The Prognostic Gender-Related Value of the Systemic Immune-Inflammation Index in Patients With Acute Coronary Syndrome

Background: Inflammation has recently been identified as a critical regulator of the pathophysiology and prognosis of acute coronary syndrome (ACS). The systemic immune–inflammation index (SII), derived from platelet, neutrophil, and lymphocyte counts, has gained attention as a potential marker for predicting adverse outcomes in cardiovascular diseases. However, the prognostic value of the SII, particularly in relation to gender differences, has not been extensively studied. Methods: Thus, we conducted a retrospective cohort study of 835 patients hospitalized for ACS at Hippokration Hospital, Thessaloniki, Greece, between 2017 and 2023. The SII was calculated using blood samples taken at admission. Logistic and Cox regression models were used to evaluate the relationship between the SII and all-cause mortality, with stratified analyses conducted according to gender. Receiver operating characteristic (ROC) analysis, Kaplan–Meier survival curves, and restricted cubic spline (RCS) modeling were also performed to assess the discriminative ability and non-linear associations of the SII with mortality. Results: A total of 835 patients were included, with a median follow-up of 25 months. An elevated SII was independently associated with increased long-term mortality, with patients in the highest SII quartile exhibiting a 2.3-fold higher risk of death compared to those in the lowest quartile (adjusted hazard ratio (aHR) = 2.31, 95% confidence interval (CI): 1.60–3.32; p < 0.001). The optimal cut-off value for the SII was identified as 1864.19. Gender-stratified analyses revealed a stronger prognostic value in women compared to men (area under the curve (AUC) = 0.70 vs 0.58; p = 0.018). The Kaplan–Meier and Cox regression analyses confirmed significantly worse survival for patients with SII levels above this threshold (p < 0.05). The RCS modeling demonstrated a non-linear relationship between the SII and mortality, with a marked increase in risk at higher levels of the SII, especially in women. Conclusions: The SII is a simple, easily accessible biomarker that independently predicts mortality in ACS patients, with notable gender-specific differences in the prognostic value of the SII. Nonetheless, incorporating SII into routine risk assessment could enhance risk stratification and improve personalized treatment strategies, particularly in settings with limited resources.