Prevalence of cerebrovascular accidents in patients with ulcerative colitis in a single academic health system

In this large retrospective review of records from a single health system, we found that the prevalence of stroke was higher in our cohort of UC patients than in Minnesota and the US as a whole. The prevalence of stroke in all patients with UC increased with age and the most common stroke subtype was ischemic (70%). The predominantly ischemic nature of the infarction in our dataset is consistent with most studies. However, most of the literature on stroke in patients with IBD has presented stroke as a problem in younger, otherwise healthy patients with severe IBD.23. In contrast, our study found that traditional risk factors for stroke are common in UC. The fact that our study captured a significant degree of UC cases in the community (outside the tertiary center) may explain this difference.

Stroke localization patterns are important in understanding the underlying pathophysiology. A relatively recent review article demonstrated that the majority of strokes identified in patients with IBD occurred in the left or right middle cerebral artery, making anterior circulation events the most commonly affected area, similar to the population. general11,15,16. A small series of patients with CD identified recurrent strokes of the posterior circulation, but the three cases described were derived from patients with recurrent strokes, which may have led to bias in the selection of patients with a predilection for this area.17. In future studies, brain imaging with vascular reconstruction should be included for all IBD patients experiencing CVA, to better inform this issue. Although it would have been ideal to classify strokes according to the TOAST criteria, the data were not available in the EMR to do so. This would have informed more about the mechanism of strokes in IBD and should be the focus of future studies. The data we had matched with the AHA and CDC data and they made a perfect comparison. Current AHA and CDC data do not include TOAST classification18.

The prevalence of stroke increased with age in patients with IBD, as in the general population. The unexpected finding was the high prevalence of stroke in postmenopausal women with UC. This phenomenon was even more pronounced in women older than 80 years with a much higher prevalence of stroke than the general population of the same age, and more than double the number of strokes observed in elderly women with CD. The prevalence of stroke in men with UC was not significantly increased compared to the general population. The presence of atrial fibrillation and cancer increased with age, but its prevalence was similar between men and women with UC and with CD, so it could not explain why older women with UC had an increase in strokes. This finding contrasts with previous work that showed that younger women with UC had a higher risk.3.14. Specifically, Ha et al. compared women with IBD (UC and CD combined) under the age of 40 with age-matched healthy controls and found that young women with IBD had an increased risk of stroke3. Variations in hormone levels and/or varying degrees of other sex-specific cumulative risk factors, such as hormonal contraceptive use, may be important factors contributing to this finding. Other researchers have shown that women with IBD are at increased risk of cardiovascular disease, and it is hypothesized that hormonal variations may impart a degree of this risk.7,8,13,19. Possible explanations are hormonal imbalance, inflammation, and endothelial dysfunction.twenty. Thus, estrogen has myriad effects on cardiovascular health as women age, and this dynamic may persist and possibly be exacerbated in the setting of IBD.twenty-one. This is evidenced in the literature supporting a role for estrogen in modulating TNF-alpha in relation to inflammation and interactions within the gut microbiome.22. Furthermore, murine studies have shown that estradiol downregulates TNF-alpha and thus protects against acute colitis.23. These findings represent an intriguing avenue of investigation to further link postmenopausal women to IBD, variations in hormone levels, and increased cerebrovascular risk. Due to the retrospective nature of this research, the impact of other risk factors for stroke, such as physical activity, BMI, and cholesterol levels, was not studied. A prospective study will be needed to further elucidate these and other important stroke risks in patients with IBD.

Limitations of our study include both its retrospective nature and the lack of correlative data to indicate the degree of disease activity in IBD patients at the time of stroke. Also, more generally, our data did not capture personal history of thrombophilia, smoking history, immobilization, recent surgery, use of central venous catheters, VTE prophylactic measures, IBD medications, and overall compliance. Missing data and differential loss to follow up may be products of our retrospective design. Our strict definition of stroke prioritized specificity over sensitivity and might have resulted in a lower stroke detection rate in our female UC and CD cohorts. However, an artificially low stroke detection rate should have favored the hypothesis that thromboembolism would not be increased in both cohorts, suggesting that our findings are not spurious. Furthermore, IBD disease activity, as illustrated by serum C-reactive protein (CRP) levels, faecal calprotectin levels, or better yet, endoscopic impression would allow inferences to be made about the degree of inflammation and thrombotic risk. This is important, as while latent disease poses a measurable degree of risk, active flares of IBD carry the greatest risk of VTE spread, atrial fibrillation, and stroke.12.24. In addition, increased disease activity is also linked to an increased risk of heart attack, stroke, and cardiovascular-related death, with elevated CRP levels acting as a proxy for disease activity.25. Finally, while it is important that we incorporate active cancer and atrial fibrillation, a more comprehensive covariate model including additional known risk factors for CVA may have produced a more comprehensive analysis.

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