Variability of biomarkers in patients with chronic heart failure and healthy controls

Eur J Heart Fail. 2017 Mar;19(3):357-365. doi: 10.1002/ejhf.669. Epub 2016 Oct 21.


Aims: Biomarkers can be used for diagnosis, risk stratification, or management of patients with heart failure (HF). Knowledge about the biological variation is needed for proper interpretation of serial measurements. Therefore, we aimed to determine and compare the biological variation of a large panel of biomarkers in healthy subjects and in patients with chronic HF.

Methods and results: The biological variability of established biomarkers [NT-proBNP and high-sensitivity troponin T (hsTnT)], novel biomarkers [galectin-3, suppression of tumorigenicity 2 (ST2), and growth differentiation factor 15 (GDF-15)], and renal/neurohormonal biomarkers (aldosterone, phosphate, parathyroid hormone, plasma renin concentration, and creatinine) was determined in 28 healthy subjects and 83 HF patients, over a period of 4 months and 6 weeks, respectively. The analytical (CVa ), intraindividual (CVi ), and interindividual (CVg ) variations were calculated, as well as the reference change value (RCV), which reflects the percentage of change that may indicate a 'relevant' change. All crude biomarker levels were significantly increased or decreased in HF patients compared with controls (all P < 0.01). Variation indices were comparable in healthy individuals and HF patients. CVi was not influenced by the individual levels of the biomarker itself. NT-proBNP and GDF-15 had relatively high CVi (21.8% and 16.6%) and RCV (61.7% and 64.3%), whereas ST2 (CVi , 15.0; RCV, 42.9%), hsTnT (CVi , 11.1; RCV, 31.4%), and galectin-3 (CVi , 8.1; RCV, 25.0%) had lower indices of variation.

Conclusion: Biological variation indices are comparable between healthy subjects and HF patients for a broad spectrum of biomarkers. NT-proBNP and GDF-15 have substantial variation, with lower variation for ST2, hsTnT, and galectin-3. These data are instrumental in proper interpretation of biomarker levels in HF patients.

Keywords: Biological variation; Biomarkers; Heart failure; Management programme; NT-proBNP.

MeSH terms

  • Adult
  • Aged
  • Aldosterone / blood
  • Biomarkers / blood
  • Case-Control Studies
  • Chronic Disease
  • Creatinine / blood
  • Female
  • Galectin 3 / blood
  • Growth Differentiation Factor 15 / blood
  • Heart Failure / blood*
  • Heart Failure / physiopathology
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein / blood
  • Linear Models
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Parathyroid Hormone / blood
  • Peptide Fragments / blood
  • Phosphates / blood
  • Renin / blood
  • Stroke Volume
  • Troponin T / blood


  • Biomarkers
  • GDF15 protein, human
  • Galectin 3
  • Growth Differentiation Factor 15
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Parathyroid Hormone
  • Peptide Fragments
  • Phosphates
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Aldosterone
  • Creatinine
  • Renin