Limited Added Value of Circulating Inflammatory Biomarkers in Chronic Heart Failure

JACC Heart Fail. 2017 Apr;5(4):256-264. doi: 10.1016/j.jchf.2017.01.008.

Abstract

Objectives: This study sought to evaluate whether a panel of biomarkers improved prognostication in patients with heart failure (HF) and reduced ejection fraction of ischemic origin using a systematized approach according to suggested requirements for validation of new biomarkers.

Background: Modeling combinations of multiple circulating markers could potentially identify patients with HF at particularly high risk and aid in the selection of individualized therapy.

Methods: From a panel of 20 inflammatory and extracellular matrix biomarkers, 2 different biomarker panels were created and added to the Seattle HF score and the prognostic model from the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study (n = 1,497), which included conventional clinical characteristics and C-reactive protein and N-terminal pro-B-type natriuretic peptide. Interactions with statin treatment were also assessed.

Results: The two models-model 1 (endostatin, interleukin 8, soluble ST2, troponin T, galectin 3, and chemokine [C-C motif] ligand 21) and model 2 (troponin T, soluble ST2, galectin 3, pentraxin 3, and soluble tumor necrosis factor receptor 2)-significantly improved the CORONA and Seattle HF models but added only modestly to their Harrell's C statistic and net reclassification index. In addition, rosuvastatin had no effect on the levels of a wide range of inflammatory and extracellular matrix markers, but there was a tendency for patients with a lower level of biomarkers in the 2 panels to have a positive effect from statin treatment.

Conclusions: In the specific HF patient population studied, a multimarker approach using the particular panel of biomarkers measured was of limited clinical value for identifying future risk of adverse outcomes.

Keywords: biomarkers; chronic ischemic heart disease; heart failure; inflammation; mortality; survival.

MeSH terms

  • Biomarkers / blood
  • Blood Proteins
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / mortality*
  • Cause of Death
  • Chemokine CCL21 / blood
  • Chronic Disease
  • Endostatins / blood
  • Galectin 3 / blood
  • Galectins
  • Heart Failure / blood*
  • Heart Failure / drug therapy
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Inflammation
  • Interleukin-1 Receptor-Like 1 Protein / blood
  • Interleukin-8 / blood
  • Mortality*
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Prognosis
  • Proportional Hazards Models
  • Rosuvastatin Calcium / therapeutic use
  • Serum Amyloid P-Component / metabolism
  • Troponin T / blood

Substances

  • Biomarkers
  • Blood Proteins
  • CCL21 protein, human
  • CXCL8 protein, human
  • Chemokine CCL21
  • Endostatins
  • Galectin 3
  • Galectins
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-8
  • LGALS3 protein, human
  • Peptide Fragments
  • Serum Amyloid P-Component
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • PTX3 protein
  • Rosuvastatin Calcium
  • C-Reactive Protein