A novel method for biological age assessment utilizing hospitalization risk of cardiovascular disease

Aging is a complex process involving physiological changes that gradually impair function in organisms. Chronological age (CA) does not fully account for variability in the aging process, whereas biological age (BA) better reflects disease risk. This study introduces Cardiovascular Disease Probability-based Biological Age (CDPBA), a novel BA algorithm. We analyzed clinical data from 11.7 million individuals aged ≥ 40 years in the National Health Insurance Service database. Using a Cox proportional hazards model, clinical biomarkers, lifestyle factors, fine particulate matter exposure, and family history were used to estimate the 10-year risk of CVD hospitalization. Individual CDPBA was computed by comparing each subject’s CVD risk with the median risk profile of the corresponding age group, thereby capturing the nonlinear relationship between CDPBA and biomarkers while maintaining interpretability. Our CDPBA algorithm exhibited a strong correlation with CA ( r > 0.92), and the estimated CDPBA distribution was symmetric with respect to CA. All-cause mortality prediction was robust (area under the receiver operating characteristic curve [AUROC]: 0.849 and 0.871 in men and women, respectively), outperforming the regression-based BA approach (AUROC: 0.777 and 0.683 for men and women, respectively). The slow-aging group mostly maintained their health, whereas the accelerated-aging group showed increasingly worse health over time. Using CVD median risk profiles, the CDPBA algorithm shows a high correlation with CA and demonstrates superior performance in predicting all-cause mortality compared to conventional regression methods. The CDPBA provides a novel, interpretable approach to biological age estimation based on cardiovascular disease hospitalization risk.