Accelerated biological aging increases the 10-year mortality risk in patients with coronary artery disease after percutaneous coronary intervention

Background Biological age (BA) is a composite indicator integrating multiple clinical and biochemical biomarkers to quantify physiological aging and reflects overall health status more accurately than chronological age (CA). Objective This study aimed to evaluate the associations between three biological age algorithms and 10-year mortality risk after percutaneous coronary intervention (PCI), to identify the most clinically applicable aging metric. Methods In this large prospective cohort study, 9,234 patients with coronary artery disease undergoing PCI were included. The primary endpoint was all-cause mortality (n = 1,122), and the secondary endpoint was cardiac mortality (n = 366), with a median follow-up of 10 years. Established algorithms, including PhenoAge, KDMAge, and a novel simplified LightBioAge, were used to calculate biological age. Biological age acceleration was defined as a regression residual of biological age over chronological age >0, while residuals ≤0 were classified as non-accelerated aging. Cox proportional hazards models were applied to assess the associations between biological age acceleration and 10-year mortality risk after PCI. Discrimination and reclassification metrics were used to evaluate the incremental predictive value of different biological age measures for mortality outcomes. Additionally, life expectancy analyses were conducted to quantify the impact of accelerated biological aging on expected survival. Results After multivariable adjustment, acceleration of all three biological age measures was independently associated with increased risks of 10-year all-cause and cardiac mortality after PCI, with PhenoAge acceleration showing the strongest risk effect. For 10-year all-cause mortality, each one standard deviation increase in LightBioAge, KDMAge, and PhenoAge acceleration was associated with hazard ratios (HRs) of 1.23, 1.27, and 1.31, respectively. As the degree of aging acceleration increased (from Q1 to Q4), the risks of all-cause and cardiac mortality rose progressively. PhenoAge acceleration provided greater improvements in discrimination and reclassification (IDI ≈1.6%; NRI 12.2–14.4%) than LightBioAge or KDMAge acceleration. Life expectancy analyses revealed that patients with accelerated biological aging experienced a significant reduction in expected lifespan, with a graded increase in life-years lost as aging acceleration worsened. For example, a 45-year-old patient with accelerated aging exhibited a marked reduction in life expectancy, most prominently under the PhenoAge model, with a loss of up to 3.91 years (95% CI, 2.78–4.89). Conclusions Accelerated biological aging, particularly as measured by PhenoAge, is an independent predictor of 10-year all-cause and cardiac mortality after PCI in patients with coronary artery disease and is associated with shortened life expectancy.