Printer Friendly

Comparative status of glycogen phosphorylase BB, myoglobin, and CK-MB for early diagnosis of acute myocardial infarction.

INTRODUCTION

Chest pain is one of the most common complaints among patients presenting to cardiology or emergency department. [1,2] Coronary artery disease is one of the cardiac diseases leading to acute myocardial infarction (AMI), angina, sudden death, and many other complications. The complications of acute myocardial infarction are maximum in the first few hours and decrease with passage of time. [3] Early accurate diagnosis and treatment of AMI can reduce the mortality and morbidity.

The majority of deaths due to AMI occur during the first 4 h, if AMI cases are diagnosed and treated effectively during the first hour (so-called golden hour), the mortality can be reduced from 9% to 3%, but if delayed for 3-4 h, mortality can be 5 times higher. [4]

Diagnosis of an acute coronary syndrome like AMI is based on the assessment of risk factors, careful and rapid assessment of electrocardiogram (ECG) and measurement of cardiac enzymes. [1,5] At present, creatine kinase-MB isoenzyme (CKMB), MB and cardiac troponins T and I (cTnI & cTnT) are used in the diagnosis of AMI. [6] However, these cardiac markers are also not satisfactory for the early diagnosis of AMI after the onset of chest pain. MB is an early and sensitive marker of cardiac cell damage but lacks specificity. [7] CKMB begins to increase between 3 and 5 h after the onset of myocardial infarction. [8] CK-MB though more specific for cardiac injury, lacks early sensitivity. [6]

Glycogen phosphorylase (GP) is bound to glycogen in sarcoplasmic reticulum and catalyzes the first step of glycogenolysis after activation, which involves the separation of glucose-1-phosphate from glycogen. [9] It has three major isoenzymes: BB (brain), MM (muscle), and LL (liver). GPBB is also found in heart muscle, including human myocardium. [10] During myocardial ischemia, activation of GPBB results in an increase in glycogen degradation. Thus, GPBB which is connected to glycogen in a macromolecular complex that is structurally bound to sarcoplasmic reticulum believes to release from glycogen and then enters the bloodstream via the T-tubulus system within 1-4 ho of onset of AMI. [11-13] Hence, this study has been aimed to compare the sensitivity and specificity of GPBB with those of MB and CKMB within 4 h after the onset of chest pain.

MATERIALS AND METHODS

This study has been conducted in the Department of Biochemistry and Cardiology, G.R. Medical College and J.A. Group of Hospitals, Gwalior. The study included 250 subjects of age group 35-75 years. Out of them, 100 were normal healthy age-matched controls and 150 of them were patients of AMI admitted to the Cardiology Department of J.A. Group of Hospitals. Each patient undergone clinical and laboratory evaluation, which included the detailed clinical history, clinical examination, ECG, chest X-ray, routine blood investigations and cardiac biomarkers (CK-MB and cTnT [card test]) as a part of routine assessment and diagnosis of AMI was made after review of all the above information by a cardiologist.

Inclusion Criteria

The patients arriving to the cardiology department within 4 h of onset of chest pain.

Exclusion Criteria

The patients arriving to hospital after 4 h of onset of chest pain, those with diabetes mellitus, chronic muscle disease, renal disease, liver disease, recent surgery, implanted pacemaker, autoimmune disease, and arthritis.

This study has been approved by the Institutional Ethical Clearance Committee and written informed consent was obtained from all the study participants.

About 5 ml of venous blood sample was taken from AMI cases (within 4 h of chest pain) and controls under all aseptic precautions. Serum was separated and kept at -20[degrees]C until the analysis was performed. Levels of MB were measured by enzyme immunoassay using life diagnostics kit, whereas CKMB was measured by the diagnostic kit supplied by ERBA. Normal reference levels of MB and CKMB were accepted as 12-92 ng/ml and <25 U/L, respectively. Levels of GPBB were measured by enzyme-linked immunosorbent assay using QAYEE-BIO for life sciences kit. Normal reference level of GPBB was accepted as 7-18.47 ng/ml (established according to the values observed in control subjects with the help of StatsDirect 3).

