Biomarker Profiles in Heart Failure Patients With Preserved and Reduced Ejection Fraction

J Am Heart Assoc. 2017 Mar 30;6(4):e003989. doi: 10.1161/JAHA.116.003989.

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.

Methods and 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 (P for 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.

Keywords: biomarker; heart failure; multimarker; pathophysiology.

MeSH terms

  • Acute Disease
  • Aged
  • Aged, 80 and over
  • Atrial Natriuretic Factor / blood*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Case-Control Studies
  • Cause of Death
  • Female
  • Heart Failure / blood*
  • Heart Failure / physiopathology
  • Hospitalization
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Mortality
  • Natriuretic Peptide, Brain / blood*
  • Neuropilins / blood*
  • Osteopontin / blood*
  • Patient Readmission
  • Peptide Fragments / blood*
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Vascular Endothelial Growth Factor / blood*
  • Retrospective Studies
  • Stroke Volume

Substances

  • Biomarkers
  • Neuropilins
  • Peptide Fragments
  • SPP1 protein, human
  • pro-brain natriuretic peptide (1-76)
  • Osteopontin
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor
  • C-Reactive Protein
  • Receptors, Vascular Endothelial Growth Factor