Abstract
BACKGROUND: Inflammation plays a critical role in post-stroke mortality. However, identification of robust and generalizable inflammatory biomarkers for post-stroke mortality remains a challenge. We conducted a comprehensive analysis of various composite inflammatory indices, evaluating the associations between these indices and post-stroke mortality by examining two cohorts, to discover trans-situationally robust indices. METHODS: Data were sourced from the National Health and Nutrition Examination Survey (NHANES) circles of 1999-2010 and 2015-2018, as well as from our stroke center. Twelve composite inflammatory indices were calculated based on peripheral blood cell, C-reactive protein, and albumin. The correlations between these indices and post-stroke mortality were evaluated using multivariate Cox proportional hazards regression analyses, with the false discovery rate (FDR) correction applied for multiple testing. The neutrophil-to-lymphocyte ratio (NLR), which demonstrated consistent significance in both NHANES and clinical cohorts, was further subjected to subgroup analyses to elucidate its relationship with post-stroke mortality across various conditions. RESULTS: This study included 1,152 participants from NHANES cohort, followed until December 31, 2019, and 2,540 patients with acute ischemic stroke (AIS) from the clinical cohort with 90-day follow-up. The NLR, whether treated as a continuous or categorical variable (classified into tertiles), was significantly associated with mortality in both NHANES (per unit increase: hazard ratio [HR] 1.101, 95% confidence interval [CI] 1.043-1.163, P(-FDR) = 0.001; T3 vs. T1: HR 2.002, 95% CI 1.555-2.577, P(-FDR) < 0.001) and clinical cohort (per unit increase: HR 1.023, 95% CI 1.010-1.037, P(-FDR) = 0.002; T3 vs. T1: HR 1.939, 95% CI 1.342-2.804, P(-FDR) = 0.009). Subgroup analyses revealed a significant interaction between NLR and time from AIS onset to admission in clinical cohort (P for interaction = 0.017), demonstrating the association was particularly strong in patients admitted within 24 h of AIS onset (HR 1.024, 95% CI 1.011-1.038, p < 0.001). CONCLUSION: The NLR may serve as a generalizable biomarker of post-stroke mortality assessment across both community and clinical settings. The correlation with mortality is pronounced in patients during early stage of AIS, underscoring the time-sensitive prognostic value of NLR.