in numerous industrial countries , cerebro - vascular accident ( cva ) has been the third common cause of death after coronary arteries diseases ( cad ) and cancers .
several studies have indicated that higher levels of inflammatory biomarkers such as c - reactive protein ( crp ) and interlukin-6 ( il-6 ) have been associated with worsening ischemic events . 
 
crp is a systemic inflammatory marker that is produced in a large amounts by hepatocytes in response to il-1 , il-6 and tnf factor .
rapid induction of crp , its long half - life ( 19 hours ) and lack of alteration during day and night in comparison with other acute phase reactants has introduced crp as an important factor for evaluation in inflammatory and infectious diseases .
nowadays , crp is a confirmed diagnostic marker for the patients with cva and recent prospective investigations showed that crp is clinically helpful for predicting the risk of the next cardiovascular diseases .
although many studies have been conducted on association of crp and cardiac diseases ; only few studies have evaluated its role in predicting mortality in stroke patients . in addition
, it can be used as biomarker at early phases in diagnosis of stroke , determining prognostic value of therapeutic programs and secondary prevention strategies . in this study
, we intended to evaluate association of crp as an inflammatory marker with acute cerebral ischemic attack characteristics , risk factors and to determine a cutoff point of hs - crp in predicting early mortality .
this study was conducted on 200 patients with impression of stroke who had been referred to emergency ward of university hospital , imam khomeini hospital , tehran , iran , within may 2009 march 2011 .
patients who had referred earlier than 24 hours after ischemic stroke were enrolled in the study .
38 patients with body temperature higher than 37.8 c , hemorrhagic stroke and those with previous inflammatory or malignant diseases were excluded .
medical history was taken from the patient or his / her relatives if the patient was unconscious or not able to speak .
patients were evaluated for age , sex , diabetes , hyperlipidemia , ischemic heart diseases , smoking and past history of stroke or hypertension .
routine laboratory tests , brain magnetic resonance imaging ( mri ) , transthoracic echocardiography ( tte ) and carotid doppler ultrasonography were done in all of the patients .
national institutes of health stroke scale ( nihss ) was used for assessing stroke severity .
type of stroke was determined based on toast ( trial of org 10172 in acute stroke treatment ) classification .
it is able to demonstrate various types of acute ischemic stroke with different etiology and is consisted of 5 sub - groups : large - vessel atherosclerosis , cardioembolic , small - vessel occlusion or lacunar , undetermined etiology , and non - atherosclerotic determined etiologies .
another sample for specific tests was stored in room temperature for 20 minutes until clotting .
serum was stored in -70 c and sent to heart center hospital of tehran university of medical sciences and hs - crp concentration was determined by turbidimetry method and roche kit ( manufactured in swiss ) with using cobaf apparatus ( model integra400 + ) .
usa ) using chi - square test and student 's t - test for univariate analysis and mantel hansel analysis for multivariate analysis .
receiver operating characteristic ( roc ) curve was drawn for demonstrating cut off point of crp for predicting patients mortality within the first week of admission .
they had been referred to emergency ward of imam khomeini hospital within may 2009march 2011 .
mean age of the patients was 67  12 years with a range of 33 - 95 years .
patients were classified into 3 age groups : 11 patients were younger than 50 years ( 6.8% ) , 81 cases were 50 - 70 years ( 50% ) and 70 patients were older than 70 years ( 43.2% ) .
clinical demographic evaluation showed hypertension in 77 ( 47.5% ) patients , diabetes in 50 ( 30.9% ) , hyperlipidemia in 56(35% ) , history of cardiovascular diseases in 46(24.8% ) , history of previous cva in 33(20.4% ) and cigarette smoking in 67(41.4% ) patients .
mean of nihss score was 9.5  8 ( min 1 and max 30 ) . according to nihss score ,
our patients were classified to 3 sub - groups : nihss score < 7 ( mild neurologic disorders ) , nihss score 7 - 13 ( moderate neurological disorders ) and nihss score > 13 ( severe neurological disorders ) . according to toast classification criteria , large vessel atherosclerosis was seen in 95 subjects ( 58.6% ) , cardioembolic in 11 ( 6.8% ) and small vessel occlusion in 56 patients ( 35% ) .
regarding roc curve analysis , appropriate cut - off point for predicting patients short time mortality was determined as 2.15 in this study .
in addition , nihss > 10 was considered as appropriate score for predicting patients short - term mortality ( fig .
roc curve of variables for predicting mortality in the patients with stroke association between hs - crp and early mortality in the patients with acute cva was significant .
mean of crp in died patients was 8.9  7 mg / dl and in survived patients was 2.2  5 mg / dl ( p = 0.0001 ) .
the hs - crp amounts showed a significant association with early mortality , diabetes , ihd ( ischemic heart diseases ) , smoking and nihss .
incidence of early onset mortality based on sub - groups of evaluated demographic variables in the investigated patients with acute ischemic stroke nihss : national institutes of health stroke scale ; rr : relative risk ; crp : c - reactive protein after multivariate analysis and adjusting for sex , age , history of heart disease , nihss score and toast , we found hs - crp as an independent factor in predicting early onset mortality .
significantly increased rate of mortality by 13.3 times was seen in patients by simultaneous crp > 2.15 and nihss > 10 as cut - off points for predicting mortality , so that out of 23 patients possessing these conditions 11(47.8% ) died . in the patients who had simultaneously crp > 2.15 ,
neurological defect severity was more than 10 and diabetes and mortality rate increased about 19 times ; so that out of 13 patients possessing these conditions , 10(76.90% ) died .
therefore , co - existence of these three factors in a patient may strongly increase the risk of mortality .
determinant criteria for mortality risk in the patients with cva and comparing them with each other are summarized in table 2 . 
 
