ABSTRACT

Corresponding Author:
Dr. Philomena James,
#14, JP Salai,
Thendral Nagar,
Sathuvachari, Vellore-9.
E-mail: indian7@gmail.com

ABSTRACT

BACKGROUND

Cerebrovascular stroke is one of the leading cause of death and disability. C-Reactive Protein is an inflammatory marker that is increased in stroke. We intended to study the role of CRP in predicting severity and short-term outcome in stroke patients.

METHOD

The study included 60 patients with acute stroke admitted within 24 hours of symptom onset. All patients were subjected to detailed history taking and neurological evaluation. Severity of stroke on admission was assessed with National Institute of Health Stroke Scale (NIHSS), while seven days later outcome was assessed with modified Rankin Score (mRS) and Barthel ADL Index (BI). CRP levels and CT Brain was done in all patients within 24 hours of admission.

RESULTS
                The mean age of the patients was 62.53±9.54. We found that CRP levels on admission was higher in ischaemic stroke patients (Mean=8.56±3.51) and there was positive correlation between CRP levels and severity assessed by NIHSS (r=0.44; p=0.004). There was positive correlation between CRP levels and short-term outcome assessed by mRS (r=0.35; p value=0.022). However, there was no positive correlation between CRP levels and severity or outcome in haemorrhagic stroke patients.

CONCLUSION

CRP levels on admission is a predictor of severity and short-term outcome in ischaemic stroke, but not haemorrhagic stroke.

KEYWORDS

C-Reactive Protein, Cerebrovascular Stroke, NIHSS.

INTRODUCTION

C-reactive protein is a marker of inflammation. It is a glycoprotein synthesized by the liver in response to cytokines produced by macrophages. Recent evidences suggest that it is also associated with atherosclerosis. This led to studies focussing on CRP as an indicator of prognosis for vascular events.

Cerebrovascular Accidents, both ischaemic and haemorrhagic stroke have been one of the leading causes of mortality and morbidity in elderly populations.^[1] However, markers predicting prognosis in these patients have not been established clearly.

The relationship between inflammation and atherosclerosis is well established. Thus, CRP being a marker of inflammation is identified as a marker for prognosis after vascular events. In addition elevated levels of CRP has also been used as an indicator of future vascular events.

The rise in CRP levels in stroke is not only due to its association with atherosclerosis, but also due to the inflammatory reaction that follows tissue damage.^[2]

Statistics

Data were prospectively collected and coded prior to analysis using the professional Statistical Package for Social Science (SPSS version 22). The description of data was in the form of mean (±) SD for quantitative data and frequency and proportion for qualitative data. Student-t Test (t) and one-way ANOVA was used for comparison between two groups and three groups regarding normally distributed (Parametric) quantitative data. Results were considered significant if p<=0.05.

RESULTS

The study involved 60 patients who were admitted within 24 hours of onset of acute stroke. Out of the 60 patients, 39 were male and 21 were female. The mean age of patients was 62.53±9.54. Based on CT Brain done at the time of admission, 41 patients had ischaemic stroke and 19 patients had haemorrhagic stroke. Table 4 and 5 shows the general characteristics of the study population.

Based on NIHSS scale, patients were classified as mild (0-7), moderate (8-14) and severe stroke (>14).^[7,8] Short-term outcome was measured by modified Rankin scale and Barthel ADL Index (BI) at 7 days. Poor outcome was defined as mRS >2.^[9-11] and BI <95.^[12]

According to NIHSS scale, 13.3% of patients had mild stroke and 48.3% and 28.3% of patients had moderate and severe stroke respectively. Based on mRS done at 7 days, 21.67% of patients had favourable outcome and 78.3% of patients had poor outcome. The mean NIHSS score was 13.23±4.49. The mean mRS for the study population is 3.67±1.25. Based on BI, 18.33% of patients had favourable outcome and 81.67% of patients had poor outcome (Fig. 1).

Fig. 1: Severity of Stroke in Study Population

The mean CRP levels in Ischaemic stroke was 8.56±3.51, while that of haemorrhagic stroke is 6.95±5.67. The demographic details of both ischaemic and haemorrhagic stroke is shown in Table 6.

There was positive correlation between CRP levels and NIHSS in Ischaemic stroke (r=0.44; p=0.004 (Fig. 2)). CRP levels in severe ischaemic stroke based on NIHSS was 10.85±3.85, while in mild and moderate stroke it was 7.50±2.82 (p value= 0.012). MRS also had a positive correlation with CRP (r=0.35; p value=0.022) (Fig. 3), while BI had negative correlation with CRP in ischaemic stroke (r=0.54; p value <0.001) (Fig. 4).

Fig. 2

Fig. 3

DISCUSSION

Stroke is the leading cause of disability in both developed and developing countries. It is the third most common cause of death.^[13] Atherosclerosis with rupture of plaque is the most important cause of stroke. Inflammation is a central process in the initiation, development and subsequent rupture of plaques. As the plaques are developing, there is recruitment of immune cells such as macrophages and T cells. These cells produce various inflammatory mediators including cytokines, proteases and free radicals which ultimately cause rupture of plaque.^[14] Brain damage further causes mobilization and migration of cells such as neutrophils and macrophages into the affected area and stimulates inflammatory response.

C-Reactive protein is produced by liver. It is usually absent in blood. Its production is stimulated by acute inflammation and usually rises within the first few hours of inflammation.^[15] Our study was done to demonstrate the association between CRP levels and severity of stroke.

NIHSS was used in this study to assess severity. Various studies have concluded that it is predictive of stroke outcomes.^[16-18] One study demonstrated that severity of stroke assessed by NIHSS at admission to be predictive of 3 month mortality and another study established it as an independent predictor of 30 days mortality.

We found that CRP levels is a predictor of severity and short-term outcome in ischaemic stroke patients. CRP levels did not correlate with severity in haemorrhagic stroke. CRP levels were positively correlated with NIHSS and mRS in ischaemic stroke. It had negative correlation with BI in ischaemic stroke.

Various studies have found an association between CRP levels and stroke. Di Napoli et al demonstrated in his study that concentration of CRP increased in the first 24 hours following stroke and this rise is associated with infarct size and hence associated with poor prognosis.^[19]

Di Napoli in another study found that CRP cannot be used in the risk stratification of stroke.^[20] Recent studies found that increased CRP levels predicted recurrence of stroke and transient ischaemic attack.

The exact mechanism for the elevation of CRP levels in severe stroke remains unexplained. Atherothrombosis being an inflammatory pathology could cause rise in acute phase reactants in the first few hours.^[15] Also, cerebral tissue injury can cause elevated CRP.^[21] Activation of coagulation by increased CRP through tissue factor expression has also been proposed as one of the possibilities.^[22] CRP, being an inflammatory marker could be associated with other pathological processes that might cause severe stroke. Some studies have shown that CRP per se can cause secondary brain damage due to complement activation.^[23]

In the above context, whether increased CRP leads to severe stroke or vice versa needs to be ascertained through larger population based studies.

The lack of inflammatory process preceding the onset of haemorrhagic stroke could well explain the finding in our study that there is no significant correlation between CRP and severity of haemorrhagic stroke. However, certain studies found as association between increased CRP and size of haematoma in haemorrhagic stroke. The probable mechanism could be the inflammatory response that occurs because of tissue injury as a result of haemorrhage.^[24] This leads to IL6 production, one of the major stimulus for CRP synthesis.^[25]

We found that although CRP levels are elevated in haemorrhagic stroke, there was no correlation with severity of stroke. Elevated CRP levels in haemorrhagic stroke is a consequence of tissue injury and does not involve in the pathogenesis. Our study revealed that rise in CRP level is more in ischaemic stroke than in haemorrhagic stroke. Other studies have also reached a similar conclusion.^[26,27]

This study has few limitations. We did not correlate the radiologic finding of CT Brain such as the size of the haemorrhage with CRP levels, as we intended to find the clinical outcome.

Another limitation is that we used a single value of CRP at the time of admission for predicting severity rather than serial measurements, which could have been more informative. Another limitation is the use of regular CRP rather than using high sensitivity CRP. The regular CRP is commonly present and readily available in most ICU setups across our country.

CONCLUSION

CRP levels measured within 24 hours of admission are elevated in both ischaemic and haemorrhagic stroke. It is a predictor for severe stroke and unfavourable outcome in ischaemic stroke, but not in haemorrhagic stroke.

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