Association of inflammatory bowel disease with cardiovascular disease, and the mediating role of inflammation: a matched-cohort study

Background: The elevated risk of cardiovascular disease (CVD) in inflammatory bowel disease (IBD) has been increasingly recognized. Although inflammation is implicated in both IBD and CVD, the IBD-CVD association through the mediation of systemic inflammation remains underexplored. Objective: To evaluate the associations between IBD and incident CVD and examine the mediating role of inflammatory biomarkers. Design: A sex- and age-matched cohort study. Methods: Using data from the UK Biobank, the study included 1494 participants with a first-ever diagnosis of IBD from 1999 to the recruitment date (2006-2010), and 14,940 matched reference individuals. The primary outcome was any CVD, whereas secondary outcomes included 7 major CVD categories and 19 specific CVD entities. Fifteen inflammatory biomarkers and indices measured at recruitment were included, serving as proxies of underlying inflammatory status. Cox proportional hazard model estimated the adjusted hazard ratios (HRs) and 95% confidence intervals (CI) of associations between IBD and CVD and between inflammatory biomarkers and CVD. Model-based mediation analyses were conducted to explore the potential mediating role of inflammatory biomarkers in IBD-CVD associations. Results: Compared with reference individuals, patients with IBD had an increased risk of any CVD (HR = 1.34, 95%CI 1.20, 1.49), ischemic heart disease (HR = 1.20, 95%CI 1.02, 1.41), heart failure (HR = 1.61, 95%CI 1.28, 2.02), arrhythmias (HR = 1.34, 95%CI 1.13, 1.59), atrial fibrillation (HR = 1.34, 95%CI 1.11, 1.62), other supraventricular arrhythmia (HR = 1.83, 95%CI 1.12, 2.99), and venous thromboembolism (HR = 1.74, 95%CI 1.38, 2.21). The mediation proportion was generally higher in Crohn's disease and in CVD subtypes (ischemic heart disease, heart failure, and arrhythmias) than in venous thromboembolism. Conclusion: IBD is associated with various CVD outcomes, and inflammatory biomarkers mediate their associations, suggesting that reducing inflammation may help alleviate cardiac burden in patients with IBD.