Original Article
Inflammatory bowel diseases increase future ischemic stroke risk: A Taiwanese population-based retrospective cohort study

https://doi.org/10.1016/j.ejim.2014.05.009Get rights and content

Highlights

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    The overall incidence of ischemic stroke was 1.12-fold higher among the IBD cohort.

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    Significantly increased risk with the increased frequency of IBD exacerbation and hospitalization.

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    The CD patients exhibited a higher risk of developing ischemic stroke.

Abstract

Background and aims

This cohort study assessed the association between inflammatory bowel disease (IBD) and the risk of future ischemic stroke.

Methods

The IBD cohort comprised adult patients (≥ 20 years old) who had received either ambulatory or inpatient care between 1998 and 2011 and IBD-free controls were randomly selected from the general population and frequency matched according to age, sex, and index year (included 18,392 patients with IBD and 73,568 control patients). Both cohorts with ischemic stroke before the index date and the ischemic stroke cases diagnosed within one year after the index date were excluded. We observed the study patients until the incidence of ischemic stroke, death, withdrawal from the insurance program, or they were lost to follow-up, or the end of 2011.

Results

The risk of ischemic stroke was 1.12-fold (95% CI, 1.02–1.23) higher among the IBD cohort than among the non-IBD cohort. Compared to the subjects without IBD, the adjusted HR of ischemic stroke was 1.15 (95% CI 1.04–1.28) in the Crohn's disease (CD) patients and 1.01 (95% CI 0.84–1.21) in the ulcerative colitis (UC) group. The risk of developing ischemic stroke significantly increased with the increased frequency of IBD exacerbation and hospitalization. Furthermore, the adjusted HR among the CD patients increased in conjunction with the number of medical visits, from 1.07 to 6.36 and the adjusted HR among the UC patients also increased in conjunction with the number of medical visits, from 1.11 to 2.10.

Conclusions

IBD exhibited an increased risk of developing ischemic stroke.

Introduction

Stroke results in the sudden loss of neurological function caused by a disruption of blood flow to the brain. Previous studies have reported that stroke is the second leading cause of death worldwide [1], [2], [3]. In Taiwan, ischemic stroke is the major type of stroke [3], [4], which is similar to reports from the rest of the world. Stroke is also among the leading causes of disability in adults [5]. The identification of risk factors for stroke is crucial for the primary and secondary prevention of stroke.

The crucial role of inflammatory mechanisms in the progression of atherosclerosis has promoted many studies focusing on whether diseases characterized by chronic inflammation, including inflammatory bowel disease (IBD), carry an increased risk of cardiovascular disease [6], [7]. Numerous previous studies have reported an increased incidence of stroke and myocardial infarction (MI) in patients with rheumatoid arthritis, psoriasis, and systemic lupus erythematosus [8], [9], [10], but studies on the risk of atherothrombotic disease among patients with IBD are inconclusive [11], [12], [13], [14], [15]. However, recent evidence showed that IBD is associated with an increased risk of stroke and MI [16], [17].

IBD mainly comprises the following two chronic intestinal disorders: Crohn's disease (CD) and ulcerative colitis (UC) in addition to microscopic colitis. IBD affects approximately 1.4 million people in the United States [18] and approximately 2.2 million people in Europe [19]. Chuang et al. recently reported that IBD is still relatively uncommon in Taiwan, but the incidence and prevalence rates are increasing [20]. The linkage between IBD and atherothrombotic disease could have a substantial influence on patient management. Therefore, we conducted this nationwide population-based retrospective cohort study to assess the association between IBD and the risk of future ischemic stroke among adult patients in Taiwan. We hypothesize that IBD is associated with the development of acute ischemic stroke and collected the study data from Taiwan's National Health Insurance Research Database (NHIRD) among adult patients (≥ 20 years old).

Section snippets

Data sources

The National Health Insurance program has been implemented in Taiwan since 1995 and provides medical cover for approximately 99% of Taiwan's population (23.74 million people) [1]. The National Health Research Institutes (NHRI) of Taiwan established the National Health Insurance Research Database (NHIRD), which contains registration files and original claims data for reimbursement. The NHRI manages the annual claims data in the NHIRD and has established electronic datasets for administrative and

Results

The IBD and non-IBD cohorts comprised 18 392 and 7 3568 cases, respectively.

Among the study patients, 64.5% were younger than 50 years, and 54.9% were women (Table 1). The mean ages of the IBD and non-IBD cohorts were 44.8  ±  16.6 and 44.5  ±  16.8 years, respectively. Compared with the non-IBD cohort, the IBD cohort had a higher prevalence of hypertension (22.7% versus 19.0%, P  <  0.001), diabetes (9.73% versus 8.11%, P  < 0.001), CAD (12.2% versus 8.66%, P  <  0.001), and cCHF (9.67% versus 7.80%, P  < 

Discussion

This study shows that the IBD cohort was at a 1.12-fold (95% CI, 1.02–1.23, Table 2) higher risk of developing subsequent ischemic stroke than the comparison cohort after adjusting for sex, age, and comorbidities. Comorbidities such as hypertension, diabetes, CAD, CHF, peripheral arterial disease, atrial fibrillation, and hyperlipidemia were significant factors associated with the occurrence of ischemic stroke. Compared with the UC patients in this study, the CD patients had a higher risk of

Author contribution

Wei-Shih Huang, Chun-Hung Tseng, and Chia-Hung Kao are responsible for the study design, coordination and drafted the manuscript. Cheng-Li Lin, Pei-Chun Chen, and Fung-Chang Sung collected data and performed analysis. Chon-Haw Tsai, Cheng-Li Lin, and Chia-Hung Kao provided some intellectual recommendation and reviewed the manuscript. Wei-Shih Huang, Chun-Hung Tseng, Cheng-Li Lin, and Chia-Hung Kao wrote the final version of the manuscript. All authors read and approved the final manuscript.

Conflicts of interests

All authors declare that there were no actual or potential conflicts of interest in this study.

Acknowledgment

This work was supported by the Aim for the Top University Plan of the National Chiao Tung University and Ministry of Education, Taiwan, R.O.C., National Science Council, Taiwan (NSC 99-2314-B-039-016-MY2), the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (DOH101-TD-B-111-004), Health and welfare surcharge of tobacco products, China Medical University Hospital Cancer Research Center of Excellence (MOHW103-TD-B-111-03, Taiwan), and the Tseng-Lien Lin

References (34)

  • 2010-statistics of cause of death

  • F.I. Hsieh et al.

    Get with the guidelines—stroke performance indicators: surveillance of stroke care in the Taiwan stroke registry: get with the guidelines—stroke in Taiwan

    Circulation

    (2010)
  • D. Leys

    Atherothrombosis: a major health burden

    Cerebrovasc Dis

    (2001)
  • R. Ross

    Atherosclerosis—an inflammatory disease

    N Engl J Med

    (1999)
  • G.K. Hansson

    Inflammation, atherosclerosis, and coronary artery disease

    N Engl J Med

    (2005)
  • O. Ahlehoff et al.

    Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study

    J Intern Med

    (2011)
  • C. Meune et al.

    Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies

    Rheumatology (Oxford)

    (2009)

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    Wei-Shih Huang and Chun-Hung Tseng contribute equally.

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