Inflammatory Bowel Disease and Acute Coronary Syndromes: From Pathogenesis to the Fine Line Between Bleeding and Ischemic Risk

2020 ◽  
Author(s):  
Martino Pepe ◽  
Eugenio Carulli ◽  
Cinzia Forleo ◽  
Marco Moscarelli ◽  
Ottavio Di Cillo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Acute Coronary Syndromes ◽  
Pathological Condition ◽  
Coronary Vessels ◽  
Bleeding Risk ◽  
Thrombotic Risk ◽  
Proinflammatory Mediators ◽  
Coronary Syndromes ◽  
Inflammatory Bowel

Abstract Inflammatory bowel disease (IBD) is a pathological condition that first involves the gastrointestinal wall but can also trigger a systemic inflammatory state and thus extraintestinal manifestations. Systemic inflammation is probably secondary to the passage of bacterial products into the bloodstream because of altered intestinal permeability and the consequent release of proinflammatory mediators. Inflammation, through several diverse pathophysiological pathways, determines both a procoagulative state and systemic endothelial dysfunction, which are both deemed to be responsible for venous and arterial thromboembolic adverse events. The management of systemic thrombotic complications is particularly challenging in this category of patients, who also present a high bleeding risk; what is more, both bleeding and thrombotic risks peak during the active phases of the disease. The literature suggests that treating physicians have been, so far, more heavily influenced by concerns about bleeding than by the thrombotic risk. Despite the absence of data provided by large cohorts or randomized studies, the high risk of arterial and venous atherothrombosis in patients with IBD seems unquestionable. Moreover, several reports suggest that when arterial thromboembolism involves the coronary vessels, causing acute coronary syndromes, ischemic complications from antithrombotic drug undertreatment are frequent and severe. This review aims to shed light on the tricky balance between the ischemic and hemorrhagic risks of patients with IBD and to highlight how difficult it is for clinicians to define a tailored therapy based on a case-by-case, careful, and unprejudiced clinical evaluation.

scholarly journals Acute Coronary Syndromes and Inflammatory Bowel Disease: The Gut–Heart Connection

2021 ◽  
Vol 10 (20) ◽  
pp. 4710
Author(s):  
Ayman Jaaouani ◽  
Abdulrahman Ismaiel ◽  
Stefan-Lucian Popa ◽  
Dan L. Dumitrascu
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Acute Coronary Syndromes ◽  
Observational Studies ◽  
Common Ground ◽  
Cochrane Library ◽  
Oral Contraceptive Pills ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
Inflammatory Bowel

(1) Background: Inflammatory bowel disease (IBD) induces a process of systemic inflammation, sharing common ground with acute coronary syndromes (ACS). Growing evidence points towards a possible association between IBD and an increased risk of ACS, yet the topic is still inconclusive. Therefore, we conducted a systematic review aiming to clarify these gaps in the evidence. (2) Methods: We conducted a systematic search on EMBASE, Cochrane Library, and PubMed, identifying observational studies published prior to November 2020. The diagnosis of IBD was confirmed via histopathology or codes. Full articles that fulfilled our criteria were included. Quality assessment was performed using the Newcastle–Ottawa scale (NOS). (3) Results: We included twenty observational studies with a total population of ~132 million subjects. Fifteen studies reported a significant association between ACS and IBD, while the remaining five studies reported no increase in ACS risk in IBD patients. (4) Conclusions: ACS risk in IBD patients is related to hospitalizations, acute active flares, periods of active disease, and complications, with a risk reduction during remission. Interestingly, a general increase in ACS risk was reported in younger IBD patients. The role of corticosteroids and oral contraceptive pills in increasing the ACS risk of IBD patients should be investigated.

scholarly journals Inflammatory bowel disease and cardiovascular diseases: a concise review

2021 ◽  
Author(s):  
Hao Wu ◽  
Tingzi Hu ◽  
Hong Hao ◽  
Michael A Hill ◽  
Canxia Xu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Inflammatory Bowel Disease ◽  
Cardiovascular Diseases ◽  
Inflammatory Cytokines ◽  
Bowel Disease ◽  
Bleeding Risk ◽  
Team Approach ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Traditional Risk Factors

Abstract Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality despite aggressive treatment of traditional risk factors. Chronic inflammation plays an important role in the initiation and progression of CVDs. Inflammatory bowel disease (IBD) is a systemic state of inflammation exhibiting increased levels of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Importantly, IBD is associated with increased risk for CVDs especially in women and young adults, including coronary artery disease, stroke, thromboembolic diseases, and arrhythmias. Potential mechanisms underlying the increased risk for CVDs in IBD patients include increased levels of inflammatory cytokines and oxidative stress, altered platelet function, hypercoagulability, decreased numbers of circulating endothelial progenitor cells, endothelial dysfunction, and possible interruption of gut microbiota. Although IBD does not appear to exacerbate the traditional risk factors for CVDs, including hypertension, hyperlipidemia, diabetes mellitus, and obesity, aggressive risk stratifications are important for primary and secondary prevention of CVDs for IBD patients. Compared to 5-ASA and corticosteroids, anti-TNF-α therapy in IBD patients was consistently associated with decreasing cardiovascular events. In the absence of contraindications, low-dose aspirin and statins appear to be beneficial for IBD patients. Low-molecular-weight heparin is also recommended for patients who are hospitalized with acute IBD flares without major bleeding risk. A multidisciplinary team approach should be considered for the management of IBD patients.

scholarly journals Anti-TNF-α Therapy Suppresses Proinflammatory Activities of Mucosal Neutrophils in Inflammatory Bowel Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Cui Zhang ◽  
Weigang Shu ◽  
Guangxi Zhou ◽  
Jian Lin ◽  
Feifei Chu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Critical Role ◽  
Mucosal Healing ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Inflammatory Bowel

Neutrophils have been found to play an important role in the pathogenesis of inflammatory bowel disease (IBD), and anti-TNF-α mAb (i.e., infliximab) therapy is demonstrated to be effective in the induction of clinical remission and mucosal healing in these patients. However, how anti-TNF-α mAb regulates the functions of neutrophils is still unknown. Herein, we found that anti-TNF-α therapy significantly downregulated infiltration of neutrophils in inflamed mucosa of IBD patients. Importantly, anti-TNF-α mAb could inhibit neutrophils to produce proinflammatory mediators, such as ROS, calprotectin, IL-8, IL-6, and TNF-α. These data indicate that TNF-α plays a critical role in the induction of mucosal inflammatory response, and that blockade of TNF-α modulates intestinal homeostasis through balancing immune responses of neutrophils.

scholarly journals Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 126 ◽  
Author(s):  
Israr Khan ◽  
Naeem Ullah ◽  
Lajia Zha ◽  
Yanrui Bai ◽  
Ashiq Khan ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Current Knowledge ◽  
Pathological Condition ◽  
Gut Flora ◽  
Core Microbiome ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn’s disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.

scholarly journals Thrombosis in the setting of obesity or inflammatory bowel disease

Blood ◽  
2016 ◽  
Vol 128 (20) ◽  
pp. 2388-2394 ◽  
Author(s):  
Steven R. Lentz
Keyword(s):  
Inflammatory Bowel Disease ◽  
High Risk ◽  
Bowel Disease ◽  
Severe Obesity ◽  
Thrombotic Risk ◽  
Anticoagulant Drugs ◽  
Extended Duration ◽  
Inflammatory Bowel ◽  
Management Challenge ◽  
Chronic Risk

Abstract Obesity and inflammatory bowel disease (IBD) are systemic inflammatory disorders that predispose to arterial and venous thrombosis through similar prothrombotic mechanisms. Obesity and IBD are chronic risk factors that lead to a persistently elevated risk of thrombosis, although the thrombotic risk with IBD appears to wax and wane with disease severity. Because of the lack of high-quality evidence to guide management decisions, approaches to the prevention and treatment of thrombosis in patients with obesity or IBD are based on extrapolation from general guidelines for antithrombotic therapy. Obesity alters the pharmacokinetics of some anticoagulant drugs, and IBD patients present the added management challenge of having a high risk of gastrointestinal bleeding while taking anticoagulants. An extended duration of anticoagulant therapy is often recommended for obese or IBD patients with unprovoked venous thromboembolism unless there is a high risk of bleeding, although more data and better biomarkers are needed to determine whether anticoagulation can be safely stopped in a subset of IBD patients during remission of active disease. Most patients with obesity or IBD require thromboprophylaxis in conjunction with hospitalization or surgery, with adjustment of anticoagulant dosing in patients with severe obesity.

scholarly journals Thrombosis in the setting of obesity or inflammatory bowel disease

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 180-187 ◽  
Author(s):  
Steven R. Lentz
Keyword(s):  
Inflammatory Bowel Disease ◽  
High Risk ◽  
Bowel Disease ◽  
Severe Obesity ◽  
Thrombotic Risk ◽  
Anticoagulant Drugs ◽  
Extended Duration ◽  
Inflammatory Bowel ◽  
Management Challenge ◽  
Chronic Risk

Abstract Obesity and inflammatory bowel disease (IBD) are systemic inflammatory disorders that predispose to arterial and venous thrombosis through similar prothrombotic mechanisms. Obesity and IBD are chronic risk factors that lead to a persistently elevated risk of thrombosis, although the thrombotic risk with IBD appears to wax and wane with disease severity. Because of the lack of high-quality evidence to guide management decisions, approaches to the prevention and treatment of thrombosis in patients with obesity or IBD are based on extrapolation from general guidelines for antithrombotic therapy. Obesity alters the pharmacokinetics of some anticoagulant drugs, and IBD patients present the added management challenge of having a high risk of gastrointestinal bleeding while taking anticoagulants. An extended duration of anticoagulant therapy is often recommended for obese or IBD patients with unprovoked venous thromboembolism unless there is a high risk of bleeding, although more data and better biomarkers are needed to determine whether anticoagulation can be safely stopped in a subset of IBD patients during remission of active disease. Most patients with obesity or IBD require thromboprophylaxis in conjunction with hospitalization or surgery, with adjustment of anticoagulant dosing in patients with severe obesity.

scholarly journals Inflammatory Bowel Disease and Thrombosis: A National Inpatient Sample Study

TH Open ◽  
2020 ◽  
Vol 04 (01) ◽  
pp. e51-e58
Author(s):  
Jessica B. Cohen ◽  
Diane M. Comer ◽  
Jonathan G. Yabes ◽  
Margaret V. Ragni
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Severity Of Illness ◽  
Disease Classification ◽  
Continuous Variables ◽  
National Inpatient Sample ◽  
Chi Square ◽  
Discharge Data ◽  
Thrombotic Risk ◽  
Inflammatory Bowel

Abstract Introduction Thrombosis is more common in inflammatory bowel disease (IBD) patients than the general population, but disease-specific correlates of thrombosis remain unclear. Methods We performed a retrospective analysis of discharge data from the National Inpatient Sample between 2009 and 2014, using International Disease Classification codes to identify IBD and non-IBD patients with or without thrombosis. We used NIS-provided discharge-level weights to reflect prevalence estimates. Categoric variables were analyzed by Rao-Scott Chi-square test, continuous variables by weighted simple linear regression, and covariates associated with thrombosis by weighted multivariable logistic regression. Results Thrombosis prevalence in IBD was significantly greater than in non-IBD, 7.52 versus 4.54%, p < 0.0001. IBD patients with thrombosis were older and more likely to be Caucasian than IBD without thrombosis, each p < 0.001. Thrombosis occurred most commonly in the mesenteric vein. Thrombotic risk factors in IBD include surgery, ports, malignancy, dehydration, malnutrition, and steroids at 53.7, 13.2, 13.1, 12.4, 8.9, and 8.2%, respectively. Those with thrombosis had greater severity of illness, 1.42 versus 0.96; length of stay, 7.7 versus 5.5 days; and mortality, 3.8 versus 1.5%; all p < 0.0001. Adjusting for age and comorbidity, odds ratios for predictors of thrombosis included ports, steroids, malnutrition, and malignancy at 1.73, 1.61, 1.34, and 1.13, respectively, while Asian race, 0.61, was protective, each p < 0.001. Conclusion Thrombosis prevalence is 1.7-fold greater in IBD than non-IBD patients. Adjusting for age and comorbidity, the odds ratio for thrombosis in IBD was 73% higher with ports, 61% higher with steroids, 34% with malnutrition, and 13% with malignancy. Whether long-term anticoagulation would benefit the latter is unknown.

scholarly journals Acute coronary syndromes with high thrombotic burden: therapeutic innovations

2020 ◽  
Vol 22 (Supplement_L) ◽  
pp. L97-L100
Author(s):  
Alberto Menozzi ◽  
Giorgio Caretta
Keyword(s):  
Acute Coronary Syndromes ◽  
Antiplatelet Agents ◽  
Bleeding Risk ◽  
Platelet Inhibition ◽  
Onset Of Action ◽  
Thrombotic Risk ◽  
P2y12 Inhibitors ◽  
Oral Medications ◽  
Platelet Receptor ◽  
Coronary Syndromes

Abstract Antiplatelet agents represent one of the cornerstones of drug therapy for acute coronary syndromes (ACS). In the last decade, the arrival of prasugrel and ticagrelor, faster and more powerful oral platelet receptor P2Y12 inhibitors compared to clopidogrel, significantly improved platelet inhibition in patients with ACS. However, the reduction of thrombotic risk came at the cost of increased bleeding risk. Despite having similar indications, prasugrel and ticagrelor have different characteristics and methods of use, essentially due to a different design of the trials in which they have been studied. The optimal use of these antiplatelets in clinical practice should therefore be tailored in individual patients. In the acute phase of ACS with high thrombotic burden, all oral P2Y12 inhibitors have limitations, mainly due to the delay of onset of action related to oral administration. In this scenario, parenteral antiplatelet agents (glycoprotein inhibitors IIb/IIIa and cangrelor) may play a key role in case of percutaneous coronary interventions of high thrombotic coronary lesions and in the prevention of early thrombotic complications. Cangrelor, an intravenous inhibitor of the P2Y2 receptor, has peculiar pharmacokinetic and pharmacodynamic characteristics that make it particularly suitable to be used as an antiplatelet during coronary angioplasty as it achieves a rapid and powerful antiplatelet effect in patients not pretreated with oral medications, and has a favourable safety profile in relation to the bleeding risk.

scholarly journals The Role of Physical Exercise in Inflammatory Bowel Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Jan Bilski ◽  
Bartosz Brzozowski ◽  
Agnieszka Mazur-Bialy ◽  
Zbigniew Sliwowski ◽  
Tomasz Brzozowski
Keyword(s):  
Inflammatory Bowel Disease ◽  
Physical Exercise ◽  
Bowel Disease ◽  
Inflammatory Process ◽  
Typical Feature ◽  
Biologically Active ◽  
Proinflammatory Mediators ◽  
Mesenteric Border ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

We reviewed and analyzed the relationship between physical exercise and inflammatory bowel disease (IBD) which covers a group of chronic, relapsing, and remitting intestinal disorders including Crohn’s disease (CD) and ulcerative colitis. The etiology of IBD likely involves a combination of genetic predisposition and environmental risk factors. Physical training has been suggested to be protective against the onset of IBD, but there are inconsistencies in the findings of the published literature. Hypertrophy of the mesenteric white adipose tissue (mWAT) is recognized as a characteristic feature of CD, but its importance for the perpetuation of onset of this intestinal disease is unknown. Adipocytes synthesize proinflammatory and anti-inflammatory cytokines. Hypertrophy of mWAT could play a role as a barrier to the inflammatory process, but recent data suggest that deregulation of adipokine secretion is involved in the pathogenesis of CD. Adipocytokines and macrophage mediators perpetuate the intestinal inflammatory process, leading to mucosal ulcerations along the mesenteric border, a typical feature of CD. Contracting skeletal muscles release biologically active myokines, known to exert the direct anti-inflammatory effects, and inhibit the release of proinflammatory mediators from visceral fat. Further research is required to confirm these observations and establish exercise regimes for IBD patients.

scholarly journals Haemorheological and haemostatic alterations in coeliac disease and inflammatory bowel disease in comparison with non-coeliac, non-IBD subjects (HERMES): a case–control study protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e026315 ◽  
Author(s):  
Zsolt Szakács ◽  
Beáta Csiszár ◽  
Péter Kenyeres ◽  
Patrícia Sarlós ◽  
Bálint Erőss ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Coeliac Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Case Control Study ◽  
Case Control ◽  
Dietary Adherence ◽  
Thrombotic Risk ◽  
Inflammatory Bowel ◽  
Control Study

IntroductionHaemorheological and haemostatic changes predispose to the development of arterial and venous thrombotic events; however, limited information is available on the status of these changes in coeliac disease (CeD) and inflammatory bowel disease (IBD). In this study, we aim to describe the haemorheological and haemostatic profiles of CeD and IBD patients in a Hungarian cohort of patients to investigate whether any alterations contribute to elevated thrombotic risk.Methods and analysisThis is a case–control study involving newly diagnosed and followed CeD and IBD patients with age-matched and sex-matched non-CeD, non-IBD subjects with an allocation ratio of 1:1:1.After informed consent is obtained, a detailed medical history will be collected, including venous and arterial thrombotic risk factors and medications. Symptoms in CeD patients will be assessed with the Gastrointestinal Symptoms Rating Scale, and disease activity in IBD patients will be determined by disease-specific scores. Dietary adherence will be assessed among CeD patients with a thorough interview together with a measurement of self-reported adherence, dietary knowledge and urine analysis (detection of gluten immunogenic peptides). In addition to routine laboratory parameters, haemorheological (ie, erythrocyte deformability and aggregation, viscosity of whole blood and plasma) and haemostatic parameters (eg, protein C, protein S and antithrombin) with immunological indicators (ie, coeliac-specific serology and antiphospholipid antibodies) will be measured from venous blood for every participant.Primary and secondary outcomes will be haemorheological and haemostatic parameters, respectively. Univariate and multivariate statistics will be used to compare CeD and IBD patients to control subjects. Subgroup analysis will be performed by disease type in IBD, (Crohn’s disease and ulcerose colitis), dietary adherence in CeD, and disease activity in IBD and CeD.Ethics and disseminationThe study was approved by the Regional and Local Research Ethics Committee, University of Pécs (Ref. No. 6917). Findings will be disseminated at research conferences and in peer-reviewed journals.Trial registration numberISRCTN49677481.

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