Long-term Risk of Stroke in Patients With Inflammatory Bowel Disease

Abstract

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 biopsy-confirmed IBD patients in Sweden between 1969 and 2019, as well as up to five matched reference individuals per patient that were randomly selected from the general population and IBD-free full siblings. Primary outcome was incident overall stroke; secondary outcomes were ischaemic and hemorrhagic stroke. 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’s 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 IBD patients (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 one additional stroke case per 93 IBD patients until then. The excess aHR was mainly driven by ischaemic stroke (aHR=1.14; 1.09-1.18) rather than hemorrhagic stroke (aHR=1.06; 0.97-1.15). The risk for ischaemic 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 IBD patients were compared with their siblings.Discussion:Patients with IBD were at an increased risk of stroke, especially of ischaemic 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 IBD patients.

Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study

“…A similar association has also been observed in a retrospective multicenter cohort study in China recently [7]. In addition, the potential association was further substantiated via some other observational studies and meta-analyses [8][9][10][11].…”

Association between inflammatory bowel disease and risk of stroke: a systematic review and meta-analysis of cohort studies

“…All in all, compared with the article of Singh et al (23), the other three articles (20)(21)(22) increased the number of cohort studies and expanded the scope of the population, making their conclusions more credible and increasing the scope of application of the conclusions. However, compared with the previous four articles, our research has the largest number of cohort studies (n = 12) and the largest sample size (n = 4,495,055), especially by including newer cohort studies (26, [34][35][36]43) published in 2021 and 2023, and a more thorough statistical analysis was conducted (e.g., preselected subgroup analyses of the types of IBD, sex, age, race/ethnicity, and duration of follow-up were conducted, and the Egger test was used to evaluate publication bias). Although the findings of our research are in line with the previously published meta-analyses on IBD and stroke, based on these advantages, our study provides relatively strong evidence that IBD is significantly associated with an increased risk of stroke.…”

“…However, the studies we included did not uniformly adjust all confounding factors, which may make the results difficult to interpret or confound associations. Third, most of the articles included in the discussion highlighted the relationship between IBD subtypes and stroke risk, however, only two articles (35,37) discussed the relationship between IBD subtypes and stroke subtypes. There is a need for more research to confirm the specific relationship between the IBD subtype and stroke subtype.…”

“…Two of the articles (27, 29) did not classify IBD as CD or UC. While only four articles (28,31,35,37) defined the type of stroke. The studies were conducted in different regions, with eight studies (26,27,29,32,33,(35)(36)(37)(38)(39) being conducted in Europe, one study in North America (28), and three studies in Asia (30,31,34,40,41).…”

“…While only four articles (28,31,35,37) defined the type of stroke. The studies were conducted in different regions, with eight studies (26,27,29,32,33,(35)(36)(37)(38)(39) being conducted in Europe, one study in North America (28), and three studies in Asia (30,31,34,40,41). According to the quality evaluation of the Newcastle-Ottawa Scale (NOS) results, three articles were of medium quality and nine articles were of high quality (see Supplementary Table 4).…”