Llorca","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/acr.20322","article-title":"Inflammatory and autoimmune mechanisms in the induction of atherosclerotic damage in systemic rheumatic diseases: Two faces of the same coin","volume":"63","author":"Bartoloni","year":"2011","journal-title":"Arthritis Care Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2217\/bmm.10.61","article-title":"Endothelial function as a functional expression of cardiovascular risk factors","volume":"4","author":"Reriani","year":"2010","journal-title":"Biomark. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bartoloni, E., Alunno, A., Valentini, V., Luccioli, F., Valentini, E., La Paglia, G.M.C., Leone, M.C., Cafaro, G., Marcucci, E., and Gerli, R. (2018). Targeting Inflammation to Prevent Cardiovascular Disease in Chronic Rheumatic Diseases: Myth or Reality. Front. Cardiovasc. Med., 5.","DOI":"10.3389\/fcvm.2018.00177"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Huang, J., Fu, X., Chen, X., Li, Z., Huang, Y., and Liang, C. (2021). Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.686155"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1136\/annrheumdis-2012-202377","article-title":"Progression to rheumatoid arthritis in early inflammatory arthritis is associated with low IL-7 serum levels","volume":"72","author":"Aegerter","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1161\/CIRCRESAHA.120.315937","article-title":"Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease","volume":"126","author":"Abbate","year":"2020","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41584-023-00969-7","article-title":"Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease","volume":"19","author":"Weber","year":"2023","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tanaka, T., Narazaki, M., and Kishimoto, T. (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol., 6.","DOI":"10.1101\/cshperspect.a016295"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1172\/JCI67526","article-title":"Collagenases and cracks in the plaque","volume":"123","author":"Libby","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1093\/eurheartj\/ehz008","article-title":"Stage-dependent differential effects of interleukin-1 isoforms on experimental atherosclerosis","volume":"40","author":"Vromman","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1177\/1759720X10378372","article-title":"The role of interleukin 6 in the pathophysiology of rheumatoid arthritis","volume":"2","author":"Srirangan","year":"2010","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/nri1882","article-title":"The immune response in atherosclerosis: A double-edged sword","volume":"6","author":"Hansson","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.coi.2015.02.008","article-title":"The IL-6\/gp130\/STAT3 signaling axis: Recent advances towards specific inhibition","volume":"34","author":"Garbers","year":"2015","journal-title":"Curr. Opin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1161\/CIRCRESAHA.108.188243","article-title":"IL-10 inhibits inflammation and attenuates left ventricular remodeling after myocardial infarction via activation of STAT3 and suppression of HuR","volume":"104","author":"Krishnamurthy","year":"2009","journal-title":"Circ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Plens-Galaska, M., Szelag, M., Collado, A., Marques, P., Vallejo, S., Ramos-Gonz\u00e1lez, M., Wesoly, J., Sanz, M.J., Peir\u00f3, C., and Bluyssen, H.A.R. (2018). Genome-Wide Inhibition of Pro-atherogenic Gene Expression by Multi-STAT Targeting Compounds as a Novel Treatment Strategy of CVDs. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02141"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41577-018-0029-z","article-title":"IFN\u03b3: Signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy","volume":"18","author":"Ivashkiv","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1080\/14712598.2016.1217988","article-title":"Room for more IL-6 blockade? Sarilumab for the treatment of rheumatoid arthritis","volume":"16","author":"June","year":"2016","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1634\/theoncologist.2018-0028","article-title":"FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome","volume":"23","author":"Le","year":"2018","journal-title":"Oncologist"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e025467","DOI":"10.1161\/JAHA.121.025467","article-title":"Relationship Between Risk of Atherosclerotic Cardiovascular Disease, Inflammation, and Coronary Microvascular Dysfunction in Rheumatoid Arthritis","volume":"11","author":"Weber","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1093\/rheumatology\/keaa725","article-title":"The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis","volume":"60","author":"Davies","year":"2021","journal-title":"Rheumatology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1093\/eurheartj\/ehy310","article-title":"Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: Analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS)","volume":"39","author":"Ridker","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Gough, P., and Myles, I.A. (2020). Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.585880"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Yang, S., Wang, J., Brand, D.D., and Zheng, S.G. (2018). Role of TNF-TNF Receptor 2 Signal in Regulatory T Cells and Its Therapeutic Implications. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00784"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/art.41752","article-title":"2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis","volume":"73","author":"Fraenkel","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/annrheumdis-2019-216655","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update","volume":"79","author":"Smolen","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00281-003-0125-3","article-title":"The TNF-alpha transgenic mouse model of inflammatory arthritis","volume":"25","author":"Li","year":"2003","journal-title":"Springer Semin. Immunopathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1002\/j.1460-2075.1991.tb04978.x","article-title":"Transgenic mice expressing human tumour necrosis factor: A predictive genetic model of arthritis","volume":"10","author":"Keffer","year":"1991","journal-title":"EMBO J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.1172\/JCI36389","article-title":"Evidence that cytokines play a role in rheumatoid arthritis","volume":"118","author":"Brennan","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1084\/jem.162.6.2163","article-title":"Cachectin\/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts","volume":"162","author":"Dayer","year":"1985","journal-title":"J. Exp. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/319516a0","article-title":"Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors","volume":"319","author":"Bertolini","year":"1986","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1084\/jem.20061531","article-title":"Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta","volume":"204","author":"Nadkarni","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1084\/jem.20040165","article-title":"Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy","volume":"200","author":"Ehrenstein","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1042\/CS20080196","article-title":"Role of TNF-alpha in vascular dysfunction","volume":"116","author":"Zhang","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/0140-6736(90)90115-L","article-title":"TNF-induced cardiomyopathy","volume":"335","author":"Hegewisch","year":"1990","journal-title":"Lancet"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.atherosclerosis.2003.10.004","article-title":"Exclusive expression of transmembrane TNF-alpha in mice reduces the inflammatory response in early lipid lesions of aortic sinus","volume":"172","author":"Canault","year":"2004","journal-title":"Atherosclerosis"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.atherosclerosis.2004.11.016","article-title":"Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice","volume":"180","author":"Ohta","year":"2005","journal-title":"Atherosclerosis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1161\/01.CIR.0000077913.60364.D2","article-title":"Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: Results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial","volume":"107","author":"Chung","year":"2003","journal-title":"Circulation"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1161\/01.CIR.0000124490.27666.B2","article-title":"Targeted anticytokine therapy in patients with chronic heart failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)","volume":"109","author":"Mann","year":"2004","journal-title":"Circulation"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1752-8062.2008.00013.x","article-title":"Effect of the soluble TNF-antagonist etanercept on tumor necrosis factor bioactivity and stability","volume":"1","author":"Mann","year":"2008","journal-title":"Clin. Transl. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1056\/NEJMoa2109927","article-title":"Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis","volume":"386","author":"Ytterberg","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1146\/annurev-med-051113-024537","article-title":"The JAK-STAT pathway: Impact on human disease and therapeutic intervention","volume":"66","author":"Schwartz","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12964-017-0177-y","article-title":"The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells","volume":"15","author":"Seif","year":"2017","journal-title":"Cell Commun. Signal."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"100853","DOI":"10.1016\/j.cpcardiol.2021.100853","article-title":"Triggers of Cardiovascular Diseases in Rheumatoid Arthritis","volume":"47","author":"Zhang","year":"2022","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s40257-013-0034-8","article-title":"Prevalence of metabolic syndrome in Beh\u00e7et disease: A case-control study in Turkey","volume":"14","year":"2013","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"iv4","DOI":"10.1093\/rheumatology\/kel313","article-title":"The heart and cardiovascular manifestations in rheumatoid arthritis","volume":"45","author":"Voskuyl","year":"2006","journal-title":"Rheumatology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1002\/art.24092","article-title":"Risk of cardiovascular mortality in patients with rheumatoid arthritis: A meta-analysis of observational studies","volume":"59","author":"Choi","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.2147\/DDDT.S99898","article-title":"Spotlight on sirukumab for the treatment of rheumatoid arthritis: The evidence to date","volume":"10","author":"Lazzerini","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"562","DOI":"10.4330\/wjc.v9.i7.562","article-title":"Sudden cardiac death in patients with rheumatoid arthritis","volume":"9","author":"Masoud","year":"2017","journal-title":"World J. Cardiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s00296-003-0357-5","article-title":"Heart rate variability in patients with rheumatoid arthritis","volume":"24","author":"Dursunoglu","year":"2004","journal-title":"Rheumatol. Int."