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

## TL;DR

People with inflammatory bowel disease have a higher risk of cardiovascular disease, and this risk is partly explained by inflammation.

## Contribution

This study identifies inflammation as a key mediator linking inflammatory bowel disease to cardiovascular disease.

## Key findings

- IBD patients had increased risk for CVD outcomes like heart failure and arrhythmias.
- Inflammatory biomarkers mediated a larger proportion of risk in Crohn’s disease compared to other IBD types.
- Reducing inflammation could help lower cardiovascular risk in IBD patients.

## Abstract

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.

To evaluate the associations between IBD and incident CVD and examine the mediating role of inflammatory biomarkers.

A sex- and age-matched cohort study.

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.

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.

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.

Association of inflammatory bowel disease with cardiovascular disease, and the mediating role of inflammation

Based on data from the UK Biobank cohort, we conducted a matched-cohort study. The study observed higher risks of any incident cardiovascular disease (CVD) and its wide range entities, including ischemic heart disease, heart failure, arrhythmias, atrial fibrillation, other supraventricular arrhythmia, and venous thromboembolism. Inflammatory mediation appeared to be higher in Crohn’s disease (CD) than in ulcerative colitis (UC) or IBD-unclassified (IBD-U), with the low-grade inflammation score (INFLA score, a comprehensive composite index assessing inflammation) mediating 14.5%, 10.5%, and 5.3% of the association, respectively. Also, the mediation proportion was generally higher in some CVD subtypes (i.e., ischemic heart disease, heart failure, and arrhythmias) than in venous thromboembolism. The study indicated that IBD was associated with an increased risk of CVD, highlighting the complex pathophysiological process between them. It also suggested that reducing inflammatory level may lower cardiac burden in patients with IBD.