title: NT-ProBNP levels in saliva and its clinical relevance to heart failure.
abstract: BACKGROUND
  Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and ∼20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels.
  
  
  METHODS
  Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at -80°C until analysis. A customised homogeneous sandwich AlphaLISA((R)) immunoassay was used to quantify NT-proBNP levels in saliva.
  
  
  RESULTS
  Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r(2) = 0.78 (p<0.01, y = 1.705× +1910.8). The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%.
  
  
  CONCLUSIONS
  We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.
authors.affiliation: The Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia.
authors.forename: Jared Yong Yang
authors.initials: JY
authors.lastname: Foo
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Wan
authors.forename: Karam
authors.initials: K
authors.lastname: Kostner
authors.forename: Alicia
authors.initials: A
authors.lastname: Arivalagan
authors.forename: John
authors.initials: J
authors.lastname: Atherton
authors.forename: Justin
authors.initials: J
authors.lastname: Cooper-White
authors.forename: Goce
authors.initials: G
authors.lastname: Dimeski
authors.forename: Chamindie
authors.initials: C
authors.lastname: Punyadeera
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*; D015203:Reproducibility of Results; D012463:Saliva / Q000737:chemistry*; D012680:Sensitivity and Specificity
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain