Association of systemic immune-inflammation index with adverse outcomes in heart failure and preserved ejection fraction

Abstract

Background: Heart failure (HF) and preserved ejection fraction (HFpEF) represents a growing health burden characterized by systemic inflammation. Yet, reliable and cost-effective inflammatory biomarkers for risk stratification in HFpEF remain limited. Aim: We sought to examine the prognostic value of systemic immune-inflammation index (SII) on outcomes in HFpEF patients. Methods: This study analyzed 458 (mean age:70.7 years; 59.2% women) participants with HFpEF admitted to the coronary care unit. HFpEF participants were grouped by SII values: Tertile 1 (SII ≤ 455.2), Tertile 2 (455.2–777.8), and Tertile 3 (SII > 777.8). Long-term associations between SII and composite outcomes, including all-cause, cardiovascular death, and HF rehospitalization, were evaluated. Decision curve analysis (DCA) assessed the clinical utility of SII-enhanced versus basic clinical models. Results: Baseline demographics, comorbidities, and laboratory parameters varied significantly across SII tertiles. Of the total participants, 211 (46.1%) experienced composite events over a mean follow-up of 41.8 months. When analyzed as a continuous variable, higher log-transformed SII was independently associated with increased risk of composite outcome of death and HF rehospitalization in the overall cohort (HR 1.50, 95% CI 1.18–1.92) and diabetic patients (HR 1.88, 95% CI 1.32–2.67), but not non-diabetic patients (HR 1.23, 95% CI 0.86–1.77) after multivariable adjustment. Similarly, in the fully adjusted tertile-based analysis, the highest SII tertile remained significantly associated with the composite outcome in the overall cohort (HR 1.70, 95% CI 1.15–2.52), with a particularly strong association observed in diabetic patients (HR 2.63, 95% CI 1.43–4.85), while no significant association was found in non-diabetic patients (HR 1.13, 95% CI 0.63–2.02). Restricted cubic splines demonstrated a linear relationship between SII and composite outcomes. SII showed superior prognostic accuracy compared to other inflammatory markers, and DCA confirmed improved clinical decision-making utility. Conclusions: In patients with HFpEF, higher SII values were positively associated with risk of death and HF hospitalization, with particularly strong prognostic value in diabetic patients. SII represents a promising, accessible biomarker for enhanced risk stratification in HFpEF.