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 » Introduction
 » Methods
 »  Results and Obse...
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SHORT COMMUNICATION
Year : 2021  |  Volume : 53  |  Issue : 6  |  Page : 484-488
 

Clinical profile and role of C-reactive protein and lactate dehydrogenase as prognostic marker and comparative efficacy of different pharmacotherapeutic agents in patients with cerebrovascular accident: An observational study


1 Department of Internal Medicine, SMCH, Silchar, Assam, India
2 Department of Anaesthesia, AMCH, Dibrugarh, Assam, India

Date of Submission01-Jul-2021
Date of Decision09-Jul-2021
Date of Acceptance10-Jul-2021
Date of Web Publication30-Dec-2021

Correspondence Address:
Dr. Dibya Jyoti Sharma
Department of Internal Medicine, SMCH, Silchar, Assam
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijp.ijp_515_21

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 » Abstract 


The current study was conducted to determine the role of C-reactive protein (CRP) and lactate dehydrogenase (LDH) as prognostic-marker and outcomes of different pharmacotherapeutic agents among patients with cerebrovascular accident (CVA). A hospital-based observational study was conducted and patients with CVA admitted were included. Serum-CRP on admission correlated positively with modified Rankin score (mRS) (r = 0.9, P < 0.001) in ischemic stroke, whereas no correlation between serum LDH with mRS (r = 0.1, P = 0.5) was observed. Neither CRP nor LDH was helpful in predicting the outcome in hemorrhagic stroke. The use of Vitamin B12 was associated with favorable outcome in ischemic CVA cases and use of folic acid was associated with favorable outcome among hemorrhagic-CVA patients.


Keywords: Acute phase substance, cerebrovascular accident, C-reactive protein, lactate dehydrogenase, prognostic marker


How to cite this article:
Sharma DJ, Singha K J, Das K, Das C, Rakesh M. Clinical profile and role of C-reactive protein and lactate dehydrogenase as prognostic marker and comparative efficacy of different pharmacotherapeutic agents in patients with cerebrovascular accident: An observational study. Indian J Pharmacol 2021;53:484-8

How to cite this URL:
Sharma DJ, Singha K J, Das K, Das C, Rakesh M. Clinical profile and role of C-reactive protein and lactate dehydrogenase as prognostic marker and comparative efficacy of different pharmacotherapeutic agents in patients with cerebrovascular accident: An observational study. Indian J Pharmacol [serial online] 2021 [cited 2022 Jan 25];53:484-8. Available from: https://www.ijp-online.com/text.asp?2021/53/6/484/334353





 » Introduction Top


C-reactive protein (CRP) is an acute-phase substance which is produced in hepatocytes. It is considered a sensitive predictor of both new onset and recurrent ischemic events.[1],[2],[3] CRP is a potential predictor of future vascular events and a potential prognostic marker following vascular events. There is a paucity of data relating to CRP as prognostic factor in cerebrovascular accident (CVA).[4],[5] CVA is one of the leading causes of death and disability in the elderly population,[6] and the indicators predicting the outcome in such patients are not clearly outlined. About three-quarter of patients with ischemic stroke have elevated levels of CRP.[7] The rise in CRP level may reflect a systemic inflammatory response following stroke and the extent of tissue injury. In animal models of focal cerebral ischemia, it has been noted that CRP increases the secondary brain damage through activating complement system.[8] The information regarding hemorrhagic stroke is also scarce. It has been observed that CRP levels increases shortly after admission and was related to hematoma volume in hemorrhagic stroke which can be attributed to inflammatory response in hematoma.[9] There are several studies which have assessed the role of CRP in the early phases of stroke as a prognostic factor of functional outcome among which most of the studies evaluated only the relation between CRP and mortality with variable results. Some studies found positive association; however, other studies did not.[10],[11]

Lactate dehydrogenase (LDH) has also been used as inflammatory marker for various inflammatory and neoplastic diseases (lymphoma, breast carcinoma, hepatocellular carcinoma, etc.,). Cerebrospinal fluid (CSF) LDH has been described as a prognostic marker in CVA patients in some studies.[12] Studies on serum LDH as prognostic marker in CVA in isolation or in combination with elevated CRP level have not been reported. Therefore, to bridge the unmet need of early prognostication of stroke patients, we attempt to study the role of CRP and LDH as the prognostic markers and their significance in outcome of CVA patients.

