Effect of Ethnicity on Plasma Levels of proBNP, BNP and NTproBNP in Subjects at Risk for Cardiovascular Disease

Abstract

Background: B-type natriuretic peptide (BNP), a hormone secreted by the heart in response to cardiac stress, has cardiac unloading, anti-fibrotic and other pleiotropic actions. Given that elevation of plasma BNP is associated with cardiovascular disease and poorer outcomes, a variety of assays have been developed. However, genetic and ethnic factors may influence plasma levels, potentially confounding BNP’s value as a biomarker. Using a diverse population we sought to determine the impact of ethnicity on three forms of BNP, specifically the prohormone proBNP1-108 (the activation of which has been shown to be reduced in some African Americans), BNP1-32 (the most active cleavage product of proBNP), and NTproBNP (the inactive cleavage product of proBNP). Methods: Subjects 45 years and older from Dade County, FL who self-identified as being at cardiovascular risk were recruited during a free, voluntary cardiovascular screening. Ethnicities represented were: Hispanic, Caucasian, and African-American. Detailed echocardiography was performed on all subjects and medical history, physical exam, and blood samples were obtained. ProBNP was measured with a novel assay (BioRad), which uses a capture antibody specific to the cleavage site of proBNP. BNP1-32 was measured with the Shionogi BNP assay, and NTproBNP with the Roche assay. Results: A total of 726 subjects were enrolled: 467 Hispanics, 200 Caucasians, and 59 African-Americans. After adjusting for age gender, BSA, BMI, use of anti-hypertensive medication, blood pressure, renal function, diabetes mellitus, left ventricular dimension and mass and left atrial dimension, NT-proBNP was found to be significantly lower (p50.02) in African Americans than in the other two ethnicities. Ethnicity however did not significantly affect either BNP1-32 or proBNP1-108. Conclusions: Compared to Caucasians, Hispanic and African American ethnicity did not affect levels of proBNP1-108 or BNP. However, African Americans had significantly lower NT-proBNP levels than Caucasians. It remains to be established whether this difference significantly affects test characteristics of NTproBNP as a biomarker. In addition, given that the NTproBNP assay is affected by the glycosylation status of its epitopes on NTproBNP, it should be investigated whether ethnicity affects glycosylation.