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 (CV(i)) of BNP and NT-proBNP hamper interpretation of changes in concentration on disease progression or treatment optimization. We therefore investigated CV(i) 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 CV(i) (n = 6; every 2 h starting at 0800), day-to-day CV(i) (n = 5; samples collected between 0800 and 1000 on 5 consecutive days), and week-to-week CV(i) (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 (0-1630) ng/L (BNP) and 570 (17-5048) ng/L (NT-proBNP). Analytical variation, week-to-week CV(i), 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 CV(i)s for BNP were 44% (BNP < or =350 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 CV(i) 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.