Aug 2026· American Journal of the Medical Sciences· 0 citations· 41 references
Medicine
TL;DR
KDM-BA, KDM-BA, PhenoAge, KDM-BAA, and PhenoAgeAccel are significantly associated with all-cause mortality among the CRS population, with a non-linear relationship observed in cerebrovascular disease.
Abstract
Background
Cardiorenal syndrome (CRS), characterized by cardiac-renal interplay, imposes a substantial clinical burden. Biological aging (BA), a comprehensive indicator for evaluating the overall aging status of an organism, is linked to individual cardiac or renal diseases, while its association with mortality in the CRS population remains unclear.
Methods
We utilized data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. CRS was defined as chronic cardiorenal comorbidities, specifically the coexistence of self-reported cardiovascular disease and calculated chronic kidney disease. BA was calculated using 12 clinical biomarkers, including the Klemera-Doubal method BA (KDM-BA) and Phenotypic Age (PhenoAge). BA acceleration (BAA), quantified as residuals from linear regression of BA on chronological age, includes KDM-BAA and PhenoAge acceleration (PhenoAgeAccel). Cox proportional hazards model and restricted cubic spline were performed to investigate these associations. Results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs).
Results
1,100 CRS participants were included in the final analysis. A 10-year increase in KDM-BA and PhenoAge in CRS participants was associated with 1.14-fold and 1.63-fold higher all-cause mortality risk, respectively. CRS participants with KDM-BAA (HR: 1.40, 95% CI: 1.13-1.73) or PhenoAgeAccel (HR: 1.54, 95% CI: 1.20-1.96) had elevated all-cause mortality risk. Meanwhile, these positive associations were more pronounced in males. Moreover, KDM-BA was associated with mortality from heart disease and cerebrovascular disease in the CRS population, with a non-linear relationship observed in cerebrovascular disease.
Conclusions
As composite indicators for aging, KDM-BA, PhenoAge, KDM-BAA, and PhenoAgeAccel are significantly associated with all-cause mortality among the CRS population. These measures may serve as potential prognostic biomarkers in this population.
TyG BA composites provide a parsimonious summary of combined metabolic-aging burden and improve risk discrimination beyond conventional clinical factors, but should not be interpreted as superior to models retaining TyG and biological age separately.
This study aims to evaluate the associations of Klemera-Doubal Method Biological Age Acceleration (KDM-BAA) and Phenotypic Age Acceleration (PAA) with all-cause and cause-specific mortality in U.S. adults with Cardio-Kidney-Metabolic (CKM) syndrome stages 0–3 and to establish risk prediction models. Data were obtained...
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