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Clinical relevance of biological variation: the lesson of brain natriuretic peptide (BNP) and NT-proBNP assay

  • Aldo Clerico , Gian Carlo Zucchelli , Alessandro Pilo , Claudio Passino and Michele Emdin
Published/Copyright: April 7, 2006
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 44 Issue 4

Abstract

The clinical relevance of brain natriuretic peptide (BNP) and N-terminal (NT)-proBNP assays as a diagnostic tool and prognostic marker in patients with cardiovascular diseases has recently been confirmed. However, several studies demonstrated variation of intra-individual BNP concentrations of >30% (ranging from 30% to 50%) with reference change values at the 95% confidence interval (i.e., the estimated critical difference) ranging from 99% to 130% in healthy subjects and heart failure patients. According to this estimated confidence interval, only a great variation in plasma BNP levels should be considered significant in an individual patient (for example, a decrease of >50% or an increase of more than two-fold). Many recent clinical studies have demonstrated that BNP variations below this estimated critical difference could also have clinical relevance. Like the concentration of other neuro-hormones, levels of plasma BNP fluctuate widely and rapidly along with heart rhythm and blood pressure variations in response to physiological stimuli. However, biological variation of BNP should not be interpreted strictly as random fluctuation around a homeostatic set point, as assumed by the common model used in all studies on biological variation of BNP reported in the literature. These results cannot be directly transferred to clinical practice. While awaiting more accurate studies, we suggest that variations of plasma BNP three-fold greater than the analytical imprecision should be considered as potentially relevant from a physiological and clinical point of view.

Keywords: acute coronary syndrome; atrial natriuretic peptide (ANP); biological variation; brain natriuretic peptide (BNP); cardiac function; cardiac natriuretic hormones; cardiovascular diseases; heart failure
Corresponding author: Aldo Clerico, MD, Laboratory of Cardiovascular Endocrinology and Cell Biology, CNR Institute of Clinical Physiology, Via Trieste 41, 56126 Pisa, Italy Phone: +39-0585-493569, Fax: +39-0585-493601

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Received: 2005-8-10
Accepted: 2005-12-28
Published Online: 2006-4-7
Published in Print: 2006-4-1

©2006 by Walter de Gruyter Berlin New York

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https://doi.org/10.1515/CCLM.2006.063
Keywords for this article
acute coronary syndrome; atrial natriuretic peptide (ANP); biological variation; brain natriuretic peptide (BNP); cardiac function; cardiac natriuretic hormones; cardiovascular diseases; heart failure

Articles in the same Issue

  1. Natriuretic peptides and evidence-based quality specifications
  2. Preanalytical variability: the dark side of the moon in laboratory testing
  3. Clinical relevance of biological variation: the lesson of brain natriuretic peptide (BNP) and NT-proBNP assay
  4. Hepatorenal syndrome
  5. Modified Levey-Jennings charts for calculated laboratory tests
  6. Increased free malondialdehyde concentrations in smokers normalise with a mixed fruit and vegetable juice concentrate: a pilot study
  7. The exponentially weighted moving average (EWMA) rule compared with traditionally used quality control rules
  8. Intermethod calibration of alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) results: application to Fibrotest® and Actitest® scores
  9. Comparison of TEST 1 with SRS 100 and ICSH reference method for the measurement of the length of sedimentation reaction in blood
  10. Multicenter evaluation of the interference of hemoglobin, bilirubin and lipids on Synchron LX-20 assays
  11. Technical evaluation of the Beckman Coulter OV-Monitor (CA 125 antigen) immunoassay
  12. Erythrocyte membrane Na+,K+-ATPase and Mg2+-ATPase activities in subjects with methylenetetrahydrofolate reductase (MTHFR) 677 C→T genotype and moderate hyperhomocysteinaemia. The role of L-phenylalanine and L-alanine
  13. Matrix metalloproteinases and their inhibitors in different acute stroke subtypes
  14. Pyrosequencing protocol requiring a unique biotinylated primer
  15. Detection of antibodies against 60-, 65- and 70-kDa heat shock proteins in paediatric patients with various disorders using Western blotting and ELISA
  16. Quantitative determination of erythrocyte folate vitamer distribution by liquid chromatography-tandem mass spectrometry
  17. Time-level relationship between indicators of oxidative stress and Glasgow Coma Scale scores of severe head injury patients
  18. Stepwise strategies in analysing haematuria and leukocyturia in screening
  19. Elevation of serum cerebral injury markers correlates with serum choline decline after coronary artery bypass grafting surgery
  20. Drug screening in urine by cloned enzyme donor immunoassay (CEDIA) and kinetic interaction of microparticles in solution (KIMS): a comparative study
  21. Release of anandamide from blood cells
  22. Rapid decrease in plasma D-lactate as an early potential predictor of diminished 28-day mortality in critically ill septic shock patients
  23. Evaluation of an immunoassay of whole blood sirolimus in pediatric transplant patients in comparison with high-performance liquid chromatography/tandem mass spectrometry
  24. Sample processing and its preanalytical impact on the measurement of circulating matrix metalloproteinases
  25. Physiological matrix metalloproteinase (MMP) concentrations: comparison of serum and plasma specimens
  26. Importance of the functional sensitivity determination of a serum hyaluronic acid assay for the prediction of liver fibrosis in patients with features of the metabolic syndrome
  27. The dilemma of invasive and non-invasive investigations for adult and paediatric non-alcoholic fatty liver disease: has the time come for a new biochemical marker?
  28. Is cystatin C a reliable renal marker in trauma?
  29. On the independence of intraindividual reference values
  30. Sixth International Symposium on Molecular Diagnostics, Graz, Austria, May 25-27, 2006
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