Impact of systemic immune inflammation index and systemic inflammation response index on all-cause and cardiovascular mortality in cardiovascular-kidney-metabolic syndrome.

BACKGROUND

The cardiovascular-kidney-metabolic (CKM) syndrome is a systemic condition defined by multifaceted interactions among metabolic risk factors, chronic kidney disorder, and cardiovascular diseases. Inflammation is essential in the pathogenesis and progression of CKM syndrome. Inflammatory markers, including the systemic immune inflammation index (SII) and the systemic inflammation response index (SIRI), function as composite indicators for assessing immune-related inflammatory status. This study seeks to address the associations between SII/SIRI and death outcomes in individuals with CKM syndrome using outcomes from the National Health and Nutrition Examination Survey (NHANES, 1999-2018).

METHODS

This cross-sectional investigation comprised 18,452 individuals (≥ 20 years) with CKM syndrome, utilizing outcomes from ten cycles of NHANES (1999-2018). Participants were divided into higher and lower SII and SIRI groups according to cut-off values established by the optimally chosen rank statistics approach. Kaplan-Meier analysis and Cox proportional hazards and Fine-Gray competing risk regression models were utilized to evaluate the links between SII/SIRI and death outcomes in CKM individuals. Stratified and subgroup analyses were performed to further corroborate the results. Restricted cubic spline (RCS) analysis was utilized to examine potential non-linear links between SII/SIRI and death outcomes in this cohort. Ultimately, time-dependent receiver operating characteristic (ROC) analysis was employed to evaluate the prediction precision of SII and SIRI regarding death outcomes in short- and long-term follow-ups.

RESULTS

Upon controlling for potential confounders, higher SII levels (≥ 898.21) correlated with a 1.42-fold elevation in the risk of all-cause mortality (ACM) (HR: 1.42, 95% CI 1.23-1.56, P < 0.001) and a 1.50-fold elevation in cardiovascular mortality (CVM) (HR: 1.50, 95% CI 1.15-1.96, P = 0.002). Increased SIRI levels (≥ 1.23) correlated with a 1.28-fold escalation in the risk of ACM (HR: 1.28, 95% CI 1.14-1.43, P < 0.001) and a 1.38-fold escalation in the risk of CVM (HR: 1.38, 95% CI 1.12-1.70, P = 0.003). RCS analysis demonstrated a U-shaped, non-linear correlation between SII/SIRI concentrations and ACM (both P < 0.001), whereas a linear link was identified between SII/SIRI levels and CVM (both P > 0.05). Time-dependent ROC analysis revealed that SII and SIRI illustrated moderate to excellent and constant prognostic efficacy for short-term and long-term mortality outcomes in individuals with CKM syndrome, with SIRI consistently outperforming SII at all assessed time intervals.

CONCLUSIONS

Higher values of SII and SIRI are related to an elevated risk of ACM and CVM in U.S. adults with CKM syndrome. SIRI had moderate, stable predictive capacities for ACM and CVM, whereas SII exhibited moderate to poor predictive capacity for both outcomes, with SIRI consistently outperforming SII across all evaluated time points. These outcomes highlight these inflammatory markers' potential in forecasting adverse mortality outcomes in this population.