ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Neuroinflammation and Neuropathy
This article is part of the Research TopicStroke Research in the Elderly: Addressing Ageism and PrognosticationView all 16 articles
A comprehensive evaluation of the associations between 12 composite inflammatory indices and all-cause mortality after stroke: a multicohort study
Provisionally accepted
- Suining Central Hospital, Suining, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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 1152 participants from NHANES cohort, followed until December 31, 2019, and 2540 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 hours of AIS onset (HR 1.024, 95% CI 1.011-1.038, P < 0.001). Conclusion: The NLR may serve as a robust 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.
Keywords: composite inflammatory index, Cross-sectional, Mortality, national health and nutrition examinationsurvey, Neutrophil-to-lymphocyte ratio, Retrospective, Stroke
Received: 25 Nov 2025; Accepted: 22 Dec 2025.
Copyright: © 2025 Zheng, He, Tang, Duan, Xing and Qian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ao Qian
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.