Measurement of plasma levels of natriuretic peptides has been used to asses
s left ventricular dysfunction and prognosis. Recently levels of the N-term
inal peptide fragment of the precursor of brain natriuretic peptide have be
en reported to be present in peripheral plasma and to be increased in chron
ic heart failure patients. Our aim in this study was to develop a radioimmu
noassay for N-terminal proBNP, to compare its plasma concentrations in cont
rol subjects and in patients with end-stage heart failure and to define its
relation to brain natriuretic peptide (BNP). A polyclonal antibody was rai
sed in rabbits against human N-terminal proBNP fragment (amino acid 1-21).
The plasma N-terminal proBNP concentrations were assayed directly without e
xtraction. No detectable cross-reactivity existed with other natriuretic pe
ptides: BNP, ANP or N-terminal proANP. The assay had a detection limit (2 S
D from zero) of 9.7 pmol/L. Plasma N-terminal proBNP was 29 (13-75) (median
(range)) pmol/L in the control group. There were no gender difference, mal
e: 28 (13-61) vs. female 33 (13-75) pmol/L, p= NS, but there was a positive
correlation to age (r=0.52, p<0.0001). In patients with end-stage heart fa
ilure the median N-terminal proBNP levels were increased significantly 616
(114-2781) pmol/L (p<0.001) and in pooled data N-terminal proBNP showed a c
lose correlation to BNP (r=0.96, p<0.0001). Size exclusion of plasma extrac
ts indicated that proBNP (1-108) may circulate both as intact prohormone an
d as split products, N-terminal proBNP(1-76) and BNP 177 - 108). Our result
s support the concept that N-terminal proBNP measurement could be a valuabl
e tool in the biochemical indication of increased cardiac wall stress.