INFLAMMATORY BOWEL DISEASES AND THE RISK OF CARDIOVASCULAR EVENTS — A LITERATURE REVIEW
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6528Keywords:
Inflammatory Bowel Diseases, Cardiovascular Risk, Atherosclerosis, Venous Thromboembolism, Endothelial DysfunctionAbstract
Inflammatory bowel disease (IBD) — ulcerative colitis (UC) and Crohn's disease (CD) — comprises chronic, immune-mediated disorders of the gastrointestinal tract whose pathophysiological impact extends beyond the intestinal mucosa. A growing body of epidemiological evidence, including large-scale meta-analyses, indicates that patients with IBD carry an elevated risk of cardiovascular events, including coronary artery disease, stroke, heart failure (HF), venous thromboembolism (VTE), and atrial fibrillation (AF), despite a relatively lower prevalence of classical atherosclerotic risk factors in this population. This risk is particularly pronounced during periods of active, uncontrolled intestinal inflammation and in younger patients, in whom the contribution of the inflammatory process to overall cardiovascular risk is proportionally greatest. This review summarizes current evidence on the epidemiology of this association and the pathophysiological mechanisms linking chronic intestinal inflammation to vascular injury, including endothelial dysfunction, a prothrombotic state, gut microbiota dysbiosis and its metabolites — notably trimethylamine N-oxide (TMAO) — and inflammatory biomarkers. The differential impact of IBD pharmacotherapy on cardiovascular risk is also addressed, with particular emphasis on Janus kinase (JAK) inhibitors, associated with an elevated risk of thromboembolic complications, in contrast to biologic agents, which in several observational studies have demonstrated a potentially cardioprotective effect. The risk profile of TNF-α inhibitors in patients with coexisting heart failure is discussed separately. Finally, recommendations for cardiovascular risk stratification and prophylaxis in this population are presented, incorporating recent dedicated expert position statements from scientific societies, alongside directions for future investigation.
Methods and Materials A systematic review of the scientific literature concerning the risk of cardiovascular events in patients with a diagnosed inflammatory bowel disease was conducted. Randomized controlled trials, meta-analyses, and [observational] studies were analyzed…
Conclusions Particular attention should be paid to the assessment of cardiovascular event risk in patients with inflammatory bowel disease, especially in those who have had the disease for many years. Patients with inflammatory bowel disease [have an] increased risk of cardiovascular events, which is primarily attributable to chronic inflammation acting on the vascular wall through endothelial dysfunction, activation of coagulation, and disturbances of the gut microbiota, with the risk correlating more strongly with disease activity than with the diagnosis itself.
References
Liu, L. F., Fan, Y. W., Lv, Y., Liu, Z. X., & Dai, X. C. (2025). Strategies for assessing and preventing cardiovascular disease risk in inflammatory bowel disease patients: A meta-analysis and meta-regression and bibliometric review. PLOS ONE, 20(7), e0327734. https://doi.org/10.1371/journal.pone.0327734
Eriksson, C., Sun, J., Bryder, M., Bröms, G., Everhov, Å. H., Forss, A., Jernberg, T., Ludvigsson, J. F., & Olén, O. (2024). Impact of inflammatory bowel disease on the risk of acute coronary syndrome: A Swedish nationwide cohort study. Alimentary Pharmacology & Therapeutics, 59(9), 1122–1133. https://doi.org/10.1111/apt.17932
Alayo, Q. A., Loftus, E. V., Jr, Yarur, A., Alvarado, D., Ciorba, M. A., de las Fuentes, L., & Deepak, P. (2023). Inflammatory bowel disease is associated with an increased risk of incident acute arterial events: Analysis of the United Kingdom Biobank. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 21(3), 761–770.e13. https://doi.org/10.1016/j.cgh.2022.08.035
Soares, C. A., Fiuza, J. G., Rodrigues, C. A. M., Craveiro, N., Gil Pereira, J., Sousa, P. C. R. F., Martins, D. C. P., Cancela, E. M., & Ministro Dos Santos, M. P. (2024). Inflammatory bowel disease and cardiac function: A systematic review of literature with meta-analysis. Therapeutic Advances in Gastroenterology, 17, 17562848241299534. https://doi.org/10.1177/17562848241299534
Sleutjes, J. A. M., van der Woude, C. J., Verploegh, P. J. P., Aribas, E., Kavousi, M., Roeters van Lennep, J. E., & de Vries, A. C. (2023). Cardiovascular risk profiles in patients with inflammatory bowel disease differ from matched controls from the general population. European Journal of Preventive Cardiology, 30(15), 1615–1622. https://doi.org/10.1093/eurjpc/zwad124
Kirchgesner, J., Beaugerie, L., Carrat, F., Andersen, N. N., Jess, T., Schwarzinger, M., & BERENICE study group (2018). Increased risk of acute arterial events in young patients and severely active IBD: A nationwide French cohort study. Gut, 67(7), 1261–1268. https://doi.org/10.1136/gutjnl-2017-314015
Zuin, M., Zuliani, G., Rigatelli, G., Favero, G. D., & Roncon, L. (2020). Atrial fibrillation in patients with inflammatory bowel disease: A systematic review and meta-analysis. European Journal of Internal Medicine, 76, 120–122. https://doi.org/10.1016/j.ejim.2020.02.029
Gardezi, S. A., Sachdeva, N., Rampurawala, I. M., Ranasinghe, A., Shehzad, M. U., Gill, K., Qureshi, R., Gupta, A., Hasan, A., Farhan, M., Hassan, A., Zulfiqar, E., Ahmed, M., & Ahmed, R. (2025). Trends and disparities in inflammatory bowel disease and cardiovascular disease-related mortality in the United States from 1999 to 2023: A CDC WONDER analysis. International Journal of Cardiology Cardiovascular Risk and Prevention, Article 200438. https://doi.org/10.1016/j.ijcrp.2025.200438
Dhaliwal, G., Patrone, M. V., & Bickston, S. J. (2024). Venous thromboembolism in patients with inflammatory bowel disease. Journal of Clinical Medicine, 13(1), Article 251. https://doi.org/10.3390/jcm13010251
Sharma, N., Tewatia, P., Harvey, P. R., & Kumar, A. (2024). Controversies in venous thromboembolism risk assessment in inflammatory bowel disease: A narrative review. Diagnostics (Basel, Switzerland), 14(19), 2112. https://doi.org/10.3390/diagnostics14192112
Gozdzik, M., Unninayar, D., Siegal, D. M., Sarker, A. K., Kim, E., Murthy, S., Benchimol, E. I., Nguyen, G. C., & McCurdy, J. D. (2025). Risk factors for venous thromboembolism in inflammatory bowel disease: A systematic review and meta-analysis by phase of care. Inflammatory Bowel Diseases, 31(8), 2286–2295. https://doi.org/10.1093/ibd/izaf078
Alnahdi, A. H., Salmon, C., Svensson, M., Chaudhry, N., Zimmermann, E. M., & Jiao, T. (2026). Major cardiovascular event risk of advanced therapies in inflammatory bowel diseases: Systematic review and meta-analysis [preprint]. medRxiv. https://doi.org/10.64898/2026.01.26.26344897
Armuzzi, A., Cross, R. K., Lichtenstein, G. R., Hou, J., Deepak, P., Regueiro, M., Wolf, D. C., Akukwe, L., Ahmad, H. A., Jain, A., Kozinn, M., Wu, H., Petersen, A., Charles, L., & Long, M. (2024). Cardiovascular safety of ozanimod in patients with ulcerative colitis: True North and open-label extension analyses. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 22(5), 1067–1076.e3. https://doi.org/10.1016/j.cgh.2023.11.018
Ytterberg, S. R., Bhatt, D. L., Mikuls, T. R., et al., & ORAL Surveillance Investigators. (2022). Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. New England Journal of Medicine, 386, 316–326. https://doi.org/10.1056/NEJMoa2109927
Neri, B., Mancone, R., Fiorillo, M., Schiavone, S. C., Migliozzi, S., & Biancone, L. (2024). Efficacy and safety of janus kinase-inhibitors in ulcerative colitis. Journal of Clinical Medicine, 13(23), Article 7186. https://doi.org/10.3390/jcm13237186
Núñez, P., Quera, R., & Yarur, A. J. (2023). Safety of janus kinase inhibitors in inflammatory bowel diseases. Drugs, 83, 1291–1307. https://doi.org/10.1007/s40265-023-01840-5
Rubin, D. T., Schreiber, S., Peyrin-Biroulet, L., Danese, S., Gianfrancesco, M. A., Soonasra, A., Sidhu, S., Vranic, I., Shelbaya, A., Gruben, D., Wei, Y., Winthrop, K. L., Curtis, J. R., Regueiro, M. D., & Dubinsky, M. C. (2026). Risk of serious infection, myocardial infarction, stroke, and thromboembolic events in patients in the United States with ulcerative colitis treated with tofacitinib compared with biologic treatments. Inflammatory Bowel Diseases, Article izag142. https://doi.org/10.1093/ibd/izag142
Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., Dugar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y. M., Wu, Y., Schauer, P., Smith, J. D., Allayee, H., Tang, W. H. W., DiDonato, J. A., Lusis, A. J., & Hazen, S. L. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472(7341), 57–63. https://doi.org/10.1038/nature09922
Gimbrone, M. A., Jr., & García-Cardeña, G. (2016). Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circulation Research, 118(4), 620–636.
Livzan, M. A., Bikbavova, G. R., Lisyutenko, N. S., Romanyuk, A. E., & Drapkina, O. M. (2024). Cardiovascular risk in patients with inflammatory bowel diseases—The role of endothelial dysfunction. Diagnostics, 14(16), Article 1722. https://doi.org/10.3390/diagnostics14161722
Liu, Y., & Dai, M. (2020). Trimethylamine N-Oxide generated by the gut microbiota is associated with vascular inflammation: New insights into atherosclerosis. Mediators of Inflammation, 2020, 4634172. https://doi.org/10.1155/2020/4634172
Mołek, P., & Nessler, J. (2021). 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure – What's new? [Wytyczne ESC 2021 dotyczące diagnostyki i leczenia ostrej oraz przewlekłej niewydolności serca – Co nowego?]. Kardiologia Inwazyjna, 16(4), 144–149. https://doi.org/10.5603/ki.87777
Kirchgesner, J., Nyboe Andersen, N., Carrat, F., Jess, T., Beaugerie, L., & BERENICE Study Group. (2020). Risk of acute arterial events associated with treatment of inflammatory bowel diseases: Nationwide French cohort study. Gut, 69(5), 852–858. https://doi.org/10.1136/gutjnl-2019-318932
Cibor, D., Domagala-Rodacka, R., Rodacki, T., Jurczyszyn, A., Mach, T., & Owczarek, D. (2016). Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications. World Journal of Gastroenterology, 22(3), 1067–1077. https://doi.org/10.3748/wjg.v22.i3.1067
Chang, J. T. (2020). Pathophysiology of inflammatory bowel diseases. New England Journal of Medicine, 383, 2652–2664. https://doi.org/10.1056/NEJMra2002697
Kristensen, S. L., Ahlehoff, O., Lindhardsen, J., Erichsen, R., Lamberts, M., Khalid, U., Nielsen, O. H., Torp-Pedersen, C., Gislason, G. H., & Hansen, P. R. (2014). Inflammatory bowel disease is associated with an increased risk of hospitalization for heart failure: A Danish nationwide cohort study. Circulation. Heart Failure, 7(5), 717–722. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001152
Sun, J., Yao, J., Olén, O., Halfvarson, J., Bergman, D., Ebrahimi, F., Rosengren, A., Sundström, J., & Ludvigsson, J. F. (2024). Risk of heart failure in inflammatory bowel disease: A Swedish population-based study. European Heart Journal, 45(28), 2493–2504. https://doi.org/10.1093/eurheartj/ehae338
Bandyopadhyay, D., Jain, V., Hajra, A., Chakraborty, S., Ghosh, R. K., & Herzog, E. (2019). Effects of inflammatory bowel disease on in-hospital outcomes in patients with congestive heart failure: A retrospective national inpatient sample study. International Journal of Cardiology. Heart & Vasculature, 23, 100355. https://doi.org/10.1016/j.ijcha.2019.100355
Sun, J., Mårild, K., Sundström, J., Bergman, D., Ebrahimi, F., Halfvarson, J., Olén, O., & Ludvigsson, J. F. (2025). Association of histologic and clinical activity with major adverse cardiovascular events in patients with inflammatory bowel disease: A cohort study. Journal of Internal Medicine. https://doi.org/10.1111/joim.70035
Vermeire, S., Van Assche, G., & Rutgeerts, P. (2004). C-reactive protein as a marker for inflammatory bowel disease. Inflammatory Bowel Diseases, 10(5), 661–665.