Statistical Analysis

Data are presented as mean [+ or -] standard deviation values. The statistical differences between cases and controls were determined by student independent sample t-test. Data analyses were performed with the Statistical Package for the Social Sciences, version 21.0 (SPSS, Chicago, Illinois, USA). Sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated, and receiver operating characteristic (ROC) curve analysis was performed with the help of StatsDirect 3.

RESULTS

A total of 250 subjects were included in this study. Of these, 150 were cases of AMI and rest 100 were controls. Table 1 and Figure 1 show the mean levels of cardiac markers in AMI cases and controls. The mean levels of cardiac markers GPBB, MB and CKMB activity were higher in AMI cases when compared to that of controls and were statistically significant at P < 0.001. Table 2 shows sensitivity, specificity, PPV and NPV of GPBB which were greater than MB and CKMB. Table 3 shows area under the curve (AUC) of GPBB, MB, and CKMB. The AUC of GPBB was greater than MB and CKMB. Figures 2-4 show ROC curve analysis of GPBB, MB, and CKMB, respectively.

DISCUSSION

Myocardial ischemia results from the reduction of coronary flow to such an extent that supply of oxygen to the myocardium does not meet the oxygen demand of myocardial tissue. When this ischemia is prolonged and irreversible, then myocardial cell death and necrosis occur which is defined as myocardial infarction.[14] AMI is the major cause of mortality and long-term morbidity in the modern world. Early and correct diagnosis is of utmost importance to enable the immediate and intensified treatment which consequently reduces the mortality. [15]

Although CKMB, MB, and cardiac troponin starts to rise early after AMI, lack sensitivity and specificity. Now, several alternative markers--for example, ischemiamodified albumin, [16] heart fatty acid binding protein. [17] and GPBB [10]--have been analyzed for the clinical diagnosis of myocardial ischemia within the first 1-3 h after the onset of chest pain. GPBB is bound to glycogen in sarcoplasmic reticulum and catalyzes the first step of glycogenolysis after activation, which involves the separation of glucose-1-phosphate from glycogen. [11] During myocardial ischemia, activation of GPBB results in an increase in glycogen degradation. GPBB isoenzyme is released into bloodstream via the T-tubules system with the peak value within the first 4 h after the onset of chest pain. [11,18] The early release of GPBB into the blood is a common result of the combination with of escalated glycogenolysis and increased permeability of cell membranes which is typical for myocardial ischemia and necrosis. [12,13,19]

In this study, we found that GPBB was the most sensitive and specific biomarker to detect myocardial infarction when compared to MB and CKMB at the first 4 h (Table 2). This finding is in agreement with Rabitzsch et al. [20] and Cubranic et al. [21] who also reported the highest sensitivity of GPBB in the early hours of chest pain. MB which appears in the blood early after AMI lacks specificity because it also increases in other muscular disorders and cannot be distinguished from that released from heart. [6] Moreover, the sensitivity and specificity of MB in our study found to be less than GPBB (Table 2). CKMB though increased in AMI within 4 h of chest pain, had low sensitivity and specificity (Table 2) as compared to GPBB and MB.

ROC curve analysis showed GPBB had the highest area under curve followed by MB and CKMB (Table 3). The better diagnostic value of GPBB compared to MB and CKMB may be due to early release from the injured myocardium.

LIMITATIONS

In this study, cTnT was estimated qualitatively and qualitative estimation detects cTnT levels above a certain level only. Another limitation of the present study is results are based on single-center only.

CONCLUSION

GPBB was the most sensitive and specific cardiac marker compared to other tested cardiac markers MB and CKMB in AMI patients during the first 4 h after the onset of chest pain. Hence, GPBB can be used for the diagnosis of AMI within 4 h of chest pain.

DOI: 10.5455/ijmsph.2017.0307202042017

REFERENCES

[1.] Pollack CV Jr, Antman EM, Hollander JE; American College of Cardiology; American Heart Association. 2007 focused update to the ACC/AHA guidelines for the management of patients with ST-segment elevation myocardial infarction: Implications for emergency department practice. Ann Emerg Med. 2008;52(4):344-55.e1.

[2.] Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, et al. ESC guidelines on management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. Rev Esp Cardiol. 2009;62(3):293, e1-47.

