Risk of Cerebrovascular Accidents and Ischemic Heart Disease in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

doi:10.1016/j.cgh.2013.08.023

Clinical Gastroenterology and Hepatology

Volume 12, Issue 3, March 2014, Pages 382-393.e1

https://doi.org/10.1016/j.cgh.2013.08.023 Get rights and content

Background & Aims

Inflammatory bowel disease (IBD) is associated with an increased risk of venous thromboembolic disease. However, it is unclear whether IBD modifies the risk of arterial thromboembolic events, including cerebrovascular accidents (CVA) and ischemic heart disease (IHD).

Methods

We performed a systematic review and meta-analysis of cohort and case-control studies that reported incident cases of CVA and/or IHD in patients with IBD and a non-IBD control population (or compared with a standardized population). We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs).

Results

We analyzed data from 9 studies (2424 CVA events in 5 studies, 6478 IHD events in 6 studies). IBD was associated with a modest increase in the risk of CVA (5 studies; OR, 1.18; 95% CI, 1.09–1.27), especially among women (4 studies; OR, 1.28; 95% CI, 1.17–1.41) compared with men (OR, 1.11; 95% CI, 0.98–1.25), and in young patients (<40–50 y old). The increase in risk was observed for patients with Crohn's disease and in those with ulcerative colitis. IBD also was associated with a 19% increase in the risk of IHD (6 studies; OR, 1.19; 95% CI, 1.08–1.31), both in patients with Crohn's disease and ulcerative colitis. This risk increase was seen primarily in women (4 studies; OR, 1.26; 95% CI, 1.18–1.35) compared with men (OR, 1.05; 95% CI, 0.92–1.21), in young and old patients. IBD was not associated with an increased risk of peripheral arterial thromboembolic events. Considerable heterogeneity was observed in the overall analysis.

Conclusions

IBD is associated with a modest increase in the risk of cardiovascular morbidity (from CVA and IHD)—particularly in women. These patients should be counseled routinely on aggressive risk factor modification.

Section snippets

Methods

This systematic review was conducted following guidance provided by the Cochrane handbook²⁰ and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.²¹ The process followed an a priori established protocol.

Search Results

Among 688 unique studies that were identified using our search strategy, 9 studies met the defined inclusion criteria for this meta-analysis (6 case-control and 3 cohort studies).8, 11, 12, 13, 14, 15, 28, 29, 30 Three cross-sectional studies that reported the prevalence of CVA, IHD, and peripheral artery disease in patients with IBD were excluded.31, 32, 33 Figure 1 summarizes the process of study identification, inclusion, and exclusion. These studies cumulatively reported 2424 CVA, 6478 IHD,

Discussion

Previous systematic reviews have not shown a significant association between IBD (CD or UC) and cardiovascular mortality.16, 17, 18 In a recent meta-analysis of cause-specific standardized mortality ratios in population-based and inception cohort studies of patients with IBD, Bewtra et al³⁵ observed that neither CD nor UC were associated with increased cardiovascular mortality in patients with IBD. Although cardiovascular mortality is a hard end point and less prone to ascertainment bias, it

Acknowledgment

S.S. and H.S. contributed equally to this work.

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: This article has an accompanying continuing medical education activity on page e22. Learning Objectives—At the end of this activity, the successful learner will be able to recognize the association between inflammatory bowel diseases and risk of cerebrovascular accidents and ischemic heart disease.

: Conflicts of interest The authors disclose no conflicts.

View full text

Original articleSystematic reviews and meta-analysesRisk of Cerebrovascular Accidents and Ischemic Heart Disease in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Background & Aims

Methods

Results

Conclusions

Section snippets

Methods

Search Results

Discussion

Acknowledgment

Inflammation, atherosclerosis, and coronary artery disease

N Engl J Med

Venous thromboembolism and atherothrombosis: an integrated approach

Circulation

Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies

Ann Rheum Dis

Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus

N Engl J Med

Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies

Arthritis Rheum

Venous thromboembolism in inflammatory bowel disease: an epidemiological review

Am J Gastroenterol

Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study

Lancet

Risk of arterial thrombotic events in inflammatory bowel disease

Am J Gastroenterol

Intra-abdominal venous and arterial thromboembolism in inflammatory bowel disease

Dis Colon Rectum

Increased carotid intima-media thickness in patients with inflammatory bowel disease

Aliment Pharmacol Ther

Disease activity in inflammatory bowel disease is associated with increased risk of myocardial infarction, stroke and cardiovascular death–a Danish nationwide cohort study

PLoS One

Risk of ischemic stroke in patients with Crohn's disease: a population-based nested case-control study

Inflamm Bowel Dis

The incidence of arterial thromboembolic diseases in inflammatory bowel disease: a population-based study

Clin Gastroenterol Hepatol

Inflammatory bowel disease is associated with an increased incidence of cardiovascular events

Am J Gastroenterol

Risk of ischaemic heart disease in patients with inflammatory bowel disease: a nationwide Danish cohort study

Gut

Inflammatory bowel disease is not a risk factor for cardiovascular disease mortality: results from a systematic review and meta-analysis

Am J Gastroenterol

Overall and cause-specific mortality in Crohn's disease: a meta-analysis of population-based studies

Inflamm Bowel Dis

Overall and cause-specific mortality in ulcerative colitis: meta-analysis of population-based inception cohort studies

Am J Gastroenterol

Secular trends in cardiovascular disease mortality, incidence, and case fatality rates in adults in the United States

Am J Med

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Ann Intern Med

Meta-analysis in clinical trials

Control Clin Trials

Measuring inconsistency in meta-analyses

BMJ

Can meta-analyses be trusted?

Lancet

GRADE guidelines: 7. Rating the quality of evidence–inconsistency

J Clin Epidemiol

Original article
Systematic reviews and meta-analyses
Risk of Cerebrovascular Accidents and Ischemic Heart Disease in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis