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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 172-179 |
| Number of pages | 8 |
| Journal | Heart |
| Volume | 111 |
| Issue number | 4 |
| Early online date | 29 Nov 2024 |
| DOIs | |
| Publication status | Published - 29 Jan 2025 |