What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiovascular-Kidney-Metabolic (CKM) syndrome (n=2812170). Intervention: CKM stage progression vs. Sustained CKM stage. Primary outcome: All-cause mortality (HR 1.38, 95% CI 1.36-1.41).

What question did this study set out to answer?

This study aims to explore the relationship between changes in cardiovascular-kidney-metabolic stages and all-cause mortality.

June 14, 2026

Stage-Specific Progression of Cardiovascular-Kidney-Metabolic Health and Mortality in a Nationwide Cohort of East Asian Adults

Key Result

Progression of Cardiovascular-Kidney-Metabolic stage was associated with a higher risk of all-cause mortality (HR 1.38; 95% CI 1.36-1.41), whereas stage improvement lowered mortality risk.

Key Points

This study aims to explore the relationship between changes in cardiovascular-kidney-metabolic stages and all-cause mortality.
Analyzed data from 2,812,170 adults aged ≥20 years over four years using health screenings.
Classified CKM stages based on clinical criteria reflecting metabolic, kidney, and cardiovascular risk.
Used multivariable Cox regression analysis to evaluate stage-specific CKM changes and mortality associations.
24% (674,465) of adults progressed in CKM stage, significantly increasing mortality risk (adjusted HR 1.38, 95% CI 1.36–1.41).
12% (335,216) improved CKM stage, associated with lower mortality risk (adjusted HR 0.93, 95% CI 0.90–0.95).
Even early progression (stage 0 to stage 1) linked to higher mortality risk (adjusted HR 1.08, 95% CI 1.01–1.15).

Study Design

Type

Cohort (n=2,812,170)

Multicenter

Yes

Structured PICO

Does change in Cardiovascular-Kidney-Metabolic (CKM) stage over 4 years affect subsequent all-cause mortality in adults?

Population

2,812,170 adults aged ≥20 years who underwent two general health screenings four years apart, followed for 6.4 years.

Exposure

Cardiovascular-Kidney-Metabolic (CKM) stage progression or improvement over a 4-year period

Comparator

Sustained CKM stage over the same 4-year period

Outcome

All-cause mortality over a subsequent 6.4-year follow-uphard clinical

Progression of Cardiovascular-Kidney-Metabolic (CKM) stage is associated with increased all-cause mortality, while improvement lowers mortality risk, highlighting the importance of monitoring and intervening across the CKM spectrum.

Main Result

Hazard Ratio: 1.38 (95% CI 1.36–1.41)

Abstract

Background: Cardiovascular-Kidney-Metabolic (CKM) syndrome represents the progressive interplay among metabolic dysfunction, kidney impairment, and cardiovascular disease (CVD), ultimately contributing to higher mortality. We investigated how changes across CKM stages correlate with subsequent all-cause mortality in a nationwide population-based cohort. Methods: We analyzed data from 2,812,170 adults aged ≥20 years who underwent two general health screenings four years apart through the Korean National Health Insurance Service, with CKM stages classified according to clinical criteria reflecting progressive metabolic, kidney, and cardiovascular risk. Stage-specific CKM stage change (improve, sustain, or progress) and its association with all-cause mortality were evaluated using multivariable Cox regression analysis, adjusted for clinicodemographic variables. Results: During the four-year exposure assessment period, 674,465 adults (24%) experienced CKM stage progress, 1,802,489 (64%) sustained their CKM stage, and 335,216 (12%) improved. Over a subsequent 6.4-year follow-up, CKM stage progress was significantly associated with an higher risk of all-cause mortality adjusted HR 1.38 (1.36–1.41), whereas CKM stage improvement was associated with a lower risk adjusted HR 0.93 (0.90–0.95). Notably, even early-stage progression (from stage 0 to stage 1) was linked to a higher mortality risk adjusted HR 1.08 (1.01–1.15), with a stepwise higher risk observed with progression to more advanced follow-up CKM stages. The association between CKM stage progress and mortality was more pronounced in older adults. Conclusion: Worsening of CKM stage is associated with higher all-cause mortality from early to advanced stages, whereas CKM stage improvement is associated with lower mortality risk. These findings provide epidemiologic real-world evidence supporting the importance of monitoring and intervening on CKM progression across its full spectrum to lower long-term mortality risk.

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