Abstract
PURPOSE: Despite primary percutaneous coronary intervention (PPCI), over 10% of ST-segment elevation myocardial infarction (STEMI) patients develop the no-reflow phenomenon, characterized by microvascular inflammation. Novel forms of cell death, such as pyroptosis (IL-1β/GSDMD/Caspase-1) and ferroptosis (ACSL4/GPX4/PTGS2), may contribute to this inflammation by promoting cytokine release and leukocyte recruitment. However, the biomarker potential of these pathways in predicting no-reflow remains unclear. This study aimed to evaluate whether serum levels of these proteins could predict no-reflow and improve risk stratification. PATIENTS AND METHODS: We enrolled 423 STEMI patients undergoing PPCI at two centers. No-reflow was defined as TIMI flow <3 following PPCI, excluding mechanical obstruction. Serum levels of pyroptosis- (IL-1β, GSDMD, Caspase-1) and ferroptosis-related proteins (ACSL4, GPX4, PTGS2) were measured using ELISA. Multivariable logistic regression identified independent predictors. The baseline model included age, sex, cardiovascular risk factors, and other baseline differences. Biomarker performance was assessed using ROC analysis, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Of 423 patients, 81 (19.1%) developed no-reflow. The no-reflow group had significantly higher IL-1β [7.41 (5.55-10.80) vs 4.91 (3.70-6.71) pg/mL, P<0.001] and GSDMD levels [2.34 (1.75-3.48) vs 2.05 (1.64-2.71) ng/mL, P=0.017]. IL-1β was an independent predictor of no-reflow in both continuous [per SD increase: adjusted OR=2.260, 95% CI 1.723-2.966, P<0.001] and categorical analyses [highest vs lowest tertile: OR=6.484, 95% CI 2.864-14.679, P<0.001]. ROC analysis showed IL-1β alone had an AUC of 0.745 (95% CI: 0.686-0.804) for no-reflow prediction. Adding IL-1β to the baseline model improved discrimination (ΔAUC=0.091, P<0.001; NRI=0.627, P<0.001; IDI=0.109, P<0.001). CONCLUSION: Elevated serum IL-1β independently predicts no-reflow in STEMI patients, and its integration into the baseline model significantly enhances diagnostic performance, suggesting IL-1β as a potential therapeutic target.