Cardiovascular-kidney-metabolic syndrome stages and increased risk of all-cause and cause-specific mortality in UK Biobank

Q: What is the main objective of the study?

To characterize the association between cardiovascular–kidney–metabolic (CKM) syndrome stages and risk of all-cause and cause-specific mortality.

Q: How was the study conducted?

The analysis used 282,952 baseline participants from the UK Biobank, monitored until November 12, 2021, with Cox regression to evaluate mortality risks by CKM stage.

Q: What did the results show about mortality across CKM stages?

Risks for all-cause and multiple cause-specific mortalities increased with advancing CKM stages, with particularly elevated hazard ratios in Stage 4 compared with Stage 0.

Q: Which groups showed stronger associations and what role did smoking play?

Younger adults (≤60 years) had stronger associations for several outcomes. Current smoking was linked to cancer mortality, while previous smoking was associated with higher all-cause and cardiovascular mortality.

Sep 29, 2026

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Cardiovascular–kidney–metabolic (CKM) syndrome represents a critical public health challenge, yet its links to mortality had not been fully clarified. Using 282,952 UK Biobank participants followed to November 12, 2021, Cox regression assessed associations between CKM stages and all-cause and cause-specific mortality across cardiovascular disease, cancer, respiratory, and digestive conditions. Over 12.7 years, mortality increased significantly with advancing CKM stages. Hazard ratios indicated markedly higher risk in Stage 4 for all-cause and cardiovascular and elevated risk for cancer, with stronger effects among younger adults and smoking-related interactions. Early detection and intervention may be crucial.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Introduction

American Journal of Preventive Cardiology 25 (2026) 101369 Contents lists available at ScienceDirect American Journal of Preventive Cardiology journal [homepage:](homepage: www.journals.elsevier.com/american-journal-of-preventive-cardiology)[ www.journals.elsevier.com/american-journal-of-preventive-cardiology](homepage: www.journals.elsevier.com/american-journal-of-preventive-cardiology) | Cardiovascular-kidney-metabolic syndrome stages and increased risk of all-cause and cause-specific mortality in UK Biobank
Tingting Xu a,b,1 , Jin Wei c,1, Ming Xud, Huiqin Li c, Silu Chenc, Hongsheng Ji c,e, Junyi Xinf,*, Yan Gao a,b,**, Mulong Duc,e,***
a School of Public Health, Nanjing Medical University, Nanjing 211166, China
b Institute of Suzhou Biobank, Suzhou Center for Disease Prevention and Control, Suzhou 215007, China
c Departments of Environmental Genomics and Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing 211166, China
d Department of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province 210009, China e Department of Biostatistics, Center for Global Health, School of Public Health, and Department of Urology, Jiangsu Key Laboratory of Urological Disease Prevention and Treatment, The Second Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, China f Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu 211166, China | | | | --- | --- | --- | | A R T I C L E I N F O
Keywords:
Cardiovascular kidney metabolic syndrome All-cause mortality
Cardiovascular diseases Cancer, respiratory diseases Digestive diseases | A B S T R A C T
Background: Cardiovascular–kidney–metabolic (CKM) syndrome poses a critical challenge for public health. However, its association with mortality risk remain inadequately characterized.
Methods: 282,952 participants at baseline from the UK Biobank were monitored until November 12, 2021. Cox regression analyses evaluated the associations between CKM stages and the risk of all-cause and cause-specific mortality, including cardiovascular diseases (CVD), cancer, respiratory diseases, and digestive system diseases. Results: Over a median follow-up of 12.7 years, 16,834 deaths occurred, including 15.8% from CVD, 50.3% from cancer, 6.0% from respiratory diseases, 3.6% from digestive system diseases, and 24.3% from other causes. The risk of all-cause, cancer, CVD, respiratory, and digestive mortality increased with advancing CKM stages (P < 0.001). Compared with Stage 0, the hazard ratios (HR) in Stage 4 were 2.34 (95% confidence interval [CI]: 2.11–2.58) for all-cause mortality, 10.15 (95% CI: 6.92–14.89) for CVD mortality, and 1.41 (95% CI: 1.23–1.62) for cancer mortality. Furthermore, younger adults (aged ≤ 60 years; P interaction < 0.001) had stronger associations with all-cause, CVD, cancer, and respiratory events. Significant associations were observed between current smoking and cancer mortality (P interaction < 0.001), and between previous smoking and all-cause and CVD mortality (P interaction < 0.001).
Conclusions: CKM stages are strongly associated with increased all-cause and cause-specific mortality. Early identification and intervention in CKM syndrome patients could be crucial for reducing premature mortality and improving public health. | | * Corresponding author at: Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu 211166, China.

FAQs

What is the main objective of the study?

To characterize the association between cardiovascular–kidney–metabolic (CKM) syndrome stages and risk of all-cause and cause-specific mortality.

How was the study conducted?

The analysis used 282,952 baseline participants from the UK Biobank, monitored until November 12, 2021, with Cox regression to evaluate mortality risks by CKM stage.

What did the results show about mortality across CKM stages?

Risks for all-cause and multiple cause-specific mortalities increased with advancing CKM stages, with particularly elevated hazard ratios in Stage 4 compared with Stage 0.

Which groups showed stronger associations and what role did smoking play?

Younger adults (≤60 years) had stronger associations for several outcomes. Current smoking was linked to cancer mortality, while previous smoking was associated with higher all-cause and cardiovascular mortality.

Sep 29, 2026

Uploaded by Terk