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Inflammatory bowel disease linked with increased stroke risk

• By ANI
• Minneapolis
• Jun 16, 2023

News

According to a large national cohort study, patients with inflammatory bowel disease (IBD) were 13% more likely to have a stroke than the general population, even decades after their diagnosis.

From 1969 to 2019, the study included all biopsy-confirmed IBD patients in Sweden, totaling approximately 85,000 people. Jiangwei Sun, PhD, of the Karolinska Institutet in Stockholm, and colleagues reported in Neurologyopens in a new tab or window that the incidence rate of stroke in these patients was 32.6 per 10,000 person-years, compared to 27.7 for matched controls (HR 1.13, 95% CI 1.08-1.17).

The risk persisted 25 years after diagnosis, resulting in one additional stroke for every 93 IBD patients. "Our study is the largest with the longest follow-up so far to investigate stroke risk in IBD patients," the researchers wrote. "These findings highlight the need for clinical vigilance about the long-term excess risk of cerebrovascular events in IBD patients."

The increased risk was driven primarily by ischemic stroke (HR 1.14, 95% CI 1.09-1.18) rather than hemorrhagic stroke (HR 1.06, 95% CI 0.97-1.15), and it was significantly higher across IBD subtypes. According to the study, the risk of Crohn's disease increased by 19% (95% CI 1.10-1.29), ulcerative colitis increased by 9% (95% CI 1.04-1.16), and unclassified IBD increased by 22% (95% CI 1.08-1.37).

The risk persisted 25 years after dChronic systemic inflammation and a shifted microbiota-gut-brain axis are two possible underlying mechanisms for stroke risk in IBD patients, according to the researchers. Chronic inflammation causes endothelial dysfunction, plaque formation, platelet activation and aggregation, and contributes to atherosclerosis and arterial stiffness, according to the researchers.

Disruptions in the microbiota-gut-brain axis have also been linked to neurodevelopmental disorders, neurodegenerative diseases, and stroke via a variety of processes such as modulated blood-brain barrier formation, myelination, microglia maturation, and neuroinflammation. Finally, the researchers noted that IBD patients are more likely to develop blood clots as a result of surgeries, fracture immobilisation, and steroid therapy.

The study discovered that women with IBD had a higher relative risk of stroke (HR 1.20, 95% CI 1.14-1.27) than men (HR 1.06, 95% CI 1.01-1.12). According to the researchers, this could be explained by differences in risk factor profiles, sex hormone-dependent mechanisms, and stroke pathophysiology.

Sun and colleagues also discovered that younger patients had a much higher relative risk of stroke. The risk was more than doubled for those who developed IBD at the age of 17 or younger (HR 2.35, 95% CI 1.52-3.62). Risk decreased with age, implying that traditional cardiovascular risk factors become more prevalent in older patients and may outweigh the risk associated with IBD. Furthermore, the study authors speculated that more severe disease activity in younger-onset IBD patients could contribute to this trend.

In terms of implications, the team stated that "screening and management of traditional stroke risk factors in IBD patients could be more urgent than in the general population to prevent fatal CVD complications."

Furthermore, "for individuals with traditional CVD risk factors, optimal anti-inflammatory therapy aiming at clinical response and remission or even endoscopic healing but with less adverse cardiovascular effects should be encouraged to reduce the excess risk of ischemic stroke," Sun and colleagues suggested.

In the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, they found biopsy-confirmed IBD patients. In addition, the team identified stroke patients and analysed medical records data from the Swedish National Patient Register. The researchers matched the IBD patients with up to five randomly selected individuals from the general population.

The primary outcome was incident overall stroke, with ischemic and hemorrhagic stroke as secondary outcomes. The researchers used flexible parametric survival models to calculate hazard ratios while controlling for factors such as hypertension, diabetes, obesity, dyslipidemia, chronic kidney disease, and chronic obstructive pulmonary disease. In order to assess any familial factors, the researchers also performed an analysis comparing stroke risk in IBD patients with their IBD-free siblings. Sun and colleagues stated that the sibling comparison confirmed the main findings.

The study's limitations, according to the researchers, included a lack of complete data on lifestyle factors that can contribute to stroke risk, such as smoking and alcohol consumption. During the study period, the diagnostic criteria for IBD and stroke changed, which may have influenced the associations. Furthermore, the study lacked data on inflammatory markers such as C-reactive protein. The researchers also cautioned that the findings might not be applicable in other settings due to differences in the incidence and prevalence of IBD and stroke across countries, regions, and ethnicities, as well as the fact that the Swedish healthcare system provides universal access "practically free of charge."