Histologic remission and major adverse cardiovascular events in patients with inflammatory bowel disease: a nationwide cohort study

Abstract Background Inflammatory bowel disease (IBD) is associated with cardiovascular diseases (CVDs). However, the impact of histologic and clinical activity on this association remains unclear. Methods We conducted a nationwide cohort study in Sweden involving 59,168 IBD patients diagnosed in 1969-2017 with histologic evaluation (i.e., histologic inflammation vs. remission) and 91,800 patients diagnosed in 1969-2020 with assessment of clinical activity (i.e., clinically active vs. quiescent IBD) in 2006-2021, followed until 31 December 2021. The primary outcome was incident major adverse cardiovascular events (MACE), a composite outcome encompassing ischemic heart disease (myocardial infarction), stroke (hemorrhagic or ischemic stroke), and heart failure. Cox proportional hazards model was applied to estimate adjusted hazard ratios (aHRs) of MACE and its subcomponents within 2 years after documented histologic inflammation (vs. remission) or clinically active IBD (vs. quiescent IBD). Results An increased 2-year risk of MACE was observed after histologic inflammation (n=868, incidence rate IR: 86.3/10,000 person-years) than after remission (n=558, IR=71.3), corresponding to one extra MACE per 331 IBD patients over 2 years after histologic inflammation (aHR=1.16 95%CI: 1.04 to 1.30). This excess risk was similar in CD (aHR=1.30 1.03 to 1.64) and UC (aHR=1.13 1.01 to 1.27). Histological inflammation was associated with an increased risk of ischemic heart disease (aHR=1.16 1.00 to 1.34), myocardial infarction (aHR=1.36 1.12 to 1.64), ischemic stroke (aHR=1.31 1.06 to 1.62), and heart failure (aHR=1.35 1.15 to 1.60), but not significantly so for hemorrhagic stroke (aHR=1.22 0.80 to 1.85). Compared to quiescent IBD, clinically active IBD was also significantly related to increased risks of MACE (IR: 131.4 vs. 93.7 per 10,000 person-years; aHR=1.54 1.46 to 1.63) as well as its subcomponents. Even in patients with clinically quiescent IBD, histologic inflammation was associated with an increased risk of myocardial infarction (aHR=1.29 1.06 to 1.58) and heart failure (aHR=1.19 1.00 to 1.43). Conclusion Histologic and clinical activity of IBD were associated with an increased MACE, including myocardial infarction, ischemic stroke, and heart failure. These findings suggest that improved disease control could provide opportunities to reduce MACE risk in IBD.