Cardioembolic stroke generally results in more severe disability, since it typically has a larger ischemic area than the other types of ischemic stroke. The correct identification of a stroke etiology as cardioembolic is important as it has been shown that these patients benefit from anticoagulation. However, it is difficult to differentiate cardioembolic strokes from non-cardioembolic strokes (atherothrombotic stroke and lacunar stroke). NT-proBNP is a well recognized biochemical marker of congestive heart failure. Recent studies suggest that NT-proBNP may be used as a marker of cardioembolic stroke.

1. Rol
pepti
le of plasm
ide (NT-p
ma N-ter
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2. a pol l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 1 7 e2 1 9
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/apme
Review Article
Role of plasma N-terminal proB-type natriuretic
peptide (NT-proBNP) level in acute cardioembolic
stroke
Pushpendra Renjen a,*, Rajender Singla b
a Senior Consultant, Neurology Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110076, India
b Resident, Neurology Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110076, India
a r t i c l e i n f o
Article history:
Received 27 July 2013
Accepted 7 August 2013
Available online 7 September 2013
Keywords:
NT-proBNP
BNP
Cardioembolic stroke
Ischemic stroke
a b s t r a c t
Cardioembolic stroke generally results in more severe disability, since it typically has a
larger ischemic area than the other types of ischemic stroke. The correct identification of a
stroke etiology as cardioembolic is important as it has been shown that these patients
benefit from anticoagulation. However, it is difficult to differentiate cardioembolic strokes
from non-cardioembolic strokes (atherothrombotic stroke and lacunar stroke). NT-proBNP
is a well recognized biochemical marker of congestive heart failure. Recent studies suggest
that NT-proBNP may be used as a marker of cardioembolic stroke.
Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
1. Review of literature
B-type natriuretic peptide (BNP) is a cardiac endocrine hor-mone
that is produced in the myocardium, brain, lungs, kid-neys,
aorta, and adrenal glands. The N-terminal-pro BNP is a
76 amino acid N-terminal fragment of BNP. These are derived
from prohormone (proBNP) comprising of 108 amino acids
which are enzymatically cleaved into BNP (32 amino acids)
and the N-terminal-pro BNP (76 amino acids).1,2
BNP and NT-proBNP are synthesized mainly in the ven-tricular
myocardium in response to myocardial wall stress.
These natriuretic peptides acts to relieve the symptoms
associated with volume expansion and pressure overload by
promoting natriuresis and diuresis, vasodilation, and the
suppression of the renin angiotensin aldosterone system.
Plasma levels of these natriuretic peptides are typically
elevated in patients with congestive heart failure (CHF)1,3e6
and the increase has been found to be proportional to the
degree of left ventricular dysfunction. 11 Also their levels are
useful in predicting adverse cardiac outcomes after AMI5,8 and
acute coronary syndrome.7,9
Plasma BNP level is frequently elevated in acute cerebral
infarction and has been associated with cardiac dysfunction,
clinical severity, and poor prognosis of cerebral infarction.10e15
The exact mechanism of elevated NT-proBNP level in acute
cerebral infarction is unknown, but there are several hypoth-eses.
First, elevated NT-proBNP in acute cerebral infarction
may be related to cardiac disorders, which may be a cause of
the infarction, a co-existing condition, or a result of the
infarction.16,17 Second, NT-proBNP production may be stimu-lated
by changes in catecholamine in acute cerebral infarction,
regardless of cardiac dysfunction.18e24 Third, inflammatory
markers or hypoxia-inducible factor that is induced in acute
cerebral infarction may stimulate NT-proBNP production.24e26
* Corresponding author.
E-mail address: pnrenjen@hotmail.com (P. Renjen).
0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.apme.2013.08.011

3. 218 a p o l l o me d i c i n e 1 0 ( 2 0 1 3 ) 2 1 7 e2 1 9
Stroke is a major cause of mortality and morbidity. In
20e30% of all strokes, a cardiac cause is detected; however, in
up to 20% of all strokes, the etiology remains unclear and
specific treatment cannot be initiated.27
Ischemic stroke can be classified by TOAST classification
which denotes five subtypes of ischemic stroke: 1) large-artery
atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion,
4) stroke of other determined etiology, and 5) stroke of unde-termined
etiology.28
It is important to differentiate the stroke subtypes, particu-larly
cardioembolic stroke from non-cardioembolic stroke
(atherothrombotic stroke and lacunar stroke) as prognosis,
outcome, formulationof strategies for treatmentandprevention
of recurrence andmanagement all differamong these subtypes.
Cardioembolic stroke generally results in more severe
disability, since it typically has a larger ischemic area than the
other types of ischemic stroke.
At present, accurate determination of the stroke subtype
immediately after admission requires magnetic resonance
imaging (MRI), magnetic resonance angiography (MRA), elec-trocardiography,
and transthoracic echocardiography.
In about 30e40% of ischemic strokes, even after an exten-sive
clinical investigation, it is not possible to determine any
one etiology. It is possible that a fraction of these strokes,
named cryptogenic, happen after an episode of paroxystic
atrial fibrillation (AF) that was not registered. Strokes due to
atrial fibrillation are usually severe, have a high recurrence
rate and result in significant morbidity and costs. The correct
identification of a stroke etiology as cardioembolic is impor-tant
as it has been shown that these patients benefit from
anticoagulation.
The development of a method to predict stroke subtype
only by drawing blood would be an examination superior to all
others. Several investigators have tried to use markers such as
the D-dimer and high sensitive C reactive protein (CRP) to
differentiate the stroke subtypes, however the diagnostic ac-curacy
of these tests has been low.29,30
Certain studies suggest that NT-proBNP may be used as a
marker of cardioembolic stroke.
Giannakoulas et al in 2005 studied NT-proBNP levels soon
after an acute ischemic stroke. They compared plasma NT-proBNP
concentrations in 30 patients with an acute ischemic
stroke with those of 30 controls. The 2 groups were adjusted
for age and gender, and there were no significant differences
in vascular risk factors and left ventricular systolic and dia-stolic
function They found that NT-proBNP levels were
elevated in patients with acute stroke (129.9 9.9 fmol/mL)
compared with the controls (90.8 6.3 fmol/mL, p 0.05). NT-proBNP
at admission was significantly higher in car-dioembolic
compared with atherothrombotic infarctions.
There was no correlation between circulating NT-proBNP and
stroke topography, infarct size, or severity as assessed by the
National Institutes of Health Stroke Scale (NIHSS).31
Jagdish C. Sharma et al investigated the significance of NT-proBNP
level in predicting the outcome of acute stroke and
found that it had has an independent prognostic value in
acute stroke patients over other cardiovascular variables and
stroke severity.32
Rodrı´guez-Ya´n˜ ez et al studied 262 patients with first
ischemic stroke who presented within the first 12 h. Stroke
subtype was evaluated by TOAST criteria. They found that
NTPro-BNP 360 pg/mL was independently associated with
cardioembolic stroke (OR: 28.51, CI95%: 5.90e136.75,
p 0.0001) and may be useful to reclassify undetermined
strokes as of cardioembolic origin.33
Asimilar studywas conductedbyFonseca et al inwhichthey
studied patients with acute ischemic stroke presenting within
72 h after stroke onset. 92 patients were included in the study.
They found that 28 (42$4%) patients had a cardioembolic cause.
Mean NTPro-BNP values for cardioembolic stroke were signifi-cantly
higher P 0$001 (491$6; 95%CI, 283$7e852$0 pg/ml) than
for non-cardioembolic ischemic stroke (124$7; 86$3e180$2 pg/
ml). They concluded thatNT-proBNPis a biomarker with a good
accuracy to predict ischemic stroke of cardioembolic cause,
namely associated with atrial fibrillation.34
2. Conclusion
From various studies it can be concluded that higher NT-proBNP
levels are associated with cardioembolic stroke and
may be useful to reclassify undetermined strokes as of car-dioembolic
origin.
Conflicts of interest
All authors have none to declare.
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