Systemic Immune-Inflammation Index Outperforms Conventional Inflammatory Markers in Predicting Cardiovascular Outcomes in Heart Failure with Preserved Ejection Fraction

Background: The systemic immune-inflammation index (SII), a novel inflammatory index integrating neutrophil, platelet, and lymphocyte counts, predicts outcomes in several cardiovascular diseases, yet its role in heart failure with preserved ejection fraction (HFpEF) remains unclear. We therefore investigated the prognostic value of SII in HFpEF patients and compares its performance against other inflammatory markers, including systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP). Methods: We retrospectively analyzed a cohort of 316 patients with HFpEF diagnosed between January 2017 and January 2021. All-cause mortality, cardiovascular mortality and HF rehospitalization were assessed over a median follow-up of 24 months. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were employed to evaluate the comparative prognostic performance of SII against SIRI, NLR and CRP. Results: Logistic regression models revealed that each 100-unit increase in SII was independently associated with elevated risks of cardiovascular mortality (OR:1.321, 95% CI:1.191– 1.467, P< 0.001) and HF rehospitalization (OR:1.168, 95% CI:1.098– 1.241, P < 0.001), but not with all-cause mortality ( P > 0.05). SII demonstrated superior prognostic performance compared to SIRI, NLR and CRP both in cardiovascular mortality (NRI range: 0.798– 1.097; IDI range: 0.094– 0.142, all P< 0.05) and HF rehospitalization (NRI range: 0.254– 0.455; IDI range: 0.016– 0.066, all P < 0.05). However, SII provided no incremental utility for all-cause mortality ( P > 0.05). Conclusion: SII emerges as a superior predictor of adverse cardiovascular outcomes in HFpEF compared to conventional inflammatory markers, supporting its use for risk stratification and as a potential therapeutic guide. Nevertheless, its association with all-cause mortality remains limited. Keywords: systemic immune-inflammation index, heart failure with preserved ejection fraction, cardiovascular outcomes