Creatinine clearance is key to solving the enigma of sex difference in in-hospital mortality after STEMI: Propensity score matching and mediation analysis

BACKGROUND: The precise impact of sex difference on in-hospital mortality in ST-elevation myocardial infarction (STEMI) patients are unclear, and the studies are no longer consistent. Therefore, we sought to evaluate the impact of sex differences in a cohort of STEMI patients. METHODS: We analyzed the data of 2647 STEMI patients enrolled in the Kermanshah STEMI Cohort from July 2017 to May 2020. To accurately clarify the relationship between sex and hospital mortality, propensity score matching (PSM) and causal mediation analysis was applied to the selected confounder and identified intermediate variables, respectively. RESULTS: Before matching, the two groups differed on almost every baseline variable and in-hospital death. After matching with 30 selected variables, 574 male and female matched pairs were significantly different only for five baseline variables and women were no longer at greater risk of in-hospital mortality (10.63% vs. 9.76%, p = 0.626). Among the suspected mediating variables, creatinine clearance (CLCR) alone accounts for 74% (0.665/0.895) of the total effect equal to 0.895(95% CI: 0.464–1.332). In this milieu, the relationship between sex and in-hospital death was no longer significant and reversed -0.233(95% CI: -0.623–0.068), which shows the full mediating role of CLCR. CONCLUSION: Our research could help address sex disparities in STEMI mortality and provide a consequence. Moreover, CLCR alone can fully explain this relationship, which can highlight the importance of CLCR in predicting the short-term outcomes of STEMI patients and provide a useful indicator for clinicians.