title: B-type natriuretic peptide signal peptide circulates in human blood: evaluation as a potential biomarker of cardiac ischemia.
abstract: BACKGROUND
  The diagnosis of cardiac necrosis such as myocardial infarction can be difficult and relies on the use of circulating protein markers like troponin. However, there is a clear need to identify circulating, specific biomarkers that can detect cardiac ischemia without necrosis.
  
  
  RESULTS
  Using specific immunoassay and tandem mass spectrometry, we show that a fragment derived from the signal peptide of B-type natriuretic peptide (BNPsp) not only is detectable in cytosolic extracts of explant human heart tissue but also is secreted from the heart into the circulation of healthy individuals. Furthermore, plasma levels of BNPsp in patients with documented acute ST-elevation myocardial infarction (n=25) rise to peak values ( approximately 3 times higher than the 99th percentile of the normal range) significantly earlier than the currently used biomarkers myoglobin, creatine kinase-MB, and troponin. Preliminary receiver-operating characteristic curve analysis comparing BNPsp concentrations in ST-elevation myocardial infarction patients and other patient groups was positive (area under the curve=0.97; P<0.001), suggesting that further, more rigorous studies in heterogeneous chest pain patient cohorts are warranted.
  
  
  CONCLUSIONS
  Our results demonstrate for the first time that BNPsp exists as a distinct entity in the human circulation and could serve as a new class of circulating biomarker with the potential to accelerate the clinical diagnosis of cardiac ischemia and myocardial infarction. Clinical Trial Registration- URL: http://www.anzctr.org.au. Unique identifier: ACTRN12609000040268.
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Maithri
authors.initials: M
authors.lastname: Siriwardena
authors.forename: Torsten
authors.initials: T
authors.lastname: Kleffmann
authors.forename: Peter
authors.initials: P
authors.lastname: Ruygrok
authors.forename: Vicky A
authors.initials: VA
authors.lastname: Cameron
authors.forename: Tim G
authors.initials: TG
authors.lastname: Yandle
authors.forename: M Gary
authors.initials: MG
authors.lastname: Nicholls
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Pemberton
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood*; D002637:Chest Pain / Q000097:blood / Q000175:diagnosis; D004562:Electrocardiography; D006801:Humans; D007118:Immunoassay; D017202:Myocardial Ischemia / Q000097:blood* / Q000175:diagnosis*; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain