Abstract Background Emerging evidence suggests that coagulation factors may play a unique role in the progression of coronary artery disease (CAD), potentially through its effects on thrombosis and inflammation. A recent study has highlighted that specific coagulation factors, particularly coagulation factor XI (F11), may confer protective effects on cardiac function through mechanisms independent of their role in coagulation 1,2. However, the prognostic significance of coagulation factors in CAD patients remains underexplored. Purpose This study aimed to evaluate the association between coagulation factors and the long-term risks in patients with multivessel CAD, with a focus on sex disparities. Methods A total of 760 patients with multivessel CAD who underwent percutaneous coronary intervention were enrolled in this study and followed up for 2 years. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, unplanned revascularization, and stroke. Baseline levels of coagulation factors (F2, F10, and F11) were analyzed as categorical variables, with optimal cutoff values determined by receiver operating characteristic curve analysis. Associations with MACCE were assessed using Cox proportional hazards models, using the group above the cutoff as the reference Results Among the enrolled patients, the mean age was 52.77 ± 10.77 years, and the majority (83.0%, n = 631) were male. Throughout the median follow-up duration of 2.08 years, 88 (11.6%) MACCE events occurred. No significant associations were observed between F2 or F10 levels and the risk of MACCE in any of the models (all P 0.05), while F11 demonstrated a significant sex-specific association with MACCE. In male patients, there were no significant associations between F11 levels and MACCE (all P 0.05). In contrast, among female patients, decreased levels of F11 (below the cutoff value of 3.55 μg/mL) were consistently associated with a significantly increased risk of MACCE across all models. In the fully adjusted model (model c), the hazard ratio (HR) reached 3.465 (95% confidence interval CI: 1.201–9.996, P = 0.021). Conclusion This study reveals a sex-specific association between F11 and the risk of 2-year MACCE in patients with multivessel CAD, indicating reduced F11 levels (3.55 μg/mL) were independently associated with worse outcomes in female patients. These findings align with prior evidence suggesting that F11 may exert cardiac protective effects, which appears to be distinct from, and potentially contradictory to, its prothrombotic role in coagulation. The observed sex disparity further underscores the importance of considering sex-specific mechanisms in risk stratification and therapeutic strategies.Gender-Stratified Associations
Zhang et al. (Sat,) studied this question.