Proteomic bioprofiles and mechanistic pathways of progression to heart failure: the HOMAGE study

Ferreira, J. P. et al. (2019) Proteomic bioprofiles and mechanistic pathways of progression to heart failure: the HOMAGE study. Circulation, 12(5), e005897. (doi: 10.1161/CIRCHEARTFAILURE.118.005897) (PMID:31104495)

Abstract

Background: Identifying the mechanistic pathways potentially associated with incident heart failure (HF) may provide a basis for novel preventive strategies. Methods and Results: To identify proteomic biomarkers and the potential underlying mechanistic pathways that may be associated with incident HF defined as the first hospitalization for HF, a nested-matched case-control design was used with cases (incident HF) and controls (without HF) selected from 3 cohorts (>20 000 individuals). Controls were matched on cohort, follow-up time, age, and sex. Two independent sample sets (a discovery set with 286 cases and 591 controls and a replication set with 276 cases and 280 controls) were used to discover and replicate the findings. Two hundred fifty-two circulating proteins in the plasma were studied. Adjusting for the matching variables age, sex, and follow-up time (and correcting for multiplicity of tests), 89 proteins were found to be associated with incident HF in the discovery phase, of which 38 were also associated with incident HF in the replication phase. These 38 proteins pointed to 4 main network clusters underlying incident HF: (1) inflammation and apoptosis, indicated by the expression of the TNF (tumor necrosis factor)-family members; (2) extracellular matrix remodeling, angiogenesis and growth, indicated by the expression of proteins associated with collagen metabolism, endothelial function, and vascular homeostasis; (3) blood pressure regulation, indicated by the expression of natriuretic peptides and proteins related to the renin-angiotensin-aldosterone system; and (4) metabolism, associated with cholesterol and atherosclerosis. Conclusions: Clusters of biomarkers associated with mechanistic pathways leading to HF were identified linking inflammation, apoptosis, vascular function, matrix remodeling, blood pressure control, and metabolism. These findings provide important insight on the pathophysiological mechanisms leading to HF.

• Item Type: Articles
• Additional Information: The research leading to these results has received funding from the European Union Commission’s Seventh Framework programme under grant agreement N° 305507 (HOMAGE). We acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart FoundationCVON2016-Early HFPEF, and CVON 2017, ShePREDICTS.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mischak, Professor Harald and Cleland, Professor John and Delles, Professor Christian and Ferreira, Mr Joao Pedro and Sattar, Professor Naveed
• Authors: Ferreira, J. P., Verdonschot, J., Collier, T., Wang, P., Pizard, A., Bär, C., Björkman, J., Boccanelli, A., Butler, J., Clark, A., Cleland, J. G., Delles, C., Diez, J., Girerd, N., González, A., Hazebroek, M., Huby, A.-C., Jukema, W., Latini, R., Leenders, J., Levy, D., Mebazaa, A., Mischak, H., Pinet, F., Rossignol, P., Sattar, N., Sever, P., Staessen, J. A., Thum, T., Vodovar, N., Zhang, Z.-Y., Heymans, S., and Zannad, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Circulation
• Publisher: American Heart Association
• ISSN: 0009-7322
• ISSN (Online): 1524-4539
• Published Online: 20 May 2019
• Copyright Holders: Copyright © 2019 American Heart Association, Inc.
• First Published: First published in Circulation 12(5):e005897
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher