Abstract 15962: Validation of the Senescence-Associated Secretome to Predict Mortality in Patients With Degenerative Aortic Valve Stenosis

Abstract

Introduction: The senescence-associated secretory phenotype (SASP) is a potential driver of age-related risk reflecting advanced biological aging. Circulating SASP components include pro-inflammatory cytokines, growth modulators and matrix remodelling proteases. Aortic valve stenosis (AVS) is the prototypical inflammatory age-associated cardiovascular disease. Hypothesis: To identify circulating SASP components with an impact on prognosis in elderly pts with AVS. Methods: In a derivation cohort (n=120), circulating levels of 24 SASP components were measured using Luminex Multiplex ELISA, before undergoing TAVR. ROC curves and Youden-index derived optimal cut-off values were used to assess the predictive power of each SASP for long-term mortality. In a validation cohort (n=198), the significant predictors of mortality identified in the derivation cohort, as well as a panel of 3 independent predictors in multivariate analyses, were prospectively validated. Results: In the derivation cohort, 9 out of 24 SASP components significantly predicted mortality in univariate analyses with AUC>0.62; only 3 (GDF-15, ICAM-1, and osteoprotegerin) remained independent predictors in multivariate analyses (all p<0.03). All 3 were confirmed as significant independent predictors of mortality in the validation cohort (see AUC curves). After adjustment for clinical parameters, a score based on the cumulative number of these 3 SASP components showed a substantial increase in long-term mortality after TAVR for each additional positive marker (see KM-curves). Conclusions: This study validates high levels of 3 SASP components reflecting different pathophysiological pathways of senescence as independent predictors of long-term mortality in AVS. Their cumulative occurrence provides a deeply improved discrimination power and, may serve as a much needed risk stratification tool in elderly patients with AVS undergoing TAVR.