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ORIGINAL ARTICLE

JIACM 2010; 11(3): 204-7

High Sensitivity C-reactive Protein (hsCRP) Level in


Cerebrovascular Accident (Stroke)
Pinky Talreja Mishra*, Rakesh Chandra**, SK Saxena**, Sanjay Verma***, Renu Jain****, Ashok Bhuyan*

Abstract
Objectives: To study, the high sensitivity C-reactive protein (hsCRP) level in Indian patients with stroke and its subtypes, to evaluate
whether hsCRP levels in stroke correlate with other risk factors, and also to evaluate the hsCRP level as a prognostic marker in
cases of different types of stroke.
Material and methods: A prospective study of 40 patients presenting with a history of focal neurological deficit of acute onset in
the form of hemiparesis, hemianaesthesia, or having evidence of presence of ischaemic or haemorrhagic infarct in CT scan of
brain was done. In all patients hsCRP levels were measured within 72 hours of presentation.
Results: Most of the patients (65%) were in the age group of 50 - 70 years. Left-sided hemiparesis with altered sensorium with
facial palsy was the most common presenting symptom. hsCRP levels were found to be increased in stroke patients and on
comparison with controls, the values were found to be significant (p < 0.001). Also, the values were found to be more in haemorrhagic
than ischaemic stroke. No significant correlation was seen with other risk factors like diabetes, dyslipidaemia. It was also seen that
patient with low GCS score had high levels of hsCRP in both types of stroke. Mean hsCRP level was 14.8 6.2 in non-survivors of
haemorrhagic and 10.7 5.4 in ischaemic stroke. These values were found to be statistically significant (p < 0.001).
Conclusion: From this study we concluded that hsCRP level is increased in cases of stroke ischaemic as well as haemorrhagic,
suggesting an inflammatory response in acute stroke. Furthermore, the increased levels correlated with larger infarct and bleed,
severe neurological deficit and worse outcome.
Key words: Ischaemic stroke, haemorrhagic stroke, hsCRP level.

Introduction
Stroke is third most common cause of death in the US as
well as the leading cause of serious, long-term disability.
Two-thirds of all strokes occur in people over age 65, with
men more affected than women, although women are
more likely to die from a stroke. Attempts to modify the
traditional risk factors have not been entirely effective
in reducing national stroke rates. The acute phase
protein, i.e., high sensitivity C-reactive protein (hsCRP)
in particular, has been the most extensively studied
marker of inflammation1. It is a novel plasma marker of
atherothrombtic disease. CRP is produced not only by
the liver but also in vascular smooth muscle cells and
adipocytes. Because it is a stable protein, its
measurement is not greatly affected by the freezing
cycle. Elevated plasma levels of CRP are not disease
specific but are sensitive markers which are produced
in response to tissue injury, infectious agents, and
inflammation. hsCRP predicts the first cardiovascular
event in several populations. It was the only

inflammatory marker that independently predicted the


risk2,3 of stroke. hsCRP level when measured prior to the
onset of clinical diseases, may be an independent
predictor of the first ischaemic stroke4. Our study was
planned to study the high sensitivity C-reactive protein
(hsCRP) level in Indian patients with stroke and its
subtypes, to evaluate whether hsCRP levels in stroke
correlate with other risk factors, and also to evaluate the
hsCRP level as a prognostic marker in cases of different
types of stroke.

Material and methods


This prospective study was conducted on 40 patients of
acute stroke, admitted to the emergency and indoor
department of K.P.S., P.G. Institute of Medicine, G.S.V.M.
College, Kanpur. Forty healthy, age and sex matched
controls not having any evidence of stroke or CAD or
previous history of TIAs were also studied for valid
comparison. Patients presenting with history of focal
neurological deficit of acute onset in the form of

* JR-III, ** Professor, *** Lecturer, Department of Medicine, **** Ex-Professor, Department of Pathology,
GSVM Medical College, Kanpur - 208022, Uttar Pradesh.

hemiparesis, hemianaesthesia or aphasia, or having


evidence of the presence of ischaemic or haemorrhagic
infarct in CT scan of the brain were included in this study.
The patients with infectious pathology, arthritis, cancer,
history of recent MI or acute coronary syndrome, history
of smoking, or those in hepatic failure were excluded
from this study. Also, patients presenting with focal
neurological deficit after 72 hrs and on drugs, e.g.,
NSAIDs, statins, hormone replacement therapy were not
included. A detailed history was taken regarding stroke,
its onset, duration, time of presentation, focal
neurological deficits, any association with seizure,
headache, vomiting, or deviation of mouth. Also, history
of diabetes, hypertension, alcohol intake was taken to
ascertain the presence of any risk factors. Clinical
examination included vitals, i.e., pulse, blood pressure,
and detailed examination of the neurological system.
Laboratory investigations including complete blood
count, ESR, serum electrolytes, fasting and postprandial
sugar, lipid profile (total cholesterol, LDL, HDL, VLDL, and
triglycerides) were measured employing standard
methods. CT scan of the head and ECG were done within
72 hours of presentation, high-sensitivity CRP (hsCRP)
levels were calculated by the immunoturbidimetry
method.

compared between cases (8.02 5.08) and controls (1.6


0.5) as shown in Table III, these values were found to
be statistically (p < 0.001) highly significant. On
comparing the hsCRP levels and other factors like
diabetes and dyslipidaemia, no significant correlation
was found. Mean hsCRP level was found to be more in
haemorrhagic stroke (11.27 7.67) than ischaemic stroke
(6.7 3.11), which was statistically significant (p < 0.05)
(Table II). It was also seen that patients with low GCS
score had high levels of hsCRP in both types of stroke.
Mean hsCRP level was 14.8 6.2 in non-survivors of
haemorrhagic and 10.7 5.4 ischaemic stroke; these
values were found to be statistically significant as shown
in Table IV. On analysing the data, correlation was found
between hsCRP level and mortality of patients with
stroke.
Table I: Presenting symptoms in various groups of
stroke at the time of admission.
S. No

Symptoms

1.

a)

Journal, Indian Academy of Clinical Medicine

18
5

45
12.5

Right-sided weakness
with altered sensorium
b) Without altered sensorium

9
3

22.5
7.5

c)

12.5

Left-sided weakness
with altered sensorium
b) Without altered sensorium

2.

a)

Results
A total of 40 patients (18 males and 22 females) of stroke
who fulfilled the inclusion criteria were analysed. Out of
these, 26 were cases of ischaemic stroke while the other
14 cases were of haemorrhagic stroke. For valid
comparison, 40 age and sex matched controls were also
taken. Other than clinical parameters, serum hsCRP levels
were measured. In the present study, 45% patients were
males whereas 55% were females; mean age of the
stroke patients was 55.9 yrs in females and 63 yrs in
males. The most prevalent risk factor was diabetes,
followed by hypertension and dyslipidaemia. The most
common presenting symptom was altered sensorium
with left-sided weakness with facial palsy (Table I). 78.5%
of haemorrhagic stroke patients and 50% of ischaemic
stroke patients were having stage 2 hypertension on
admission. The different clinical and biochemical
parameters of ischaemic and haemorrhagic stroke cases
are compared in Table II. When mean hsCRP levels were

With aphasia

Table II: Showing clinical and biochemical parameters


in ischaemic and haemorrhagic stroke.
Variable

Ischaemic
(n = 14)

Haemorrhagic
(n = 26)

Age (yrs)

58.3

52.76

Sex (M/F)

12/14

6/8

Diabetes %

34.6%

57.1%

Hypertension %

23.0%

50%

Dyslipidaemia %

38.4%

28.5%

6.7 3.11

11.27 7.67

19

Mean hsCRP mg/dl


Survivors

Table III: Mean hsCRP level in controls and cases.


Patients
under study

No. of patients
N = 80

Mean hsCRP level


(mg/dl)

Controls

40

1.6 0.5

Cases

40

8.02 5.08

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July-September, 2010

205

Table IV: Showing mean hsCRP in relation to morbidity


and GCS score.

as an independent predictor of new end-point events (P


< 0.0001).

Mean hsCRP level (mg/dl)


Ischaemic
stroke

Haemorrhagic
stroke

GCS score (< 8)

8.6 3.0

7.6 2.0

Survivors

3.02 1.9

6.93.8

Non-survivors

10.7 5.4

14.8 6.2

Discussion
Stroke is the third leading cause of mortality in the western
world and also a major cause of disability. Recently, it was
shown that elevated CRP levels independently predict the
risk of future stroke and transient ischaemic attack in the
elderly5. To analyse the role of hsCRP in stroke, the present
study was undertaken. It was conducted on 40 stroke
patients, among them, 26 were cases of ischaemic stroke
and the other 14 were cases of haemorrhagic stroke. A
control group having 40 persons, had been taken
randomly from healthy subjects who were similarly
evaluated as the stroke cases.
The age distribution of the patients in this study was
between 30 and 90 years. Mean age was 55.9 years in
females and 63 years in male. The risk of stroke increased
with increasing age as was found in the present study.
These findings were in corroboration with a study by
Bamford et al6. Besides old age, diabetes mellitus (42.5%)
was the most common risk factor found in various study
populations, followed by hypertension (32.5%) and
dyslipidaemia 35%). Kannel7 reported that diabetes
doubles the risk of stroke. Benson and Sacco8 observed
that hypertension confers a relative risk for stroke of 3- to
5-fold.
The most common presentation in the present study was
altered sensorium with left-sided hemiparesis with facial
palsy (45%).When the hsCRP levels were measured within
72 hours of admission, it was found to be high in cases of
stroke. Similar observations have been reported by various
other workers also. Di Napoli9 et al in their study included
128 patients. The CRP values within 24 hours and between
48 to 72 hours were 1.3 (0.5 to 3.3) and 1.0 (0.5 to 2.3) mg/
dl respectively. Arenillas10 et al, in their study showed that
a high-sensitivity CRP level above the receiver operating
characteristic curve cut-off value of 1.41 mg/dl emerged

206

When hsCRP levels were compared in different types of


stroke, the mean hsCRP level was more in haemorrhagic
than ischaemic stroke. These results are different from
those of Yoshiyuki Wakugawa11 et al in the Hisayama study
in which they observed no clear association between
hsCRP levels and haemorrhagic stroke occurrence. This
may be due to the presence of some confounding factors
like obesity, elderly age, or due to large size of the bleed
in our study secondarily leading to ischaemia, and thus
increasing the hsCRP level. On comparing hsCRP levels
with other risk factors, no significant correlation was found.
Earlier reports in the available literature have not
commented regarding correlation of hsCRP level with
other risk factors.
In both ischaemic and haemorrhagic stroke, higher CRP
concentration correlates with severe neurological deficit.
This finding was similar to observations by Guo12 et al in
which they had observed higher concentrations on
admission correlated with leucocyte count and blood
glucose level, larger infarct, severe neurological deficit and
worse outcome. Kerstin Winbeck13 et al observed that an
increase in CRP level between 12 and 24 hours after the
onset of symptoms, predicts an unfavourable outcome
and is associated with an increase in the incidence of
cerebrovascular and cardiovascular events. It was also
seen that patients who expired had high hsCRP levels than
those who survived both types of stroke. Thus, there was
a relation between the hsCRP level and mortality. Higher
the hsCRP level, more is the chance of mortality. Mitchell
SV Elkind14 et al observe high-sensitivity CRP, but not LpPLA2, was associated with stroke severity. After adjusting
for confounders, hs-CRP was associated with the risk of
death (adjusted hazard ratio, 2.11; 95% confidence interval,
1.18 - 3.75).
From this study we concluded that hsCRP level is increased
in cases of stroke ischaemic as well as haemorrhagic,
suggesting an inflammatory response in acute stroke.
Furthermore, the increased levels correlated with larger
infarct and bleed, severe neurological deficit, and worse
outcome. As we had a small sample size, a larger study is
needed to endorse our observations, and to analyse
further about association between hsCRP level and

Journal, Indian Academy of Clinical Medicine

Vol. 11, No. 3

July-September, 2010

haemorrhagic stroke occurrence. A larger study should


also focus on whether hsCRP level needs to be included
as a health screening protocol.

infarction. Lancet 1991; 337: 1521.


7.

Kannel, McGreen. Diabetes most common risk factor. Arch


Inern Med 1979; 54 : 312-424.

8.

Benson RT, Sacco RL. Stroke prevention: hypertension,


diabetes, tobacco, and lipids. Neurol Clin 2000; 18 (2): 30919.

9.

Di Napoli M, Papa F, Bocola V. C-reactive protein in ischaemic


stroke: an independent prognostic factor. Stroke 2001; 32:
917-24.

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