Aim of the study

This study was conducted to assess the etiology, clinical features as well as to estimate CRP and LDH as prognostic markers in patients suffering from cerebrovascular events. The secondary outcome was assessed for the role of intravenous mannitol, Vitamin B12 injection, and oral folic acid supplementation in the outcome of ischemic and haemorrhagic stroke, respectively; which are used as the part of standard of care in stroke patients.


 » Methods Top


This study was undertaken among indoor patients admitted in the medicine department of Silchar Medical College and Hospital from July 2020 to May 2021 (No SMC/753 dated Silchar January 20, 2021).

Study design

The present study is a hospital-based, prospective, observational study.

Sample size

Patients admitted in the medicine department of Silchar Medical College and Hospital with cerebrovascular accident who fulfilled the inclusion criteria over a period of 10 months from July 2020 to May 2021were included in the analysis.

Inclusion and exclusion criteria

All symptomatic patients with CVA who will be admitted in the medicine department of Silchar Medical College and Hospital were included in the study. Patients who were excluded from the preview of the study includes (1) patients with multiple sclerosis, intracranial space occupying lesion, meningitis, (2) patients with psychiatric disorder, (3) pregnant and lactating mothers, (4) children <12 years of age, and (5) patients who refused to give consent.

Data collection

A detailed clinical history and complete physical and neurological examination was done in all cases. All routine hematological and biochemical investigations such as complete blood count, renal function test, as well as the inflammatory markers such as serum CRP, LDH was evaluated. Noncontrast computed tomography (NCCT) scan of the brain was done in patients. The results for each parameter for the categorical data were represented in numbers and percentages, whereas continuous data were presented as average (mean, standard deviation) which was depicted in tables and figures as per need.

Statistical analysis

Statistical analysis will be carried out by Microsoft Excel/SPSS software. During the analysis of data, continuous variables were compared using the Student t-test, whereas the categorical variables were compared using the Chi-square test and descriptive statistics was used as per need. Differences in distribution will be tested with the Fisher's exact test and X2 test. P ≤ 0.05 is considered statistically significant.


 » Results and Observations Top


This study was a hospital-based, prospective, observational study including 50 patients presenting with cerebrovascular accident in the Department of General Medicine, Silchar Medical College and Hospital from between July 2020 to May 2021. The study participants were investigated by various radiological and biochemical test along with comprehensive clinical examination, and the results were analyzed using the Chi-square test and Student's t-test. In all analysis, a P < 0.05 was considered statistically significant.

The mean age of the study population was 61.68 ± 12.07 years ranging from 30 to 91 years. The patients were classified into two groups according to the NCCT brain at admission: Group A included 28 patients with acute ischemic stroke with mean age (62.81 ± 9.8 years) and Group B included 22 patients with intracerebral hemorrhage with mean age of 60.14 ± 14.5 years. The outcome was measured by modified Rankin score (mRS) and poor outcome was defined as mRS parameter >2. The outcomes were assessed in 7 days after admission by mRS value and showed poor outcome in 22 patients (44%). The mean mRS of the overall patients was 2.96 ± 2.3. Serum CRP level on admission was positively correlated with mRS parameter (r = 0.6, P < 0.001). The demographic characteristics of both groups of the study were almost identical, as shown in [Table 1]. However, more patients in hemorrhagic stroke group had higher baseline blood pressure value as compared to ischemic stroke group.
Table 1: Baseline characteristics in both ischemic and hemorrhagic cerebrovascular accident groups

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In ischemic stroke serum CRP on admission correlated positively with mRS (r = 0.9, P < 0.001). Mean serum CRP in patients with poor outcome according to mRS parameter was 40 ± 9.2 mg/L, whereas in those with favorable outcome, the mean was 22.64 ± 2.8 mg/L (P < 0.001), as depicted in [Table 2], whereas serum LDH has no correlation with mRS (r = 0.1, P = 0.5). In hemorrhagic stroke, there was no correlation between CRP and mRS (r = 0.3, P = 0.165). The mean serum CRP in patients with poor outcome was 9.60 ± 5.9 mg/L, whereas those with favorable outcome, the mean was 2.82 ± 1.90 mg/L (P = 0.165). There was no correlation between serum LDH with mRS parameter (r = 0.03, P = 0.9) in predicting the outcome of CVA patients. On comparing both groups, it was found that CRP was significantly higher in ischemic stroke than in hemorrhagic stroke. CRP was 33.18 ± 11.3 in ischemic stroke compared to 4.36 ± 9.5 in hemorrhagic stroke (P < 0.001).
Table 2: Association between level of C-reactive protein and outcome

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All patients were managed as per standard protocol used for stroke patients in our institute. On analyzing the pharmacological treatment received by the patients in our study, intravenous mannitol was found not to be associated with significant difference in outcome between ischemic and hemorrhagic stroke. On the other hand, intravenous Vitamin B12 injection use was associated with improved outcome in ischemic stroke, whereas folic acid supplementation led to better outcome in hemorrhagic stroke patients, as shown in [Table 3].
Table 3: Association between pharmacological treatment on outcome in both groups of cerebrovascular accident

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 » Discussion Top


Stroke is one of the leading causes of death in developed and developing countries. Stroke induces systemic inflammatory response through mobilizing and migration of peripheral immune cells into the brain. It has been observed in Rotterdam study, that high CRP is associated with the risk of future stroke, although it is not beneficial for individual stroke outcome prediction.[13] On the contrary, it was observed that high level of CRP is associated with increased risk of ischemic stroke and transient ischemic attack (TIA) in a study done in Framingham.[3] An association between high CRP and stroke presentation, outcomes and future vascular events were found in CVA patients in other studies.[2],[4],[14],[15],[16],[17],[18]

The measurement of CSF LDH was found to be significantly high in newborn infants with perinatal ischemia. The longer half-life of LDH in CSF and high intracellular concentration explain the high LDH sensitivity in cerebral ischemia. It has been observed in several studies that the value of LDH measured within 8 h of stoke was significantly higher in patients with neurological deficits in comparison to TIA.[19],[20],[21] In a study done by Shoaeb et al., it was found that serum CRP predicts the outcome in ischemic stroke not in hemorrhagic stroke and it also had positive correlation with mRS value in ischemic stroke.[22] Elevated CRP level was associated with higher incidence of ischemic stroke but not with hemorrhagic stroke was also reported by a retrospective study done in Japan[23] which is echoed similarly in our study. In another study done by Parakh et al.,[12] no correlation was noted between serum LDH and both ischemic as well as hemorrhagic stroke and its outcome, which was in concordance with the present study.

Among acute stroke patients who received intravenous mannitol treatment as per routine management; no significant difference in outcome was observed between infarct and hemorrhagic stroke. In a previous study, intravenous mannitol when used in acute stroke was found be safe but not associated with improved short term outcome.[24] Patients with hemorrhagic stroke had better outcome with folic acid supplementation, whereas patients with acute stroke with infarct who received intravenous Vitamin B12 had good outcome. This was in concordance with a previous study which observed reduced serum Vitamin B12 level in ischemic stroke and low folic acid level in hemorrhagic stroke patients, respectively.[25]


 » Conclusion Top


In the current study, we found that serum CRP level was positively correlated with the outcome of ischemic stroke but not with hemorrhagic stroke and serum LDH had no correlation with the outcome of both ischemic and hemorrhagic stroke. Thus, CRP concentration can be used as a screening investigation for determining the severity of ischemic stroke.

Ethical consideration

The study was undertaken with due clearance from the ethical committee of our institute which follows the Helsinki guidelines for research. Informed consent was obtained from patients or attendant before the inclusion in our study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

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Di Napoli M, Elkind MS, Godoy DA, Singh P, Papa F, Popa-Wagner A. Role of C-reactive protein in cerebrovascular disease: A critical review. Expert Rev Cardiovasc Ther 2011;9:1565-84.  Back to cited text no. 1
    
2.
Di Napoli M, Papa F, Bocola V. C-reactive protein in ischemic stroke: An independent prognostic factor. Stroke 2001;32:917-24.  Back to cited text no. 2
    
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Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR. C-reactive protein and outcome after ischemic stroke. Stroke 1999;30:981-5.  Back to cited text no. 4
    
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Di Napoli M, Di Gianfi lippo G, Sollecito A, Bocola V. C-reactive protein and outcome after fi rst-ever ischemic stroke. Stroke 2000;31:238-9.  Back to cited text no. 5
    
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Jauch EC, Saver JL, Adams HP Jr., Bruno A, Connors JJ, Demaerschalk BM, et al. Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870-947.  Back to cited text no. 6
    
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Smith CJ, Emsley HC, Vail A, Georgiou RF, Rothwell NJ, Tyrrell PJ, et al. Variability of the systemic acute phase response after ischemic stroke. J Neurol Sci 2006;251:77-81.  Back to cited text no. 7
    
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Gill R, Kemp JA, Sabin C, Pepys MB. Human C-reactive protein increases cerebral infarct size after middle cerebral artery occlusion in adult rats. J Cereb Blood Flow Metab 2004;24:1214-8.  Back to cited text no. 8
    
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Di Napoli M, Godoy DA, Campi V, Masotti L, Smith CJ, Parry Jones AR, et al. C-reactive protein in intracerebral hemorrhage: Time course, tissue localization, and prognosis. Neurology 2012;79:690-9.  Back to cited text no. 9
    
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Montaner J, Fernandez-Cadenas I, Molina CA, Ribó M, Huertas R, Rosell A, et al. Poststroke C-reactive protein is a powerful prognostic tool among candidates for thrombolysis. Stroke 2006;37:1205-10.  Back to cited text no. 10
    
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Topakian R, Strasak AM, Nussbaumer K, Haring HP, Aichner FT. Prognostic value of admission C-reactive protein in stroke patients undergoing IV thrombolysis. J Neurol 2008;255:1190-6.  Back to cited text no. 11
    
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Parakh N, Gupta HL, Jain A. Evaluation of enzymes in serum and cerebrospinal fluid in cases of stroke. Neurol India 2002;50:518-9.  Back to cited text no. 12
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Bos MJ, Schipper CM, Koudstaal PJ, Witteman JC, Hofman A, Breteler MM. High serum C-reactive protein level is not an independent predictor for stroke: The Rotterdam Study. Circulation 2006;114:1591-8.  Back to cited text no. 13
    
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Anuk T, Assayag EB, Rotstein R, Fusman R, Zeltser D, Berliner S, et al. Prognostic implications of admission inflammatory profile in acute ischemic neurological events. Acta Neurol Scand 2002;106:196-9.  Back to cited text no. 14
    
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Arenillas JF, varez-Sabin J, Molina CA, Chacon P, Montaner J, Rovira A, et al. C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease. Stroke 2003;34:2463-8.  Back to cited text no. 15
    
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Christensen H, Boysen G. C-reactive protein and white blood cell count increases in the first 24 hours after acute stroke. Cerebrovasc Dis 2004;18:214-9.  Back to cited text no. 16
    
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Elkind MS, Tai W, Coates K, Paik MC, Sacco RL. High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med 2006;166:2073-80.  Back to cited text no. 17
    
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Koçer A, Canbulat C, Gözke E, Ilhan A. C-reactive protein is an indicator for fatal outcomes in first-time stroke patients. Med Sci Monit 2005;11:R540-4.  Back to cited text no. 18
    
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Castellanos M, Leira R, Serena J, Pumar JM, Lizasoain I, Castillo J, et al. Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke 2003;34:40-6.  Back to cited text no. 19
    
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Harraf F, Sharma AK, Brown MM, Lees KR, Vass RI, Kalra L. A multicentre observational study of presentation and early assessment of acute stroke. BMJ 2002;325:17.  Back to cited text no. 20
    
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Ariesen MJ, Claus SP, Rinkel GJ, Algra A. Risk factors for intracerebral hemorrhage in the general population: A systematic review. Stroke 2003;34:2060-5.  Back to cited text no. 21
    
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Chei CL, Yamagishi K, Kitamura A, Kiyama M, Imano H, Ohira T, et al. C-reactive protein levels and risk of stroke and its subtype in Japanese: The Circulatory Risk in Communities Study (CIRCS). Atherosclerosis 2011;217:187-93.  Back to cited text no. 23
    
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Bereczki D, Mihálka L, Szatmári S, Fekete K, Di Cesar D, Fülesdi B, et al. Mannitol use in acute stroke: Case fatality at 30 days and 1 year. Stroke 2003;34:1730-5.  Back to cited text no. 24
    
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Bayir A, Ak A, Ozdinç S, Seydanoğlu A, Köstekçi SK, Kara F. Acute-phase vitamin B12 and folic acid levels in patients with ischemic and hemorrhagic stroke: Is there a relationship with prognosis? Neurol Res 2010;32:115-8.  Back to cited text no. 25
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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