[3.] Francis M. Rapid bedside whole blood cardiac specific troponin-T immunoassay for diagnosis of acute myocardial infarction. Am Heart J. 1995;75(12):842-5.

[4.] Alhashemi JA. Diagnostic accuracy of a bedside qualitative immunochromatographic test for acute myocardial infarction. Am J Emerg Med. 2006;24(2):149-55.

[5.] Pollack CV Jr, Braunwald E. 2007 update to the ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: Implications for emergency department practice. Ann Emerg Med. 2008;51(5):591-606.

[6.] Wu AH, Feng YJ, Contois JH, Pervaiz S. Comparison of myoglobin, creatine kinase-MB, and cardiac troponin I for diagnosis of acute myocardial infarction. Ann Clin Lab Sci. 1996;26(4):291-300.

[7.] McQueen MJ, Holder D, El-Maraghi NR. Assessment of the accuracy of serial electrocardiograms in the diagnosis of myocardial infarction. Am Heart J. 1983;105(2):258-61.

[8.] Nigam PK. Biochemical markers of myocardial injury. Indian J Clin Biochem. 2007;22(1):10-7.

[9.] Entman ML, Bornet EP, Van Winkle WB, Goldstein MA, Schwartz A. Association of glycogenolysis with cardiac sarcoplasmic reticulum: II. Effect of glycogen depletion, deoxycholate solubilization and cardiac ischemia: Evidence for a phorphorylase kinase membrane complex. J Mol Cell Cardiol. 1977;9(7):515-28.

[10.] Rabitzsch G, Mair J, Lechleitner P, Noll F, Hofmann U, Krause EG, et al. Immunoenzymometric assay of human glycogen phosphorylase isoenzyme BB in diagnosis of ischemic myocardial injury. Clin Chem. 1995;41(7):966-78.

[11.] Krause EG, Rabitzsch G, Noll F, Mair J, Puschendorf B. Glycogen phosphorylase isoenzyme BB in diagnosis of myocardial ischaemic injury and infarction. Mol Cell Biochem. 1996;160-161:289-95.

[12.] Lacnak B, Stejskal D, Jedelsky L, Karpisek M, Sprongl L. Utilization of glycogen phosphorylase BB measurement in the diagnosis of acute coronary syndromes in the event of chest pain. Vnitr Lek. 2007;53:1164-9.

[13.] Stejskal D, Lacnak B, Jedelsky L, Stepanova L, Proskova J, Solichova P, et al. Use of glycogen phosphorylase BB measurement with POCT in the diagnosis of acute coronary syndromes. A comparison with the ELISA method. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007;151(2):247-9.

[14.] Alam GK, Lieb DB. Biochemical markers of myocardial ischemia in renal failure. Hosp Physician. 2002;1:27-31.

[15.] Gravning J, Kjekshus J. The perfect biomarker in acute coronary syndrome: A challenge for diagnosis, prognosis, and treatment. Eur Heart J. 2008;29(23):2827-8.

[16.] Christenson RH, Duh SH, Sanhai WR, Wu AH, Holtman V, Painter P, et al. Characteristics of an Albumin Cobalt Binding Test for assessment of acute coronary syndrome patients: A multicenter study. Clin Chem. 2001;47(3):464-70.

[17.] Alhadi HA, Fox KA. Do we need additional markers of myocyte necrosis: The potential value of heart fatty-acid-binding protein. QJM. 2004;97(4):187-98.

[18.] Peetz D, Post F, Schinzel H, Schweigert R, Schollmayer C, Steinbach K, et al. Glycogen phosphorylase BB in acute coronary syndromes. Clin Chem Lab Med. 2005;43(12):1351-8.

[19.] Hofmann U, Rabitzsch G, Loster K, Handschack W, Noll F, Krause EG. Immunenzymometric assay for the heart specific glycogen phosphorylase BB in human serum using monoclonal antibodies. Biomed Biochim Acta. 1989;48(2-3):S132-6.

[20.] Rabitzsch G, Mair J, Lechleitner P, Noll F, Hofmann V, Krause EG, et al. Isoenzyme BB of glycogen phosphorylase b and myocardial infarction. Lancet. 1993;341(8851):1032-3.

