Associations of biological aging and biological age acceleration with mortality in patients with cardiorenal syndrome: A prospective cohort study.

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.