Dissecting the Complexity of Inflammatory Bowel Disease (IBD) A Prospective Study With Focus on Cardiovascular Risk

Emerging evidence points to shared pathophysiological mechanisms between IBD and Cardiovascular disease (CVD), including genetic overlap (e.g., NOD2, CDKN2B, stromelysin, and ApoE polymorphisms), shared environmental triggers like smoking, and convergent immune pathways Disruption of both intestinal epithelial and vascular endothelial barriers through cytokines like TNF-a may provide a mechanistic link between gut inflammation and vascular pathology. In addition, gut microbiota alterations commonly seen in IBD have been implicated in the pathogenesis of cardiovascular conditions such as atherosclerosis.

There is still an unmet need to evaluate the real amount of CV risk in patients with IBD because of the lack of prospective trials, and the limitation of the available CV risk scores designed for an older background population compared to the patients with IBD. In addition, there is a lack of a systematic and combined evaluation of other possible shared risk factors, such as genetic polymorphisms or dysbiosis, and more importantly, the need to evaluate the full systematic dataset prospectively and with a hypothesis-free powerful methodology, such as artificial intelligence (AI)-driven algorithms.

Our first objective is to prospectively evaluate the occurrence of MACEs in a large cohort (±300) of IBD patients enrolled within the Unit of Gastroenterology of the IRCCS San Donato Policlinic, San Donato Milanese (Mi), and followed for 2 years. The occurrence of MACEs will be compared as a whole or individually with those of an age/gender-matched cohort under follow-up at the Unit of Cardiology of the same Institution in the CV PREVITAL study (NCT053399841). The occurrence of the MACEs in IBD patients will be evaluated by the PI and collaborators during the periodic control visit that will occurred at least after one and 2 years since the enrolling in this study, but that usually occur also more frequently (every 3-6 months) according to the underlying condition of IBD.

The secondary objectives will be to correlate the clinical characteristics of IBD patients (disease activity, therapy, etc.) and to undertake an extensive multi-omics, metabolic, and histological evaluation to identify additional risk factors which might increase the occurrence of MACES as compared to control population.