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

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.