Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure The HOMAGE Study

Joao Pedro Ferreira, Job Verdonschot, Timothy Collier, Ping Wang, Anne Pizard, Christian Bar, Jens Bjorkman, Alessandro Boccanelli, Javed Butler, Andrew Clark, John G. Cleland, Christian Delles, Javier Diez, Nicolas Girerd, Arantxa Gonzalez, Mark Hazebroek, Anne-Cecile Huby, Wouter Jukema, Roberto Latini, Joost LeendersDaniel Levy, Alexandre Mebazaa, Harald Mischak, Florence Pinet, Patrick Rossignol, Naveed Sattar, Peter Sever, Jan A. Staessen, Thomas Thum, Nicolas Vodovar, Zhen-Yu Zhang, Stephane Heymans, Faiez Zannad*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 reninangiotensin- 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.

Original languageEnglish
Article number005897
Number of pages12
JournalCirculation-Heart Failure
Volume12
Issue number5
DOIs
Publication statusPublished - May 2019

Keywords

  • apoptosis
  • atherosclerosis
  • blood pressure
  • heart failure
  • proteomics
  • CARDIOVASCULAR BIOMARKERS
  • NATRIURETIC PEPTIDE
  • RECEPTOR
  • ASSOCIATION
  • PREDICTORS
  • SELECTION
  • PROTEINS
  • DESIGN
  • DIFFERENTIATION
  • EPIDEMIOLOGY

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