Abstract
Introduction: Bone morphogenetic protein 10 (BMP10) plays a central role in cardiac embryogenesis and is known to facilitate cardiac repair after myocardial injury in adults. The prognostic value of BMP10 in heart failure (HF) remains largely unknown. Objectives: To identify biological processes related to elevated BMP10 concentrations and to investigate the prognostic utility of circulating BMP10 in HF patients. Methods: Serum BMP10 concentrations were measured in 2085 chronic HF patients from the European BIOSTAT cohort using a prototype electrochemiluminescence immunoassay developed by Roche Diagnostics. First, we performed gene set enrichment analysis to identify biological pathways related to elevated BMP10. Next, we examined the predictive value of BMP10 for all-cause mortality, HF hospitalization and a combined endpoint of mortality and/or HF hospitalization on top of an established risk score, atrial fibrillation (AF) and stroke using Cox-regression analysis after log-transformation and standardization. Results were validated in an independent cohort of HF patients (n=1487). Results: High BMP10 was related to pathways of growth and growth factor activity, regulation of bone, extracellular region, and response to hormones/glucocorticoids. After adjusting for the BIOSTAT risk scores, AF and stroke, log-BMP10 remained a strong predictor of 2-year all-cause mortality (Hazard Ratio [HR] =1.17, Confidence Interval [CI]= 1.06-1.28), HF hospitalization (HR [CI]=1.13 [1.03-1.25]) and the combined endpoint (HR [CI]=1.10 [1.02-1.19]). Similar trends were seen in the validation cohort (Figure 1). Conclusions: BMP10 is an independent predictor of HF-rehospitalization and all-cause mortality in patients with HF.
Published Version
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