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ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 3  |  Page : 1072-1076

Ischemia-modified albumin for evaluating severity and predicting prognosis in patients with acute cerebrovascular disease


Department of Neuropscychiatry, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt

Date of Submission12-Feb-2019
Date of Decision12-Mar-2019
Date of Acceptance17-Mar-2019
Date of Web Publication30-Sep-2020

Correspondence Address:
Mona S El-Kholy
Elbajour, Menofia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_65_19

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  Abstract 


Objective
To evaluate the role of serum ischemia-modified albumin (IMA) level in cerebrovascular stroke and its relation to the severity or prognosis in patients with acute cerebrovascular disease.
Background
It was recently demonstrated that IMA levels increase in the acute phase of cerebrovascular diseases. Yet the data regarding IMA levels in various types of cerebrovascular events are still insufficient.
Patients and methods
A case–control study on 100 consecutive patients and 75 normal individuals as controls was conducted. National Institute of Health Stroke Scale and Glasgow Coma Scale were assessed at admission time. Lesion volume was calculated using computed tomography scan. IMA levels were measured at the same time using the available chemical method. Patients were followed up after 3 months, and the modified Rankin scale (MRS) was evaluated.
Results
IMA was significantly higher in the patient group than in the control group (96.83 ± 12.01 vs. 44.47 ± 5.28, P < 0.001). There were significantly higher mean values of IMA in patients with ischemic stroke than those with hemorrhagic stroke (P = 0.036). Regarding severity, serum IMA concentrations were positively correlated with National Institute of Health Stroke Scale (r = 0.252, P = 0.01) and lesion volume calculated by computed tomography scan (r = 0.21, P = 0.04) but inversely correlated with Glasgow Coma Scale score (r = −0.227, P = 0.02). Regarding prognosis, on applying MRS 3 months after stroke, this study showed that MRS had no statistically significant correlation with IMA (r = 0.01, P = 0.938).
Conclusion
IMA levels are higher in patients with acute cerebrovascular disease compared with healthy individuals. The level of IMA is higher in patients with ischemic stroke than those with hemorrhagic stroke. IMA can be used as an indicator of stroke severity.

Keywords: cerebrovascular disease, ischemia-modified albumin, prognosis, severity


How to cite this article:
Okda MA, El-Kabany RA, Soliman HS, El-Kholy MS. Ischemia-modified albumin for evaluating severity and predicting prognosis in patients with acute cerebrovascular disease. Menoufia Med J 2020;33:1072-6

How to cite this URL:
Okda MA, El-Kabany RA, Soliman HS, El-Kholy MS. Ischemia-modified albumin for evaluating severity and predicting prognosis in patients with acute cerebrovascular disease. Menoufia Med J [serial online] 2020 [cited 2020 Oct 28];33:1072-6. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/1072/296707




  Introduction Top


Acute cerebrovascular disease (ACVD) is a common disorder of the nervous system that typically affects blood vessels in the brain and mainly includes cerebral infarction, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), which can result in severe neurological impairment or even death [1],[2].

The absence of a widely available and sensitive diagnostic test for acute cerebral ischemia remains a significant limitation in the diagnosis and management of stroke. In the absence of such test, the diagnosis is mainly based on history and clinical examination and radiological images [3].

However, studies conducted worldwide have focused on the identification of biochemical markers to improve early diagnosis and to distinguish between ischemic and hemorrhagic stroke, in similar to the way in which troponin is used to diagnose acute myocardial infarction [4].

One biochemical marker, ischemia-modified albumin (IMA), has been widely studied in tissue ischemia in recent years. IMA appears to be an early indicator of myocardial ischemia, which is detectable before the occurrence of myocardial infarction. Moreover, serum IMA level increases in mesenteric thrombosis, pulmonary embolism, stroke, and other ischemic diseases. Thus, in addition to being a predictor of myocardial infarction, IMA may be a useful marker for ACVD [5],[6].

The precise mechanisms for production of IMA during ischemia are not known but have localized modification in the amino terminal of human serum albumin during ischemia, which leads to reduction in cobalt binding to this modified N-terminus [7],[8].

Many reports indicate that the factors involved in ischemia that can induce these in-vivo changes to albumin may include acidosis, free radical damage, membrane energy-dependent sodium and calcium pump disruption, reduced oxygen tension, and free iron and copper ion exposure. These conditions necessary for altering the metal binding site of human serum albumin are known to occur within minutes of the onset of ischemia, and their effect on albumin could be detectable up to 6 h after the ischemic event [9].


  Patients and Methods Top


From May 2016 to January 2018, this case–control study was conducted in Neuropsychiatry Department, Menofia University Hospital, Egypt. The study consisted of 100 consecutive patients, including 50 patients with brain ischemia, 30 patients with ICH, and 20 patients with SAH, as well as a 75-member control group of normal individuals matched for age and sex. An informed consent was obtained from each participant. The exclusion criteria included patients with other ischemic diseases, abnormal serum albumin levels, advanced hepatic, renal, or cardiac insufficiency, hematomas related to tumor, trauma, coagulopathy, chronic inflammatory or infectious diseases, and pulmonary embolism or thrombotic diseases related to systemic circulation or pregnancy. All patients were subjected to full history taking; complete clinical and neurological examination; MRI brain for diagnosis of brain lesions and calculation of lesion volume; disease severity evaluation at the time of admission using National Institute of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS); blood samples for routine blood tests, including complete blood count, prothrombin time, concentration, international normalized ratio, liver profile, kidney profile, serum uric acid, and blood glucose level; and measurement of serum IMA concentrations. Blood samples were taken within 24 h of symptom onset, and levels were measured using enzyme-linked immunosorbent assay kit for IMA (human IMA instant enzyme-linked immunosorbent assay BMS2069INST; Affymetrix eBioscience, Vienna, Austria). Serum samples were prepared by 15 min of centrifugation at 3000 rpm. Specimens to be used for measuring IMA serum concentrations were pipetted into Eppendorf tubes and stored at −80°C. Modified Rankin scale (MRS) was performed 3 months after stroke onset to measure the degree of disability/dependence.

Statistical analysis

It was conducted using statistical package of the social sciences, version 20 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean ± SD and analyzed applying Student's t-test. Qualitative data were expressed as number and percentage and analyzed applying χ2-test. P value of less than 0.05 was considered statistically significant.


  Results Top


This case–control study consisted of 100 consecutive patients (mean ± SD age, 51.48 ± 11.72 years), including 50 with barthel index (BI), 30 with ICH, and 20 with SAH, as well as a 75-member control group (mean ± SD age, 49.64 ± 8.91 years). Overall, 58% of the patients were males and 42% were females, whereas in the control group, 73.3% were males and 26.7% were females, as shown in [Table 1].
Table 1: Age and sex distribution of patients with cerebrovascular stroke and control group

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Patients with stroke were compared with the control group regarding vascular risk factors; there was a significantly higher prevalence of hypertension, atrial fibrillation, and carotid artery stenosis in patients with stroke than controls (P = 0.001, 0.012, and <0.001, respectively). Moreover, the mean value of BMI was significantly higher in patients than control group (P < 0.001). The mean ± SD values of NIHSS and GCS in patients with stroke were 14.24 ± 5.17 and 12.10 ± 2.54, respectively [Table 2].
Table 2: Clinical characteristics of patients with cerebrovascular stroke and control group

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Patients with stroke had significantly higher mean levels of cholesterol, total cholesterol, low density lipoprotein cholesterol and serum albumin than control group (P < 0.001 for each). However, the mean levels of high density lipoprotein cholesterol were significantly lower in patients than control group (P = 0.004).

