title: Pro-B-type natriuretic peptide(1-108) circulates in the general community: plasma determinants and detection of left ventricular dysfunction.
abstract: OBJECTIVE
  The purpose of this study was to investigate circulating pro-B-type natriuretic peptide (proBNP(1-108)) in the general community and evaluate its ability to detect left ventricular (LV) dysfunction.
  
  
  BACKGROUND
  The current concept for cardiac endocrine function is that, in response to cardiac stress, the heart secretes B-type natriuretic peptide (BNP(1-32)) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP(1-76)) after intracardiac cleavage of their molecular precursor, proBNP(1-108). We hypothesized that proBNP(1-108) circulates in normal human subjects and that it is a useful biomarker for LV dysfunction.
  
  
  METHODS
  Our population-based study included a cohort of 1,939 adults (age ≥45 years) from Olmsted County, Minnesota, with 672 participants defined as healthy. Subjects underwent in-depth clinical characterization, detailed echocardiography, and measurement of proBNP(1-108). Independent factors associated with proBNP(1-108) and test characteristics for the detection of LV dysfunction were determined.
  
  
  RESULTS
  ProBNP(1-108) in normal humans was strongly influenced by sex, age, heart rate, and body mass index. The median concentration was 20 ng/l with a mean proBNP(1-108) to NT-proBNP(1-76) ratio of 0.366, which decreased with heart failure stage. ProBNP(1-108) was a sensitive (78.8%) and specific (86.1%) biomarker for detecting LV systolic dysfunction, which was comparable to BNP(1-32), but less than NT-proBNP(1-76), in several subsets of the population.
  
  
  CONCLUSIONS
  ProBNP(1-108) circulates in the majority of healthy humans in the general population and is a sensitive and specific biomarker for the detection of systolic dysfunction. The proBNP(1-108) to NT-proBNP(1-76) ratio may provide insights into altered proBNP(1-108) processing during heart failure progression. Thus, this highly specific assay for proBNP(1-108) provides important new insights into the biology of the BNP system.
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Department of Medicine and Physiology, Mayo Clinic, Rochester, Minnesota, USA. macheret.fima@mayo.edu
authors.forename: Fima
authors.initials: F
authors.lastname: Macheret
authors.forename: Guido
authors.initials: G
authors.lastname: Boerrigter
authors.forename: Paul
authors.initials: P
authors.lastname: McKie
authors.forename: Lisa
authors.initials: L
authors.lastname: Costello-Boerrigter
authors.forename: Brian
authors.initials: B
authors.lastname: Lahr
authors.forename: Denise
authors.initials: D
authors.lastname: Heublein
authors.forename: Sharon
authors.initials: S
authors.lastname: Sandberg
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cataliotti
authors.forename: Kent
authors.initials: K
authors.lastname: Bailey
authors.forename: Richard
authors.initials: R
authors.lastname: Rodeheffer
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D012680:Sensitivity and Specificity; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain