The Incidence of Arterial Thromboembolic Diseases in Inflammatory Bowel Disease: A Population-Based Study

doi:10.1016/j.cgh.2007.09.016

Clinical Gastroenterology and Hepatology

Volume 6, Issue 1, January 2008, Pages 41-45

https://doi.org/10.1016/j.cgh.2007.09.016 Get rights and content

Background & Aims: We aimed to determine if there was an increased risk for arterial thromboembolic diseases (ATED) in inflammatory bowel disease (IBD). Methods: We used the University of Manitoba IBD Epidemiology Database (1984–2003) (n = 8060), and a matched cohort (n = 80,489) drawn from the Manitoba Health administrative database. Each IBD case and non-IBD control has a unique personal health identification number and each health system encounter is identified by a diagnostic code (International Classification of Diseases, 9th revision [ICD-9]). We compared the IBD with the non-IBD cohorts for the incidence of ATED events following the index case diagnosis of IBD including: ischemic heart disease (ICD-9-Clinical Modification [CM] codes 410–414.x), cerebrovascular disease (ICD-9-CM codes 430–436.x), and undifferentiated ATED (ICD-9-CM codes 440.x and 445.x). The incidence rate of 1 episode or more of these diseases was assessed in relation to the individual person-years of follow-up evaluation. Incidence rates and incidence rate ratios (IRRs) were computed for all IBD, and stratified by IBD diagnosis, sex, and age. Results: For ischemic heart disease, risk was increased for all IBD (IRR, 1.26; 95% confidence interval [CI], 1.11–1.44) and was increased for Crohn’s disease and ulcerative colitis in both, males and females. For cerebrovascular disease, only Crohn’s disease was associated with increased risk (IRR, 1.32; 95% CI, 1.05–1.66), and for undifferentiated ATED only females (IRR, 1.96; 95% CI, 1.24–3.10) and those aged 0 to 39 years (IRR, 19.95; 95% CI, 1.81–219.92) and 40 to 59 years (IRR, 3.17; 95% CI, 1.27–7.91) had significantly increased risks. Conclusions: IBD patients are more likely to have cardiac ATED, regardless of diagnosis or sex. Crohn’s disease has an increased risk for cerebral ATED. Smoking, the prothrombotic aspect of systemic inflammation, or a genetic predisposition may contribute to the risk.

Section snippets

Data Sources

Data for this study were derived from the Manitoba Health administrative databases. Manitoba Health provides universal health insurance for Manitoba residents, which includes coverage for physician and hospital services. Manitoba Health maintains computerized records that are based on the use of health care services by individuals in the province, including admission to a hospital and physician visits. For each physician service the patient’s identification, the date of service, the diagnosis

Results

The characteristics of the study population are presented in Table 1, and the characteristics of those who were diagnosed with ATED are shown in Table 2. The incidence rates per 10,000 person-years among the IBD subjects were 21.6 for ischemic heart disease ATEDs (ICD-9-CM codes 410–414), 13.1 for cerebrovascular ATEDs (ICD-9-CM codes 430–436), and 2.5 for undifferentiated ATEDs (ICD-9-CM codes 444 and 445) (Table 3). For ischemic heart disease events there was a significantly increased risk

Discussion

An increased association of IBD and arterial thromboses was raised in case reports and case series more than 2 decades ago.16, 17, 18 The issue of premature atherosclerosis in young persons with Crohn’s disease recently was raised in a report of lower-extremity arterial occlusions in young patients with Crohn’s colitis and premature atherosclerosis.¹⁹ An increased potential for arterial vascular disease in IBD has been corroborated by others.²⁰ This group²⁰ recently has investigated the early

