Biological Age Acceleration and All-Cause Mortality in Moderate to Severe Aortic Valve Stenosis: A Prospective Cohort Study

BACKGROUND: Biological age acceleration (BAA) is a promising aging surrogate, but its prognostic value in moderate to severe aortic valve stenosis (AVS) remains undetermined. OBJECTIVES: In this study, the authors sought to explore the association between BAA and all-cause mortality in patients with moderate to severe AVS. METHODS: A total of 559 patients were selected in the ARISTOTLE (Aortic Valve Diseases Risk Factor Assessment and Prognosis Model Construction) study. BAA was measured with the use of clinical biomarkers based on the KDM-BA and PhenoAge algorithms. Cox regression, restricted cubic spline (RCS) regression, and incremental predictive value analyses were used to evaluate the association between BAA and mortality. RESULTS: Among 559 patients (mean age 64.80 years, 315 [56.4%] male), there were 153 cases (27.4%) of all-cause mortality during median 35.50 months of follow-up (range: 18.47-57.03 months). Kaplan-Meier curves revealed significantly elevated mortality in the highest quartile of BAA for both measures (KDM-BA: 38.8% [HR: 2.72; 95% CI: 1.73-4.29]; PhenoAge: 41.1% [HR: 3.26; 95% CI: 2.01-5.27]; both log-rank P < 0.0001). After fully adjusting for confounders, each SD increase in BAA was significantly associated with higher mortality (KDM-BA acceleration: HR: 1.36 [95% CI: 1.15-1.61]; PhenoAge acceleration: HR: 1.35 [95% CI: 1.17-1.56]). RCS regression revealed a significant linear BAA-mortality relationship. The addition of BAA into the basic model for all-cause mortality improved C-statistics (both P < 0.001), continuous-free net reclassification improvement value (both P = 0.013), and integrated discrimination improvement value (both P < 0.05). CONCLUSIONS: Biomarker-derived BAA is independently associated with increased all-cause mortality in moderate to severe AVS patients, highlighting its potential as a prognostic indicator.