@article{1fe52bbb29874f49844b96a9d2f6356c,
title = "Proteomic Bioprofiles and Mechanistic Pathways of Progression to Heart Failure The HOMAGE Study",
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.",
keywords = "apoptosis, atherosclerosis, blood pressure, heart failure, proteomics, CARDIOVASCULAR BIOMARKERS, NATRIURETIC PEPTIDE, RECEPTOR, ASSOCIATION, PREDICTORS, SELECTION, PROTEINS, DESIGN, DIFFERENTIATION, EPIDEMIOLOGY",
author = "Ferreira, {Joao Pedro} and Job Verdonschot and Timothy Collier and Ping Wang and Anne Pizard and Christian Bar and Jens Bjorkman and Alessandro Boccanelli and Javed Butler and Andrew Clark and Cleland, {John G.} and Christian Delles and Javier Diez and Nicolas Girerd and Arantxa Gonzalez and Mark Hazebroek and Anne-Cecile Huby and Wouter Jukema and Roberto Latini and Joost Leenders and Daniel Levy and Alexandre Mebazaa and Harald Mischak and Florence Pinet and Patrick Rossignol and Naveed Sattar and Peter Sever and Staessen, {Jan A.} and Thomas Thum and Nicolas Vodovar and Zhen-Yu Zhang and Stephane Heymans and Faiez Zannad",
note = "Funding Information: The research leading to these results has received funding from the European Union Commission's Seventh Framework Programme under grant agreement No. 305507 (HOMAGE [Heart Omics in Ageing consortium]). We acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with the support of the Dutch Heart Foundation CVON2016-Early HFPEF, and CVON 2017, ShePREDICTS. Funding Information: Drs Ferreira, Rossignol, and Zannad are supported by the French National Research Agency Fighting Heart Failure (ANR-15-RHU-0004), by the French PIA project Lorraine Universit{\'e} d{\textquoteright}Excellence GEENAGE (ANR-15-IDEX-04-LUE) programs, and the Contrat de Plan Etat R{\'e}gion Lorraine and FEDER IT2MP. Dr Mis-chak is the co-founder and co-owner of Mosaiques Diagnostics. Dr Mebazaa received honoraria for lectures from Roche and Abbott, consultation fees from Sanofi and Servier, and research grants from Adrenomed and Sphyngotec. The other authors report no conflicts. Funding Information: The research leading to these results has received funding from the European Union Commission{\textquoteright}s Seventh Framework Programme under grant agreement No. 305507 (HOMAGE [Heart Omics in Ageing consortium]). We acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with the support of the Dutch Heart Foundation CVON2016-Early HFPEF, and CVON 2017, ShePREDICTS. Publisher Copyright: {\textcopyright} 2019 American Heart Association, Inc.",
year = "2019",
month = may,
doi = "10.1161/CIRCHEARTFAILURE.118.005897",
language = "English",
volume = "12",
journal = "Circulation-Heart Failure",
issn = "1941-3289",
publisher = "Lippincott Williams & Wilkins",
number = "5",
}