Panel of emerging cardiac biomarkers contributes for prognosis rather than diagnosis in chronic heart failure

Biomark Med. 2014;8(6):777-89. doi: 10.2217/bmm.14.31.

Abstract

Background: As complex disease, heart failure is associated with various pathophysiological and biochemical disorders. No single biomarker is able to display all these characteristics. Therefore, we evaluated a multimarker panel together with the biochemical gold-standard NT-proBNP. Part of the panel are markers for angiogenesis (Endostatin, IBP-4, IBP-7, sFlt-1 as antiangiogenetic factors and PLGF as angiogenectic factor), myocyte stress (GDF-15), extracellular matrix remodelling (galectin-3, mimecan and TIMP-1), inflammation (galectin-3) and myocyte injury (hs-TnT).

Methods: All markers (Roche Diagnostics, Penzberg, Germany) were assessed in a cohort of 149 patients with chronic heart failure and 84 healthy controls.

Results: All markers were positively correlated with ln NT-proBNP (each p < 0.05). Furthermore, they were significantly elevated in patients with chronic heart failure (each p < 0.05). All markers increased significantly with severity of LV dysfunction and severity of New York Heart Association class (each p < 0.05), except for PLGF and Mimecan (each p = NS). With the exception of endostatin, mimecan and PLGF, all other markers were further significant predictors for all-cause mortality in a 3-year follow-up. In a multimarker approach of the five biomarkers with the best performance (NT-proBNP, hs-TnT, TIMP-1, GDF-15 and IBP-4), the event rate was superior to NT-proBNP alone and increased significantly and progressively with the number of elevated biomarkers.

Conclusion: All emerging markers increased stepwise with the severity of symptoms and LV dysfunction and offer important prognostic information in chronic heart failure, except for PLGF and mimecan. Five biomarkers with different pathophysiological background incorporated additive prognostic value in heart failure. Prognostication in heart failure may be further improved through a multimarker approach.

Keywords: GDF-15; chronic heart failure; emerging biomarkers; highly sensitive troponin; natriuretic peptides.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Proteins
  • Chronic Disease
  • Endostatins / blood
  • Female
  • Follow-Up Studies
  • Galectin 3 / blood
  • Galectins
  • Growth Differentiation Factor 15 / blood
  • Heart Failure / blood*
  • Heart Failure / diagnosis*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Placenta Growth Factor
  • Pregnancy Proteins / blood
  • Prognosis
  • Survival Rate
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Troponin T / blood
  • Vascular Endothelial Growth Factor Receptor-1 / blood
  • Ventricular Dysfunction, Left / blood
  • Ventricular Dysfunction, Left / diagnosis
  • Ventricular Dysfunction, Left / mortality
  • Ventricular Dysfunction, Left / physiopathology

Substances

  • Biomarkers
  • Blood Proteins
  • Endostatins
  • GDF15 protein, human
  • Galectin 3
  • Galectins
  • Growth Differentiation Factor 15
  • Intercellular Signaling Peptides and Proteins
  • LGALS3 protein, human
  • OGN protein, human
  • PGF protein, human
  • Peptide Fragments
  • Pregnancy Proteins
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Placenta Growth Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1