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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 inflammation 1 . 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 risk 2,3 of stroke. hsCRP level when measured prior to the onset of clinical diseases, may be an independent predictor of the first ischaemic stroke 4 . 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

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.

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

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

N

%

1.

a) Left-sided weakness with altered sensorium

18

45

b) Without altered sensorium

5

12.5

2.

a) Right-sided weakness with altered sensorium

9

22.5

b) Without altered sensorium

3

7.5

c) With aphasia

5

12.5

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%

Mean hsCRP mg/dl

6.7 ± 3.11

11.27 ± 7.67

Survivors

19

9

Table III: Mean hsCRP level in controls and cases.

Patients

No. of patients N = 80

Mean hsCRP level (mg/dl)

under study

Controls

40

1.6 ± 0.5

Cases

40

8.02 ± 5.08

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Table IV: Showing mean hsCRP in relation to morbidity and GCS score.

 

Mean hsCRP level (mg/dl)

Ischaemic

Haemorrhagic

stroke

stroke

GCS score (< 8)

8.6 ± 3.0

7.6 ± 2.0

Survivors

3.02± 1.9

6.9±3.8

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 elderly 5 . 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 al 6 . 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%). Kannel 7 reported that diabetes doubles the risk of stroke. Benson and Sacco 8 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 Napoli 9 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.Arenillas 10 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

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

< 0.0001).

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 Wakugawa 11 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 Guo 12 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 Winbeck 13 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 Elkind 14 et al observe high-sensitivity CRP, but not Lp- PLA2, 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

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haemorrhagic stroke occurrence. A larger study should also focus on whether hsCRP level needs to be included as a health screening protocol.

References

1. Pearson TA, Mensah GA, Alexander RW. Marker of inflammation and cardiovascular diseases: application to clinical and public health practice. A statement for health- care profession from the Centres for Disease Control and Prevention and the American Heart Association.Circulation 2003; 107: 499-511.

2. Ridker PM,Buring JE,Shih J. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998; 98 (8): 731-3.

3. Ridker PM,Rifai N,Rose L. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347 (20): 1557-65.

4. Ridker PM, Cushman M, Stampfer MJ.Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336 (14): 973-9.

5. Rost NS, Wolf PA, Kase CS et al. Plasma concentration of C- reactive protein and risk of ischaemic stroke and transient ischaemic attack: the Framingham study. Stroke 2001; 32 (11): 2575-9.

6. Bamford J, Sandercock PAG, Dennis M et al.Classification of natural history of clinical identifiable subtypes of cerebral

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): 309-

19.

9. Di Napoli M, Papa F, Bocola V. C-reactive protein in ischaemic stroke: an independent prognostic factor. Stroke 2001; 32:

917-24.

10. Arenillas JF, Alvarez-Sabin J, Molina CA. C-reactive protein predicts further ischaemic events in first transient ischaemic attack or stroke patients with intracranial large artery occlusive disease. Stroke 2003; 34 (10): 2463-8.

11. Yoshiyuki Wakugawa,Yutaka Kiyohara,Yumihiro Tanizaki et al. C-reactive protein and risk of first ever ischaemic and haemorrhagic stroke in a general Japanese population. Stroke 2006; 37: 27-32.

12. Guo Y, Jiang X, Chen S et al . C-reactive protein as an important prognostic marker for ischaemic stroke. Zhonghua Yu Fang Yi Xue Za Zhi 2003; 37: 102-4.

13. Kerstin Winbeck, Hogler Poppert, Thorleif Etgen et al. Prognostic relevance of early serial C-reactive protein measurements after first ischaemic stroke. Stroke 2002; 33:

2459-64.

14. Mitchell SV Elkind, Wanling Tai, Kristen Coates et al. High- Sensitivity C-Reactive Protein, Lipoprotein-Associated Phospholipase A 2 , and Outcome After Ischaemic Stroke. Arch Intern Med 2006; 166: 2073-80.

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