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Fang YJ, Hsieh HH, Lin HJ, Lin CL, Lee WY, Chen CH, Tsai FJ, You BJ, Tien N, Lim YP. Relationship between venous thromboembolism and inflammatory bowel disease in Taiwan: a nationwide retrospective cohort study. BMC Cardiovasc Disord 2025; 25:153. [PMID: 40050756 PMCID: PMC11884027 DOI: 10.1186/s12872-025-04600-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 02/21/2025] [Indexed: 03/10/2025] Open
Abstract
BACKGROUND Inflammation significantly influences thrombosis development, with venous thromboembolism (VTE) risk linked to various systemic inflammatory diseases, but not fully established in inflammatory bowel disease (IBD). Using a population-based cohort study conducted in Taiwan, we investigated the impact of IBD on the risk of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE), as well as the impact of anti-IBD treatments. METHODS A study was conducted on a cohort of patients with IBD diagnosed between 2010 and 2019 using the National Health Insurance database. The risks of VTE, DVT, and PE, as well as anti-IBD treatment use, were examined using Cox proportional hazard regression analysis. RESULTS The overall number of person-years recorded for 12,126 patients with IBD (mean age: 49.18 years; 55.31% male) and 12,126 controls (mean age: 49.19 years; 55.31% male) was 64,057 and 72,056, with a follow-up duration for the two cohorts was 5.28 and 5.94 years, respectively. After adjusting for age, gender, and comorbidities, the adjusted hazard ratios (aHRs) of VTE, DVT, and PE in patients with IBD were 5.58 [95% confidence interval (CI) = 3.97-7.87], 5.48 (95% CI = 3.83-7.86), and 4.96 (95% CI = 2.00-12.35) times higher, respectively, than those in the control cohort. Male patients with IBD and those under the age of 50 were more likely to develop VTE (aHR = 8.54, 95% CI = 2.00-12.35; aHR = 15.75, 95% CI = 5.73-43.26, respectively). Compared to the cohort of patients with IBD receiving no treatment, patients receiving anti-IBD treatments did not show a significant change in the risk of developing VTE. Additionally, compared to the IV steroid cohort, patients with IBD who only used oral steroids had a substantially lower incidence of VTE, particularly with average doses of ≤ 80 mg (aHR = 0.24, 95% CI = 0.10-0.59). CONCLUSION Patients with IBD are at an increased risk of developing VTE, particularly DVT and PE. While our study found that anti-IBD treatments did not significantly alter this risk, proactive management of associated factors and close monitoring remains essential for preventing VTE in this population. Identifying and addressing specific associated factors should be prioritized in clinical practice to mitigate the heightened risk of VTE in IBD patients.
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Affiliation(s)
- Yi-Jen Fang
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung-Hsing University, Taichung, Taiwan
- Digestive Disease Center, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Hui-Hsia Hsieh
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 66, Sec. 1, Fengxing Rd., Tanzi Dist, Taichung, 427213, Taiwan.
- Department of Pharmacy, College of Pharmacy, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist, Taichung City, 406040, Taiwan.
| | - Heng-Jun Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Wan-Yi Lee
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 66, Sec. 1, Fengxing Rd., Tanzi Dist, Taichung, 427213, Taiwan
- Department of Pharmacy, College of Pharmacy, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist, Taichung City, 406040, Taiwan
| | - Chi-Hua Chen
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 66, Sec. 1, Fengxing Rd., Tanzi Dist, Taichung, 427213, Taiwan
| | - Fuu-Jen Tsai
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
- Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan
- Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan
| | - Bang-Jau You
- Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan
| | - Ni Tien
- Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan
- Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan
| | - Yun-Ping Lim
- Department of Pharmacy, College of Pharmacy, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist, Taichung City, 406040, Taiwan.
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
- Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
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Livzan MA, Bikbavova GR, Lisyutenko NS, Romanyuk AE, Drapkina OM. Cardiovascular Risk in Patients with Inflammatory Bowel Diseases-The Role of Endothelial Dysfunction. Diagnostics (Basel) 2024; 14:1722. [PMID: 39202210 PMCID: PMC11353271 DOI: 10.3390/diagnostics14161722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 07/31/2024] [Accepted: 08/07/2024] [Indexed: 09/03/2024] Open
Abstract
Inflammatory bowel disease (IBD) is associated with an increased risk of cardiovascular disease (CVD). Cardiovascular pathology in people with IBD has not been well studied to date, and a direct link between cardiovascular events and IBD has not been established. The mechanisms underlying this association include the parallel and dynamic interaction of inflammation, modulation of the composition of the gut microbiota, endothelial dysfunction, thrombogenicity, and increased endothelial and epithelial permeability. Endothelial dysfunction is a common aspect of the pathogenesis of IBD and atherosclerotic CVD and can be considered one of the most important factors leading to the development and progression of cardiovascular pathology in patients with IBD. The purpose of this literature review is to describe the mechanisms underlying the development of endothelial dysfunction and disorders of the structure and function of the gut-vascular barrier in the pathogenesis of the cardiovascular manifestation of IBD.
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Affiliation(s)
- Maria A. Livzan
- Department of Faculty Therapy, Omsk State Medical University, 644099 Omsk, Russia;
| | - Galiya R. Bikbavova
- Department of Internal Medicine and Endocrinology, Omsk State Medical University, 644099 Omsk, Russia;
| | - Natalya S. Lisyutenko
- Department of Internal Medicine and Endocrinology, Omsk State Medical University, 644099 Omsk, Russia;
| | - Alisa E. Romanyuk
- Faculty of Medicine, Omsk State Medical University, 644099 Omsk, Russia;
| | - Oxana M. Drapkina
- National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia;
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Mami W, Znaidi-Marzouki S, Doghri R, Ben Ahmed M, Znaidi S, Messadi E. Inflammatory Bowel Disease Increases the Severity of Myocardial Infarction after Acute Ischemia-Reperfusion Injury in Mice. Biomedicines 2023; 11:2945. [PMID: 38001946 PMCID: PMC10669621 DOI: 10.3390/biomedicines11112945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 09/26/2023] [Accepted: 09/28/2023] [Indexed: 11/26/2023] Open
Abstract
(1) Background: Increased risk of myocardial infarction (MI) has been linked to several inflammatory conditions, including inflammatory bowel disease (IBD). However, the relationship between IBD and MI remains unclear. Here, we implemented an original mouse model combining IBD and MI to determine IBD's impact on MI severity and the link between the two diseases. (2) Methods: An IBD model was established by dextran sulfate sodium (DSS) administration in drinking water, alone or with oral C. albicans (Ca) gavage. IBD severity was assessed by clinical/histological scores and intestinal/systemic inflammatory biomarker measurement. Mice were subjected to myocardial ischemia-reperfusion (IR), and MI severity was assessed by quantifying infarct size (IS) and serum cardiac troponin I (cTnI) levels. (3) Results: IBD mice exhibited elevated fecal lipocalin 2 (Lcn2) and IL-6 levels. DSS mice exhibited almost two-fold increase in IS compared to controls, with serum cTnI levels strongly correlated with IS. Ca inoculation tended to worsen DSS-induced systemic inflammation and IR injury, an observation which is not statistically significant. (4) Conclusions: This is the first proof-of-concept study demonstrating the impact of IBD on MI severity and suggesting mechanistic aspects involved in the IBD-MI connection. Our findings could pave the way for MI therapeutic approaches based on identified IBD-induced inflammatory mediators.
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Affiliation(s)
- Wael Mami
- Plateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomolécules, Venins et Applications Théranostiques (LR20IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia;
| | - Soumaya Znaidi-Marzouki
- Laboratoire de Transmission, Contrôle et Immunobiologie des Infections (LR16IPT02), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia; (S.Z.-M.); (M.B.A.)
| | - Raoudha Doghri
- Département d’Anatomie et Cytologie Pathologiques, Institut Salah-Azaeiz, Université El-Manar, Tunis 1006, Tunisia;
| | - Melika Ben Ahmed
- Laboratoire de Transmission, Contrôle et Immunobiologie des Infections (LR16IPT02), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia; (S.Z.-M.); (M.B.A.)
| | - Sadri Znaidi
- Laboratoire de Microbiologie Moléculaire, Vaccinologie et Développement Biotechnologique (LR16IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia;
- Unité Biologie et Pathogénicité Fongiques, Département Mycologie, Institut Pasteur, INRA, 75015 Paris, France
| | - Erij Messadi
- Plateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomolécules, Venins et Applications Théranostiques (LR20IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia;
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Arvanitakis K, Koufakis T, Popovic D, Maltese G, Mustafa O, Doumas M, Giouleme O, Kotsa K, Germanidis G. GLP-1 Receptor Agonists in Obese Patients with Inflammatory Bowel Disease: from Molecular Mechanisms to Clinical Considerations and Practical Recommendations for Safe and Effective Use. Curr Obes Rep 2023; 12:61-74. [PMID: 37081371 DOI: 10.1007/s13679-023-00506-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/09/2023] [Indexed: 04/22/2023]
Abstract
PURPOSE OF REVIEW To discuss current literature and provide practical recommendations for the safe and effective use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in people with inflammatory bowel disease (IBD) and type 2 diabetes (T2D) and/or obesity. The molecular mechanisms that justify the potential benefits of GLP-1 RA in IBD and the links between IBD, obesity, and cardiovascular disease are also discussed. RECENT FINDINGS Preliminary data suggest that GLP-1 RA can modulate crucial pathways in the pathogenesis of IBD, such as chronic inflammation circuits, intestinal tight junctions, and gut microbiome dysbiosis, setting the stage for human trials to investigate the role of these agents in the treatment of IBD among people with or without diabetes and obesity. However, gastrointestinal side effects related to GLP-1 RA need appropriate clinical management to mitigate risks and maximize the benefits of therapy in people with IBD. GLP-1 RA originally emerged as drugs for the treatment of hyperglycemia and are currently licensed for the management of T2D and/or overweight/obesity. However, their wealth of pleiotropic actions soon raised expectations that they might confer benefits on non-metabolic disorders. Future studies are expected to clarify whether GLP-1 RA deserve an adjunct place in the arsenal of drugs against IBD.
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Affiliation(s)
- Konstantinos Arvanitakis
- Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
- Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636, Thessaloniki, Greece
| | - Theocharis Koufakis
- Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Djordje Popovic
- Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Medical Faculty, University of Novi Sad, Novi Sad, Serbia
| | - Giuseppe Maltese
- Department of Diabetes and Endocrinology, Epsom & St Helier University Hospitals, Surrey, SM5 1AA, UK
- Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Sciences & Medicine, King's College, London, UK
| | - Omar Mustafa
- Department of Diabetes, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
- King's College London, London, UK
| | - Michael Doumas
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Olga Giouleme
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Kalliopi Kotsa
- Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Georgios Germanidis
- Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece.
- Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636, Thessaloniki, Greece.
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Britzen-Laurent N, Weidinger C, Stürzl M. Contribution of Blood Vessel Activation, Remodeling and Barrier Function to Inflammatory Bowel Diseases. Int J Mol Sci 2023; 24:ijms24065517. [PMID: 36982601 PMCID: PMC10051397 DOI: 10.3390/ijms24065517] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/09/2023] [Accepted: 03/10/2023] [Indexed: 03/17/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) consist of a group of chronic inflammatory disorders with a complex etiology, which represent a clinical challenge due to their often therapy-refractory nature. In IBD, inflammation of the intestinal mucosa is characterized by strong and sustained leukocyte infiltration, resulting in the loss of epithelial barrier function and subsequent tissue destruction. This is accompanied by the activation and the massive remodeling of mucosal micro-vessels. The role of the gut vasculature in the induction and perpetuation of mucosal inflammation is receiving increasing recognition. While the vascular barrier is considered to offer protection against bacterial translocation and sepsis after the breakdown of the epithelial barrier, endothelium activation and angiogenesis are thought to promote inflammation. The present review examines the respective pathological contributions of the different phenotypical changes observed in the microvascular endothelium during IBD, and provides an overview of potential vessel-specific targeted therapy options for the treatment of IBD.
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Affiliation(s)
- Nathalie Britzen-Laurent
- Division of Surgical Research, Department of Surgery, Translational Research Center, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany
- Correspondence:
| | - Carl Weidinger
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
| | - Michael Stürzl
- Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany
- Division of Molecular and Experimental Surgery, Translational Research Center, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
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6
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Lugonja SI, Pantic IL, Milovanovic TM, Grbovic VM, Djokovic BM, Todorovic ŽD, Simovic SM, Medovic RH, Zdravkovic ND, Zdravkovic ND. Atherosclerotic Cardiovascular Disease in Inflammatory Bowel Disease: The Role of Chronic Inflammation and Platelet Aggregation. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:554. [PMID: 36984554 PMCID: PMC10059701 DOI: 10.3390/medicina59030554] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 03/03/2023] [Accepted: 03/06/2023] [Indexed: 03/14/2023]
Abstract
Background and Objectives: Atherosclerosis is one of inflammatory bowel disease's most significant cardiovascular manifestations. This research aimed to examine the relationship between biochemical, haemostatic, and immune parameters of atherosclerosis and ulcerative colitis patients and its relationship to platelet aggregation. Materials and Methods: A clinical, observational cross-sectional study was performed, during which the tested parameters were compared in the experimental and control groups. The patients were divided into four groups. The first group had 25 patients who had ulcerative colitis and atherosclerosis. The second group included 39 patients with ulcerative colitis without atherosclerosis. The third group comprised 31 patients suffering from atherosclerosis without ulcerative colitis, and the fourth group comprised 25 healthy subjects. Results: In our study, we registered statistically higher levels of inflammatory markers like SE, CRP, Le, fecal calprotectin, TNF-α, and IL-6, as well as the higher value of thrombocytes and thrombocyte aggregation in the group of patients with ulcerative colitis compared to the control group. Lower levels of total cholesterol and LDL were also recorded in patients with ulcerative colitis and atherosclerosis and ulcerative colitis without atherosclerosis compared to healthy control. Triglyceride and remnant cholesterol were higher in patients with ulcerative colitis and atherosclerosis when compared to patients with ulcerative colitis and healthy control but lower than in patients with atherosclerosis only. Conclusions: Several inflammatory markers and platelet aggregation could be good discrimination markers for subjects with ulcerative colitis with the highest risk of atherosclerosis.
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Affiliation(s)
- Sofija I. Lugonja
- Division of Gastroenterology, Department of Internal Medicine, General Hospital “Djordje Joanovic”, 5 Dr. Vase Savica Street, 23000 Zrenjanin, Serbia
| | - Ivana L. Pantic
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 2 Dr. Koste Todorovica Street, 11000 Belgrade, Serbia
| | - Tamara M. Milovanovic
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, 2 Dr. Koste Todorovica Street, 11000 Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, 8 Dr. Subotica Starijeg Street, 11000 Belgrade, Serbia
| | - Vesna M. Grbovic
- Department of Physical Medicine and Rehabilitation, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
- Center for Physical Medicine and Rehabilitation, University Clinical Center Kragujevac, 30 Zmaj Jovina Street, 34000 Kragujevac, Serbia
| | - Bojana M. Djokovic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
- Clinic for Cardiology, University Clinical Center Kragujevac, 30 Zmaj Jovina Street, 34000 Kragujevac, Serbia
| | - Željko D. Todorovic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
- Clinic for Hematology, University Clinical Center Kragujevac, 30 Zmaj Jovina Street, 34000 Kragujevac, Serbia
| | - Stefan M. Simovic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
- Clinic for Cardiology, University Clinical Center Kragujevac, 30 Zmaj Jovina Street, 34000 Kragujevac, Serbia
| | - Raša H. Medovic
- Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
- Pediatric Clinic, University Clinical Center Kragujevac, 30 Zmaj Jovina Street, 34000 Kragujevac, Serbia
| | - Nebojsa D. Zdravkovic
- Department of Medical Statistics and Informatics, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
| | - Natasa D. Zdravkovic
- Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
- Clinic for Gastroenterology and Hepatology, University Clinical Center Kragujevac, 30 Zmaj Jovina Street, 34000 Kragujevac, Serbia
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Güven İE, Candemir M, Başpınar B, Cankurtaran RE, Kayaçetin E. Evaluation of Tp-e interval and Tp-e/QTc ratio in patients with inflammatory bowel disease. Wien Klin Wochenschr 2023; 135:14-21. [PMID: 36289090 DOI: 10.1007/s00508-022-02100-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 09/16/2022] [Indexed: 01/21/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD), a multisystemic inflammatory disorder, has been associated with increased risk of cardiovascular problems, including complications such as conduction defects and arrhythmias. Therefore, the early assessment of the risk factors predisposing to ventricular arrhythmias is crucial, since it can improve clinical outcomes. The objective of the present study is to evaluate ventricular repolarization by using Tp‑e interval and Tp-e/QTc ratio as candidate markers of ventricular arrhythmias in patients with IBD. METHODS The presented study was designed as a single-center prospective cohort study. The study population consisted of 175 patients with IBD and 175 healthy volunteers. The Tp‑e interval, corrected QT (QTc), and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. These parameters were compared between groups. RESULTS The groups were similar in terms of electrocardiographic findings such as heart rate, QRS interval, and QTc interval. However, Tp‑e interval (87.0 ms, interquartile range, IQR 81.0-105.0 ms vs. 84.0 ms, IQR 74.0-92.0 ms; p < 0.001) and Tp-e/QTc ratio (0.21 ± 0.04 vs. 0.19 ± 0.05; p < 0.001) were significantly increased in IBD patient group compared to control group. Notably, a positive correlation was demonstrated between Tp‑e interval, Tp-e/QTc ratio and disease duration (Spearman's Rho = 0.36, p < 0.001 for Tp‑e; Spearman's Rho = 0.28, p < 0.001 for Tp-e/QTc). CONCLUSION This study demonstrated that IBD patients are at increased risk of disrupted ventricular repolarization (increased Tpe, Tpe/QTc ratio). In addition, a positive correlation was demonstrated between Tp‑e interval, Tp-e/QTc ratio, and disease duration. Therefore, IBD patients, especially those with long-standing diseases, should be more closely screened for ventricular arrhythmias.
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Affiliation(s)
| | - Mustafa Candemir
- Department of Cardiology, Gazi University School of Medicine, Ankara, Turkey
| | - Batuhan Başpınar
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
| | - Rasim Eren Cankurtaran
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
- Department of Gastroenterology, Ankara Yildirim Beyazit University School of Medicine, Ankara, Turkey
| | - Ertuğrul Kayaçetin
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
- Department of Gastroenterology, Ankara Yildirim Beyazit University School of Medicine, Ankara, Turkey
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S Y, Kedia S, Teja V, Vuyyuru SK, Yadav N, Sahu P, Jain S, Yadav DP, Bopanna S, Mouli VP, Madhu D, Sharma R, Das P, Makharia G, Ahuja V. Thromboembolism is associated with poor prognosis and high mortality in patients with inflammatory bowel disease: A case-control study. Indian J Gastroenterol 2022; 41:325-335. [PMID: 36063357 DOI: 10.1007/s12664-021-01237-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 12/22/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND The information on the risk of thromboembolism (TE) in inflammatory bowel disease (IBD) and its predictors are lacking, especially from developing countries. The present study evaluated the prevalence, predictors, and prognosis of TE in IBD. METHODS This case-control study included 35 patients with IBD (ulcerative colitis [UC, n = 25]; Crohn's disease [CD], n = 10) and history of TE, from a cohort of 3597 patients (UC n = 2752, CD n = 845) under follow-up from 2005 to 2018. Details on demographics, extraintestinal manifestations (EIMs), patient status, type and outcomes of TE, treatment details, and disease course were compared with IBD patients without TE (age, gender, and duration of follow-up matched) in the ratio of 1:4. RESULTS Prevalence of TE in IBD was 0.9% (UC-0.89%, CD-1.2%). Among TE patients (mean age: 34.9 ± 13.1 years, 48.6% males), median duration from diagnosis to TE was 12 (inter-quartile range [IQR]: 3-36) months, 37% had other EIMs, 94.1% had moderate/severe disease at time of TE, 62.8% had steroid-dependent/refractory disease, and 5 patients (14.2%) died because of disease-related complications. Lower limb was the commonest site (57.1%), 14.3% had pulmonary TE, and 31.4% had involvement of multiple sites. Phenotypically, more patients with TE (among UC) had steroid-dependent disease (60% vs. 25%, p = 0.001), pancolitis (76% vs. 36%, p = 0.002), chronic continuous disease course (44% vs. 19%, p = 0.009), and acute severe colitis (48% vs. 18%, p = 0.002), of which the latter three were also independent predictors of TE. CONCLUSION Approximately 1% of patients with IBD develop thromboembolism relatively early during their disease course, and TE is associated with severe disease and higher disease-related complications including mortality.
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Affiliation(s)
- Yadukrishna S
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Varun Teja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Sudheer Kumar Vuyyuru
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Nidhi Yadav
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Pabitra Sahu
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Saransh Jain
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Dawesh P Yadav
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Sawan Bopanna
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Venigalla Pratap Mouli
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Deepak Madhu
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Raju Sharma
- Department of Radiology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110 029, India.
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9
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Tien N, Wu TY, Lin CL, Wu CJ, Hsu CY, Fang YJ, Lim YP. Impact of Inflammatory Bowel Disease (IBD) and IBD Medications on Risk of Hyperlipidemia and in vitro Hepatic Lipogenic-Related Gene Expression: A Population-Based Cohort Study. Front Med (Lausanne) 2022; 9:910623. [PMID: 35770006 PMCID: PMC9234280 DOI: 10.3389/fmed.2022.910623] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 05/16/2022] [Indexed: 11/13/2022] Open
Abstract
Patients with inflammatory bowel disease (IBD) present a higher risk of developing cardiovascular diseases (CVDs) due to chronic inflammation, which plays an essential role in atherogenesis. Hyperlipidemia is another risk factor for CVDs; however, the association between IBD, IBD medications, and hyperlipidemia remains controversial. We conducted a nationwide, population-based, retrospective, cohort study to examine the effect of IBD and IBD medications on the risk of developing hyperlipidemia. The effects of IBD medications on the expression of lipogenesis-related hepatic genes were also evaluated. We obtained data from the Longitudinal Health Insurance Database of Taiwan from patients with new-onset IBD and a comparison cohort of patients without IBD. A Cox proportional hazards regression model was used to analyze the difference in the risk of developing hyperlipidemia between the two cohorts. We also examined the influence of IBD medications on the expression of lipogenesis-related hepatic genes. After adjusting for comorbidities and confounding factors, the case group (N = 14,524) had a higher risk for hyperlipidemia than the control group (N = 14,524) [adjusted hazards ratio (aHR), 2.18]. Patients with IBD that did not receive IBD medications exhibited a significantly higher risk of hyperlipidemia (aHR, 2.20). In those treated with IBD medications, the risk of developing hyperlipidemia was significantly lowered than those without such medications (all aHR ≤ 0.45). Gene expression analysis indicated that IBD medications downregulated the expression of lipogenesis-related genes. Screening blood lipids in IBD patients is needed to explore the specific role and impact of IBD medications in the development of CVD.
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Affiliation(s)
- Ni Tien
- Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan
- Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan
| | - Tien-Yuan Wu
- Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan
- Department of Pharmacology, School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Jui Wu
- Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan
| | - Chung-Y Hsu
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Yi-Jen Fang
- Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, Department of Environmental Health, Kaohsiung Medical University, Kaohsiung, Taiwan
- National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan
- Digestive Disease Center, Show Chwan Memorial Hospital, Changhua, Taiwan
- Yi-Jen Fang
| | - Yun-Ping Lim
- Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan
- Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- *Correspondence: Yun-Ping Lim ;
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10
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Dilillo A, Del Giudice E, Cucchiara S, Viola F, Mallardo S, Isoldi S, Iorfida D, Bloise S, Marcellino A, Martucci V, Sanseviero M, De Luca E, Protano C, Marotta D, Ventriglia F, Lubrano R. Evaluation of Risk for Thromboembolic Events in Pediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2022; 74:599-604. [PMID: 35129153 DOI: 10.1097/mpg.0000000000003398] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The occurrence of thrombotic events in adult patients with inflammatory bowel disease (IBD) is linked to multiple interactions between hereditary and acquired risk factors. There are few published data concerning children with iBD. The aim of this study was to investigate the presence of thromboembolic risk factors also in children with iBD. METHODS We enrolled three groups of children: one with Crohn disease (cD), one with ulcerative colitis (Uc), and a control group of healthy subjects. For all the participants the potential thromboembolic risk was evaluated clinically and with laboratory tests. RESULTS We studied: 30 children (25.6%) with CD, 28 (23.9%) with UC, and 59 (50.4%) healthy control subjects. Regarding Pediatric Crohn Disease Activity Index, no significant differences between thromboembolic risk factors and disease activity were detected. Instead, in the patients with UC, stratified with the Pediatric Ulcerative Colitis Activity Index, there was a statistically significant difference in serum fibrinogen levels between patients with mild and moderate/severe disease [3.8 (3.2-4.5) g/L vs 5.7 (4.8-6.2) g/L, P < 0.0032]. serum homocysteine levels were lower in healthy controls than in CD (P = 0.176) and UC (P = 0.026). An increased level ofhomocysteine in UC with a homozygous mutation in the methylene tetrahydrofolate reductase C677T gene was also observed. CONCLUSIONS Our study showed that children with IBD have clinical features, acquired and congenital factors that can increase thrombotic risk, similarly to adults.
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Affiliation(s)
- Anna Dilillo
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Emanuela Del Giudice
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Salvatore Cucchiara
- Maternal Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome
| | - Franca Viola
- Maternal Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome
| | - Saverio Mallardo
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Sara Isoldi
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Donatella Iorfida
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Silvia Bloise
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Alessia Marcellino
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Vanessa Martucci
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Mariateresa Sanseviero
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Enrica De Luca
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Carmela Protano
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Daniela Marotta
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Flavia Ventriglia
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
| | - Riccardo Lubrano
- Pediatric and Neonatology Unit, Maternal and Child Department, Sapienza University of Rome, Polo Pontino, Latina
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11
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Ollech JE, Waizbard A, Lubetsky A, Kopylov U, Goren I, Dotan I, Yanai H. Venous Thromboembolism Among Patients With Inflammatory Bowel Diseases is Not Related to Increased Thrombophilia: A Case-Control Study. J Clin Gastroenterol 2022; 56:e222-e226. [PMID: 34231498 DOI: 10.1097/mcg.0000000000001578] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 05/12/2021] [Indexed: 01/01/2023]
Abstract
GOAL The aim was to assess whether thrombophilia significantly contributes to the risk of venous thromboembolic events (VTEs) in patients with inflammatory bowel disease (IBD). BACKGROUND Patients with IBD have a high risk of VTE. The underlying mechanism has been only partially defined. METHODS A case-control study in adults with IBD and an episode of VTE (IBD-VTE) were matched and compared with non-IBD patients with a VTE (non-IBD-VTE). The study population was comprised of patients seen in 2 tertiary medical centers in Israel between 2000 and 2013. Characteristics of IBD and risk factors for VTE were retrieved from medical charts, and a comprehensive thrombophilia panel was completed in all patients. RESULTS Forty-four IBD-VTE cases (27 Crohn's disease) were matched with 127 non-IBD-VTE controls. The majority of VTE had a clear etiology and were considered provoked events. Provoked and unprovoked VTE rates were not different between the 2 groups. Likewise, thrombophilia rates were similar among patients with IBD-VTE and controls (40.9% vs. 53.5%, respectively, P=0.14). However, among patients with unprovoked VTE, thrombophilia rates were significantly lower in the IBD-VTE group compared with controls (42.1% vs. 70.7%, respectively, P=0.03). Among patients with IBD-VTE, an unprovoked event, and negative thrombophilia, 77% had active inflammation at the time of VTE. CONCLUSION Thrombophilia rates are similar among patients with IBD-VTE and controls but are less common among patients with unprovoked IBD-VTE. This finding suggests that either inflammation or other novel pathways drive VTE in patients with IBD.
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Affiliation(s)
- Jacob E Ollech
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah-Tikva
- Sackler Faculty of Medicine, Tel Aviv University
| | - Amir Waizbard
- Sackler Faculty of Medicine, Tel Aviv University
- Department of Gastroenterology and Hepatology, Tel Aviv Sourasky Medical Center, Tel Aviv
| | - Aaron Lubetsky
- Sackler Faculty of Medicine, Tel Aviv University
- The Institute of Thrombosis and Hemostasis
| | - Uri Kopylov
- Sackler Faculty of Medicine, Tel Aviv University
- Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel
| | - Idan Goren
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah-Tikva
- Sackler Faculty of Medicine, Tel Aviv University
| | - Iris Dotan
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah-Tikva
- Sackler Faculty of Medicine, Tel Aviv University
| | - Henit Yanai
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah-Tikva
- Sackler Faculty of Medicine, Tel Aviv University
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12
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Michels A, Lillicrap D, Yacob M. Role of von Willebrand factor in venous thromboembolic disease. JVS Vasc Sci 2022; 3:17-29. [PMID: 35028601 PMCID: PMC8739873 DOI: 10.1016/j.jvssci.2021.08.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 08/23/2021] [Indexed: 02/07/2023] Open
Abstract
Objective Evolving evidence of the shared risk factors and pathogenic mechanisms in arterial and venous thrombosis questions of the strict vascular dichotomy of arterial vs venous. The connection between arterial and venous thrombosis has been highlighted by common underlying inflammatory processes, a concept known as thromboinflammatory disease. Using this relationship, we can apply knowledge from arterial disease to better understand and potentially mitigate venous disease. A protein that has been extensively studied in atherothrombotic disease and inflammation is von Willebrand factor (VWF). Because many predisposing and provoking factors of venous thromboembolism (VTE) have been shown to directly modulate VWF levels, it is, perhaps, not surprising that VWF has been highlighted by several recent association studies of patients with VTE. Methods In the present narrative review, we investigated more deeply the effects of VWF in venous disease by synthesizing the data from clinical studies of deep vein thrombosis of the limbs, pulmonary embolism, portal and cerebral vein thrombosis, and the complications of thrombosis, including post-thrombotic syndrome, venous insufficiency, and chronic thromboembolic pulmonary hypertension. We have also discussed the findings from preclinical studies to highlight novel VWF biochemistry in thrombosis and therapeutics. Results Across the spectrum of venous thromboembolic disease, we consistently observed that elevated VWF levels conferred an increased risk of VTE and long-term venous complications. We have highlighted important findings from VWF molecular research and have proposed mechanisms by which VWF participates in venous disease. Emerging evidence from preclinical studies might reveal novel targets for thromboinflammatory disease, including specific VWF pathophysiology. Furthermore, we have highlighted the utility of measuring VWF to prognosticate and risk stratify for VTE and its complications. Conclusions As the prevalence of inflammatory processes, such as aging, obesity, and diabetes increases in our population, it is critical to understand the evolving role of VWF in venous disease to guide clinical decisions and therapeutics.
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Affiliation(s)
- Alison Michels
- Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada.,Division of Cardiovascular Surgery, Queen's University, Kingston Health Sciences Centre, Kingston, Ontario, Canada
| | - David Lillicrap
- Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada
| | - Michael Yacob
- Division of Cardiovascular Surgery, Queen's University, Kingston Health Sciences Centre, Kingston, Ontario, Canada
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13
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Saggi S, Lekoubou A, Ovbiagele B. Prevalence and Predictors of Stroke in Patients with Crohn's Disease: A Nationwide Study. J Stroke Cerebrovasc Dis 2021; 31:106258. [PMID: 34923435 DOI: 10.1016/j.jstrokecerebrovasdis.2021.106258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 11/02/2021] [Accepted: 11/28/2021] [Indexed: 12/08/2022] Open
Abstract
OBJECTIVES Mounting evidence points to the microbiome as a susceptibility factor for neurological disorders. Patients with Crohn's disease (CD) are at higher ischemic stroke (IS) risk, but no large scale epidemiologic studies have identified risk factors for stroke in this population. MATERIALS AND METHODS We analyzed the 2017 Nationwide Inpatient Sample (NIS) dataset to identify patients with a discharge diagnosis of Crohn's disease using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) code K50.X. We identified patients with a primary/secondary discharge diagnosis of IS using ICD-10-CM code I63.X. We compared sociodemographic and clinical variables between stroke and non-stroke patients with CD. Logistic regression analysis was applied to identify factors associated with IS. RESULTS Of 30,212 patients with CD, 369 (1.2 %) had a discharge diagnosis of IS. Older age (odds ratio [OR], 1.03 [95% CI, 1.02-1.04], top quartile income (OR, 1.58 [95% CI, 1.10-2.30]), and hospitalization in a South Atlantic (OR, 1.82 [95% CI, 1.11-3.14]), East South Central (OR, 2.30 [95% CI, 1.28-4.25]), or West South Central hospital (OR, 2.40 [95% CI, 1.39-4.28]) were independently associated with IS. Clinical variables independently associated with IS in patients with CD included: atrial fibrillation (OR, 1.66 [95% CI, 1.15-2.33]), atherosclerosis (OR, 2.41 [95% CI, 1.32-4.10]), hyperlipidemia (OR, 1.69 [95% CI, 1.33-2.15]), hypertension (OR, 1.53 [95% CI, 1.18-1.98]) and valvular disease (OR, 1.62 [95% CI, 1.01-2.48). CONCLUSION A subset of traditional stroke risk factors are associated with IS in patients with CD. CD patients with these conditions could be targeted for vascular risk reduction and surveillance.
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Affiliation(s)
- Satvir Saggi
- University of California, San Francisco School of Medicine
| | - Alain Lekoubou
- Department of Neurology, Penn State University, Hershey Medical Center, Hershey, PA, USA.
| | - Bruce Ovbiagele
- Department of Neurology, University of California, San Francisco
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14
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Mohamud S, Oyawusi M, Weir R, Millis RM, Dehkordi O. Case Report: Ulcerative Colitis with Multiple Dural Venous Thrombosis. Case Rep Neurol 2021; 13:504-509. [PMID: 34720954 PMCID: PMC8460916 DOI: 10.1159/000515155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 01/21/2021] [Indexed: 11/19/2022] Open
Abstract
Background Cerebral sinus vein thrombosis (CVT) is a rare but serious complication associated with ulcerative colitis (UC), an idiopathic autoimmune inflammatory disease of the gastrointestinal tract. Management approaches for CVT remain unclear but may include anticoagulation and surgical thrombectomy. Herein, we report a case of a 23-year-old male who developed CVT with a history of UC. The patient was presented to Howard University Hospital when he slipped and fell. On arrival at the hospital, he complained of a headache with an aching sensation, associated with light/sound sensitivity. The patient had a history of uncontrolled UC. He had positive bloody diarrhea, lower abdominal pain, but denied any other neurological deficit. Computed tomography of the head showed left frontoparietal lobe hypodensities. Neurological exam was nonfocal. Vital signs were within normal range, but the patient experienced some memory loss and personality changes. Subsequent diagnosis of CVT was made with magnetic resonance angiography and magnetic resonance venography. Immediate treatment with low-molecular-weight intravenous heparin (18 IU/kg) was introduced. His UC was managed with methylprednisolone (60 mg IV daily), proton pump inhibitors, mesalamine, ciprofloxacin, and metronidazole. His condition gradually improved. On discharge, he was prescribed prednisone, azathioprine for his UC, levetiracetam for seizure, and warfarin with an INR goal of 2-3. In conclusion, the sudden onset and/or acute worsening of neurological status such as headache and mental confusion in a patient with UC should alert the treating physician about the possibility of CVT so that timely intervention could be employed to prevent disabling and potentially lethal sequelae of this disease.
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Affiliation(s)
- Safia Mohamud
- Department of Neurology, Howard University Hospital, Washington, District of Columbia, USA
| | - Mosunmola Oyawusi
- Department of Neurology, Howard University Hospital, Washington, District of Columbia, USA
| | - Roger Weir
- Department of Neurology, Howard University Hospital, Washington, District of Columbia, USA
| | - Richard M Millis
- Department of Pathophysiology, College of Medicine, American University of Antigua, Osbourn, Antigua
| | - Ozra Dehkordi
- Department of Neurology, Howard University Hospital, Washington, District of Columbia, USA
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15
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Ghoneim S, Weissman S, Wang L, Aziz M, Atoot A, Sandhu D, Swaminath A, Feuerstein JD. Impact of inflammatory bowel disease on hospital outcomes in acute ischemic stroke: a nationwide cohort study. Int J Colorectal Dis 2021; 36:1759-1764. [PMID: 33733312 DOI: 10.1007/s00384-021-03912-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/15/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE Patients with inflammatory bowel disease (IBD) have an increased risk of venous thrombotic events. The impact IBD has on arterial thrombosis is not well characterized. We aimed to identify the impact of IBD on hospital outcomes in patients admitted for acute ischemic stroke (AIS). METHODS This is a retrospective cohort study utilizing the 2017 National Inpatient Sample. We identified all adult patients with a principal diagnosis of AIS and compared those with a concurrent diagnosis of IBD to those without-subgrouped by ulcerative colitis (UC) and Crohn's disease (CD). Outcomes were mortality and healthcare usage among IBD patients with AIS. Multivariate analysis was used to control for confounders. Analyses were performed using STATA. RESULTS Five hundred twenty-four thousand and forty-five patients were admitted for AIS in 2017; of them 2200 (0.41%) had a concurrent diagnosis of IBD. The presence of IBD did not significantly affect in-hospital mortality (4.09% vs. 4.01%) among patients admitted for AIS [OR 1.07 95% CI: 0.65-1.76], with similar findings upon subgroup analysis of UC [OR 0.91, 95% CI: 0.39-2.09] and CD [OR 1.17, 95% CI: 0.62-2.19]. Mean hospital length of stay and charges/costs in AIS were similar irrespective of IBD. CONCLUSIONS UC and CD do not appear to be associated with a higher risk of mortality or increased healthcare usage in AIS. AIS risk assessment in patients with IBD is important but should be done in a similar fashion to the general population.
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Affiliation(s)
- Sara Ghoneim
- Department of Internal Medicine, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH, USA
| | - Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, 7600 River Road, North Bergen, NJ, 07047, USA.
| | - Linda Wang
- Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Muhammad Aziz
- Division of Gastroenterology, University of Toledo Medical Center, Toledo, OH, USA
| | - Adam Atoot
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, 7600 River Road, North Bergen, NJ, 07047, USA
| | - Dalbir Sandhu
- Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Arun Swaminath
- Division of Gastroenterology, Inflammatory Bowel Disease Program, Lenox Hill Hospital, New York, NY, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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16
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What Links an Increased Cardiovascular Risk and Inflammatory Bowel Disease? A Narrative Review. Nutrients 2021; 13:nu13082661. [PMID: 34444821 PMCID: PMC8398182 DOI: 10.3390/nu13082661] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Revised: 07/27/2021] [Accepted: 07/27/2021] [Indexed: 02/08/2023] Open
Abstract
Several studies have shown increased rates of cardiovascular disease (CVD) in patients suffering from inflammatory bowel disease (IBD), particularly in cases of early atherosclerosis and myocardial infarction. IBD most frequently begins at an early age, patients usually present normal weight and remain under constant care of a physician, as well as of a nutritionist. Therefore, the classical risk factors of CVD are not reflected in the higher prevalence of CVD in the IBD population. Still, both groups are characterised by chronic inflammation and display similar physiopathological mechanisms. In the course of IBD, increased concentrations of pro-inflammatory cytokines, such as C-reactive protein (CRP) and homocysteine, may lead to endothelial dysfunctions and the development of CVD. Furthermore, gut microbiota dysbiosis in patients with IBD also constitutes a risk factor for an increased susceptibility to cardiovascular disease and atherosclerosis. Additionally, diet is an essential factor affecting both positively and negatively the course of the aforementioned diseases, whereas several dietary patterns may also influence the association between IBD and CVD. Thus, it is essential to investigate the factors responsible for the increased cardiovascular (CV) risk in this group of patients. Our paper attempts to review the role of potential inflammatory and nutritional factors, as well as intestinal dysbiosis and pharmacotherapy, in the increased risk of CVD in IBD patients.
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17
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Dos Santos Ramos A, Viana GCS, de Macedo Brigido M, Almeida JF. Neutrophil extracellular traps in inflammatory bowel diseases: Implications in pathogenesis and therapeutic targets. Pharmacol Res 2021; 171:105779. [PMID: 34298111 DOI: 10.1016/j.phrs.2021.105779] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 07/04/2021] [Accepted: 07/19/2021] [Indexed: 02/07/2023]
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD). Among the various immune cells involved in IBD, neutrophils are the first to infiltrate and appear to contribute to the impairment of the epithelial barrier, destruction of tissues by oxidative and proteolytic damage, as well as to the perpetuation of inflammation by the release of cytokines and chemokines associated with pro-inflammatory effects. In addition to basic effector mechanisms, such as phagocytosis and chemotaxis, neutrophils can also form extracellular traps (NETs), which is made up of a mesh-like structure - which contains its chromatin (DNA + histones) together with granules and enzymes, such as myeloperoxidase (MPO) and neutrophilic elastase (NE) - and that acts as a trap that can result in the death of extracellular pathogens and/or can promote tissue damage. Recent evidence indicates that NETs also play an important and significant role in the pathogenesis of IBD. Previous studies have reported increased levels of NETs in tissue and serum samples from patients with IBD, as well as in experimental colitis. In this review, we discuss current knowledge about the formation of NETs and their role in the pathophysiology of IBD, pointing out potential mechanisms by which NETs promote tissue damage, as well as their involvement in complications associated with IBD. In addition, we propose potential targets for therapy to regulate the production of NETs, making it possible to expand the current spectrum of therapies for IBD.
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Affiliation(s)
- Anderson Dos Santos Ramos
- Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
| | | | | | - Juliana Franco Almeida
- Department of Cellular Biology, University of Brasilia, Brasilia, Brazil; Department of Cellular and Molecular Biology, Federal University of Paraíba, Paraíba, Brazil.
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18
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Nuñez P, García Mateo S, Quera R, Gomollón F. Inflammatory bowel disease and the risk of cardiovascular diseases. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 44:236-242. [PMID: 33223261 DOI: 10.1016/j.gastrohep.2020.09.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 09/11/2020] [Accepted: 09/24/2020] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD) includes both ulcerative colitis and Crohn's disease, which are well recognised as chronic systemic and immune-mediated conditions that frequently involve extraintestinal manifestations. Although comorbidities have long been the subject of research in other chronic inflammatory diseases, this concept is also emerging in IBD. Many pathologies have been linked to IBD, including cardiovascular disease, which is the main cause of death in developed countries. IBD patients are at increased risk of conditions such as early atherosclerosis and myocardial infarction or venous thrombosis and pulmonary thromboembolism. The aim of this review is to make an approximation of the physiopathology of the different manifestations of cardiovascular disease in patients with IBD and how to prevent them.
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Affiliation(s)
- Paulina Nuñez
- Universidad de Chile, Hospital San Juan de Dios, Sección de Gastroenterología, Santiago, Chile
| | - Sandra García Mateo
- Servicio de Aparato Digestivo. Hospital Clínico Universitario «Lozano-Blesa», IIS Aragón, Zaragoza, España
| | - Rodrigo Quera
- Clínica Las Condes, Departamento de Gastroenterología, Programa de Enfermedad Inflamatoria Intestinal, Santiago, Chile
| | - Fernando Gomollón
- Departamento de Medicina, Facultad de Medicina, IIS Aragón, Zaragoza, España.
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19
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Solitano V, Fiorino G, D'Amico F, Peyrin-Biroulet L, Danese S. Thrombosis in IBD in the Era of JAK Inhibition. Curr Drug Targets 2020; 22:126-136. [PMID: 32881668 DOI: 10.2174/1389450121666200902164240] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 07/15/2020] [Accepted: 07/15/2020] [Indexed: 01/06/2023]
Abstract
Patients with inflammatory bowel diseases (IBD) have an increased risk of thrombosis. The interaction between inflammation and coagulation has extensively been studied. It is well-- known that some drugs can influence the haemostatic system, but several concerns on the association between therapies and increased risk of thrombosis remain open. While biologics seem to have a protective role against thrombosis via their anti-inflammatory effect, some concerns about an increased risk of thrombosis with JAK inhibitors have been raised. We conducted a literature review to assess the association between biologics/small molecules and venous/arterial thrombotic complications. An increased risk of venous and arterial thrombosis was found in patients treated with corticosteroids, whereas anti-TNFα were considered protective agents. No thromboembolic adverse event was reported with vedolizumab and ustekinumab. In addition, thromboembolic events rarely occurred in patients with ulcerative colitis (UC) after therapy with tofacitinib. The overall risk of both venous and arterial thrombosis was not increased based on the available evidence. Finally, in the era of JAK inhibitors, the treatment should be individualized by evaluating the pre-existing potential thrombotic risk balanced with the intrinsic risk of the medication used.
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Affiliation(s)
- Virginia Solitano
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Gionata Fiorino
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | | | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
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20
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Grewal HK, Bansal M, Garg A, Kasliwal RR, Bhan A, Gautam D. Left Ventricular Thrombus and Cardioembolic Stroke in a Patient with Ulcerative Colitis: A Case Report. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2020; 9:67-70. [PMID: 33519347 PMCID: PMC7839577 DOI: 10.4103/sjmms.sjmms_525_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 04/16/2020] [Accepted: 08/20/2020] [Indexed: 12/02/2022]
Abstract
Left ventricular (LV) thrombi usually occur in the setting of global or regional LV systolic dysfunction and are extremely rare in the absence of LV wall motion abnormalities. We report here a case of a 23-year-old female who presented with cardioembolic stroke due to ulcerative colitis. To determine the cause of stroke, several investigations and evaluations were carried out, but the results were mostly normal or unremarkable. Transthoracic echocardiography revealed an oscillating pedunculated globular mass, which was eventually resected due to recurrent transient ischemic attacks. The histopathology of the excised mass revealed it to be an organized thrombus with acute and chronic inflammatory cells and fibroblasts. The uncommon etiology combined with the unusual appearance of the thrombus presented a major diagnostic and therapeutic dilemma for this exceedingly rare cause for intracardiac thrombus formation. Therefore, it would be useful to have a low threshold for screening patients with active inflammatory bowel disease for possible ventricular thrombosis before discharge, especially if other risk factors are present.
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Affiliation(s)
- Hardeep Kaur Grewal
- Department of Clinical and Preventive Cardiology, Pathology and Blood Bank, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Manish Bansal
- Department of Clinical and Preventive Cardiology, Pathology and Blood Bank, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Arun Garg
- Department of Neurology, Pathology and Blood Bank, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Ravi R Kasliwal
- Department of Clinical and Preventive Cardiology, Pathology and Blood Bank, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Anil Bhan
- Department of Cardiac Surgery, Pathology and Blood Bank, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Dheeraj Gautam
- Department of Laboratory Medicine, Pathology and Blood Bank, Medanta-The Medicity, Gurgaon, Haryana, India
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21
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Weissman S, Sinh P, Mehta TI, Thaker RK, Derman A, Heiberger C, Qureshi N, Amrutiya V, Atoot A, Dave M, Tabibian JH. Atherosclerotic cardiovascular disease in inflammatory bowel disease: The role of chronic inflammation. World J Gastrointest Pathophysiol 2020; 11:104-113. [PMID: 32832194 PMCID: PMC7403753 DOI: 10.4291/wjgp.v11.i5.104] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 04/24/2020] [Accepted: 06/27/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) causes systemic vascular inflammation. The increased risk of venous as well as arterial thromboembolic phenomena in IBD is well established. More recently, a relationship between IBD and atherosclerotic cardiovascular disease (ASCVD) has been postulated. Systemic inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus, have well characterized cardiac pathologies and treatments that focus on prevention of disease associated ASCVD. The impact of chronic inflammation on ASCVD in IBD remains poorly characterized. This manuscript aims to review and summarize the current literature pertaining to IBD and ASCVD with respect to its pathophysiology and impact of medications in order to encourage further research that can improve understanding and help develop clinical recommendations for prevention and management of ASCVD in patients with IBD.
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Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Preetika Sinh
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, United States
| | - Tej I Mehta
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57108, United States
| | - Rishi K Thaker
- Department of Medicine, New York Presbyterian, Brooklyn, NY 11215, United States
| | - Abraham Derman
- Department of Medicine, Mount Sinai-Saint Luke’s Roosevelt, NY 10025, United States
| | - Caleb Heiberger
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57108, United States
| | - Nabeel Qureshi
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Viralkumar Amrutiya
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Adam Atoot
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Maneesh Dave
- Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, CA 95817, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
- David Geffen School of Medicine at UCLA, Los Angeles, CA 90001, United States
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22
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Kim JM, Cheon JH. Pathogenesis and clinical perspectives of extraintestinal manifestations in inflammatory bowel diseases. Intest Res 2020; 18:249-264. [PMID: 32295331 PMCID: PMC7385581 DOI: 10.5217/ir.2019.00128] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 11/25/2019] [Accepted: 03/06/2020] [Indexed: 12/13/2022] Open
Abstract
A considerable number of patients with inflammatory bowel disease (IBD) experience extraintestinal manifestations (EIMs), which can present either before or after IBD diagnosis. Unraveling the pathogenic pathways of EIMs in IBD is challenging because of the lack of reliable criteria for diagnosis and difficulty in distinguishing EIMs from external pathologies caused by drugs or other etiologies. Optimizing treatment can also be difficult. Early diagnosis and management of EIM revolve around multidisciplinary teams, and they should have the resources necessary to make and implement appropriate decisions. In addition, specialists of the affected organs should be trained in IBD treatment. Furthermore, patient awareness regarding the extraintestinal symptoms of IBD is of paramount importance for improving patient understanding of disease and health outcomes. Herein, we review the pathogenesis and clinical perspectives of EIMs in IBD.
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Affiliation(s)
- Jung Min Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Avison Biomedical Research Center, Severance Hospital, Seoul, Korea
- Affiliate Faculty, Pohang University of Science and Technology (POSTECH), Pohang, Korea
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23
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Characteristics of Hemorheology in Patients with Acute Severe Ulcerative Colitis and the Clinical Study of Rivaroxaban Anticoagulant Therapy. HEPATITIS MONTHLY 2020. [DOI: 10.5812/hepatmon.92536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Lowenfeld L, Cologne KG. Postoperative Considerations in Inflammatory Bowel Disease. Surg Clin North Am 2019; 99:1095-1109. [PMID: 31676050 DOI: 10.1016/j.suc.2019.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Treatment of inflammatory bowel disease (IBD) is often multidimensional, requiring both medical and surgical therapies at different times throughout the course of the disease. Both medical and surgical treatments may be used in the acute setting, during a flare, or in a more elective maintenance role. These treatments should be planned as complementary and synergistic. Gastroenterologists and colorectal surgeons should collaborate to create a cohesive treatment plan, arranging the sequence and timing of various treatments. This article reviews the anticipated postoperative recovery after surgical treatment of IBD, possible postoperative complications, and considerations of timing surgery with medical therapy.
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Affiliation(s)
- Lea Lowenfeld
- Surgery, Division of Colorectal Surgery, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Suite 7418, Los Angeles, CA 90033, USA
| | - Kyle G Cologne
- Surgery, Division of Colorectal Surgery, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Suite 7418, Los Angeles, CA 90033, USA.
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Higashiyama M, Sugita A, Koganei K, Wanatabe K, Yokoyama Y, Uchino M, Nagahori M, Naganuma M, Bamba S, Kato S, Takeuchi K, Omori T, Takagi T, Matsumoto S, Nagasaka M, Sagami S, Kitamura K, Katsurada T, Sugimoto K, Takatsu N, Saruta M, Sakurai T, Watanabe K, Nakamura S, Suzuki Y, Hokari R. Management of elderly ulcerative colitis in Japan. J Gastroenterol 2019; 54:571-586. [PMID: 31025187 PMCID: PMC6685935 DOI: 10.1007/s00535-019-01580-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 04/08/2019] [Indexed: 02/04/2023]
Abstract
Japan has the largest aging society, where many elderly people have intractable diseases including ulcerative colitis (UC). Along with the increasing total number of UC patients, the number of elderly UC patients has also been increasing and will continue to do so in the future. Although the clinical features and natural history of UC in the elderly have many similarities with UC in the non-elderly population, age-specific concerns including comorbidities, immunological dysfunction, and polypharmacy make the diagnosis and management of elderly UC challenging compared to UC in non-elderly patients. Based on increasing data related to elderly UC patients from Japan, as well as other countries, we reviewed the epidemiology, clinical course, differential diagnosis, management of comorbidities, surveillance, medical therapy, and surgery of UC in the elderly.
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Affiliation(s)
- Masaaki Higashiyama
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
| | - Akira Sugita
- Inflammatory Bowel Disease Center, Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, Japan
| | - Kazutaka Koganei
- Inflammatory Bowel Disease Center, Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, Japan
| | - Kenji Wanatabe
- Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Yoko Yokoyama
- Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Motoi Uchino
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Masakazu Nagahori
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Shigeki Bamba
- Division of Clinical Nutrition, Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Shingo Kato
- Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Ken Takeuchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Centre, Sakura, Chiba, Japan
| | - Teppei Omori
- Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Tomohisa Takagi
- Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satohiro Matsumoto
- Department of Gastroenterology, Saitama Medical Center, Jichi Medical University, Saitama, Japan
| | - Mitsuo Nagasaka
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Shintaro Sagami
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Kazuya Kitamura
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
| | - Takehiko Katsurada
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Noritaka Takatsu
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Toshiyuki Sakurai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kazuhiro Watanabe
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Shiro Nakamura
- Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Yasuo Suzuki
- Inflammatory Bowel Disease Center, Toho University Sakura Medical Centre, Sakura, Chiba, Japan
| | - Ryota Hokari
- Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
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Winderman R, Rabinowitz SS, Vaidy K, Schwarz SM. Measurement of Microvascular Function in Pediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2019; 68:662-668. [PMID: 30601366 DOI: 10.1097/mpg.0000000000002252] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Altered vascular flow is known to both play a role in the pathogenesis and influence the severity of inflammatory bowel disease (IBD). This phenomenon has been described in other systemic conditions and contributes to disease progression by facilitating inflammation and thrombosis. Microvascular dysfunction may represent an early sign of generalized vascular disease (VD). It manifests by failure to achieve a normal response of vasodilation and increased blood flow following a period of vaso-occlusion. Although thromboembolic complications are well described in IBD, their pathogenesis is not fully understood. This study sought to assess microvascular responsiveness in pediatric subjects with IBD, by recording postocclusion peripheral arterial pulsatile volume changes. PATIENTS AND METHODS A total of 32 pediatric subjects were studied, including 16 with IBD and 16 age-matched controls. All patients with IBD were in clinical remission, and none had known VD. Vascular reactivity was evaluated using the Itamar Medical EndoPAT2000, a noninvasive device utilizing plethysmography to measure microvascular flow. Results were reported as the reactive hyperemia index (RHI), indicating post- to preocclusion pulsatile volume changes. RESULTS Baseline characteristics, including body mass index, plasma lipid levels, hemoglobin, and serum albumin, were similar in both study groups. All patients with IBD were in clinical remission, assessed by standard disease activity scoring methods. Measurements of microvascular function indicated patients with IBD exhibited a mean RHI both within the range associated with VD risk in adults (≤1.67) and significantly lower than that in controls (IBD vs control = 1.66 vs 2.02, P = 0.036). CONCLUSIONS Microvascular plethysmography is a safe and noninvasive method for assessing microvascular function in children with IBD. Patients with IBD in clinical remission demonstrate an attenuated, postocclusion microvascular hyperemic response, compared with the normal response in controls. These findings suggest pediatric IBD subjects with a mean RHI within the VD "at risk" range should be monitored for thromboembolic phenomena. Further studies in a larger patient population and over longer periods should be conducted to validate our findings and to determine the importance of these measurements in guiding IBD management.
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Affiliation(s)
- Rebecca Winderman
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital at Downstate, SUNY-Downstate Medical Center, Brooklyn, NY
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Bernardino VR, Rodrigues AC, Panarra A. Raynaud's phenomenon and inflammatory bowel disease: The possible role of microcirculation. Eur J Intern Med 2019; 62:e16. [PMID: 30737060 DOI: 10.1016/j.ejim.2019.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Accepted: 02/01/2019] [Indexed: 10/27/2022]
Affiliation(s)
- Vera R Bernardino
- Unidade de Doenças Auto-Imunes, Internal Medicine Department 7.2, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal.
| | - Ana Catarina Rodrigues
- Unidade de Doenças Auto-Imunes, Internal Medicine Department 7.2, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal
| | - António Panarra
- Unidade de Doenças Auto-Imunes, Internal Medicine Department 7.2, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal
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28
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Abdalla AO, Alluri D, Hassaballa M, Calvo L, Otaki F. A Case of Cerebral Venous Sinus Thrombosis Presenting During Relapse of Ulcerative Colitis. AMERICAN JOURNAL OF CASE REPORTS 2019; 20:419-422. [PMID: 30928992 PMCID: PMC6454583 DOI: 10.12659/ajcr.913429] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Patient: Male, 27 Final Diagnosis: Cerebral venous sinus thrombosis Symptoms: Headache • seizure • weakness Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology
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Affiliation(s)
- Abubaker O Abdalla
- Department of Internal Medicine, University of Nevada, School of Medicine, Reno, NV, USA
| | - Deepti Alluri
- Department of Internal Medicine, University of Nevada, School of Medicine, Reno, NV, USA
| | - Mohamed Hassaballa
- Department of Internal Medicine, University of Nevada, School of Medicine, Reno, NV, USA
| | - Lisa Calvo
- Department of Internal Medicine, University of Nevada, School of Medicine, Reno, NV, USA
| | - Fouad Otaki
- Department of Gastroenterology, Oregon Health and Science University, Portland, OR, USA
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29
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Bunu DM, Timofte CE, Ciocoiu M, Floria M, Tarniceriu CC, Barboi OB, Tanase DM. Cardiovascular Manifestations of Inflammatory Bowel Disease: Pathogenesis, Diagnosis, and Preventive Strategies. Gastroenterol Res Pract 2019; 2019:3012509. [PMID: 30733802 PMCID: PMC6348818 DOI: 10.1155/2019/3012509] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 11/18/2018] [Accepted: 12/06/2018] [Indexed: 12/16/2022] Open
Abstract
Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory diseases that targets mainly the gastrointestinal tract. The clinical presentation of IBD includes both gastrointestinal manifestations and extraintestinal manifestations (EIM). The reported cardiovascular manifestations in IBD patients include pericarditis, myocarditis, venous and arterial thromboembolism, arrhythmias, atrioventricular block, heart failure, endocarditis, valvulopathies, and Takayasu arteritis. The aim of this article is to review the available literature about the possible pathogenic mechanisms and determine preventive measures capable of reducing the incidence and severity of the cardiovascular manifestations. In IBD patients, the incidence of cardiovascular manifestations is low, but higher than that in the general population. Therefore, clinicians should pay attention to any new modification that might indicate cardiovascular involvement in IBD patients, and they should consider chronic inflammatory diseases in patients with cardiac conditions without an evident cause. Considering the role of inflammation in the development of cardiovascular manifestations, the management should include prevention of flares and maintenance of remission for as long as possible. Preventive measures should also include active screening and strict control of the cardiovascular risk factors in all IBD patients.
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Affiliation(s)
- Diana-Maria Bunu
- Department of Cardiology, Institute of Cardiovascular Diseases, Timisoara 300310, Romania
| | | | - Manuela Ciocoiu
- Department of Pathophysiology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700111, Romania
| | - Mariana Floria
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700111, Romania
- 3rd Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital Iasi, Iasi, Romania
| | - Claudia-Cristina Tarniceriu
- Department of Morpho-Functional Sciences I, Discipline of Anatomy, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700111, Romania
| | - Oana-Bogdana Barboi
- Institute of Gastroenterology and Hepatology-“Sf. Spiridon” County Clinical Emergency Hospital Iasi, Iasi, Romania
- “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700111, Romania
| | - Daniela-Maria Tanase
- Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700111, Romania
- 3rd Internal Medicine Clinic, “Sf. Spiridon” County Clinical Emergency Hospital Iasi, Iasi, Romania
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30
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Atherosclerosis and inflammation: overview and updates. Clin Sci (Lond) 2018; 132:1243-1252. [PMID: 29930142 DOI: 10.1042/cs20180306] [Citation(s) in RCA: 508] [Impact Index Per Article: 72.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 05/08/2018] [Accepted: 05/10/2018] [Indexed: 01/22/2023]
Abstract
The concept that inflammation participates pivotally in the pathogenesis of atherosclerosis and its complications has gained considerable attention, but has not yet entered clinical practice. Experimental work has elucidated molecular and cellular pathways of inflammation that promote atherosclerosis. The recognition of atherogenesis as an active process rather than a cholesterol storage disease or a repository of calcium has highlighted some key inflammatory mechanisms. For example, mononuclear phagocytes contribute to all stages of this disease, illustrating the link between inflammation and atherosclerosis. From a clinical perspective, harnessing inflammation may now help target therapeutics, change guidelines, and enter daily practice. Multiple lines of incontrovertible evidence have proven a causal role for low-density lipoprotein (LDL) cholesterol in atherosclerosis, and we have highly effective tools for lowering LDL, consequently reducing events. Yet, even with intense LDL reduction, events still occur. Inflammation can explain some of this residual risk. An anti-inflammatory intervention has now proven capable of improving outcomes in individuals well treated with LDL-lowering agents. A suite of trials are now pursuing anti-inflammatory therapies in this context. Assessment and treatment of residual inflammatory risk are poised to provide new inroads into preventive cardiology. This brief review aims to explore the potential mechanisms underlying the association of inflammation and atherogenesis, and their clinical consequences.
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31
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Prijić R, Premužić V, Brinar M, Krznarić Ž, Jelaković B, Čuković-Čavka S. Increased arterial stiffness - similar findings in patients with inflammatory bowel disease without prior hypertension or diabetes and in patients with well-controlled hypertension. Blood Press 2018; 27:240-246. [PMID: 29790793 DOI: 10.1080/08037051.2018.1476055] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
PURPOSE Chronic inflammatory diseases are related with earlier onset of atherosclerosis. We hypothesized that inflammatory bowel disease patients with chronic, systemic inflammation have an increased arterial stiffness associated with the disease duration. Also, we wanted to compare arterial stiffness markers between inflammatory bowel disease and well-controlled hypertension patients. MATERIALS AND METHODS A total of 89 inflammatory bowel disease patients (60 patients with Crohn's disease and 29 patients with ulcerative colitis, age range 20-64 years) without history of arterial hypertension or diabetes were enrolled and age matched with a control group of patients (73 patients, age range 25-69 years, 41 (56.1%) males) with known history of well-controlled arterial hypertension. We have used a noninvasive device that simultaneously measures brachial blood pressure and estimates PWV and AIx in inflammatory bowel disease and hypertension groups of patients. RESULTS Patients with pathological PWV values were significantly older, had significantly longer duration of inflammatory bowel disease, higher values of serum cholesterol and HDL-cholesterol, and higher AIx (17.4% vs. 9.8%) (all p < .05). Higher PWV was associated with age and duration of inflammatory bowel disease in the linear regression model. PWV values were higher in hypertensive patients in the first two age quartiles while interestingly, in the last two quartiles, PWV was lower than in inflammatory bowel disease group of patients. CONCLUSIONS Chronic subclinical inflammation is responsible for dyslipidemia and accelerated atherosclerosis which consequently alterates arterial elasticity. Inflammatory bowel disease and its duration should also be considered a risk factor for subclinical organ damage, as well as hypertension.
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Affiliation(s)
- Radovan Prijić
- a Department of Gastroenterology and Hepatology , University Hospital Centre Zagreb , Zagreb , Croatia
| | - Vedran Premužić
- b Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation , University Hospital Centre Zagreb, University of Zagreb School of Medicine , Zagreb , Croatia
| | - Marko Brinar
- c Department of Gastroenterology and Hepatology , University Hospital Centre Zagreb, University of Zagreb School of Medicine , Zagreb , Croatia
| | - Željko Krznarić
- c Department of Gastroenterology and Hepatology , University Hospital Centre Zagreb, University of Zagreb School of Medicine , Zagreb , Croatia
| | - Bojan Jelaković
- b Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation , University Hospital Centre Zagreb, University of Zagreb School of Medicine , Zagreb , Croatia
| | - Silvija Čuković-Čavka
- c Department of Gastroenterology and Hepatology , University Hospital Centre Zagreb, University of Zagreb School of Medicine , Zagreb , Croatia
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Alkim H, Koksal AR, Boga S, Sen I, Alkim C. Etiopathogenesis, Prevention, and Treatment of Thromboembolism in Inflammatory Bowel Disease. Clin Appl Thromb Hemost 2017; 23:501-510. [PMID: 26893444 DOI: 10.1177/1076029616632906] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2025] Open
Abstract
The close relationship between inflammation and thrombosis affects the progression and severity of inflammatory bowel disease (IBD). The prevalence of venous thromboembolism (VTE) varies between 1% and 7% among patients with IBD. The VTE risk in patients with IBD is at least 3 times higher than that in the normal general population. The absolute risk is very high during hospitalization, active disease, and surgery. The IBD-related VTE occurs at younger ages and recurs more frequently. The development of thrombosis in IBD is due to the interaction of many hereditary and acquired risk factors. Each patient diagnosed with IBD should be evaluated for a personal and family history of thrombosis and for prothrombotic drug use. Although procoagulant factors are increased during the natural course of inflammation, natural anticoagulants and fibrinolytic activity are decreased. Although IBD is accepted as a prothrombotic condition, there is no treatment that can remove this risk from daily practice. Patient training is required to control important factors, such as long-term immobilization and smoking. Oral contraceptives and hormone replacement therapy should be avoided. Inducing permanent disease remission must be the key approach for the prevention of thrombosis. Low-molecular-weight heparin (LMWH) is the basis of prophylactic treatment, which reduces the thrombosis risk by 50%. Prophylaxis with LMWH should be administered to all patients with IBD hospitalized due to disease attack or surgery. Long-term or even life-long anticoagulation therapy should be planned if there is insufficient disease control, recurrent VTE attacks, positive thrombophilia tests, or thrombosis in vital veins.
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Affiliation(s)
- Huseyin Alkim
- 1 Department of Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
| | - Ali Riza Koksal
- 1 Department of Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
| | - Salih Boga
- 1 Department of Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
| | - Ilker Sen
- 1 Department of Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
| | - Canan Alkim
- 1 Department of Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
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Zhang J, Guo Z, Yang W, Zhu Z, Kong W, Zheng S, Jiang L, Fei X, Chen Y, Liu J. D-Dimer levels are correlated with disease activity in Crohn's patients. Oncotarget 2017; 8:63971-63977. [PMID: 28969045 PMCID: PMC5609977 DOI: 10.18632/oncotarget.19250] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 06/04/2017] [Indexed: 12/14/2022] Open
Abstract
Various indices have been used to assess Crohn's disease (CD). However, the question of whether the Crohn's Disease Activity Index (CDAI) is associated with coagulation function has not been fully confirmed. In this study, we examined the association between CDAI and the coagulation and fibrinolysis parameters. In a retrospective and observational cohort study, the CDAI of 108 patients from two hospital centers was calculated, and its correlations with the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalization ratio (INR), fibrinogen (Fg) and plasma D-Dimer were investigated. Significant differences were found for PT, APTT, TT, INR, Fg and D-Dimer between the healthy controls and CD patients. However, no significant difference was found between the CDAI-High and CDAI-Low groups of CD patients. Moreover, the CDAI was positively correlated with the level of D-Dimer in CD patients of two hospitals, regardless of the detection method (hospital 1: r=0.3268, p= 0.0042; hospital 2: r=0.5553, p=0.0008). Among the blood coagulation and fibrinolysis parameters, the D-Dimer level was highly correlated with CDAI in CD patients. Thus, the level of D-Dimer expression may be a promising new marker for assessing CD disease activity.
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Affiliation(s)
- Junwu Zhang
- Department of Clinical Laboratory, Wenzhou Traditional Chinese Medicine Hospital, 325000 Wenzhou, China
| | - Zhen Guo
- Department of Clinical Laboratory, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009 Hangzhou, China
| | - Wei Yang
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, 310014 Hangzhou, China
| | - Zhongliang Zhu
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, 310014 Hangzhou, China
| | - Wanzhong Kong
- Department of Clinical Laboratory, Wenzhou Traditional Chinese Medicine Hospital, 325000 Wenzhou, China
| | - Sujie Zheng
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, 310014 Hangzhou, China
| | - Lei Jiang
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, 310014 Hangzhou, China
| | - Xianming Fei
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, 310014 Hangzhou, China
| | - Yanxia Chen
- Department of Rheumatology, Zhejiang Provincial People's Hospital, Hangzhou Medical College, 310014 Hangzhou, China
| | - Jinlin Liu
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, 310014 Hangzhou, China.,Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, 310014 Hangzhou, China
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Sturm A, Maaser C, Mendall M, Karagiannis D, Karatzas P, Ipenburg N, Sebastian S, Rizzello F, Limdi J, Katsanos K, Schmidt C, Jeuring S, Colombo F, Gionchetti P. European Crohn's and Colitis Organisation Topical Review on IBD in the Elderly. J Crohns Colitis 2017; 11:263-273. [PMID: 27797918 DOI: 10.1093/ecco-jcc/jjw188] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Revised: 09/17/2016] [Accepted: 10/18/2016] [Indexed: 12/12/2022]
Abstract
This ECCO topical review of the European Crohn's and Colitis Organisation [ECCO] focuses on the epidemiology, pathophysiology, diagnosis, management and outcome of the two most common forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis, in elderly patients. The objective was to reach expert consensus to provide evidence-based guidance for clinical practice.
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Affiliation(s)
- Andreas Sturm
- Department of Gastroenterology, DRK Kliniken Berlin I Westend. Akademisches Lehrkrankenhaus der Charite, Spandauer Damm 130, 14050 Berlin, Germany
| | - Christian Maaser
- Outpatients Department of Gastroenterology and Department of Geriatrics, Hospital Lüneburg, Bögelstraße 1, 21339 Lüneburg, Germany
| | - Michael Mendall
- Croydon University Hospital, Mayday Road, CR4 7YE Thornton Heath; & St George's Medical School, Cranmer Terrace SW17 ORE, UK
| | - Dimitrios Karagiannis
- Department of Gastroenterology, Iatriko Kentro Athinon, Dervenakion St. 3, 14572 Athens, Greece
| | - Pantelis Karatzas
- Department of Gastroenterology, Evangelismos Hospital, 45-47 Ypsilantou Street, 10676 Athens, Greece
| | - Nienke Ipenburg
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands
| | - Shaji Sebastian
- IBD Unit, Hull & East Yorkshire NHS Trust, Anlaby Road, Hull HU3 2JZ, UK
| | - Fernando Rizzello
- IBD Unit, DIMEC, University of Bologna, Via Massarenti, 9, 40138 Bologna, BO, Italy
| | - Jimmy Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust, Manchester M8 5RB, Institute of Inflammation and Repair, Manchester Academic Health Sciences, University of Manchester, UK
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, University and Medical School of Ioannina, PO Box 1186, 45110 Ioannina, Greece
| | - Carsten Schmidt
- Department of Internal Medicine IV, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany
| | - Steven Jeuring
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center (MUMC), PO Box 5800, 6202 AZ Maastricht, The Netherlands
| | - Francesco Colombo
- Dipartimento di Area Chirurgica, Ospedale "Luigi Sacco"- Polo Universitario, ASST Fatebenefratelli Sacco, Milano, Italy
| | - Paolo Gionchetti
- IBD Unit, DIMEC, University of Bologna, Via Massarenti, 9, 40138 Bologna, BO, Italy
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35
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Wu P, Jia F, Zhang B, Zhang P. Risk of cardiovascular disease in inflammatory bowel disease. Exp Ther Med 2016; 13:395-400. [PMID: 28352306 PMCID: PMC5348671 DOI: 10.3892/etm.2016.3966] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 11/04/2016] [Indexed: 02/07/2023] Open
Abstract
Cardiovascular disease (CVD) can arise because of chronic inflammation and inflammatory bowel disease (IBD) is one such disease where the risk for CVD and eventual heart failure is increased considerably. The incidence of IBD, which refers to both ulcerative colitis and Crohn's disease, has been on the increase in several countries and is a potential risk factor for CVD. Although IBD can potentially cause venous thromboembolism, its significance in arterial stiffening, atherosclerosis, ischemic heart disease and myocardial infarction is only being realized now and it is currently under debate. However, several studies with large groups of patients have demonstrated the association of IBD with heart disease. It has been suggested that systemic inflammation as observed in IBD patients leads to oxidative stress and elevated levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), which lead to phenotypic changes in smooth muscle cells and sets into motion a series of events that culminate in atherosclerosis and CVD. Besides the endogenous factors and cytokines, it has been suggested that due to the compromised intestinal mucosal barrier, endotoxins and bacterial lipopolysaccharides produced by intestinal microflora can enter into circulation and activate inflammatory responses that lead to atherosclerosis. Therapeutic management of IBD-associated heart diseases cannot be achieved with simple anti-inflammatory drugs such as corticosteroids and anti-TNF-α antibodies. Treatment with existing medications for CVDs, aspirin, platelet aggregation inhibitors and statins is found to be acceptable and safe. Nevertheless, further research is needed to assess their efficacy in IBD patients suffering from heart disease.
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Affiliation(s)
- Ping Wu
- Department of Gastroenterology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
| | - Fangyuan Jia
- Department of Gastroenterology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
| | - Bao Zhang
- Department of Gastroenterology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
| | - Peiying Zhang
- Department of Cardiology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu 221009, P.R. China
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36
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Bjøri E, Arshad N, Johnsen HS, Hansen JB, Braekkan SK. Hospital-related first venous thromboembolism and risk of recurrence. J Thromb Haemost 2016; 14:2368-2375. [PMID: 27589573 DOI: 10.1111/jth.13492] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Indexed: 11/27/2022]
Abstract
Essentials Recurrence risk after a hospital-related venous thromboembolism (VTE) is underinvestigated. We explored this association in a cohort of patients with a first VTE from the Tromsø study. Stratification on hospital-related factors revealed considerable differences in recurrence risk. The recurrence risk was high in cases with a VTE related to hospitalization for medical illness. SUMMARY Background Hospitalization is a well-established risk factor for first venous thromboembolism (VTE), but the risk of recurrence, particularly in patients hospitalized for conditions other than cancer or surgery, has scarcely been investigated. The cumulative incidence of recurrence in hospital-related VTE may be influenced by the competing risk of death. Objectives To investigate the risk of recurrence and mortality among patients with a first hospital-related VTE in models with and without death as a competing event. Methods Information on hospital-related risk factors was collected in 822 patients with a first-lifetime VTE derived from the Tromsø study. Recurrent VTEs and deaths were recorded during follow-up (1994-2012). Results During a median of 2.79 years of follow-up, 132 patients experienced a recurrent VTE. Stratification on hospital-related factors revealed considerable differences in recurrence risk. The 5-year cumulative incidence of recurrence was 27.4%, 11.0% and 20.1% in patients with incident VTEs related to cancer, surgery or other medical illness, respectively, and 18.4% in patients with a non-hospital-related first VTE. The mortality rates were high for all subgroups of hospital-related VTE, except for surgery-related events. Consequently, the cumulative incidence of recurrence dropped in the competing risk analyses, showing a 5-year cumulative incidence of 14.4%, 11.7% and 9.7% in patients with a first VTE related to hospitalization for other medical illness, cancer or surgery, respectively. Conclusions Our findings suggest that patients with incident VTEs related to hospitalization for medical illness other than cancer or surgery have a high recurrence-risk, even in the presence of competing risk of death.
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Affiliation(s)
- E Bjøri
- Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center, UiT - The Arctic University of Norway, Tromsø, Norway
| | - N Arshad
- Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center, UiT - The Arctic University of Norway, Tromsø, Norway
| | - H S Johnsen
- Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center, UiT - The Arctic University of Norway, Tromsø, Norway
| | - J-B Hansen
- Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center, UiT - The Arctic University of Norway, Tromsø, Norway
- Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
| | - S K Braekkan
- Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center, UiT - The Arctic University of Norway, Tromsø, Norway
- Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
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37
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Raghu Subramanian C, Triadafilopoulos G. Care of inflammatory bowel disease patients in remission. Gastroenterol Rep (Oxf) 2016; 4:261-271. [PMID: 27899522 PMCID: PMC5193066 DOI: 10.1093/gastro/gow032] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Revised: 08/21/2016] [Accepted: 09/04/2016] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease (IBD) comprises two distinct conditions: ulcerative colitis and Crohn’s disease, both of which are chronic, relapsing disorders carrying significant morbidity, mortality and healthcare costs. With growing attention to coordinated healthcare for patients with chronic systemic diseases, this review focuses on the care of IBD patients in remission, their concerns, quality of life, follow-up, the role of primary care physicians and the IBD-specific aspects of long-term care. We did an extensive PubMed search for articles pertaining to IBD patients in remission and, along with the authors’ experience, formulated a comprehensive review. The difficulties faced by IBD patients in remission include but are not limited to education and employment concerns, psychosocial issues, problems related to health insurance, nutrition, fertility and infections. This review also addresses newer treatment modalities, the debatable effects of smoking on IBD and the importance of vaccination. IBD in remission can be a challenge due to its multifaceted nature; however, with a coordinated approach by gastroenterologists and other involved practitioners, several of these issues can be addressed.
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38
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De Caterina R, D'Ugo E, Libby P. Inflammation and thrombosis - testing the hypothesis with anti-inflammatory drug trials. Thromb Haemost 2016; 116:1012-1021. [PMID: 27535617 DOI: 10.1160/th16-03-0246] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 07/16/2016] [Indexed: 12/17/2022]
Abstract
The hypothesis of atherosclerosis as an inflammatory process has been a leitmotiv in cardiology for the past 20 years, and has now led to the launch of clinical trials aimed at testing whether drugs that primarily target inflammation can reduce cardiovascular events. Inflammation indeed drives all phases of atherosclerosis, from inception, through progression, and ultimately acute thrombotic complications (plaque rupture and probably plaque erosion). Since plaque rupture and erosion cause most acute coronary syndromes, appropriately tuned anti-inflammatory treatments should limit myocardial infarction and cardiovascular death. Beyond interrupting inflammation-related plaque disruption, such treatments might, however, also ameliorate the propensity to thrombosis once the trigger (plaque rupture or erosion) has occurred. Several lines of evidence support this view: experimental data document the role of inflammation in platelet activation, tissue factor-mediated coagulation, hyperfibrinogenaemia, impaired activity of natural anticoagulants (including those expressed by endothelial cells), and reduced fibrinolytic activity. Supporting evidence also derives from the involvement of inflammation in venous thrombosis, a process that commonly occurs in the absence of traditional risk factors for atherosclerosis but is associated with several inflammatory diseases including obesity. Ongoing trials, in addition to evaluating effects on primary outcomes, will afford the opportunity to probe the possibility that anti-inflammatory interventions that yield salutary changes in biomarkers of the thrombotic/fibrinolytic balance also translate into reduction of clinical events.
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Affiliation(s)
- Raffaele De Caterina
- Raffaele De Caterina, MD, PhD, Institute of Cardiology, "G. d'Annunzio" University - Chieti, C/o Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy, Tel.: +39 0871 41512, Fax: +39 0871 402817, E-mail:
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39
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Kitzenberg D, Colgan SP, Glover LE. Creatine kinase in ischemic and inflammatory disorders. Clin Transl Med 2016; 5:31. [PMID: 27527620 PMCID: PMC4987751 DOI: 10.1186/s40169-016-0114-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 08/02/2016] [Indexed: 12/20/2022] Open
Abstract
The creatine/phosphocreatine pathway plays a conserved and central role in energy metabolism. Compartmentalization of specific creatine kinase enzymes permits buffering of local high energy phosphates in a thermodynamically favorable manner, enabling both rapid energy storage and energy transfer within the cell. Augmentation of this metabolic pathway by nutritional creatine supplementation has been shown to elicit beneficial effects in a number of diverse pathologies, particularly those that incur tissue ischemia, hypoxia or oxidative stress. In these settings, creatine and phosphocreatine prevent depletion of intracellular ATP and internal acidification, enhance post-ischemic recovery of protein synthesis and promote free radical scavenging and stabilization of cellular membranes. The creatine kinase energy system is itself further regulated by hypoxic signaling, highlighting the existence of endogenous mechanisms in mammals that can enhance creatine metabolism during oxygen deprivation to promote tissue resolution and homeostasis. Here, we review recent insights into the creatine kinase pathway, and provide rationale for dietary creatine supplementation in human ischemic and inflammatory pathologies.
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Affiliation(s)
- David Kitzenberg
- Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, 12700 East 19th Ave. MS B-146, Aurora, CO, 80045, USA.,Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA
| | - Sean P Colgan
- Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, 12700 East 19th Ave. MS B-146, Aurora, CO, 80045, USA.,Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA
| | - Louise E Glover
- Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, 12700 East 19th Ave. MS B-146, Aurora, CO, 80045, USA. .,Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
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40
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Di Sabatino A, Santilli F, Guerci M, Simeone P, Ardizzone S, Massari A, Giuffrida P, Tripaldi R, Malara A, Liani R, Gurini E, Aronico N, Balduini A, Corazza GR, Davì G. Oxidative stress and thromboxane-dependent platelet activation in inflammatory bowel disease: effects of anti-TNF-α treatment. Thromb Haemost 2016; 116:486-95. [PMID: 27305860 DOI: 10.1160/th16-02-0167] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 05/13/2016] [Indexed: 02/06/2023]
Abstract
Patients with inflammatory bowel disease (IBD) are at higher risk of venous thromboembolism and coronary artery disease despite having a lower burden of traditional risk factors. Platelets from IBD patients release more soluble CD40 ligand (CD40L), and this has been implicated in IBD platelet hyper-activation. We here measured the urinary F2-isoprostane 8-iso-prostaglandin (PG)2α (8-iso-PGF2α), urinary 11-dehydro-thromboxane (TX) B2 (11-dehydro-TXB2) and plasma CD40L in IBD patients, and explored the in vitro action of anti-tumour necrosis factor (TNF)-α antibody infliximab on IBD differentiating megakaryocytes. Urinary and blood samples were collected from 124 IBD patients and 37 healthy subjects. Thirteen IBD patients were also evaluated before and after 6-week infliximab treatment. The in vitro effect of infliximab on patient-derived megakaryocytes was evaluated by immunoflorescence microscopy and by flow cytometry. IBD patients had significantly (p<0.0001) higher urinary 8-iso-PGF2α and 11-dehydro-TXB2 as well as plasma CD40L levels than controls, with active IBD patients displaying higher urinary and plasma values when compared to inactive patients in remission. A 6-week treatment with infliximab was associated with a significant reduction of the urinary excretion of 8-iso-PGF2α and 11-dehydro-TXB2 (p=0.008) and plasma CD40L (p=0.001). Infliximab induced significantly rescued pro-platelet formation by megakaryocytes derived from IBD patients but not from healthy controls. Our findings provide evidence for enhanced in vivo TX-dependent platelet activation and lipid peroxidation in IBD patients. Anti-TNF-α therapy with infliximab down-regulates in vivo isoprostane generation and TX biosynthesis in responder IBD patients. Further studies are needed to clarify the implication of infliximab induced-proplatelet formation from IBD megakaryocytes.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Giovanni Davì
- Prof. Giovanni Davì, Internal Medicine and Center of Excellence on Aging, "G. D'Annunzio" University Foundation, Via Colle dell'Ara, 66013 Chieti, Italy, E-mail:
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Nowak M, Królak-Nowak K, Sobolewska-Włodarczyk A, Fichna J, Włodarczyk M. Elevated risk of venous thromboembolic events in patients with inflammatory myopathies. Vasc Health Risk Manag 2016; 12:233-8. [PMID: 27350751 PMCID: PMC4902147 DOI: 10.2147/vhrm.s75308] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Venous thromboembolism (VTE) is a multifactorial disease manifesting as either deep vein thrombosis or pulmonary embolism. Its prevalence makes VTE a significant issue for both the individual – as a negative factor influencing the quality of life and prognosis – and the society due to economic burden. VTE is the third most common vascular disorder in Western countries, after myocardial infarction and stroke, making it a major cause of in-hospital mortality, responsible for 5%–10% of hospital deaths. Despite many studies conducted, only 50%–60% provoking factors have been identified, while the remaining 40%–50% have been classified as idiopathic or unprovoked. Chronic inflammatory disorders, with their underlying prothrombotic state, reveal an increased risk of VTE (six to eight times) compared with the general population. Among the inflammatory disorders, we can identify inflammatory myopathies – a group of rare, chronic diseases featuring weakness and inflammation of muscles with periods of exacerbation and remission; their main classes are polymyositis and dermatomyositis. The objective of this review is to emphasize the need of VTE prophylaxis in individuals with inflammatory myopathies in order to reduce morbidity and mortality rates among those patients and improve their quality of life and prognosis.
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Affiliation(s)
- Michał Nowak
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Katarzyna Królak-Nowak
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | | | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Marcin Włodarczyk
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
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42
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Schicho R, Marsche G, Storr M. Cardiovascular complications in inflammatory bowel disease. Curr Drug Targets 2016. [PMID: 25642719 DOI: 10.2174/138945011666650202161500] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Over the past years, a growing number of studies have indicated that patients suffering from inflammatory bowel disease (IBD) have an increased risk of developing cardiovascular disease. Both are chronic inflammatory diseases and share certain pathophysiological mechanisms that may influence each other. High levels of cytokines, C-reactive protein (CRP), and homocysteine in IBD patients may lead to endothelial dysfunction, an early sign of atherosclerosis. IBD patients, in general, do not show the typical risk factors for cardiovascular disease but changes in lipid profiles similar to the ones seen in cardiovascular events have been reported recently. Higher levels of coagulation factors frequently occur in IBD which may predispose to arterial thromboembolic events. Finally, the gut itself may have an impact on atherogenesis during IBD through its microbiota. Microbial products are released from the inflamed mucosa into the circulation through a leaky barrier. The induced rise in proinflammatory cytokines could contribute to endothelial damage, artherosclerosis and cardiovascular events. Although large retrospective studies favor a link between IBD and cardiovascular diseases, the mechanisms behind still remain to be determined.
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Affiliation(s)
| | | | - Martin Storr
- Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
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43
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Schicho R, Marsche G, Storr M. Cardiovascular complications in inflammatory bowel disease. Curr Drug Targets 2016; 16:181-8. [PMID: 25642719 DOI: 10.2174/1389450116666150202161500] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2014] [Revised: 01/08/2015] [Accepted: 01/16/2015] [Indexed: 02/07/2023]
Abstract
Over the past years, a growing number of studies have indicated that patients suffering from inflammatory bowel disease (IBD) have an increased risk of developing cardiovascular disease. Both are chronic inflammatory diseases and share certain pathophysiological mechanisms that may influence each other. High levels of cytokines, C-reactive protein (CRP), and homocysteine in IBD patients may lead to endothelial dysfunction, an early sign of atherosclerosis. IBD patients, in general, do not show the typical risk factors for cardiovascular disease but changes in lipid profiles similar to the ones seen in cardiovascular events have been reported recently. Higher levels of coagulation factors frequently occur in IBD which may predispose to arterial thromboembolic events. Finally, the gut itself may have an impact on atherogenesis during IBD through its microbiota. Microbial products are released from the inflamed mucosa into the circulation through a leaky barrier. The induced rise in proinflammatory cytokines could contribute to endothelial damage, artherosclerosis and cardiovascular events. Although large retrospective studies favor a link between IBD and cardiovascular diseases, the mechanisms behind still remain to be determined.
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Affiliation(s)
| | | | - Martin Storr
- Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria.
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He Z, Si Y, Jiang T, Ma R, Zhang Y, Cao M, Li T, Yao Z, Zhao L, Fang S, Yu B, Dong Z, Thatte HS, Bi Y, Kou J, Yang S, Piao D, Hao L, Zhou J, Shi J. Phosphotidylserine exposure and neutrophil extracellular traps enhance procoagulant activity in patients with inflammatory bowel disease. Thromb Haemost 2015; 115:738-51. [PMID: 26660948 DOI: 10.1160/th15-09-0710] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Accepted: 11/08/2015] [Indexed: 12/28/2022]
Abstract
Inflammatory bowel disease (IBD)-associated thromboembolic event often lacks precise aetiology. The aim of this study was to investigate the contribution of phosphatidylserine (PS) exposure and neutrophil extracellular traps (NETs) towards the hypercoagulable state in IBD. We demonstrated that the levels of PS exposed MPs and the sources of MP-origin, platelets, erythrocytes, leukocytes and cultured endothelial cells (ECs) were higher in IBD groups than in healthy controls using flow cytometry and confocal microscopy. Wright-Giemsa and immunofluorescence staining demonstrated that the elevated NETs were released by activated IBD neutrophils or by control neutrophils treated with IBD sera obtained from patients with the active disease. MPs and MP-origin cells in IBD groups, especially in active stage, markedly shortened coagulation time and had increased levels of fibrin, thrombin and FXa production as assessed by coagulation function assays. Importantly, we found that on stimulated ECs, PS rich membranes provided binding sites for FXa and FVa, promoting fibrin formation while TNF blockage or IgG depletion attenuated this effect. Treatment of control neutrophils with TNF and isolated IgG from PR3-ANCA-positive active IBD patients also resulted in the release of NETs. Blockade of PS with lactadherin prolonged coagulation time, decreased fibrin formation to control levels, and inhibited the procoagulant enzymes production in the MPs and MP-origin cells. NET cleavage by DNase I partly decreased PCA in IBD or stimulated neutrophils. Our study reveals a previously unrecognised link between hypercoagulable state and PS exposure or NETs, and may further explain the epidemiological association of thrombosis within IBD patients.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Jialan Shi
- Jialan Shi, MD, PhD, or Jin Zhou, MD, PhD, or Lirong Hao, MD, PhD, Department of Medicine, or Daxun Piao, MD, PhD, Department of General Surgery, First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China, E-mail:
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Abstract
Thrombosis in inflammatory bowel disease (IBD) is an increasingly noted extraintestinal manifestation with high morbidity and mortality. While controlling the activity of the disease with the appropriate therapy, thromboembolism prophylaxis should be applied to all patients. All common risk factors for thromboembolism are also valid for patients with IBD; however, it is clear that uncontrolled disease and hospitalization are major disease-specific risk factors for venous thromboembolism in patients with IBD. Pharmacological thromboprophylaxis with currently available anticoagulants does not increase the risk of further bleeding in patients with IBD with mild-to-moderate bleeding. In severe bleeding or with increased risk of further bleeding due to other comorbid conditions, thromboprophylaxy with mechanical methods should be the treatment option. Whether thrombosis is the cause or the result of intestinal inflammation remains to be elucidated, and other issues in the etiology, such as the role of intestinal flora in thrombosis pathogenesis, will be the subject of future studies.
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Increased risk of stroke among patients with Crohn's disease: a population-based matched cohort study. Int J Colorectal Dis 2015; 30:645-53. [PMID: 25608496 DOI: 10.1007/s00384-015-2132-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/08/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Crohn's disease (CD) is one type of inflammatory bowel disease (IBD) that has been speculated to share prognostic factors with the development of stroke. There is controversial information in the literature regarding the association between CD and stroke. The present cohort study estimated the risk of subsequent stroke among CD patients compared with matched comparison subjects drawn from a population-based dataset in Taiwan. METHOD This study drew data from the Taiwan National Health Insurance Database to conduct a historical cohort study. The study cohort comprised 3309 CD patients, and the comparison cohort comprised 13,236 subjects without an IBD. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses stratifying by age group and gender. RESULTS After adjusting for selected medical co-morbidities and recent prescriptions of selected pharmaceuticals, the hazard ratio (HR) for subsequent stroke among patients with CD was found to be 1.911 (95% confidence interval (CI) = 1.65-2.22) that of comparison subjects. While we did not detect an association between stroke and CD among patients aged 30-40 years, we did detect increased risks for stroke among CD patients aged 40-50 years (HR = 2.29) and those aged over 50 years (HR = 1.88). We also found women (HR = 2.39) to be at a greater risk than men (HR = 1.50). CONCLUSION This study reports an increased HR for subsequent stroke among CD patients when compared to matched comparison patients without IBD in an Asian population.
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Giannotta M, Tapete G, Emmi G, Silvestri E, Milla M. Thrombosis in inflammatory bowel diseases: what's the link? Thromb J 2015; 13:14. [PMID: 25866483 PMCID: PMC4393581 DOI: 10.1186/s12959-015-0044-2] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Accepted: 02/26/2015] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease affects more than 2 million people in Europe, with almost 20% of patients being diagnosed in pediatric age. Patients with inflammatory bowel disease are at increased risk of thromboembolic complications which may affect patients’ morbidity and mortality. The risk of the most common thromboembolic events, such as deep venous thrombosis and pulmonary embolism, are estimated to be three-fold increased compared to controls, but many other districts can be affected. Moreover, patients with ulcerative colitis and Crohn’s disease experience thromboembolic events at a younger age compared to general population. Many factors have been investigated as determinants of the pro-thrombotic tendency such as acquired risk factors or genetic and immune abnormalities, but a unique cause has not been found. Many efforts have been focused on the study of abnormalities in the coagulation cascade, its natural inhibitors and the fibrinolytic system components and both quantitative and qualitative alterations have been demonstrated. Recently the role of platelets and microvascular endothelium has been reviewed, as the possible link between the inflammatory and hemostatic process.
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Affiliation(s)
- Martina Giannotta
- Gastroenterology Department, AOU Careggi Regional Referral Center for Inflammatory Bowel Disease, Florence, Italy
| | - Gherardo Tapete
- Gastroenterology Department, AOU Careggi Regional Referral Center for Inflammatory Bowel Disease, Florence, Italy
| | - Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Florence and Patologia Medica Unit, AOU Careggi, Florence, Italy
| | - Elena Silvestri
- Department of Experimental and Clinical Medicine, University of Florence and Patologia Medica Unit, AOU Careggi, Florence, Italy
| | - Monica Milla
- Gastroenterology Department, AOU Careggi Regional Referral Center for Inflammatory Bowel Disease, Florence, Italy
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Singh S, Kullo IJ, Pardi DS, Loftus EV. Epidemiology, risk factors and management of cardiovascular diseases in IBD. Nat Rev Gastroenterol Hepatol 2015; 12:26-35. [PMID: 25446727 DOI: 10.1038/nrgastro.2014.202] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
IBD is an established risk factor for venous thromboembolism. In the past few years, studies have suggested that patients with IBD might also be at an increased risk of coronary heart disease and stroke. The increased risk is thought to be similar to the level of risk seen in patients with other chronic systemic inflammatory diseases such as rheumatoid arthritis. The risk of developing these conditions is particularly increased in young adults with IBD, and more so in women than in men. Conventional cardiovascular risk factors are not over-represented in patients with IBD, so the increased risk could be attributable to inflammation-mediated atherosclerosis. Patients with IBD often have premature atherosclerosis and have biochemical and genetic markers similar to those seen in patients with atherosclerotic cardiovascular disease. The role of chronic inflammation in IBD-associated cardiovascular disease merits further evaluation. Particular attention should be given to the increased risk observed during periods of increased disease activity and potential modification of the risk by immunosuppressive and biologic therapies for IBD that can modify the disease activity. In addition, preclinical studies suggest that cardiovascular medications such as statins and angiotensin-converting enzyme inhibitors might also favourably modify IBD disease activity, which warrants further evaluation.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Iftikhar J Kullo
- Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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Zezos P, Kouklakis G, Saibil F. Inflammatory bowel disease and thromboembolism. World J Gastroenterol 2014; 20:13863-13878. [PMID: 25320522 PMCID: PMC4194568 DOI: 10.3748/wjg.v20.i38.13863] [Citation(s) in RCA: 107] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 05/24/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of vascular complications. Thromboembolic complications, both venous and arterial, are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality. Patients with IBD are more prone to thromboembolic complications and IBD per se is a risk factor for thromboembolic disease. Data suggest that thrombosis is a specific feature of IBD that can be involved in both the occurrence of thromboembolic events and the pathogenesis of the disease. The exact etiology for this special association between IBD and thromboembolism is as yet unknown, but it is thought that multiple acquired and inherited factors are interacting and producing the increased tendency for thrombosis in the local intestinal microvasculature, as well as in the systemic circulation. Clinicians' awareness of the risks, and their ability to promptly diagnose and manage tromboembolic complications are of vital importance. In this review we discuss how thromboembolic disease is related to IBD, specifically focusing on: (1) the epidemiology and clinical features of thromboembolic complications in IBD; (2) the pathophysiology of thrombosis in IBD; and (3) strategies for the prevention and management of thromboembolic complications in IBD patients.
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Tsai MS, Lin CL, Chen HP, Lee PH, Sung FC, Kao CH. Long-term risk of mesenteric ischemia in patients with inflammatory bowel disease: a 13-year nationwide cohort study in an Asian population. Am J Surg 2014; 210:80-6. [PMID: 25457233 DOI: 10.1016/j.amjsurg.2014.08.026] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 07/16/2014] [Accepted: 08/10/2014] [Indexed: 12/30/2022]
Abstract
BACKGROUND It is unclear whether patients with inflammatory bowel disease (IBD) have higher risks of developing mesenteric ischemia. METHODS We enrolled 9,363 patients who had been hospitalized because of IBD between January 1998 and December 2010, along with 37,452 control patients who were matched at a 1:4 proportion for age, sex, and index year. We accounted the cumulative incidences and hazard ratios (HRs) of developing mesenteric ischemia during the 13-year study period. RESULTS Patients with IBD had a considerably higher incidence rate of subsequent mesenteric ischemia compared with the controls (22.7 vs 3.09 per 10,000 person-years), with adjusted HR of 6.33 (95% confidence interval: 4.75 to 8.43). A multivariate stratified analysis showed that the mesenteric ischemia risk after adjustment for comorbidities is significantly higher in patients of all age groups, particularly in patients younger than 44 years (adjusted HR: 48.0; 95% confidence interval: 11.3 to 203.9). Moreover, patients with IBD were at highest risk of developing mesenteric ischemia within the first year of follow-up. CONCLUSIONS Careful follow-up and effective therapy are necessary to reduce the excessive risk in these patients.
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Affiliation(s)
- Ming-Shian Tsai
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Hsin-Pao Chen
- Department of Colorectal Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Po-Huang Lee
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Fung-Chang Sung
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 404, Taiwan
| | - Chia-Hung Kao
- Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 404, Taiwan; Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.
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