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SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 13 NUMBER 1 • JULY 2016
41
dyspnoea. Race also plays a role, with a higher variability being
seen in African-Americans than Caucasians.
2
Studies conducted
in Africa found reference values higher than those recommended
by the manufacturer.
5
A recent study showed that the reference
value for NT-pro-BNP depends on age over 50 years.
6
Another study
containing nonagenarian patients reported a link between values
of NT-pro-BNP and echocardiographic anomalies.
7
Levels of BNP are lower for obese patients compared to non-
obese. In addition, it was observed that genetics plays a role in the
variability of BNP levels. Along with age, gender, genetics and body
mass index, there are other physiological reasons for the variability
of BNP.
Renal function also affects levels of BNP, significantly increased
levels being recorded for those with renal dysfunction. Patients
on haemodialysis showed significant rhythmic oscillations in BNP
levels, compared to healthy subjects.
2
In the Breathing Not Properly
study, BNP predictors from ‘the grey area’ in the absence of heart
failure included age, atrial fibrillation, lower body mass index and
anaemia.
2
The lack of a single set of normal values due to different idiopathic
levels and the available commercial kits can lead to confusion in
clinical application. While some researchers claim that values above
100 pg/ml indicate heart failure, others suggest a value above
200 pg/ml. The ADHERE study, which included over 48 000 patients,
indicated as prognosticators of mortality values over 430 pg/ml.
8
In all cited conditions, a careful clinical examination, accompanied
by an echocardiographic examination that evaluates the systolic–
diastolic function, should be complementary to BNP analysis for
diagnostic strategy and implementation of treatment.
9
Heart failure
Chronic heart failure is an illness that is appearing with increasing
frequency, especially in elderly patients. Nevertheless, classification
is often difficult due to non-specific symptoms and the lack of a
‘gold standard’ protocol for a correct diagnosis.
9
The European
guidelines from 2008 highlight the role of natriuretic peptides as
potential markers of heart failure.
9
Measurement of plasma concentrations of BNP has proved to
be a very efficient screening technique for the identification of
patients with various heart diseases, regardless of aetiology and
the degree of systolic dysfunction of the left ventricle, which has
the potential to develop into manifested heart failure and has a
high risk of producing a cardiovascular event. Recently, the Food
and Drug Administration approved NT-pro-BNP for the evaluation
of the prognosis of patients with congestive heart failure and acute
coronary syndromes. Determination of BNP level was also approved
for risk segregation in acute coronary syndromes.
10
Multiple studies have confirmed the efficiency of the
determination of BNP concentrations in the plasma of patients with
acute dyspnoea. The Breathing Not Properly study is an example, in
which 1 586 patients participated.
9
In addition, studies such as Val-
HeFT
11,12
and COPERNICUS
13
indicated that chronic treatment with
beta-blockers and blockers of the renin–angiotensin–aldosterone
system leads to a reduction in levels of natriuretic peptides in the
plasma and improved the prognosis, which is possibly a reflection
of the improvement in cardiac function secondary to treatment.
2
Together with its role in acute decompensated heart failure,
levels of BNP are also high for diastolic dysfunction. Increased BNP
levels can be found with isolated diastolic dysfunction, hypertrophic
cardiomyopathy, or associated with systolic dysfunction. Echo-
cardiographic parameters correlated with BNP levels include mass
index of the left ventricle, its end-diastolic volume and isometric
relaxation time. The further the stage of diastolic dysfunction the
higher the levels of BNP.
2
Other heart diseases
As with congestive heart failure, BNP level has a prognostic value for
acute coronary syndromes. BNP is additive with, and independent
of, the increases in troponin I for these syndromes.
2
A sub-study of Breathing Not Properly showed that plasma
levels of BNP were high for patients with atrial fibrillation that was
not diagnosed with congestive heart failure, but its levels were not
different in the presence of heart failure.
2
In addition, levels of BNP
were high with heart valve diseases and aortic stenosis, and were
linearly related to the symptoms. Moreover, levels over 190 pg/ml
foresaw a negative evolution, suggesting that BNP can be used for
identification of subgroups of patients that would benefit from a
replacement of the aortic valve. In addition, BNP level was increased
with aortic insufficiency.
2
For patients with mitral insufficiency, an increased BNP level
was correlated with mortality and the onset of congestive heart
failure, regardless of the degree of regurgitation present on
echocardiography, suggesting that BNP is a reflection of its atrial
and ventricular consequences.
2
Finally, it was proven that NT-pro-
BNP was correlated with symptoms and echocardiographic severity
of mitral stenosis.
2
In addition, the levels of BNP were increased in
patients with pulmonary embolism and pulmonary hypertension.
2
In unstable angina, NT-pro-BNP represents an effective marker
of the damage produced by cardiac ischaemia. The severity of the
coronary disease is shown by an increase in the levels of NT-pro-
BNP. In addition, in the case of acute coronary syndromes, NT-pro-
BNP had an immuno-modulating role and offered important
information for the prognosis of patients.
1
Castro
et al
.
14
divided 87 patients with non-ST-segment elevation
acute coronary syndrome into two groups: 37 (42.5%) with
unstable angina and 50 (57.5%) with non-ST-segment elevation
myocardial infarction. Left ventricular ejection fraction above 40%
was found in 86.2% of the total sample. Serum levels of NT-proBNP
were higher in patients with non-ST-segment elevation myocardial
infarction than in those with unstable angina (
p
< 0.001).
14
Increased levels of NT-pro-BNP were associated with increases
in troponin I (rs = 0.425,
p
< 0.001), peak CK-MB (rs = 0.458,
p
< 0.001) and low left ventricular ejection fraction (rs = –0.345,
p
= 0.002); no correlation was found with the TIMI risk score (rs =
0.082,
p
= 0.44). Multivariate analysis revealed that left ventricular
ejection fraction and troponin I levels were independently correlated
with NT-pro-BNP levels (
p
= 0.017 and
p
= 0.002, respectively).
14
Renal failure
Renal failure complicates congestive heart failure so often that
many have suggested a ‘cardio–renal’ syndrome, which influences
survival, duration of hospitalisation and re-admission ratio.
2
A sub-
study of PRIDE
15
showed a reduction in the sensitivity and specificity
of NT-pro-BNP in the diagnosis of heart failure for persons with renal
failure, and also showed that its concentration tends to be more
affected by renal dysfunction than BNP levels.
2
The levels of BNP are
known to be significantly increased for patients on haemodialysis,
and they are known to decrease after dialysis.
2