comparing of multivariate factors with early death in the patients with stroke nihss : national institutes of health stroke scale ; rr : relative risk ; crp : c - reactive protein
the results of present study showed that hs - crp in the patients with acute ischemic cva who had died within the first week after manifesting symptoms was significantly higher than survived patients .
in addition , hs - crp levels more than 2.15 mg / dl were considered as cut - off point for predicting mortality in this study .
in addition , a large number of previous studies have reported that increasing crp at the first hours after stroke was associated with risk of mortality .
montaner et al . introduced crp as a powerful factor for predicting mortality after cva . 
 
ischemic damage to brain resulted in disturbance in neuroglia activity especially astrocytes adhered to endothelial .
therefore , these cells release cytokines and inflammatory factors that resulted in neuron necrosis and vessels endothelial permeability . at the same time by impaired blood brain barrier ( bbb )
permeability , neutrophils by exiting through endothelial cells , enters into tissues and increase inflammatory markers concentration . as a consequence ,
it is considerable that numerous articles recommend application of nihss system for more accuracy in stroke severity . 
  cut - off point of > 10 for nihss was shown in present study that in combination with an elevated crp > 2.15 was associated with 13 times increase in mortality .
similarly , studies performed by basic et al . and shenhar et al . showed association of nihss and increase in inflammatory factors .
neurological defect severity and its association with elevated crp were shown in ischemic cycles so that more ischemia resulted in more neurological defect severity . among 16 dead cases , 14 ( 30.4% )
patients had history of heart diseases and significant association was seen between hs - crp and mortality in relation to ischemic heart disease .
in addition , a meta - analysis study indicated that crp is directly associated with ischemic heart diseases , stroke and mortality risk . 
 
time of hs - crp evaluation was a determining factor in early predicting mortality in this study .
maximum of plasma crp concentration has been usually reported within 36 to 48 hours after initiating signs of stroke .
a study by winbeck et al . showed that the most appropriate time for obtaining blood samples was 12 - 24 hours after initiating signs and can predict the risk of cardiac and cerebral vascular events . in the present study ,
this study showed that there was a direct association between hs - crp and mortality within the first week after stroke .
cut - off point of crp was 2.15 mg / dl and measuring hs - crp within the first hours after stroke increase the predicting rate of early mortality risk .
as up to now , a blood biomarker that can introduce accurate information about cause and outcome after stroke has not been known yet , cut - off point of hs - crp can be used for therapeutic decision making .
 backgroundhigh sensitive c - reactive protein ( hs - crp ) is a systemic inflammatory marker that is produced in a large amount by hepatocytes in response to interleukin-1 ( il-1 ) , il-6 and tumor necrosis factor after ischemic stroke.methodsmeasurement of hs - crp in the first 24 hours of onset in 162 patients suffering from ischemic stroke was done . 
 relation of crp with the risk of early mortality , national institutes of health stroke scale ( nihss ) , stroke subtypes and other factors was determined.resultsregarding to roc curve analysis , appropriate cut - off point for predicting patients short time mortality was equal to 2.15 mg / dl in this study . 
 significantly increased rate of mortality by 13.3 times was seen in patients with simultaneous crp > 2.15 mg / dl and nihss > 10.conclusionthe result of this study showed that there is a direct association between hs - crp and mortality within the first week after stroke . 
 measuring hs - crp within the first hours after stroke increases the predicting rate of early mortality risk with cut - off point of 2.15 . 