Pro-B-Type Natriuretic Peptide1-108 Circulates in the General Community Plasma Determinants and Detection of Left Ventricular Dysfunction

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 (BNP1-32) 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 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 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. (J Am Coll Cardiol 2011;57:1386-95) (C) 2011 by the American College of Cardiology Foundation