Pro-B-type natriuretic peptide 1-108 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 H Ikeda, Alessandro Cataliotti, Kent R Bailey, Richard Rodeheffer, John C Jr. Burnett

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Objectives: 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.

Original languageEnglish (US)
Pages (from-to)1386-1395
Number of pages10
JournalJournal of the American College of Cardiology
Volume57
Issue number12
DOIs
StatePublished - Mar 22 2011

Fingerprint

Brain Natriuretic Peptide
Left Ventricular Dysfunction
Biomarkers
Heart Failure
Population
Systems Biology
pro-brain natriuretic peptide (1-76)
Echocardiography
Body Mass Index
Heart Rate
methylarginyl-lysyl-prolyl-tryptophyl-tert-leucyl-leucyl-ethyl ester

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Pro-B-type natriuretic peptide 1-108 circulates in the general community : Plasma determinants and detection of left ventricular dysfunction. / Macheret, Fima; Boerrigter, Guido; McKie, Paul; Costello-Boerrigter, Lisa; Lahr, Brian; Heublein, Denise; Sandberg, Sharon; Ikeda, Yasuhiro H; Cataliotti, Alessandro; Bailey, Kent R; Rodeheffer, Richard; Burnett, John C Jr.

In: Journal of the American College of Cardiology, Vol. 57, No. 12, 22.03.2011, p. 1386-1395.

Research output: Contribution to journalArticle

Macheret, Fima ; Boerrigter, Guido ; McKie, Paul ; Costello-Boerrigter, Lisa ; Lahr, Brian ; Heublein, Denise ; Sandberg, Sharon ; Ikeda, Yasuhiro H ; Cataliotti, Alessandro ; Bailey, Kent R ; Rodeheffer, Richard ; Burnett, John C Jr. / Pro-B-type natriuretic peptide 1-108 circulates in the general community : Plasma determinants and detection of left ventricular dysfunction. In: Journal of the American College of Cardiology. 2011 ; Vol. 57, No. 12. pp. 1386-1395.
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abstract = "Objectives: 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.",
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AU - McKie, Paul

AU - Costello-Boerrigter, Lisa

AU - Lahr, Brian

AU - Heublein, Denise

AU - Sandberg, Sharon

AU - Ikeda, Yasuhiro H

AU - Cataliotti, Alessandro

AU - Bailey, Kent R

AU - Rodeheffer, Richard

AU - Burnett, John C Jr.

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N2 - Objectives: 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.

AB - Objectives: 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.

KW - biomarker

KW - BNP

KW - heart failure

KW - natriuretic peptide

KW - NT-proBNP

KW - proBNP

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