Abstract P199: Proteomic Markers of Aortic Stenosis: The Atherosclerosis Risk in Communities Study

Abstract

Introduction: Although prevalence of aortic stenosis (AS) is increasing, little is known regarding circulating proteins predictive of AS development. Hypothesis: Novel circulating proteins associated with AS hemodynamics and clinical outcomes can be discovered using plasma proteomics. Methods: In the community-based Atherosclerosis Risk in Communities study, we measured plasma proteomics using the SOMAscan aptamer-affinity assay (n=4,877 aptamers; Somalogic Inc.) at study Visits 3 (V3; 1992-94; n=11,430) and 5 (V5; 2011-2013; n=4,899). Multivariable linear regression was used to estimate cross-sectional associations of log-transformed proteins at V5 with aortic valve (AV) peak velocity (Vmax) assessed by protocol echocardiography at a false discovery rate (FDR) of <0.05. We then assessed the association of Vmax-related proteins at V3 with incident AV-related hospitalizations post-V3 using multivariable Cox proportional hazard models at FDR of <0.05. All models adjusted for cardiovascular risk factors and diseases at the time of visit. Results: At V5 (age 76 ± 5 years; 43% male; 18% Black adults), 946 proteins were cross-sectionally associated with Vmax. At V3, (age 60 ± 6 years; 46% male; 21% Black), 84 of these were associated with risk of AS-related hospitalization post-V3 (median follow-up 22.2 [IQR 14.4 - 24.8] years, n=912 events). Of these 84 proteins, 52 were also cross-sectionally associated with the Dimensionless index (DI) at V5. Hierarchical clustering based on V5 AV hemodynamic indices identified one cluster of 14 proteins associated with lower hemodynamic AS severity and risk of AV-related hospitalization ( Figure ). Proteins in the remaining three clusters were associated with higher Vmax, lower DI, and higher risk of AV-related hospitalization. The nine proteins in cluster 4 were also associated with lower indexed AV area. Conclusion: We identified 52 circulating proteins with robust associations with AV hemodynamics and hospitalization risk, providing potential novel biomarkers for AS risk.