Systemic immune-inflammation index as a predictor of statin residual cardiovascular risk compared with C-reactive protein

BACKGROUND: Despite statins reducing cardiovascular (CV) disease risk, residual inflammatory risk persists in treated patients. The systemic immune-inflammation index (SII), integrating platelet, neutrophil, and lymphocyte counts, has emerged as a novel biomarker of systemic inflammation and immune dysregulation. This study evaluated the systemic immune-inflammation index (SII) as a predictor of residual CV mortality compared to C-reactive protein (CRP) in statin users. METHOD: This study included 8211 adults with statin use from the National Health and Nutritional Examination Surveys (NHANES) 1999-2018 and were followed for survival through December 31, 2019. Cox proportional hazard models were used to investigate the associations between natural log-transformed SII (lnSII) and cardiovascular mortality. Predictive accuracy was compared via receiver operating characteristic (ROC) curves. RESULT: During the follow-up period of 6.92 (3.75, 11) years, a total of 2261 all-cause deaths and 796 cardiovascular deaths were recorded. After adjusting for covariates, higher baseline SII was significantly associated with an elevated risk of CV mortality (hazard ratio [HR] for per unit increase in natural log-transformed SII (lnSII), 1.241; 95 % confidence interval [CI], 1.009-1.527). The ROC curve analysis demonstrated SII's superior predictive accuracy (AUC, 0.760; 95 %CI, 0.744-0.776) over CRP (AUC, 0.749; 95 % CI, 0.733-0.765). CONCLUSION: Among patients receiving contemporary statins, SII was shown to be an independent predictor of future CV death. SII outperformed CRP as an inflammatory biomarker for residual CV risk in statin-treated patients.