Protein biomarkers of new-onset heart failure: insights from the Heart Omics and Ageing cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study

Girerd, N. et al. (2023) Protein biomarkers of new-onset heart failure: insights from the Heart Omics and Ageing cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study. Circulation: Heart Failure, 16(5), pp. 426-441. (doi: 10.1161/CIRCHEARTFAILURE.122.009694) (PMID:37192292) (PMCID:PMC10179982)

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Background: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone. Methods: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and HOMAGE cohort (562/871). Results: In single protein analysis, after adjusting for matching variables and clinical risk factors (and correcting for multiple testing), 62 proteins were associated with incident HF in ARIC, 16 in FHS, and 116 in HOMAGE cohort. Proteins associated with incident HF in all cohorts were BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), eukaryotic translation initiation factor 4E-BP1 (4E-binding protein 1), hepatocyte growth factor (HGF), Gal-9 (galectin-9), TGF-alpha (transforming growth factor alpha), THBS2 (thrombospondin-2), and U-PAR (urokinase plasminogen activator surface receptor). The increment in C-index for incident HF based on a multiprotein biomarker approach, in addition to clinical risk factors and NT-proBNP, was 11.1% (7.5%–14.7%) in ARIC, 5.9% (2.6%–9.2%) in FHS, and 7.5% (5.4%–9.5%) in HOMAGE cohort, all P<0.001), each of which was a larger increase than that for NT-proBNP on top of clinical risk factors. Complex network analysis revealed a number of overrepresented pathways related to inflammation (eg, tumor necrosis factor and interleukin) and remodeling (eg, extracellular matrix and apoptosis). Conclusions: A multiprotein biomarker approach improves prediction of incident HF when added to natriuretic peptides and clinical risk factors.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Cleland, Professor John and Delles, Professor Christian and Ferreira, Mr Joao Pedro and Sattar, Professor Naveed and Pellicori, Dr Pierpaolo
Authors: Girerd, N., Levy, D., Duarte, K., Ferreira, J. P., Ballantyne, C., Collier, T., Pizard, A., Björkman, J., Butler, J., Clark, A., Cleland, J. G., Delles, C., Diez, J., González, A., Hazebroek, M., Ho, J., Huby, A.-C., Hwang, S.-J., Latini, R., Mariottoni, B., Mebazaa, A., Pellicori, P., Sattar, N., Sever, P., Staessen, J. A., Verdonschot, J., Heymans, S., Rossignol, P., and Zannad, F.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Circulation: Heart Failure
Publisher:American Heart Association
ISSN (Online):1941-3297
Published Online:16 May 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Circulation: Heart Failure 16(5): 426-441
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190666HOMAGE: Heart OMics in AGEingChristian DellesEuropean Commission (EC)305507Institute of Cardiovascular & Medical Sciences