title: Biomarker Profiles in Heart Failure Patients With Preserved and Reduced Ejection Fraction.
abstract: BACKGROUND
  Biomarkers may help us to unravel differences in the underlying pathophysiology between heart failure (HF) patients with a reduced ejection fraction (HFrEF) and a preserved ejection fraction (HFpEF). Therefore, we compared biomarker profiles to characterize pathophysiological differences between patients with HFrEF and HFpEF.
  
  
  RESULTS
  We retrospectively analyzed 33 biomarkers from different pathophysiological domains (inflammation, oxidative stress, remodeling, cardiac stretch, angiogenesis, arteriosclerosis, and renal function) in 460 HF patients (21% HFpEF, left ventricular ejection fraction ≥45%) measured at discharge after hospitalization for acute HF. The association between these markers and the occurrence of all-cause mortality and/or HF-related rehospitalizations at 18 months was compared between patients with HFrEF and HFpEF. Patients were 70.6±11.4 years old and 37.4% were female. Patients with HFpEF were older, more often female, and had a higher systolic blood pressure. Levels of high-sensitive C-reactive protein were significantly higher in HFpEF, while levels of pro-atrial-type natriuretic peptide and N-terminal pro-brain natriuretic peptide were higher in HFrEF. Linear regression followed by network analyses revealed prominent inflammation and angiogenesis-associated interactions in HFpEF and mainly cardiac stretch-associated interactions in HFrEF. The angiogenesis-specific marker, neuropilin and the remodeling-specific marker, osteopontin were predictive for all-cause mortality and/or HF-related rehospitalizations at 18 months in HFpEF, but not in HFrEF (Pfor interaction <0.05).
  
  
  CONCLUSIONS
  In HFpEF, inflammation and angiogenesis-mediated interactions are predominantly observed, while stretch-mediated interactions are found in HFrEF. The remodeling marker osteopontin and the angiogenesis marker neuropilin predicted outcome in HFpEF, but not in HFrEF.
authors.affiliation: Department of Cardiology, University Medical Center Groningen University of Groningen, The Netherlands.
authors.forename: Jasper
authors.initials: J
authors.lastname: Tromp
authors.affiliation: Department of Cardiology, University Medical Center Groningen University of Groningen, The Netherlands.|Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Mohsin A F
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Cardiology, University Medical Center Groningen University of Groningen, The Netherlands.
authors.forename: IJsbrand T
authors.initials: IT
authors.lastname: Klip
authors.affiliation: Department of Cardiology, University Medical Center Groningen University of Groningen, The Netherlands.|Department of Cardiology, Heart Center Oldenburg, European Medical School Oldenburg-Groningen, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Department of Cardiology, University Medical Center Groningen University of Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: Department of Social- and Welfare Studies, Faculty of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Tiny
authors.initials: T
authors.lastname: Jaarsma
authors.affiliation: Department of Cardiology, University Medical Center Groningen University of Groningen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Hillege
authors.affiliation: Department of Cardiology, University Medical Center Groningen University of Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Department of Cardiology, University Medical Center Groningen University of Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
authors.affiliation: Department of Cardiology, University Medical Center Groningen University of Groningen, The Netherlands a.a.voors@umcg.nl.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D002423:Cause of Death; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology; D006760:Hospitalization; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009026:Mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D039921:Neuropilins / Q000097:blood*; D053495:Osteopontin / Q000097:blood*; D010359:Patient Readmission; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D040262:Receptors, Vascular Endothelial Growth Factor / Q000097:blood*; D012189:Retrospective Studies; D013318:Stroke Volume
chemical_list: D015415:Biomarkers; D039921:Neuropilins; D010446:Peptide Fragments; C506895:SPP1 protein, human; C109794:pro-brain natriuretic peptide (1-76); D053495:Osteopontin; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D002097:C-Reactive Protein; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: biomarker; heart failure; multimarker; pathophysiology