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1136\/heartjnl-2018-313313","article-title":"Interplay of inflammation, oxidative stress and cardiovascular disease in rheumatoid arthritis","volume":"104","author":"Abbate","year":"2018","journal-title":"Heart"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/art.20853","article-title":"Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: A population-based cohort study","volume":"52","author":"Crowson","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1093\/rheumatology\/kep253","article-title":"Hand deformities are important signs of disease severity in patients with early rheumatoid arthritis","volume":"48","author":"Johnsson","year":"2009","journal-title":"Rheumatology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/s10067-024-06878-8","article-title":"Association of congestive heart failure with mortality in individuals with rheumatoid arthritis: A cohort study","volume":"43","author":"Wang","year":"2024","journal-title":"Clin. Rheumatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0049-0172(79)80005-0","article-title":"Extraarticular manifestations of rheumatoid arthritis","volume":"8","author":"Hurd","year":"1979","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/art.41979","article-title":"Myocardial Dysfunction and Heart Failure in Rheumatoid Arthritis","volume":"74","author":"Park","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11926-020-00922-7","article-title":"Is There a Brain\/Heart Interaction in Rheumatoid Arthritis and Seronegative Spondyloartropathies? A Combined Brain\/Heart Magnetic Resonance Imaging Reveals the Answer","volume":"22","author":"Koutsogeorgopoulou","year":"2020","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/imr.12605","article-title":"Suppression of inflammation and acquired immunity by IL-37","volume":"281","author":"Cavalli","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1001\/jamacardio.2018.2695","article-title":"Myocarditis in Duchenne Muscular Dystrophy After Changing Steroids","volume":"3","author":"Abutaleb","year":"2018","journal-title":"JAMA Cardiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1161\/CIRCRESAHA.117.311812","article-title":"Cardiomyopathies: An Overview","volume":"121","author":"Braunwald","year":"2017","journal-title":"Circ. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"482-9c","DOI":"10.1093\/eurheartj\/ehu403","article-title":"Cardiovascular disease in patients with chronic inflammation: Mechanisms underlying premature cardiovascular events in rheumatologic conditions","volume":"36","author":"Mason","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e19658","DOI":"10.1097\/MD.0000000000019658","article-title":"Cardiovascular outcomes in patients with co-existing coronary artery disease and rheumatoid arthritis: A systematic review and meta-analysis","volume":"99","author":"Wang","year":"2020","journal-title":"Medicine"},{"key":"ref_92","first-page":"1839","article-title":"Chronic inflammation and atherosclerosis","volume":"138","author":"Weber","year":"2013","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.joms.2014.03.034","article-title":"Rheumatoid nodule in the lower lip of a patient with rheumatoid arthritis: A novel case report and review of literature","volume":"72","author":"Kato","year":"2014","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1253\/circj.CJ-19-0705","article-title":"Cardiac Arrhythmias in Autoimmune Diseases","volume":"84","author":"Balsam","year":"2020","journal-title":"Circ. J."},{"key":"ref_95","first-page":"516","article-title":"QT and QT dispersion intervals in long-standing and moderately active rheumatoid arthritis: Results from a multicentre cross-sectional study","volume":"38","author":"Erre","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"102671","DOI":"10.1016\/j.jaccas.2024.102671","article-title":"Aortic Regurgitation and Rheumatoid Arthritis","volume":"29","author":"Selinski","year":"2024","journal-title":"JACC Case Rep."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Rydell, E., Jacobsson, L.T., Saxne, T., and Turesson, C. (2023). Cardiovascular disease risk in early rheumatoid arthritis: The impact of cartilage oligomeric matrix protein (COMP) and disease activity. BMC Rheumatol., 7.","DOI":"10.1186\/s41927-023-00367-2"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.semarthrit.2020.11.005","article-title":"C-reactive protein and implications in rheumatoid arthritis and associated comorbidities","volume":"51","author":"Pope","year":"2021","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s10067-017-3897-x","article-title":"Association between leptin and IL-6 concentrations with cardiovascular risk in patients with rheumatoid arthritis","volume":"37","year":"2018","journal-title":"Clin. Rheumatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1002\/acr.24885","article-title":"Circulating Adipokines and Associations With Incident Cardiovascular Disease in Rheumatoid Arthritis","volume":"75","author":"Federico","year":"2023","journal-title":"Arthritis Care Res."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"P\u00e0mies, A., Llop, D., Ibarretxe, D., Rosales, R., Girona, J., Masana, L., Vallv\u00e9, J.C., and Paredes, S. (2024). Enhanced Association of Novel Cardiovascular Biomarkers Fetuin-A and Catestatin with Serological and Inflammatory Markers in Rheumatoid Arthritis Patients. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25189910"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nrrheum.2014.37","article-title":"Rheumatoid arthritis: Treating cardiovascular risk in RA requires multidisciplinary care","volume":"10","author":"Mankad","year":"2014","journal-title":"Nat. Rev. Rheumatol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/4\/629\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:11:43Z","timestamp":1760029903000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/4\/629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":102,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["life15040629"],"URL":"https:\/\/doi.org\/10.3390\/life15040629","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,9]]}}}