Chronological versus physiological age for 10-year survival estimation: a real-world healthsystem-wide cohort analysis

BACKGROUND: Benefits from clinical guidelines often only exceed harms after 10 years (payoff time). Based on population norms, guidelines are often discontinued at 75 years of age, but survival likely differs for those with complex chronic disease. We compare estimates based on age alone versus the physiologically based Veterans Ageing Cohort Study-Charlson Comorbidity Index (VACS-CCI) among all patients in care, and among patients with diabetes or HIV. METHODS: Estimates for patients in care within the US Veterans Health Administration (VHA) with a clinic visit in 2007-17 (followed thru 2021) were compared using C-statistics, Brier Scores, and calibration curves. "Physiological age" was defined as the chronological age at which median VACS-CCI matched US population survival estimates. Among those with 10-year follow-up, we compared percent correctly classified using age ≥75 years vs. VACS-CCI score of ≥42. FINDINGS: Among 6.6 million (51.4% ≥ 65 years; 25.2% with diabetes; 0.5% with HIV) VACS-CCI improved discrimination over age (Overall C-statistic: 0.81 vs. 0.74; Brier Score 0.239 vs. 0.262). Among 65-year-old males-females, "physiological age" exceeded chronological age by 4.6-3.1 years overall; 8.6-7.8 years for diabetes; and 13.5-11.6 years for HIV. Compared to age ≥75 years, VACS-CCI improved correct classification of survival for 1 in 13.3 overall; 1 in 7.8 with diabetes; and 1 in 6.4 with HIV. INTERPRETATION: Compared to chronological age alone, VACS-CCI offers an improved method to identify those likely to reach minimum payoff time, especially for those with complex chronic diseases. Use of clinical data to assess "physiological age" could improve healthcare value. FUNDING: This work was supported by National Institutes of Health NIAAA: P01 AA029545, U24 AA020794 and the Emory Center for AIDS Research (P30AI050409).