High intraindividual variation of B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with stable chronic heart failure

Background: Plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are promising markers for heart failure diagnosis, prognosis, and treatment. Insufficient data on the intraindividual biological variation (CVi) of BNP and NT-proBNP hamper interpretation of changes in concentration on disease progression or treatment optimization. We therefore investigated CVi values in stable heart failure patients. Methods: We recruited 43 patients with stable chronic heart failure living in Curacao (22 males, 21 females; median age, 63 years; range, 20-86 years; New York Heart Association classes I-III). Samples were collected for within-day CVi (n = 6; every 2 h starting at 0800), day-to-day CVi (n = 5; samples collected between 0800 and 1000 on 5 consecutive days), and week-to-week CVi (n = 6; samples collected between 0800 and 1000 on the same day of the week for 6 consecutive weeks). NT-proBNP (Roche) and BNP (Abbott) were measured by immunoassay. Results: Median (range) concentrations were 134 (01630) ng/L (BNP) and 570 (17-5048) ng/L (NT-proBNP). Analytical variation, week-to-week CVi, and reference change values were 8.4%, 40%, and 113% (BNP), and 3.0%, 35%, and 98% (NT-proBNP). Week-to week CV(i)s were inversely related to median BNP concentrations. Week-to week CVis for BNP were 44% (BNP less than or equal to350 ng/L) and 30% (BNP >350 ng/L). Both BNP and NT-proBNP increased between 0800 and 1000. Median NT-proBNP/BNP ratios were inversely related to median BNP concentrations. Conclusions: The high CV(i)s hamper interpretation of changes in BNP and NT-proBNP concentrations and may partly explain their poor diagnostic values in chronic heart failure. Easily modifiable determinants to lower CVi have not been identified. The value of BNP and NT-proBNP for chronic heart failure diagnosis, and especially for follow-up and treatment optimization of individuals, remains largely to be established. (C) 2004 American Association for Clinical Chemistry.