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Long-term Risk of Stroke in Patients With Inflammatory Bowel Disease: A Population-Based, Sibling-Controlled Cohort
Jiangwei Sun1, Jonas Halfvarson2, Peter Appelros2
1From the Department of Medical Epidemiology and Biostatistics (J.S., D.B., F.E., B.R., J.F.L.), Karolinska Institutet, Stockholm; Department of Gastroenterology (J.H.), and University Health Care Research Center (P.A.), Faculty of Medicine and Health, Örebro University, Sweden; Department of Gastroenterology and Hepatology (F.E.), Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland; Clinical Epidemiology Division (O.O.), Department of Medicine Solna, Karolinska Institutet, Stockholm; Sachs' Children and Youth Hospital (O.O.), Stockholm South General Hospital; Department of Clinical Science and Education Södersjukhuset (O.O.), Karolinska Institutet, Stockholm; Department of Pediatrics (J.F.L.), Örebro University Hospital, Sweden; and Division of Digestive and Liver Disease (J.F.L.), Department of Medicine, Columbia University Medical Center, New York, NY. jiangwei.sun@ki.se.
Insights
Patients with inflammatory bowel disease (IBD) have a higher long-term risk of stroke, particularly ischemic stroke, across all subtypes. This increased risk persists for at least 25 years post-diagnosis, emphasizing the need for ongoing monitoring.
Area of Science:
- Gastroenterology
- Neurology
- Epidemiology
Background:
- Inflammatory bowel disease (IBD) is linked to increased thromboembolic events.
- Long-term stroke risk in IBD patients requires further investigation.
Purpose of the Study:
- To determine if biopsy-confirmed IBD increases the long-term risk of stroke.
- To analyze stroke risk across different IBD subtypes and compare it to matched controls and siblings.
Main Methods:
- A Swedish cohort study (1969-2019) included 85,006 IBD patients and matched controls/siblings.
- Stroke outcomes (overall, ischemic, hemorrhagic) were identified via the National Patient Register.
- Flexible parametric survival models estimated adjusted hazard ratios (aHRs).
Main Results:
- IBD patients had a 13% higher risk of overall stroke (aHR 1.13) compared to references.
- The elevated risk, primarily from ischemic stroke, persisted for 25 years.
- Increased ischemic stroke risk was observed across Crohn's disease, ulcerative colitis, and IBD-unclassified.
Conclusions:
- Patients with IBD face a significantly increased long-term risk of stroke, especially ischemic events.
- This risk is consistent across IBD subtypes and persists for decades.
- Clinical vigilance for cerebrovascular events is crucial in long-term IBD management.
Background And Objectives:
Patients with inflammatory bowel disease (IBD) are at an increased risk of thromboembolic events, but evidence on the long-term risk of stroke remains scarce. We aimed to explore whether patients with a biopsy-confirmed IBD had an increased long-term risk of stroke.
Methods:
This cohort included all patients with biopsy-confirmed IBD in Sweden between 1969 and 2019 and up to 5 matched reference individuals per patient who were randomly selected from the general population and IBD-free full siblings. The primary outcome was incident overall stroke; secondary outcomes were ischemic and hemorrhagic strokes. Stroke was identified from the Swedish National Patient Register by using both primary and secondary diagnoses. Adjusted hazard ratios (aHRs) for stroke were estimated by flexible parametric survival models.
Results:
A total of 85,006 patients with IBD (including Crohn disease [CD, n = 25,257], ulcerative colitis [UC, n = 47,354], and IBD-unclassified [IBD-U, n = 12,395]), 406,987 matched reference individuals, and 101,082 IBD-free full siblings were included in the analysis. We observed 3,720 incident strokes in patients with IBD (incidence rate [IR] 32.6 per 10,000 person-years) and 15,599 in reference individuals (IR 27.7; aHR 1.13, 95% CI 1.08-1.17). The elevated aHR remained increased even 25 years after diagnosis, corresponding to 1 additional stroke case per 93 patients with IBD until then. The excess aHR was mainly driven by ischemic stroke (aHR 1.14; 1.09-1.18) rather than hemorrhagic stroke (aHR 1.06; 0.97-1.15). The risk of ischemic stroke was significantly increased across IBD subtypes (CD [IR 23.3 vs 19.2; aHR 1.19; 1.10-1.29], UC [IR 25.7 vs 22.6; aHR 1.09; 1.04-1.16], and IBD-U [IR 30.5 vs 22.8; aHR 1.22; 1.08-1.37]). Similar results were found when patients with IBD were compared with their siblings.
Discussion:
Patients with IBD were at an increased risk of stroke, especially of ischemic events, irrespective of the IBD subtype. The excess risk persisted even 25 years after diagnosis. These findings highlight the need for clinical vigilance about the long-term excess risk of cerebrovascular events in patients with IBD.
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