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Comparative Study
. 2025 Nov;90(2):605-616.
doi: 10.1007/s12020-025-04390-w. Epub 2025 Aug 18.

Comparative performance of multiple inflammatory indices across different stages of cardiovascular-kidney-metabolism syndrome: A Multi-Cohort Study

Lingyuan Hu  1   2   3 , Zhuotong Wang  1   2   3 , Jiaqi Chen  1   2 , Aomiao Chen  1   2   3 , Geningyue Wang  1   3   4 , Xinran Xie  1   2   3 , Qiuyu He  1   2   3 , Yaoming Xue  1   2   3 , Zhiyong Wu  5 , Zongji Zheng  6   7   8 , Yijie Jia  9   10   11
Affiliations
Comparative Study

Comparative performance of multiple inflammatory indices across different stages of cardiovascular-kidney-metabolism syndrome: A Multi-Cohort Study

Lingyuan Hu et al. Endocrine. 2025 Nov.

Abstract

Background: This study investigated the associations between different inflammatory indices and mortality in CKM patients at various stages, with the goal of identifying the best inflammatory predictors of survival for each stage of CKM.

Patients and methods: Data from 18,700 representative CKM patients in NHANES 1999-2014 and 94,760 CKM patients from the UKB were analysed. The inflammatory index was calculated on the basis of the blood cell count and biochemical indicators. A multivariate Cox proportional hazards model was applied to analyse the associations between inflammatory indices and all-cause mortality stratified by CKM stage.

Results: The advanced lung cancer inflammation index (ALI) has the best predictive performance for early CKM stages (NHANES: stage 2: AUC(t) = 0.600; stage 3: AUC(t) = 0.636; stage 4: AUC(t) = 0.678; UKB: stage 1: AUC(t) = 0.613; stage 3: AUC(t) = 0.666), with higher ALI levels correlated with lower all-cause mortality risk. In contrast, the monocyte‒lymphocyte ratio (MLR), neutrophil‒lymphocyte ratio (NLR), and systemic inflammation response index (SIRI) are correlated with an increased risk of all-cause mortality. The SIRI demonstrates superior predictive performance in the advanced stages of CKM.

Conclusion: This study demonstrated that the ALI was negatively associated with all-cause mortality and exhibited optimal performance and robustness in predicting the prognosis of patients with early-stage CKM, whereas the SIRI showed superior predictive performance in the advanced stages of CKM.

Keywords: All-cause mortality; Cardiovascular-kidney-metabolic syndrome; Inflammatory indices; Prognosis.

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Conflict of interest statement

Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Ethics approval: The US participants in this study have provided written consent for the NHANES study, and no additional ethical approval is required. UK Biobank was conducted according to the guidelines of the Declaration of Helsinki and had approval from the North West Multicentre Research Ethics Committee (REC reference: 21/NW/0157), and all participants provided written informed consent. No additional ethical approval was required. Consent to participate: Informed consent was obtained from all individual participants included in the study.

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