TY - JOUR
T1 - Pro-B-type natriuretic peptide1-108 circulates in the general community
T2 - Plasma determinants and detection of left ventricular dysfunction
AU - Macheret, Fima
AU - Boerrigter, Guido
AU - McKie, Paul
AU - Costello-Boerrigter, Lisa
AU - Lahr, Brian
AU - Heublein, Denise
AU - Sandberg, Sharon
AU - Ikeda, Yasuhiro
AU - Cataliotti, Alessandro
AU - Bailey, Kent
AU - Rodeheffer, Richard
AU - Burnett, John C.
PY - 2011/3/22
Y1 - 2011/3/22
N2 - 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.
AB - 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.
KW - BNP
KW - NT-proBNP
KW - biomarker
KW - heart failure
KW - natriuretic peptide
KW - proBNP
UR - http://www.scopus.com/inward/record.url?scp=79952661776&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952661776&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2011.01.005
DO - 10.1016/j.jacc.2011.01.005
M3 - Article
C2 - 21414536
AN - SCOPUS:79952661776
SN - 0735-1097
VL - 57
SP - 1386
EP - 1395
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 12
ER -