Patients with stroke had significantly higher mean levels of IMA than control group (96.83 ± 12.01 vs. 44.47 ± 5.28, P < 0.001; [Table 3]).
Table 3: Comparison between ischemia-modified albumin levels in patients with stroke and control group

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On performing MRI brain, patients with ischemic stroke showed the following: 18 were cardioembolic, with mean ± SD lesion volume of 56.78 ± 21.74 ml; 14% were atherosclerotic, with mean ± SD lesion volume of 59.42 ± 20.64 ml; 10% were lacunar, with mean ± SD lesion volume of 947.48 ± 30.03 ml; and 8% were cryptogenic, with mean ± SD lesion volume of 51.22 ± 34.88 ml. However, patients with hemorrhagic stroke showed the following: 30% had ICH and 20% had SAH, with mean ± SD lesion volume of 51.11 ± 25.69 ml.

There were significantly higher mean values of IMA in patients with ischemic stroke than those with hemorrhagic stroke (105.01 ± 10.81 U/ml for ischemic stroke vs. 99.24 ± 12.89 U/ml for ICH, and 97.74 ± 13.36 U/ml for SAH, P = 0.036; [Table 4]).
Table 4: Comparison between ischemia-modified albumin levels in ischemic and hemorrhagic cerebrovascular stroke

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There was a significant positive correlation between serum IMA levels with lesion volume calculated by computed tomography scan (r = 0.21, P = 0.04; [Table 5]).
Table 5: Correlation between biomarker levels in patients with stroke with lesion volume calculated by computed tomography scan

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Serum IMA concentrations were positively correlated with NIHSS score (r = 0.252, P < 0.01) but inversely correlated with GCS score (r=−0.227, P < 0.02) in patients with stroke.

On applying MRS, six (6.0%) patients had died, 22 (22.0%) had severe disability, eight (8.0%) had moderately severe disability, 20 (20.0%) had moderate disability, 18 (18.0%) had slight disability, 18 (18.0%) had no significant disability, and eight (8.0%) had no symptoms at all. There was no significant difference between patients with ischemic stroke and those with hemorrhagic stroke regarding MRS.

Our study showed that MRS had no statistically significant correlation with IMA (r = 0.01, P = 0.938).


  Discussion Top


Patients with stroke were compared with the control group regarding vascular risk factors; there was a significantly higher prevalence of hypertension, atrial fibrillation, and carotid artery stenosis in patients with stroke than controls. Moreover, the mean value of BMI was significantly higher in patients than control group. However, in the study by Hu et al. [10], the incidence of smoking (P = 0.026), alcohol consumption (P = 0.039), and hypertension (P = 0.011) in patients with stroke was higher than that in healthy controls, whereas other demographic characteristics such as mean age, sex composition, diabetes mellitus, and hypercholesterolemia showed no differences.

Patients with stroke had significantly higher mean levels of IMA than control group. This agreed with the study of Gunduz et al. [7], which showed a statistically significant difference between the mean IMA levels in BI, ICH, and SAH patient groups and the control group (P < 0.0001).

Jena et al. [11] showed a highly significant increase in serum IMA (P < 0.0001) in acute ischemic stroke cases in comparison with controls. In the study by Abboud et al. [12], there was a statistically significant difference between control and patients regarding IMA (P = 0.000).

Regarding patients with stroke, our study showed significant higher mean values of IMA in patients with ischemic stroke than those with hemorrhagic stroke. This was in agreement with the study of Gunduz et al. [7] who showed elevated IMA levels with a diagnosis of ischemic stroke (P = 0.0029).

Many studies explained the association of IMA with ischemic brain injury. With increasing ischemia following acute stroke, there occurs anaerobic metabolism of glucose leading to excess production of lactic acid causing acidosis, which may also lead to IMA formation [13].

Ischemia also produces necrosis by starving neurons of glucose, which in turn leads to failure of mitochondria to produce ATP, which leads to failure of energy-dependent functions of cells such as ion pumps. This energy-dependent pump failure may be the reason behind the generation of IMA. During ischemia and reperfusion modification hampering, the binding capacity of albumin for cobalt may occur owing to acidosis, decreased oxygen tension, and generation of free radicals, leading to the formation of IMA, as stated by Jena et al. [11] and Ertekin et al. [14].

However, the study by Abboud et al. [12] reported significantly higher IMA levels in patients with ICH and those with BI, without any difference between ischemia and hemorrhage groups, and this did not come in agreement with our study. This may be explained by few number of patients group in this study and the difference in clinical presentations of acute strokes between different studies.

In this study, there were significant positive correlations between serum IMA levels with lesion volume calculated by computed tomography scan. One might predict that a larger lesion volume would lead to a greater inflammatory response and increased release of central nervous system tissue biomarkers into systemic circulation.

Considering severity, this study showed significant positive correlations between IMA levels with NIHSS in patients with stroke, whereas there were significant negative correlations between IMA levels with GCS in patients with stroke, and this agreed with the study of Jena et al. [11]. This means that IMA concentrations in serum will increase following disease severity and can be regarded as biomarkers for evaluating disease severity.

Three months after stroke on applying MRS, this study showed that MRS had no statistically significant correlation with IMA.


  Conclusion Top


IMA levels are higher in patients with ACVDs compared with healthy individuals. This increase renders IMA a useful marker for the early diagnosis of ACVD. The level of IMA is higher in patients with ischemic stroke than those with hemorrhagic stroke.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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O'donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries [the INTERSTROKE study]: a case–control study. Lancet 2010; 376:112–123.  Back to cited text no. 1
    
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Sbarouni E, Georgiadou P, Kremastinos DT, Voudris V. Ischemia modified albumin: is this marker of ischemia ready for prime time use? Hellenic J Cardiol 2008; 49:260–266.  Back to cited text no. 5
    
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Herisson F, Delaroche O, Auffray-Calvier E, Duport BD, Guillon B. Ischemia modified albumin and heart fatty acid-binding protein: could early ischemic cardiac biomarkers be used in acute stroke management? J Stroke Cerebrovasc Dis 2010; 19:279–282.  Back to cited text no. 6
    
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Gunduz A, Turedi S, Mentese A, Altunayoglu V, Turan I, Karahan SC, et al. Ischemia-modified albumin levels in cerebrovascular accidents. Am J Emerg Med 2008; 26:874–878.  Back to cited text no. 7
    
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Abboud H, Labreuche J, Meseguer E, Lavallee PC, Simon O, Olivot JM, et al. Ischemia modified albumin in acute stroke. Cerebrovasc Dis 2008; 23:216–220.  Back to cited text no. 8
    
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Lippi G, Montagnana M, Guidi GC. Albumin cobalt binding and ischemia modified albumin generation: an endogenous response to ischemia. Int J Cardiol 2006; 108:410–411.  Back to cited text no. 9
    
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Hu L, Dong MX, Zhao H, Xu GH, Qin XY. Fibulin-5: a novel biomarker for evaluating severity and predicting prognosis in patients with acute intracerebral haemorrhage. Eur J Neurol 2016; 23:1195–1201.  Back to cited text no. 10
    
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Jena I, Mohapatra PC, Mohanty NR. Ischemia modified albumin: a biochemical marker of acute stroke. Int J Pharm Bio Sci 2016; 7:15–19.  Back to cited text no. 11
    
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Abboud H, Labreuche J, Meseguer E, Lavallee PC, Simon O, Olivot JM, et al. Ischemia-modified albumin in acute stroke. Cerebrovasc Dis 2007; 23:216–220.  Back to cited text no. 12
    
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Jickling GC, Sharp FR. Blood biomarkers of ischemic stroke. Neurotherapeutics 2011; 8:349–360.  Back to cited text no. 13
    
14.
Ertekin B, Kocak S, Dundar ZD, Girisgin S, Cander B, Gul M, et al. Diagnostic value of ischemia-modified albumin in acute coronary syndrome and acute ischemic stroke. Pak J Med Sci 2013; 29:1003–1007.  Back to cited text no. 14
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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