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REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
40
VOLUME 13 NUMBER 1 • JULY 2016
Diagnostic and prognostic values of B-type natriuretic
peptides (BNP) and N-terminal fragment brain natriuretic
peptides (NT-pro-BNP)
LORENA MARIES, IOAN MANITIU
Correspondence to: Lorena Maries
Loxan Magnus Medical, Bucharest, Romania
e-mail:
lorenamaries@yahoo.comIoan Manitiu
Lucian Blaga University, Sibiu, Romania
Previously published in
Cardiovasc J Afr
2013;
24
: 286–289
S Afr J Diabetes Vasc Dis
2016;
13
: 40–43
B-type natriuretic peptide (BNP) is a member of a four-
natriuretic peptide family that shares a common 17-peptide
ring structure. The N-terminal fragment (NT-pro-BNP) is
biologically inert, but both are secreted in the plasma in
equimolar quantities and both have been evaluated for use
in the management of congestive heart failure. BNP and
NT-pro-BNP are frequently used in the diagnosis of congestive
heart failure and the distinction between patients with
dyspnoea of cardiac or pulmonary origin. Values of NT-pro-
BNP are affected by age or the presence of one or several
co-morbidities such as chronic renal failure, type 2 diabetes,
and acute coronary syndrome. ‘Normal’ values of these
peptides also vary depending on the type of test used. The
performance characteristics of these tests vary depending on
the patients on whom they are used and the manufacturer.
For this reason, the determination of reference values for this
peptide represents such a challenge.
Keywords:
natriuretic peptides, prognostic values, NT-pro-BNP
Introduction
BNP was initially discovered in the porcine brain, but the largest
concentrations are found in the heart. It is a peptide with 32 amino
acids, synthesised in the ventricles as a response to stretching of
the myocytes and/or pressure overload. It is released as an active
hormone and as an inactive N-terminal fragment (NT-pro-BNP).
1
Once released in the blood flow, BNP has numerous physiological
actions, their net effect being to reduce pre- and post-load.
Specifically, BNP produces a decreased vascular tonus by relaxing
the smooth muscles, leading to a decrease in post-load. In addition,
it induces a movement of fluid into the interstitial space, thus
leading to a decrease in pre-load.
BNP reduces the proliferation of fibroblasts and smooth muscle
cells, sympathetic nervous activity, water and salt retention, release
of the antidiuresis hormone, and synthesis of aldosterone and
its release from the adrenal glands. In the kidneys, BNP increases
glomerular filtration rate and renal blood flow by increasing the
outgoing arterial tonus and decreasing the ingoing one. In addition
it decreases the release of renin and the reabsorption of sodium,
leading to diuresis and natriuresis.
2
The N-terminal fragment of BNP is derived from proteolysis of
pro-BNP, which is composed of 108 amino acids. It consists of 76
amino acids and has recently caused great interest, due to its possible
role in monitoring heart failure and distinguishing acute coronary
syndromes. Its effects on diuresis and natriuresis in patients with
congestive heart failure represent a compensatory mechanism for
stress on the myocytes, which leads to ventricular dysfunction.
1
Diagnostic and prognostic value of BNP and
NT-pro-BNP
Serum levels of natriuretic peptides are important, not just as
indicators of numerous cardiovascular deficiencies but also
as markers of their severity.
1
For patients with acute coronary
syndromes, the determination of BNP levels offers predictive
information on the apportioning of risk, in the absence of elevation
in the S-T interval. In addition, BNP and NT-pro-BNP have prognostic
signification for acute pulmonary embolism.
1
The diagnostic value was recently confirmed by Coutance
et
al
.
3
Even if high levels of BNP demonstrate a high sensitivity for
detecting patients with risk of sudden death, the specificity of this
neurohormone is decreased. A diverse analysis between mortality
and levels of BNP was recently conducted by Nunez and his team,
which demonstrated a positive linear correlation between the risk
of death and BNP level.
4
With regard to the prognostic value of NT-pro-BNP for chronic
heart failure, the Val-HeFT study (Valsartan Heart Failure Trial)
demonstrated the positive nature of advanced heart failure.
Moreover, BNP concentrations appeared significantly increased in
patients with dilated cardiomyopathy and cardiovascular disease
in NYHA classes III or IV, but it could not predict mortality or the
requirement for a heart transplant.
1
Variability of BNP
Despite the evidence that BNP is secreted in ventricular overload
states, there is an individual and inter-individual variation in both
healthy subjects and those with stable chronic heart failure, which
makes the interpretation of BNP levels difficult. Multiple studies have
shown that only changes in BNP level larger than approximately
113 to 130% and changes in NT-pro-BNP larger than 90 to 98%
can be considered to have exceeded individual, inter-individual and
analytical variations.
2
There are several reasons for these variations. In healthy subjects,
BNP level is connected to gender and age; its levels increase with
age and are higher in women than in men. Despite increases with
age, BNP and NT-pro-BNP proved effective in excluding congestive
heart failure in an elderly population that presented with acute