The metabolic vulnerability index as a novel tool for mortality risk stratification in a large-scale population-based cohort

Metabolic malnutrition and inflammation—key mechanism links to redox imbalance—are fundamental pathologies that accelerate aging and disease progression, ultimately leading to death. The recently proposed metabolic vulnerability index (MVX) integrates multiple circulatory biomarkers closely linked t...

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Main Authors: Jialin Li, Qiuhong Man, Yingzhe Wang, Mei Cui, Jincheng Li, Kelin Xu, Zhenqiu Liu, Li Jin, Xingdong Chen, Chen Suo, Yanfeng Jiang
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Redox Biology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213231725000989
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author Jialin Li
Qiuhong Man
Yingzhe Wang
Mei Cui
Jincheng Li
Kelin Xu
Zhenqiu Liu
Li Jin
Xingdong Chen
Chen Suo
Yanfeng Jiang
author_facet Jialin Li
Qiuhong Man
Yingzhe Wang
Mei Cui
Jincheng Li
Kelin Xu
Zhenqiu Liu
Li Jin
Xingdong Chen
Chen Suo
Yanfeng Jiang
author_sort Jialin Li
collection DOAJ
description Metabolic malnutrition and inflammation—key mechanism links to redox imbalance—are fundamental pathologies that accelerate aging and disease progression, ultimately leading to death. The recently proposed metabolic vulnerability index (MVX) integrates multiple circulatory biomarkers closely linked to both metabolic and inflammatory factors. This study aims to assess MVX's potential to predict mortality in community-based population. In this large community-based prospective study, we included UK Biobank participants who underwent plasma metabolomics analysis. Gender-specific MVX scores were calculated based on six established biomarkers of mortality. Linear and non-linear associations between MVX and mortality were assessed using Cox proportional hazards models and restricted cubic spline models, respectively. Among the 274,092 UKB participants, 24,241 all-cause deaths occurred during a median follow-up period of 13.7 years. A significant, graded positive association was observed between MVX quartiles and all-cause mortality risk (P for trend <0.05), with the highest MVX quartile exhibiting the greatest risk (HR = 1.21 and 95 % CI = 1.16–1.25 after full adjustment). Females had higher MVX score than males (P < 0.05), but males with the same MVX score faced a greater mortality risk. Baseline age and comorbidities interacted (P for interaction <0.05 and synergy index >1) with MVX on mortality risk. Longitudinal analyses showed that females with persistently high MVX score had a significantly increased risk of mortality (HR = 1.39 in fully adjusted model). Collectively, these findings highlight MVX as a novel tool that captures metabolic and potential redox vulnerabilities in community residents, and serves as a valuable resource for identifying high-risk individuals of mortality. Further research is warranted to investigate the underlying mechanisms and establish causal relationships.
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spelling doaj-art-5364a7ecc0dd428194c64defab385da02025-08-20T02:06:44ZengElsevierRedox Biology2213-23172025-04-018110358510.1016/j.redox.2025.103585The metabolic vulnerability index as a novel tool for mortality risk stratification in a large-scale population-based cohortJialin Li0Qiuhong Man1Yingzhe Wang2Mei Cui3Jincheng Li4Kelin Xu5Zhenqiu Liu6Li Jin7Xingdong Chen8Chen Suo9Yanfeng Jiang10Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China; Fudan University, Taizhou Institute of Health Sciences, Taizhou, Jiangsu, 225326, ChinaDepartment of Laboratory Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, ChinaDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, ChinaDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, ChinaHuman Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China; Fudan University, Taizhou Institute of Health Sciences, Taizhou, Jiangsu, 225326, ChinaMinistry of Education Key Laboratory of Public Health Safety, Department of Biostatistics, School of Public Health, Fudan University, Shanghai, 200032, China; Fudan University, Taizhou Institute of Health Sciences, Taizhou, Jiangsu, 225326, ChinaHuman Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China; Fudan University, Taizhou Institute of Health Sciences, Taizhou, Jiangsu, 225326, ChinaState Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200433, China; Fudan University, Taizhou Institute of Health Sciences, Taizhou, Jiangsu, 225326, ChinaState Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200433, China; Fudan University, Taizhou Institute of Health Sciences, Taizhou, Jiangsu, 225326, China; Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, 322000, ChinaMinistry of Education Key Laboratory of Public Health Safety, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China; Fudan University, Taizhou Institute of Health Sciences, Taizhou, Jiangsu, 225326, China; Corresponding author. School of Public Health, Fudan University, 130 Dong'an Rd, Shanghai, 200032, China.Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China; Fudan University, Taizhou Institute of Health Sciences, Taizhou, Jiangsu, 225326, China; Corresponding author. Human Phenome Institute, Fudan University, 2005 Songhu Rd, Shanghai, 200438, China.Metabolic malnutrition and inflammation—key mechanism links to redox imbalance—are fundamental pathologies that accelerate aging and disease progression, ultimately leading to death. The recently proposed metabolic vulnerability index (MVX) integrates multiple circulatory biomarkers closely linked to both metabolic and inflammatory factors. This study aims to assess MVX's potential to predict mortality in community-based population. In this large community-based prospective study, we included UK Biobank participants who underwent plasma metabolomics analysis. Gender-specific MVX scores were calculated based on six established biomarkers of mortality. Linear and non-linear associations between MVX and mortality were assessed using Cox proportional hazards models and restricted cubic spline models, respectively. Among the 274,092 UKB participants, 24,241 all-cause deaths occurred during a median follow-up period of 13.7 years. A significant, graded positive association was observed between MVX quartiles and all-cause mortality risk (P for trend <0.05), with the highest MVX quartile exhibiting the greatest risk (HR = 1.21 and 95 % CI = 1.16–1.25 after full adjustment). Females had higher MVX score than males (P < 0.05), but males with the same MVX score faced a greater mortality risk. Baseline age and comorbidities interacted (P for interaction <0.05 and synergy index >1) with MVX on mortality risk. Longitudinal analyses showed that females with persistently high MVX score had a significantly increased risk of mortality (HR = 1.39 in fully adjusted model). Collectively, these findings highlight MVX as a novel tool that captures metabolic and potential redox vulnerabilities in community residents, and serves as a valuable resource for identifying high-risk individuals of mortality. Further research is warranted to investigate the underlying mechanisms and establish causal relationships.http://www.sciencedirect.com/science/article/pii/S2213231725000989MortalityMetabolic vulnerabilityMetabolic malnutritionInflammationProspective study
spellingShingle Jialin Li
Qiuhong Man
Yingzhe Wang
Mei Cui
Jincheng Li
Kelin Xu
Zhenqiu Liu
Li Jin
Xingdong Chen
Chen Suo
Yanfeng Jiang
The metabolic vulnerability index as a novel tool for mortality risk stratification in a large-scale population-based cohort
Redox Biology
Mortality
Metabolic vulnerability
Metabolic malnutrition
Inflammation
Prospective study
title The metabolic vulnerability index as a novel tool for mortality risk stratification in a large-scale population-based cohort
title_full The metabolic vulnerability index as a novel tool for mortality risk stratification in a large-scale population-based cohort
title_fullStr The metabolic vulnerability index as a novel tool for mortality risk stratification in a large-scale population-based cohort
title_full_unstemmed The metabolic vulnerability index as a novel tool for mortality risk stratification in a large-scale population-based cohort
title_short The metabolic vulnerability index as a novel tool for mortality risk stratification in a large-scale population-based cohort
title_sort metabolic vulnerability index as a novel tool for mortality risk stratification in a large scale population based cohort
topic Mortality
Metabolic vulnerability
Metabolic malnutrition
Inflammation
Prospective study
url http://www.sciencedirect.com/science/article/pii/S2213231725000989
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