CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 7, August 2013
AFRICA
287
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 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 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 led to a reduction in levels of
natriuretic peptides in the plasma and improved the prognosis,
which was 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. Echocardiographic 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
