Abstract 20145: Multiple Novel Plasma Biomarkers are Associated With Aortic Stenosis
Introduction: Calcific aortic valve disease (CAVD) can progress to aortic stenosis (AS) when the remodeling of valve tissue is sufficiently severe to result in hemodynamic changes. The discovery of biomarkers represents a complementary approach to echocardiography in stratifying risk and timing of intervention in CAVD, and has the advantage of providing insight into potential causal factors for the disease. Only a limited number of circulating plasma biomarkers have been reported to be associated with AS and there are no medical therapies to prevent or slow the progression of CAVD.
Objective: We leveraged an academic biobank linked to electronic health record data to generate a large AS case/control sample. We then utilized a multiplexed biomarker approach to novel biomarker discovery.
Methods/Results: We applied natural language processing algorithms to cardiac ECHO reports and intersected results with the Penn Medicine Biobank to generate a sample of 1,071 patients with a range of AS (mild to severe), and age and sex matched controls (n=1,026). As expected, plasma levels of lipoprotein(a) [Lp(a)] were significantly higher in subjects with AS (54.0 +/- 2.4 mg/dl) compared with controls (42.8 +/- 1.9 mg/dl, p=3.0E-04). Banked plasma samples were screened against a panel of 50 candidate biomarkers using Luminex Bead Assays. Using multivariable modeling to control for clinical covariates and after correcting for multiple testing, 11 proteins were found to be significantly different in AS subjects with a Bonferroni corrected p-value of 1E-3. We confirmed previous reports of increased pro-BNP (p=7.4E-09), and FGF-23 (p=7.7E-06) in subjects with AS and identified 9 novel circulating proteins that are significantly different in AS, including syndecan-4 (p=1.1E-10) and GDF-15 (p=4.6E-09).
Conclusions: Biomarker discovery for CAVD and AS represents a new approach to diagnosis and can shed light on disease pathogenesis. We report 9 novel biomarkers significantly different in AS patients compared with matched controls using a large case-control study.
Author Disclosures: A. Small: None. D. Kiss: None. J. Chirinos: None. S. Damrauer: None. J. Giri: None. M. Guerraty: None. G. Ferrari: None. D. Rader: None.
- © 2016 by American Heart Association, Inc.