The association between systemic immune-inflammatory index and cardiac biomarkers among US population: a cross-sectional study

BACKGROUND: The systemic immune-inflammatory index (SII), calculated from platelet, neutrophil, and lymphocyte counts, is a novel marker of inflammation potentially relevant to cardiac disease. While cardiac biomarkers are used clinically, the relationship between SII and these markers in the general population is unclear. METHODS: We analyzed data from 3206 US adults (aged 20-85 years) in the 1999-2004 National Health and Nutrition Examination Survey (NHANES). Multivariable linear regression models, adjusted for demographics, comorbidities, and lifestyle factors, assessed cross-sectional associations of SII with cardiac biomarkers. Nonlinearity was examined using restricted cubic splines. Subgroup analyses explored effect modification. RESULTS: SII showed a consistent positive association with C-reactive protein (CRP) levels across all models (All P < 0.001). In contrast, the positive association of SII with NT-pro BNP observed in the unadjusted model (β = 0.20; 95% CI 0.11, 0.29; P < 0.001) was attenuated and became non-significant after full adjustment in the general population. Subgroup analyses showed significantly positive associations between SII and NT-pro BNP specifically in individuals aged > 55 years (β = 0.17; 95% CI 0.014, 0.33), and in those with myocardial infarction (MI) (β = 0.82; 95% CI 0.22, 1.43) or angina pectoris (AP) (β = 0.73; 95% CI 0.19, 1.47). The robust SII-CRP association was confirmed in subgroups. Dose-response relationships were supported by spline analyses. CONCLUSIONS: SII is persistently associated with CRP levels, supporting its role as an inflammatory indicator. Significant associations between SII and NT-pro BNP were observed only in specific high-risk subgroups (aged > 55 years, MI or AP patients), but not in the fully adjusted general population. These findings suggest SII may have particular relevance in specific cardiovascular contexts.