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Abstract
Background We evaluated the potential of circulating bone morphogenetic protein 10 (BMP10) as a biomarker for atrial stress and remodelling in patients with heart failure (HF), in comparison to N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also assessed the predictive value of BMP10 for adverse clinical outcomes.
Methods BMP10 levels were quantified in 2085 chronic HF patients from the European BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) cohort and in 1487 patients from the Scottish validation cohort. Multivariable linear regression identified independent associates of BMP10. Proteomic analysis of 6369 proteins with subsequent gene set enrichment analysis was used to explore biological pathways associated with elevated BMP10. Cox proportional hazards models adjusting for established risk factors were used to associate BMP10 levels with clinical outcomes, including all-cause mortality and HF hospitalisation.
Results In a multivariable model including clinical and echocardiographic parameters, log-transformed and standardised BMP10 levels were significantly associated with a history of atrial fibrillation (Sβ=0.419; p<0.001), and with echocardiographic features reflecting atrial stress, such as increased left atrial diameter (Sβ=0.075; p=0.048). By contrast, these were not among the strongest associates of NT-proBNP levels. Gene set enrichment analysis showed significant overrepresentation in pathways of muscle contraction and extracellular matrix organisation. Higher log-transformed and standardised BMP10 levels predicted a combined outcome of 2-year all-cause mortality and HF rehospitalisation (HR=1.10, 95% CI=1.02–1.19), with the validation cohort yielding comparable results.
Conclusion BMP10 emerges as a novel biomarker reflecting atrial stress and remodelling in chronic HF patients. Its additional predictive value for adverse outcomes underscores its potential utility in enhancing risk stratification and guiding therapeutic interventions in HF management.
- Heart failure
- Biomarkers
- Cardiovascular Diseases
- Risk Assessment
Data availability statement
Data are available upon reasonable request. The data used in this study are available upon request from the corresponding author, subject to any restrictions imposed by the data providers or institutions involved.
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Data availability statement
Data are available upon reasonable request. The data used in this study are available upon request from the corresponding author, subject to any restrictions imposed by the data providers or institutions involved.
Footnotes
Contributors DCHC: methodology, validation, formal analysis, writing—original draft, visualisation. VB: investigation, data curation, writing—review and editing. BJvE: methodology, formal analysis, validation, writing—review and editing. AAV: conceptualisation, writing—review and editing. RAdB: conceptualisation, writing—review and editing. JMtM: conceptualisation, methodology, writing—review and editing. SM: writing—review and editing. PK: methodology. CCL: writing—review and editing. NS: methodology, writing—review and editing, supervision, project administration, conceptualisation. Guarantor: DCHC.
Funding Drs. Suthahar and de Boer are supported by the Netherlands Heart Foundation (CVON SHE-PREDICTS-HF, grant 2017-21; CVON RED-CVD, grant 2017-11; CVON PREDICT2, grant 2018-30; and CVON DOUBLE DOSE, grant 2020B005). Dr. de Boer is also supported by the European Research Council (ERC CoG 818715, SECRETE-HF).This study was funded by the European Union. Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or HADEA. Neither the European Union nor the granting authority can be held responsible for them. This project has received funding from the European Union under grant agreement No 101095653
Competing interests RAdB has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Novo Nordisk, and Roche; has had speaker engagements with and/or received fees from and/or served on an advisory board for Abbott, AstraZeneca, Bristol Myers Squibb, Cardior Pharmaceuticals GmbH, Novo Nordisk, and Roche; has received travel support from Abbott, Cardior Pharmaceuticals GmbH and Novo Nordisk. AAV received consultancy fees from Anacardio, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Corteria, Merck, Novartis, Novo Nordisk, Eli Lilly, Moderna, Roche Diagnostics, SalubrisBio. CCL has received consultancy fees and/or research grants from Amgen, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Novo Nordisk and Servier. SM is an employee at Roche Diagnostics International, Rotkreuz, Switzerland. The remaining authors have nothing to disclose.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer-reviewed.
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