# A comprehensive evaluation of the associations between 12 composite inflammatory indices and all-cause mortality after stroke: a multicohort study

## TL;DR

This study finds that the neutrophil-to-lymphocyte ratio (NLR) is a reliable predictor of death after stroke in both general and clinical populations.

## Contribution

The study identifies NLR as a trans-situationally robust biomarker for post-stroke mortality across community and clinical settings.

## Key findings

- NLR was significantly associated with post-stroke mortality in both NHANES and clinical cohorts.
- The association between NLR and mortality was strongest in patients admitted within 24 hours of stroke onset.
- NLR showed consistent significance across different statistical models and subgroup analyses.

## Abstract

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.

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.

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).

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.