A narrative review of sex-related differences in inflammatory bowel disease-associated cardiovascular and thrombotic risk: epidemiology, mechanisms, and prevention strategies.

Background and Objective: Inflammatory bowel disease (IBD) is increasingly recognized as a systemic inflammatory disorder associated not only with gastrointestinal morbidity but also with arterial atherosclerotic cardiovascular disease (ASCVD) and venous thromboembolism (VTE). Although men generally retain a higher absolute cardiovascular event burden in the general population, women with IBD, particularly younger and premenopausal women, may experience a disproportionate relative increase in selected arterial events. This narrative review aimed to summarize sex-related differences in IBD-associated cardiovascular and thrombotic risk, with emphasis on epidemiology, biological mechanisms, and prevention strategies. Methods: Targeted searches of PubMed/MEDLINE and major society statements were performed, prioritizing meta-analyses, population-based cohorts, sex-stratified studies, consensus documents, mechanistic studies, and selected clinical trials. Evidence was synthesized narratively across four domains: epidemiology of ASCVD and VTE in IBD, sex-specific risk patterns, mechanistic pathways linking intestinal inflammation to vascular dysfunction and thrombosis, and practical prevention approaches. Key Content and Findings: Available evidence supports a modest but significant increase in arterial cardiovascular risk in IBD and a more pronounced increase in VTE risk, particularly during active disease, hospitalization, corticosteroid exposure, and sustained systemic inflammation. Sex-related differences appear most relevant for relative arterial risk estimates, while interpretation must distinguish relative from absolute risk. Proposed mechanisms include endothelial and microvascular dysfunction, platelet activation, increased thrombin generation, altered estrogen signaling, estrogen receptor beta dysregulation, menopause, exogenous hormone exposure, and the potential contribution of the estrobolome as a gut microbiome-estrogen interface. Additional modifiers include obesity, smoking, pregnancy/postpartum status, and advanced therapies such as JAK inhibitors, whose cardiovascular safety profile remains heterogeneous. Conclusions: Cardiovascular prevention in IBD should integrate conventional risk-factor assessment with IBD-specific risk enhancers, careful interpretation of sex-stratified data, aggressive inflammatory control, steroid-sparing treatment, individualized hormone assessment, and appropriate thromboprophylaxis. Future studies should report both relative and absolute cardiovascular risk and better define sex-specific mechanisms and prevention pathways in IBD.