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Inflammatory bowel disease and cardiovascular diseases

Published:September 01, 2022DOI:https://doi.org/10.1016/j.amjmed.2022.08.012

      Highlights

      • Inflammatory bowel disease is associated with an increased risk of coronary artery disease, atrial fibrillation and stroke
      • Inflammatory bowel disease is associated with an increased risk of heart failure hospitalization
      • Ulcerative colitis but not Crohn's disease is associated with an increased risk of heart failure
      • Potential mechanisms between inflammatory bowel disease and cardiovascular diseases included atherosclerosis/endothelial dysfunction, dyslipidemia, thrombocytosis, dysbiosis of gut microbiota, and inflammatory bowel disease medications.

      Abstract

      Background and aim

      : Emerging data showed patients with chronic inflammatory disorders, including inflammatory bowel disease, are more likely to develop atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. This article aims to review the evidence of those associations.

      Methods

      PubMed was searched from inception to January 2022 using the keywords, including inflammatory bowel diseases, Crohn's disease, ulcerative colitis, atherosclerotic cardiovascular disease, coronary artery disease, cardiovascular disease, atrial fibrillation, heart failure, and premature coronary artery disease. Relevant literature, including retrospective/prospective cohort studies, clinical trials, meta-analyses, and guidelines were reviewed and summarized.

      Results

      Both ulcerative colitis and Crohn's disease are associated with an increased risk of atherosclerotic cardiovascular diseases, cerebrovascular accidents, premature coronary artery disease, and atrial fibrillation. Ulcerative colitis is associated with an increased risk of heart failure. The increased atrial fibrillation occurred during inflammatory bowel disease flares and persistent activity, but not during periods of remission. Hypotheses for the mechanism underlying the association of inflammatory bowel disease and atherosclerotic cardiovascular diseases include shared risk factors (i.e., obesity, diabetes, smoking, diet) and pathophysiology (gut microbiome dysfunction), or adverse effects from inflammatory bowel disease itself or its treatment (i.e., chronic inflammation, dyslipidemia, thrombocytosis, steroids).

      Conclusion

      Inflammatory bowel disease is associated with an increased risk of atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. A multidisciplinary team with gastroenterologists and cardiologists is needed to optimize the care for patients with inflammatory bowel disease and associated cardiac diseases.

      Keywords

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      REFERENCES

        • Levine JS
        • Burakoff R.
        Extraintestinal Manifestations of Inflammatory Bowel Disease.
        Gastroenterol Hepatol (N Y). 2011; 7: 235-241
        • Alatab S
        • Sepanlou SG
        • Ikuta K
        • et al.
        The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.
        The Lancet Gastroenterology & Hepatology. 2020; 5: 17-30https://doi.org/10.1016/S2468-1253(19)30333-4
        • Grundy SM
        • Stone NJ
        • Bailey AL
        • et al.
        2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        Circulation. 2019; 139https://doi.org/10.1161/CIR.0000000000000624
        • Barquera S
        • Pedroza-Tobías A
        • Medina C
        • et al.
        Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease.
        Archives of Medical Research. 2015; 46: 328-338https://doi.org/10.1016/j.arcmed.2015.06.006
        • Mason JC
        • Libby P.
        Cardiovascular disease in patients with chronic inflammation: mechanisms underlying premature cardiovascular events in rheumatologic conditions.
        Eur Heart J. 2015; 36: 482-489https://doi.org/10.1093/eurheartj/ehu403
        • Cho JH.
        The genetics and immunopathogenesis of inflammatory bowel disease.
        Nat Rev Immunol. 2008; 8: 458-466https://doi.org/10.1038/nri2340
      1. Mirkov MU, Verstockt B, Cleynen I. Genetics of inflammatory bowel disease: beyond NOD2. The Lancet Gastroenterology & Hepatology. 2017;2(3):224-234. doi:10.1016/S2468-1253(16)30111-X

        • Ni J
        • Wu GD
        • Albenberg L
        • Tomov VT.
        Gut microbiota and IBD: causation or correlation?.
        Nat Rev Gastroenterol Hepatol. 2017; 14: 573-584https://doi.org/10.1038/nrgastro.2017.88
        • Guan Q.
        A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease.
        Journal of Immunology Research. 2019; 2019: 1-16https://doi.org/10.1155/2019/7247238
        • Lamb CA
        • Kennedy NA
        • Raine T
        • et al.
        British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults.
        Gut. 2019; 68 (Suppl): s1-s106https://doi.org/10.1136/gutjnl-2019-318484
        • Feng W
        • Chen G
        • Cai D
        • Zhao S
        • Cheng J
        • Shen H.
        Inflammatory Bowel Disease and Risk of Ischemic Heart Disease: An Updated Meta-Analysis of Cohort Studies.
        J Am Heart Assoc. 2017; 6https://doi.org/10.1161/JAHA.117.005892
        • Lee MT
        • Mahtta D
        • Chen L
        • et al.
        Premature Atherosclerotic Cardiovascular Disease Risk Among Patients with Inflammatory Bowel Disease.
        Am J Med. 2021; 134 (e2): 1047-1051https://doi.org/10.1016/j.amjmed.2021.02.029
        • Kirchgesner J
        • Beaugerie L
        • Carrat F
        • et al.
        Increased risk of acute arterial events in young patients and severely active IBD: a nationwide French cohort study.
        Gut. 2018; 67: 1261-1268https://doi.org/10.1136/gutjnl-2017-314015
        • Kirchgesner J
        • Nyboe Andersen N
        • Carrat F
        • Jess T
        • Beaugerie L
        Risk of acute arterial events associated with treatment of inflammatory bowel diseases: nationwide French cohort study.
        Gut. 2020; 69: 852-858https://doi.org/10.1136/gutjnl-2019-318932
        • Singh S
        • Singh H
        • Loftus EVJ
        • Pardi DS.
        Risk of cerebrovascular accidents and ischemic heart disease in patients with inflammatory bowel disease: a systematic review and meta-analysis.
        Clin Gastroenterol Hepatol. 2014; 12 (e1quiz e22): 382-393https://doi.org/10.1016/j.cgh.2013.08.023
        • Aniwan S
        • Pardi DS
        • Tremaine WJ
        • Loftus EVJ.
        Increased Risk of Acute Myocardial Infarction and Heart Failure in Patients With Inflammatory Bowel Diseases.
        Clin Gastroenterol Hepatol. 2018; 16 (e1): 1607-1615https://doi.org/10.1016/j.cgh.2018.04.031
        • Zuin M
        • Zuliani G
        • Rigatelli G
        • Favero GD
        • Roncon L.
        Atrial fibrillation in patients with inflammatory bowel disease: A systematic review and meta-analysis.
        Eur J Intern Med. 2020; 76: 120-122https://doi.org/10.1016/j.ejim.2020.02.029
        • Kristensen SL
        • Lindhardsen J
        • Ahlehoff O
        • et al.
        Increased risk of atrial fibrillation and stroke during active stages of inflammatory bowel disease: a nationwide study.
        Europace. 2014; 16: 477-484https://doi.org/10.1093/europace/eut312
        • Choi YJ
        • Choi EK
        • Han KD
        • et al.
        Increased risk of atrial fibrillation in patients with inflammatory bowel disease: A nationwide population-based study.
        World J Gastroenterol. 2019; 25: 2788-2798https://doi.org/10.3748/wjg.v25.i22.2788
        • Can G
        • Ekmen N
        • Can H
        • et al.
        Is there any link between atrial arrhythmias and inflammatory bowel disease?.
        Saudi J Gastroenterol. 2021; 27: 289-295https://doi.org/10.4103/sjg.sjg_622_20
        • Pemmasani G
        • Elgendy I
        • Mamas MA
        • Leighton JA
        • Aronow WS
        • Tremaine WJ.
        Epidemiology and Clinical Outcomes of Patients With Inflammatory Bowel Disease Presenting With Acute Coronary Syndrome.
        Inflammatory Bowel Diseases. 2021; 27: 1017-1025https://doi.org/10.1093/ibd/izaa237
        • Kumar A
        • Lukin DJ.
        Incident heart failure is a predictor of adverse outcomes in inflammatory bowel disease.
        Eur J Gastroenterol Hepatol. 2020; 32: 205-215https://doi.org/10.1097/MEG.0000000000001648
        • Kristensen SL
        • Ahlehoff O
        • Lindhardsen J
        • et al.
        Inflammatory bowel disease is associated with an increased risk of hospitalization for heart failure: a Danish Nationwide Cohort study.
        Circ Heart Fail. 2014; 7: 717-722https://doi.org/10.1161/CIRCHEARTFAILURE.114.001152
        • Koutroumpakis E
        • Ramos-Rivers C
        • Regueiro M
        • et al.
        Association Between Long-Term Lipid Profiles and Disease Severity in a Large Cohort of Patients with Inflammatory Bowel Disease.
        Dig Dis Sci. 2016; 61: 865-871https://doi.org/10.1007/s10620-015-3932-1
        • Nezu T
        • Hosomi N
        • Aoki S
        • Matsumoto M.
        Carotid Intima-Media Thickness for Atherosclerosis.
        J Atheroscler Thromb. 2016; 23: 18-31https://doi.org/10.5551/jat.31989
        • Millasseau SC
        • Stewart AD
        • Patel SJ
        • Redwood SR
        • Chowienczyk PJ.
        Evaluation of Carotid-Femoral Pulse Wave Velocity.
        Hypertension. 2005; 45: 222-226https://doi.org/10.1161/01.HYP.0000154229.97341.d2
        • Korkmaz H
        • Onalan O.
        Evaluation of endothelial dysfunction: flow-mediated dilation.
        Endothelium. 2008; 15: 157-163https://doi.org/10.1080/10623320802228872
        • Wu GC
        • Leng RX
        • Lu Q
        • Fan YG
        • Wang DG
        • Ye DQ.
        Subclinical Atherosclerosis in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.
        Angiology. 2017; 68: 447-461https://doi.org/10.1177/0003319716652031
        • Toth PP.
        High-Density Lipoprotein and Cardiovascular Risk.
        Circulation. 2004; 109: 1809-1812https://doi.org/10.1161/01.CIR.0000126889.97626.B8
        • Harchaoui KEL
        • Visser ME
        • Kastelein JJP
        • Stroes ES
        • Dallinga-Thie GM.
        Triglycerides and Cardiovascular Risk.
        Curr Cardiol Rev. 2009; 5: 216-222https://doi.org/10.2174/157340309788970315
        • Talstad I
        • Rootwelt K
        • Gjone E.
        Thrombocytosis in Ulcerative Colitis and Crohn's Disease.
        Scandinavian Journal of Gastroenterology. 1973; 8: 135-138https://doi.org/10.1080/00365521.1973.12096682
        • Thapa SD
        • Hadid H
        • Imam W
        • et al.
        Persistent Reactive Thrombocytosis May Increase the Risk of Coronary Artery Disease Among Inflammatory Bowel Disease Patients.
        Dig Dis Sci. 2015; 60: 3062-3068https://doi.org/10.1007/s10620-015-3701-1
        • Schippa S
        • Conte MP.
        Dysbiotic Events in Gut Microbiota: Impact on Human Health.
        Nutrients. 2014; 6: 5786-5805https://doi.org/10.3390/nu6125786
        • Ahmadmehrabi S
        • Tang WHW.
        Gut microbiome and its role in cardiovascular diseases.
        Curr Opin Cardiol. 2017; 32: 761-766https://doi.org/10.1097/HCO.0000000000000445
        • Wilson A
        • Teft WA
        • Morse BL
        • et al.
        Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease.
        Dig Dis Sci. 2015; 60: 3620-3630https://doi.org/10.1007/s10620-015-3797-3
        • Souverein PC
        • Berard A
        • Van Staa TP
        • et al.
        Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case-control study.
        Heart. 2004; 90: 859-865https://doi.org/10.1136/hrt.2003.020180
        • Lewis JD
        • Scott FI
        • Brensinger CM
        • et al.
        Increased Mortality Rates With Prolonged Corticosteroid Therapy When Compared With Antitumor Necrosis Factor-α-Directed Therapy for Inflammatory Bowel Disease.
        Am J Gastroenterol. 2018; 113: 405-417https://doi.org/10.1038/ajg.2017.479
        • Ytterberg SR
        • Bhatt DL
        • Mikuls TR
        • et al.
        Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis.
        New England Journal of Medicine. 2022; 386: 316-326https://doi.org/10.1056/NEJMoa2109927
        • Sands BE
        • Colombel JF
        • Ha C
        • et al.
        Lipid Profiles in Patients With Ulcerative Colitis Receiving Tofacitinib-Implications for Cardiovascular Risk and Patient Management.
        Inflamm Bowel Dis. 2021; 27: 797-808https://doi.org/10.1093/ibd/izaa227
        • Olivera PA
        • Lasa JS
        • Bonovas S
        • Danese S
        • Peyrin-Biroulet L.
        Safety of Janus Kinase Inhibitors in Patients With Inflammatory Bowel Diseases or Other Immune-mediated Diseases: A Systematic Review and Meta-Analysis.
        Gastroenterology. 2020; 158 (e12): 1554-1573https://doi.org/10.1053/j.gastro.2020.01.001
        • Biedermann L
        • Fournier N
        • Misselwitz B
        • et al.
        High Rates of Smoking Especially in Female Crohn's Disease Patients and Low Use of Supportive Measures to Achieve Smoking Cessation–Data from the Swiss IBD Cohort Study.
        Journal of Crohn's & Colitis. 2015; 9: 819-829
        • Kang EA
        • Han K
        • Chun J
        • et al.
        Increased Risk of Diabetes in Inflammatory Bowel Disease Patients: A Nationwide Population-based Study in Korea.
        J Clin Med. 2019; 8: E343https://doi.org/10.3390/jcm8030343
        • Ananthakrishnan AN.
        Epidemiology and risk factors for IBD.
        Nature Reviews Gastroenterology &amp. 2015; 12 (Hepatology): 205-218https://doi.org/10.1038/nrgastro.2015.34
        • Xu J
        • Eilat-Adar S
        • Loria C
        • et al.
        Dietary fat intake and risk of coronary heart disease: the Strong Heart Study.
        The American Journal of Clinical Nutrition. 2006; 84: 894-902https://doi.org/10.1093/ajcn/84.4.894
        • Chan SSM
        • Chen Y
        • Casey K
        • et al.
        Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort Studies.
        Clin Gastroenterol Hepatol. 2022; 20: 1048-1058https://doi.org/10.1016/j.cgh.2021.06.049
        • Aron-Wisnewsky J
        • Clément K
        The gut microbiome, diet, and links to cardiometabolic and chronic disorders.
        Nat Rev Nephrol. 2016; 12: 169-181https://doi.org/10.1038/nrneph.2015.191
        • Weissman S
        • Sinh P
        • Mehta TI
        • et al.
        Atherosclerotic cardiovascular disease in inflammatory bowel disease: The role of chronic inflammation.
        World J Gastrointest Pathophysiol. 2020; 11: 104-113https://doi.org/10.4291/wjgp.v11.i5.104
        • Wu H
        • Hu T
        • Hao H
        • Hill MA
        • Xu C
        • Liu Z.
        Inflammatory bowel disease and cardiovascular diseases: a concise review.
        European Heart Journal Open. 2022; 2: oeab029https://doi.org/10.1093/ehjopen/oeab029
        • Costello SP
        • Hughes PA
        • Waters O
        • et al.
        Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial.
        JAMA. 2019; 321: 156-164https://doi.org/10.1001/jama.2018.20046
      2. Paramsothy S, Kamm MA, Kaakoush NO, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. The Lancet. 2017;389(10075):1218-1228. doi:10.1016/S0140-6736(17)30182-4

        • Moayyedi P
        • Surette MG
        • Kim PT
        • et al.
        Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial.
        Gastroenterology. 2015; 149 (e6): 102-109https://doi.org/10.1053/j.gastro.2015.04.001