Muresan, S., & Slevin, M. (2024). C-reactive protein: An inflammatory biomarker and a predictor of neurodegenerative disease in patients with inflammatory bowel disease?. Cureus, 16(4), Article e59009. https://doi.org/10.7759/cureus.59009
Ke, Y., Zhu, W., Kaisaier, W., & Chen, Y. (2024). Risk of atrial fibrillation in patients with inflammatory bowel disease: A systematic review and meta-analysis. International Journal of Cardiology Heart & Vasculature, 55, Article 101531. https://doi.org/10.1016/j.ijcha.2024.101531
Kristensen, S. L., Lindhardsen, J., Ahlehoff, O., Erichsen, R., Lamberts, M., Khalid, U., Torp-Pedersen, C., Nielsen, O. H., Gislason, G. H., & Hansen, P. R. (2014). Increased risk of atrial fibrillation and stroke during active stages of inflammatory bowel disease: A nationwide study. Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology: Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology, 16(4), 477–484. https://doi.org/10.1093/europace/eut312
Khan, A., & Azzam, M. A. (2025). Inflammatory bowel disease and stroke: Exploring hidden vascular risks. Cureus, 17(2), Article e79304. https://doi.org/10.7759/cureus.79304
Ungaro, R., Chang, H. L., Côté-Daigneault, J., Mehandru, S., Atreja, A., & Colombel, J. F. (2016). Statins associated with decreased risk of new onset inflammatory bowel disease. The American Journal of Gastroenterology, 111(10), 1416–1423. https://doi.org/10.1038/ajg.2016.233
Claytor, J., Rajauria, P., Peraza, J., Colombel, J., & Ungaro, R. (2025). Statin use is associated with lower odds of IBD-related surgery among patients with moderate-to-severe inflammatory bowel disease. Inflammatory Bowel Diseases. https://doi.org/10.1093/ibd/izaf227
Peppas, S., Piovani, D., Peyrin-Biroulet, L., Danese, S., & Bonovas, S. (2020). Statins and inflammatory bowel disease: Where do we stand?. European Journal of Internal Medicine, 75, 10–14. https://doi.org/10.1016/j.ejim.2020.02.017
Marín-Jiménez, I., Carpio, D., Hernández, V., Muñoz, F., Zatarain-Nicolás, E., Zabana, Y., Mañosa, M., Rodríguez-Moranta, F., Barreiro-de Acosta, M., & Gutiérrez Casbas, A. (2025). Spanish Working Group in Crohn's Disease and Ulcerative Colitis (GETECCU) position paper on cardiovascular disease in patients with inflammatory bowel disease. Documento de posicionamiento del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre la enfermedad cardiovascular en los pacientes con enfermedad inflamatoria intestinal. Gastroenterologia y Hepatologia, 48(5), 502314. https://doi.org/10.1016/j.gastrohep.2024.502314
Masson, W., Fernández-Villar, G., & Martinez-Elhelou, S. (2025). Management of atherosclerotic cardiovascular risk in inflammatory bowel disease: Current perspectives. Advances in Therapy, 42(5), 2118–2134. https://doi.org/10.1007/s12325-025-03154-2
Othon-Martínez, D., Peña-Muñoz, S. V., Riojas-Barrett, M., Vidales-López, G., Sánchez Guzmán, J. M., & Kwapisz, L. (2025). Bridging the gut and the heart—Exploring pathophysiology, risk factors, and therapeutic implications of cardiovascular disease in inflammatory bowel disease. Journal of Investigative Medicine. https://doi.org/10.1177/10815589251346966
Piazza, I., Burti, C., Assolari, A., Greco, S., Benetti, A., Cosentini, R., & Ferrero, P. (2022). Acute myocarditis as first presentation of severe ulcerative colitis in a young man. Multidisciplinary management and long-term follow-up. Journal of Cardiology Cases, 26(1), 46–50. https://doi.org/10.1016/j.jccase.2022.02.008
Papadimitraki, E. D., Ahamed, M., & Bunce, N. H. (2011). Acute myocardial infarction complicating active ulcerative colitis: A case report. Case Reports in Cardiology, 2011, 876896. https://doi.org/10.1155/2011/876896
Rustgi, S. D., Kayal, M., & Shah, S. C. (2020). Sex matters: Impact on pathogenesis, presentation and treatment of inflammatory bowel disease. Nature Reviews Gastroenterology & Hepatology, 17(10), 578–590. https://doi.org/10.1038/s41575-020-0272-5
Greuter, T., Manser, C., Pittet, V., Vavricka, S. R., Biedermann, L., & on behalf of Swiss IBDnet, an official working group of the Swiss Society of Gastroenterology (2020). Gender differences in inflammatory bowel disease. Digestion, 101(Suppl 1), 98–104. https://doi.org/10.1159/000504701
Cohen-Heyman, N., & Chodick, G. (2025). Inflammatory bowel disease is associated with an increased risk of cardiovascular events in a sex- and age-dependent manner: A historical cohort study. International Journal of Cardiology Cardiovascular Risk and Prevention, Article 200363. https://doi.org/10.1016/j.ijcrp.2025.200363
Mastoridou, E. M., Fousekis, F. S., Sakellariou, X. M., Mpakogiannis, K., Nikas, D. N., Michalis, L. K., Katsanos, K. H., & Milionis, H. (2025). The cardiovascular effects of inflammatory bowel disease therapy with biologics and small molecules: A comprehensive review. Journal of Clinical Medicine, 14(18), Article 6476. https://doi.org/10.3390/jcm14186476
Deepak, P., & Sandborn, W. J. (2017). Ustekinumab and anti-interleukin-23 agents in Crohn's disease. Gastroenterology Clinics of North America, 46(3), 603–626. https://doi.org/10.1016/j.gtc.2017.05.013
Ashraf, H., Bodapati, A., Hanif, A., Okafor, D. K., Katyal, G., Kaur, G., & Khan, S. (2023). Safety and efficacy of biologic therapies (ustekinumab and vedolizumab) in the treatment of inflammatory bowel disease (IBD): A systematic review. Cureus, 15(11), e48338. https://doi.org/10.7759/cureus.48338
Grillo, T. G., Silveira, C. F. da S. M. P., Quaglio, A. E. V., Dutra, R. M., Baima, J. P., Bazan, S. G. Z., & Sassaki, L. Y. (2023). Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease: A review of the literature. World Journal of Cardiology, 15(5), 217–228. https://doi.org/10.4330/wjc.v15.i5.217
Kwon, H. J., Coté, T. R., Cuffe, M. S., Kramer, J. M., & Braun, M. M. (2003). Case reports of heart failure after therapy with a tumor necrosis factor antagonist. Annals of Internal Medicine, 138(10), 807–811. https://doi.org/10.7326/0003-4819-138-10-200305200-00008
Khan, A., et al. (2025). Beyond the gut: Inflammatory bowel disease as a driver of cardiovascular and thromboembolic risk—A systematic review and meta-analysis of 1.4 million patients. Gastrointestinal Disorders, 7(4), Article 78. https://doi.org/10.3390/gidisord7040078
Sleutjes, J. A. M., Roeters van Lennep, J. E., van der Woude, C. J., & de Vries, A. C. (2021). Thromboembolic and atherosclerotic cardiovascular events in inflammatory bowel disease: Epidemiology, pathogenesis and clinical management. Therapeutic Advances in Gastroenterology, 14, Article 17562848211032126. https://doi.org/10.1177/17562848211032126
Chen, B., Collen, L. V., Mowat, C., Isaacs, K. L., Singh, S., Kane, S. V., Farraye, F. A., Snapper, S., Jneid, H., Lavie, C. J., & Krittanawong, C. (2022). Inflammatory bowel disease and cardiovascular diseases. The American Journal of Medicine, 135(12), 1453–1460. https://doi.org/10.1016/j.amjmed.2022.08.012
Kristensen, S. L., Ahlehoff, O., Lindhardsen, J., Erichsen, R., Jensen, G. V., Torp-Pedersen, C., Nielsen, O. H., Gislason, G. H., & Hansen, P. R. (2013). Disease activity in inflammatory bowel disease is associated with increased risk of myocardial infarction, stroke and cardiovascular death—A Danish nationwide cohort study. PLoS ONE, 8(2), Article e56944. https://doi.org/10.1371/journal.pone.0056944
Noble, O., Jeon, D., Lewis, M., Fan, C., Nasir, K., & Abraham, B. P. (2025). From gut inflammation to cardiovascular conflagration: Mapping IBD's cardiometabolic risks. Current Atherosclerosis Reports, 27(1), Article 89. https://doi.org/10.1007/s11883-025-01329-4
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