Unexplained week‐to‐week variation in BNP and NT‐proBNP is low in chronic heart failure patients during steady state

Abstract

Background: The usefulness of brain-natriuretic-peptide (BNP) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) for monitoring of chronic heart failure (CHF) patients has been questioned because of high levels of unexplained variation. Aims: Week-to-week total variance (CV T ), unexplained variation (CV I ), reference change values (RCV), index of individualities (IOI) and number of samples (N) with week-to-week intervals needed to estimate the underlying homeostatic set point (T15%) for BNP and NTproBNP were calculated in pre-specified stable CHF patients. Methods and results: We measured plasma concentrations of BNP and NT-proBNP, clinical and laboratory variables in 20 CHF patients with a 7-days interval. Only patients considered to be in steady state were included. The CV I was 15% (BNP) and 8% (NT-proBNP). CV T was 16% (BNP) and 8% (NT-proBNP) and RCV was 43% (BNP) and 23% (NT-proBNP). IOI was 0.14 for BNP and 0.03 for NT-proBNP and N was 1 for BNP and 1 for NT-proBNP.Conclusions: Our data demonstrate that unexplained variation of BNP and NT-proBNP is low in CHF patients during steady state, which is a prerequisite for the use of these peptides for monitoring of the disease.

Variability of N-Terminal Probrain Natriuretic Peptide in Stable Chronic Heart Failure and Its Relation to Changes in Clinical Variables

“…The key to understanding these results is the rigidity of the definition of stability of heart failure. In studies that expended large efforts to ascertain stability (12,25,26 ) the CVs found were lower than in studies with less strict criteria (9,11 ). Consequently, we found The dotted lines indicate 1.96 ϫ SD of the mean of the differences (95% confidence with P Ͻ 0.05).…”

“…Previous reported studies on short-or long-term variability found RCVs around 100% (8, 9 ) (11 ), others found CVs between 20% and 30% (10,12,13,25,26 ). The key to understanding these results is the rigidity of the definition of stability of heart failure.…”

“…The skewed distribution of NT-proBNP values can be converted by log-transformation to a normal distribution (12,25 ), a process that results in lower CVs and eliminates the problem of a paradoxical decrease Ͼ100%. It must be emphasized, however, that CVs derived by this approach would apply only to log-transformed values, thus limiting clinical applicability.…”

B‐Type Natriuretic Peptide: Application in the Community

“…[2][3][4][5] While these studies have differed somewhat in their results, they have all been consistent in showing significant variability in values among patients with stable heart failure. A summary of these data would suggest that the reference change value (RCV) for BNP is approximately 50% and is modestly less for NTproBNP.…”

Advantages of the lognormal approach to determining reference change values for N-terminal propeptide B-type natriuretic peptide

“…Currently, there is no consensus on which approach (nANOVA or lognormal) to determining RCV is better. Data on biological variation of NT-proBNP have been published with markedly differing results (reviewed in [13]), mainly related to the use of data transformation, particularly in patients with chronic heart failure [14,15]. As component of variation is computed based on nANOVA, the distributional assumptions underlying the use of this method should be satisfied, which is not the case for skewed distributions, as NT-proBNP's.…”