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Patients with inflammatory bowel disease are at increased risk of atherothrombotic disease: A systematic review with meta-analysis
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Patients with inflammatory bowel disease (IBD) are known to be at increased risk for venous thrombosis, while their risk for arterial ischemic events is debated. The purpose of this study was to conduct a systematic review of the published literature on the risk of myocardial infarction (MI) in IBD patients and to identify any potential risk factors.
The present study was performed according to PRISMA, with a systematic search on PubMed, Cochrane, and Google Scholar. Risk of MI was the primary end point, while all causes of death and stroke were secondary endpoints. Both univariate and multivariate pooled analysis were performed.
An overall population of 515,455 controls and 77,140 persons with IBD (26,852, 34.8% Crohn's disease, CD and 50,288, 65.2% ulcerative colitis, UC) was included. Mean age was similar across controls and IBD. Persons with CD and UC had lower rates of hypertension (14.5% vs. 14.6% vs. 25%), diabetes (2.9% vs. 5.2% vs. 9.2%) and dyslipidaemia (3.3% vs. 6.5% vs. 16.1%) compared to controls. Smoking did not significantly differ (17% vs. 17.5% vs. 10.6%). Pooled results of multivariate adjustment showed that, after a 5 years-follow-up, both CD and UC were at increased risk of MI (respectively HR 1.36 [1.12–1.64] and HR 1.24 [1.05–1.46]), of death (HR 1.55 [1.27–1.90] and HR 1.29 [1.01–1.64]), and of other CV disease as stroke (HR 1.22 [1.01–1.49] and HR 1.09 [1.03–1.15], all 95% CI).
Persons with IBD are at increased risk of MI, despite a lower prevalence of the classic risk factors for MI (hypertension, diabetes, dyslipidemia).
Novel long non-coding RNAs of relevance for ulcerative colitis pathogenesis
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The study aimed to identify yet unknown and uncharacterized long non-coding RNAs (lncRNAs) in treatment-naïve ulcerative colitis (UC), and to define their possible roles in UC pathogenesis. For that purpose, accurate quantification methods for lncRNA transcript detection, multiple and “stringent” strategies were applied. New insights in the regulation of functional genes and pathways of relevance for UC through expression of lncRNAs are expected.
The study was based on sequencing data derived from a data set consisting of treatment-naïve UC patients (n = 14) and control subjects (n = 16). Two complementary aligners were used to identify lncRNAs. Several different steps were used to validate differential expression including plotting the reads over the annotation for manual inspection. To help determine potential lncRNA involvement in biological processes, KEGG pathway enrichment was done on protein-coding genes which co-expressed with the lncRNAs.
A total of 99 lncRNAs were identified in UC. The lncRNAs which were not previously characterized (n = 15) in UC or other autoimmune diseases were selected for down-stream analysis. In total, 602 protein-coding genes correlated with the uncharacterized lncRNAs. KEGG pathway enrichment analysis revealed involvement of lncRNAs in two significantly enriched pathways, lipid and atherosclerosis, and T-cell receptor signaling.
This study identified a set of 15 yet uncharacterized lncRNAs which may be of importance for UC pathogenesis. These lncRNAs may serve as potential diagnostic biomarkers and might be of use for the development of UC treatment strategies in the future.
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Recent literature has shown an association between atherosclerotic cardiovascular disease and inflammatory bowel disease, potentially mediated through chronic inflammatory pathways. However, there is a paucity of data demonstrating this relationship among young patients with premature atherosclerotic cardiovascular disease.
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We identified 147,600 patients and 9485 patients with premature and extremely premature atherosclerotic cardiovascular disease, respectively. Compared with controls, there was a higher prevalence of overall inflammatory bowel disease among premature (0.96% vs 0.84%; odds ratio [OR] 1.14; 95% confidence interval [CI], 1.08-1.21) and extremely premature (1.36% vs 0.75%; OR 1.82; 95% CI, 1.52-2.17) patients. After adjustment, these associations attenuated in both premature and extremely premature groups (OR 1.07; 95% CI, 1.00-1.14 and OR 1.61; 95% CI, 1.34-1.94, respectively).
Inflammatory bowel disease is associated with higher odds of extremely premature atherosclerotic cardiovascular disease, especially for those age ≤40 years. With increasing age, this risk is attenuated by traditional cardiometabolic factors such as obesity, hypertension, diabetes, smoking, and dyslipidemia. Prospective studies are needed to assess the role of early intervention to decrease cardiovascular risk among young patients with inflammatory bowel disease.
Inflammatory Bowel Disease as a Precondition for Stroke or TIA: A Matter of Crohn's Disease Rather than Ulcerative Colitis
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Citation Excerpt :
Although we depicted a higher general risk of stroke or TIA in patients with IBD, after separate analyses, only CD was identified as having a strong association with the occurrence of CVEs within 15 years of diagnosis.3,8–10 In a comparable study in which 75% of participants were observed for a minimum of 10 years, Bernstein et al. also demonstrated an increased risk of CVE in connection with CD rather than UC.11 These findings could potentially be explained by differences between the two diseases.
As a chronic systemic inflammation may be associated with an increased risk of vascular events, the aim of the present study was to assess the incidence of stroke and transient ischemic attack (TIA) in patients with inflammatory bowel disease over a period of 15 years.
This cohort study included patients for whom the initial diagnosis of an inflammatory bowel disease (IBD) (Crohn's disease: CD and ulcerative colitis: UC) was documented anonymously between 2000 and 2015 in 1,262 general practices in Germany. IBD patients were matched to patients without IBD using propensity scores based on age, sex, physician, co-diagnoses and co-therapies. Cox regression models were used to study the incidence of stroke and TIA as a function of CD and UC.
Each of the matched groups included 11,947 participants. In the IBD group, 43.5% had CD and 56.5% UC respectively. Higher incidences of both stroke and TIA were detected for IBD (stroke: 279.0 versus 222.6 cases per 100,000 patient years, HR 1.30, p=0.011; TIA: 203.1 versus 141.1 cases per 100,000 patient years, HR 1.42, p=0.006). Stroke and TIA incidences (cases per 100,000 patient years) were higher than in controls (stroke: 314.7 versus 204.5, HR: 1.50, p=0.013; TIA: 183.8 versus 95.3, HR: 1.93, p=0.004) in CD patients only. No relevant differences in incidences were found for patients with UC.
While CD turned out to be a relevant precondition for stroke or TIA, this was not the case for UC.
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: Supported in part by a Crohn’s and Colitis Foundation of Canada Research Scientist Award (C.N.B.).

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Original article—alimentary tractThe Incidence of Arterial Thromboembolic Diseases in Inflammatory Bowel Disease: A Population-Based Study

Section snippets

Data Sources

Results

Discussion

Gastroenterology

Mayo Clin Proc

Gastroenterology

Mayo Clin Proc

Am J Gastroenterol

Neurol Sci

Am J Gastroenterol

The incidence of venous thromboembolic disease among patients with IBD: a population-based study

Thromb Haemost

Hospitalization-based major comorbidity of inflammatory bowel disease in Canada

Can J Gastroenterol

Mutations in clotting factors and inflammatory bowel disease

Am J Gastroenterol

Crohn’s disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort

Gut

Divergent patterns of total and cancer mortality in ulcerative colitis and Crohn’s disease patients: the Florence IBD study 1978-2001

Gut

Survival and cause specific mortality in patients with inflammatory bowel disease: a long term outcome study in Olmsted County, Minnesota, 1940–2004

Gut

Meta-analysis: mortality in Crohn’s disease

Aliment Pharmacol Ther

A population-based case control study of potential risk factors for IBD

Am J Gastroenterol

Registries and administrative data: organization and accuracy

Med Care

Original article—alimentary tract
The Incidence of Arterial Thromboembolic Diseases in Inflammatory Bowel Disease: A Population-Based Study