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

Study Questions:

What is the ability of circulating pro-B-type natriuretic peptide (proBNP1-108) to detect left ventricular (LV) dysfunction in the general population?


This population-based study included a cohort of 1,939 adults (ages ≥45 years) from Olmsted County, MN, with 672 participants defined as healthy. Individuals from the study cohort 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. The p < 0.05 was considered significant.


The study investigators reported that proBNP1-108 in normal individuals 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 (from stage 0 to stages A to C). For optimal discrimination of ejection fraction <40% or >40% in the total population, the cutpoint proBNP1-108 value was 65 ng/L, reflecting a sensitivity of 78.8% and a specificity of 86.1%, which was comparable to BNP1-32, but less than NT-proBNP1-76, in several subsets of the population (p < 0.05 in multiple data subsets). The best performance of this assay was in female and younger subgroups.


The study authors concluded that proBNP1-108 circulates in the majority of healthy humans in the general population, and is a sensitive and specific biomarker for the detection of systolic dysfunction. In addition, they suggest that proBNP1-108 to NT-proBNP1-76 ratio may provide insights into altered proBNP1-108 processing during heart failure progression.


This is an important study because traditional BNP assays have been associated with substantial variability to make meaningful comparisons. Although there remain several limitations, the ratio of proBNP1-108 to NT-proBNP1-76 ratio and the proBNP1-108 assay given its sensitivity and specificity may replace the traditional BNP assays as more studies validating these findings in other cohorts of heart failure emerge. Also as the authors point out, age and gender need to be considered when developing ranges for normal individuals.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound

Keywords: Biological Markers, Heart Failure, Heart Rate, Ventricular Dysfunction, Left, Echocardiography, Natriuretic Peptide, Brain

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