Analytic Issues for Clinical Use of B-Type Natriuretic Peptide and N-Terminal Pro B-Type Natriuretic Peptide

Abstract

B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone (NT-proBNP) have emerged as the preferred candidates for diagnosis of heart failure, as well as other clinical applications. Several commercially available assays have been developed for point-of-care determination as well as for high-throughput automated laboratory platforms. Knowledge of preanalytic and analytic issues as well as sources of inter— and intraindividual variability in BNP and NT-proBNP is crucial for clinicians to allow correct interpretation of test results in routine practice. A few practical points for the clinical use of BNP and NT-proBNP include the following: Blood sampling may be performed without a standardized period of rest or posture. However, heavy physical exercise should be avoided before blood sampling. Blood for BNP determination must be collected in EDTA-coated plastic tubes, whereas for NT-proBNP serum or plasma collected in glass or plastic tubes is acceptable. Although the available assays for BNP correlate closely, owing to lack of assay standardization no two BNP assays are analytically equivalent at present. Therefore, reference and decision limits cannot be translated from one BNP assay to another. The stability of BNP is, to some extent, dependent on the assay used and requires refrigeration if samples are to be tested more than 4 h after sampling. NT-proBNP is stable for 2 d at room temperature. Because of analytic imprecision and biological variation, only NT-proBNP changes >25% from baseline and BNP concentration changes >40% correlate well with clinical course in follow-up of patients with heart failure. Erroneous test results with BNP or NT-proBNP assays are very rare but may occur from analytic inferences, such as the presence of fibrin strands or heterophilic antibodies and autoantibodies in patient samples.