Biological Age Acceleration and All-Cause Mortality in Moderate to Severe Aortic Valve Stenosis

Figures

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  Figure 1. Flowchart of the Study This flowchart illustrates the sequential selection of the population from the ARISTOTLE study, which initially enrolled 640 patients with moderate to severe aortic valve stenosis. After the exclusion of 29 patients with missing baseline data, 611 patients were eligible for biological age assessment. Further exclusions were made for 22 patients with extreme biological age values and 30 patients lost to follow-up, resulting in a cohort of 559 patients. This cohort formed the basis for the further analyses exploring the association between biological age acceleration and clinical outcomes. ARISTOTLE = Aortic Valve Diseases Risk Factor Assessment and Prognosis Model Construction; KDM-BA = Klemera-Doubal–method biological age.

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  Figure 2. Association of BAA With All-Cause Mortality According to Kaplan-Meier Survival Curves Kaplan-Meier survival curves depict the overall survival probability stratified by quartiles (Q1-Q4) of biological age acceleration (BAA). (A) Overall survival probability difference among KDM-BA acceleration groups. (B) Overall survival probability difference among PhenoAge acceleration groups. Significantly elevated all-cause mortality in the highest quartile (Q4) of BAA was observed (both P for log-rank <0.0001). Among patients with moderate to severe aortic valve stenosis, greater BAA was strongly associated with worse survival rate. KDM-BA = Klemera-Doubal–method biological age.

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  Figure 3. Dose-Response Relationship Between BAA and All-Cause Mortality Risk Restricted cubic spline analyses illustrate the continuous association of biological age acceleration (BAA) with all-cause mortality, expressed as hazard ratio (HR). (A) Association between KDM-BA acceleration and all-cause mortality risk. (B) Association between PhenoAge acceleration and all-cause mortality risk. No significant nonlinear relationship was observed. Greater BAA was associated with higher all-cause mortality risk. The red dashed line represents HR = 1. The blue and green solid lines show the HRs. The blue and green shaded areas represent the 95% CIs. CKDM-BA, Klemera-Doubal–method biological age.

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  Figure 4. Subgroup Analysis of Biological Age Acceleration (BAA) and All-Cause Mortality Risk Subgroup analyses were performed aiming to present the association between BAA and all-cause mortality across key clinical subgroups. (A) Associations for KDM-BA–derived acceleration. (B) Associations for PhenoAge-derived acceleration. The results demonstrate that the elevated mortality risk associated with BAA is generally consistent across most subgroups, with significant interaction between smoking and KDM-BA acceleration (P = 0.011). The blue and green dots indicate the HR values. The blue and green solid lines represent the 95% CI. AVS = aortic valve stenosis; KDM-BA = Klemera-Doubal–method biological age.

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  Central Illustration. Association Between BASA and All-Cause Mortality Risk in Moderate to Severe AVS This study aimed to explore the association between biological age acceleration (BAA) and all-cause mortality risk in moderate to severe aortic valve stenosis (AVS) patients. Two BAA algorithms (KDM-BA acceleration and PhenoAge acceleration) were calculated as the regression residuals of biological age and chronologic age (CA), where biological age was calculated from clinical biomarkers and CA. Kaplan-Meier survival curves demonstrated that greater BAA was strongly associated with worse survival rate. After fully adjusting for confounders, multivariable Cox regression analysis showed that each SD increase in both BAA measures was significantly associated with increased all-cause mortality risks. KDM-BA = Klemera-Doubal method biological age.