Pro-B-type natriuretic peptide1-108 circulates in the general community: Plasma determinants and detection of left ventricular dysfunction

Fima Macheret, Guido Boerrigter, Paul McKie, Lisa Costello-Boerrigter, Brian Lahr, Denise Heublein, Sharon Sandberg, Yasuhiro Ikeda, Alessandro Cataliotti, Kent Bailey, Richard Rodeheffer, John C. Burnett

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Objectives: The purpose of this study was to investigate circulating pro-B-type natriuretic peptide (proBNP1-108) 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 (BNP1-32) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP1-76) after intracardiac cleavage of their molecular precursor, proBNP1-108. We hypothesized that proBNP1-108 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 proBNP1-108. Independent factors associated with proBNP1-108 and test characteristics for the detection of LV dysfunction were determined. Results: ProBNP1-108 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 proBNP1-108 to NT-proBNP1-76 ratio of 0.366, which decreased with heart failure stage. ProBNP1-108 was a sensitive (78.8%) and specific (86.1%) biomarker for detecting LV systolic dysfunction, which was comparable to BNP1-32, 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 proBNP1-108 to NT-proBNP1-76 ratio may provide insights into altered proBNP1-108 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.

Original languageEnglish (US)
Pages (from-to)1386-1395
Number of pages10
JournalJournal of the American College of Cardiology
Issue number12
StatePublished - Mar 22 2011


  • BNP
  • NT-proBNP
  • biomarker
  • heart failure
  • natriuretic peptide
  • proBNP

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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