What question did this study set out to answer?

The research aims to explore the relationship between staging of cardiovascular-kidney-metabolic syndrome and associated mortality risks.

January 10, 2026American Journal of Preventive Cardiology3 citationsOpen Access

Associations between cardiovascular-kidney-metabolic syndrome staging and risks of all-cause and cardiovascular mortality: a systematic review and meta-analysis

HDHuimin DingMyongji University LJLiqun JiangMyongji University YZYiqiu ZhaoWaseda University

Key Points

The research aims to explore the relationship between staging of cardiovascular-kidney-metabolic syndrome and associated mortality risks.
Conducted a systematic review of relevant literature

Structured PICO

Do advancing cardiovascular-kidney-metabolic (CKM) syndrome stages increase the risk of all-cause and cardiovascular mortality?

Population

10,330,498 participants from 9 cohort studies

Intervention

Advancing cardiovascular-kidney-metabolic (CKM) syndrome stages (Stages 1-4)

Comparator

CKM Stage 0

Outcome

All-cause, cardiovascular disease (CVD), coronary heart disease (CHD), or stroke mortalityhard clinical

Advancing CKM stages are associated with progressively higher mortality risks, validating the AHA CKM staging framework for early risk assessment and targeted prevention.

Abstract

Background: Cardiovascular, kidney, and metabolic disorders are closely interconnected and jointly increase atherosclerotic burden and mortality risk. In 2023, the American Heart Association introduced the cardiovascular-kidney-metabolic (CKM) syndrome as a staged framework to characterize this multisystem risk. However, evidence linking CKM stages to mortality has not yet been quantitatively synthesized. Methods: We conducted a PROSPERO-registered (CRD420251161180) systematic review and meta-analysis following MOOSE and PRISMA guidelines. Four databases (PUBMED,Web of science, Embase, Cochrane library)were searched through August 8, 2025. Cohort studies assessing CKM stages (0-4) and reporting all-cause, cardiovascular disease (CVD), coronary heart disease (CHD), or stroke mortality were synthesized using random-effects models, with subgroup, meta-regression, and sensitivity analyses. Results: 9 cohort studies including 10,330,498 participants were analyzed. Mortality risk increased significantly with advancing CKM stages. Compared with Stage 0, Stage 4 was associated with markedly higher risks of all-cause mortality (HR = 3.82, 95% CI: 2.24-6.52), CVD mortality (HR = 6.38, 95% CI: 5.22-7.80), CHD mortality (HR = 9.19, 95% CI: 6.93-12.20), and stroke mortality (HR = 5.48, 95% CI: 4.28-7.02). Meta-regression identified age and educational attainment as significant effect modifiers and sources of heterogeneity. In sex-stratified analyses, all-cause mortality was consistently higher in women across CKM stages, whereas CVD mortality was higher in women at earlier stages but higher in men at later stages. Leave-one-out (LOO) sensitivity analyses and publication bias assessments supported the robustness of these findings. Conclusions: Advancing CKM stages are associated with progressively higher mortality risks, highlighting their value for early risk assessment and targeted prevention.

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