Key result
CKM stage 4 mortality falls ~30% since 1999 despite a recent upward trend.
Why the study?
Long-term mortality trends and geographic inequities for advanced cardiovascular-kidney-metabolic syndrome stages 4 and 4b are not well characterized.
Observational
Effect estimate: AAPC -1.31% (95% CI -1.52 to -1.10)
Absolute Event Rate: 353.3% vs 505.54%
Mortality from advanced cardiovascular-kidney-metabolic stages in the US declined overall from 1999 to 2023 but rebounded in the past decade, with substantial geographic inequities.
Post-2013 reversal in CKM stage 4 mortality trends urges clinical vigilance; leaves open drivers and prevention targets.
Introduction: Advanced cardiovascular-kidney-metabolic (CKM) syndrome includes stage 4, defined by clinical cardiovascular disease in the CKM context, and stage 4b, defined as stage 4 with kidney failure. Long-term mortality trends and geographic inequities for these advanced stages are not well characterized. Methods: We performed an ecological time-series and spatial analysis of U.S. death certificate data from the CDC WONDER Multiple Cause of Death database, 1999-2023. Using an operational death-certificate-based proxy, stage 4 was defined by clinical cardiovascular disease codes, and stage 4b as stage 4 with concurrent renal failure (N17-N19). We calculated annual age-adjusted mortality rates (AAMRs), estimated annual percent change (APC) and average annual percent change (AAPC) using joinpoint regression, and mapped 2023 state- and county-level rates and derived metrics, including Stage 4b share within Stage 4. County clustering was assessed using Local Moran's I. Results: From 1999 to 2023, age-adjusted mortality declined for stage 4 from 505.54 to 353.30 per 100,000 population (average annual percent change, -1.31%; 95% confidence interval, -1.52 to -1.10) and for stage 4b from 45.95 to 33.98 per 100,000 (-1.18%; -1.75 to -0.34). However, trends reversed in the past decade: stage 4 increased after 2013 (annual percent change, +1.17%), whereas stage 4b increased after 2015 (+4.63%). Stage 4 mortality formed a high-burden belt across the Deep South and Appalachia, whereas stage 4b hotspots were more dispersed. Stage 4b share showed corridor-like clustering across parts of the Great Plains and Mountain West. Conclusion: Mortality from operationally defined advanced CKM stages declined overall but rebounded in the past decade, with substantial geographic inequities. Surveillance that tracks both absolute burden and the kidney failure-associated component of advanced CKM mortality may help target integrated cardio-renal risk reduction strategies.
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Xia et al. (2026) conducted an observational in Cardiovascular-kidney-metabolic (CKM) syndrome stages 4 and 4b. Time period (1999-2023) vs. 1999 baseline was evaluated on Age-adjusted mortality rate for CKM stage 4 (per 100,000 population) (AAPC -1.31%, 95% CI -1.52 to -1.10). Age-adjusted mortality for CKM stage 4 declined from 505.54 to 353.30 per 100,000 population between 1999 and 2023, though trends reversed and increased by 1.17% annually after 2013.
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