[21.] Cubranic Z, Madzar Z, Matijevic S, Dvornik S, Fisic E, Tomulic V, et al. Diagnostic accuracy of heart fatty acid binding protein (H-FABP) and glycogen phosphorylase isoenzyme BB (GPBB) in diagnosis of acute myocardial infarction in patients with acute coronary syndrome. Biochem Med (Zagreb). 2012;22(2):225-36.

Vedika Rathore (1), Puneet Rastogi (2), Chandel Y S (3), Neelima Singh (1), Roshan Kumar Mahat (1)

(1) Department of Biochemistry, Gajra Raja Medical College and J.A. Group of Hospitals, Gwalior, Madhya Pradesh, India, (2) Department of Cardiology, Gajra Raja Medical College and J.A. Group of Hospitals, Gwalior, Madhya Pradesh, India, (3) Department of Obstetrics and Gynaecology, Army College of Medical Sciences, New Delhi, India

Correspondence to: Vedika Rathore, E-mail: ved_sin26@rediffmail.com

Received: March 15, 2017; Accepted: April 02, 2017

Caption: Figure 1: Status of cardiac markers in acute myocardial infarction cases and controls

Caption: Figure 2: The receiver operating characteristic curve analysis of glycogen phosphorylase BB within 4 h of onset of acute myocardial infarction

Caption: Figure 3: The receiver operating characteristic curve analysis of myoglobin within 4 h of onset of acute myocardial infarction

Caption: Figure 4: The receiver operating characteristic curve analysis of creatine kinase MB within 4 h of onset of acute myocardial infarction
Table 1: Mean levels of cardiac markers in AMI cases and
controls

                            Mean [+ or -] SD
Parameters
                    Controls                AMI cases

GPBB (ng/ml)  11.79 [+ or -] 2.82     61.59 [+ or -] 33.85 **
MB (ng/ml)    62.79 [+ or -] 26.38   184.77 [+ or -] 65.92 **
CKMB (U/L)    19.21 [+ or -] 5.71     27.64 [+ or -] 13.34 **

** Highly significant (P<0.001). GPBB: Glycogen phosphorylase
BB, MB: Myoglobin, CKMB: Creatine kinase MB, AMI: Acute
myocardial infarction, SD: Standard deviation

Table 2: Sensitivity, specificity, PPV and NPV of cardiac markers
within 4 h of onset of AMI

Parameters              Cut off               Sensitivity (%)

GPBB         [greater than or equal to] 19         96.00
MB           [greater than or equal to] 92         90.66
CKMB         [greater than or equal to] 25         34.00

Parameters   Specificity (%)   PPV (%)     NPV (%)

GPBB              98.00         98.63       94.23
MB                85.00         90.07       85.86
CKMB              86.00         78.46       46.49

GPBB: Glycogen phosphorylase BB, MB: Myoglobin, CKMB: Creatine kinase
MB, AMI: Acute myocardial infarction, PPV: Positive predictive value,
NPV: Negative predictive value

Table 3: The ROC curve analysis of cardiac markers within 4 h of onset
of AMI

                                                   CI
Parameters   AUC    Standard   P value
                     error               Lower limit   Upper limit

GPBB        0.995    0.002      0.000       0.989         0.999
MB          0.963    0.009      0.000       0.944         0.982
CKMB        0.697    0.032      0.000       0.633         0.762

GPBB: Glycogen phosphorylase BB, MB: Myoglobin, CKMB: Creatine kinase
MB, AMI: Acute myocardial infarction, ROC: Receiver operating
characteristic, AUC: Area under the curve, CI: Confidence interval
COPYRIGHT 2017 Association of Physiologists, Pharmacists and Pharmacologists
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2017 Gale, Cengage Learning. All rights reserved.

 
Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Research Article; creatine kinase MB
Author:Rathore, Vedika; Rastogi, Puneet; Chandel, Y.S.; Singh, Neelima; Mahat, Roshan Kumar
Publication:International Journal of Medical Science and Public Health
Article Type:Report
Date:Jul 1, 2017
Words:2485
Previous Article:Diagnostic value of mean corpuscular volume in the detection of vitamin B12 deficiency.
Next Article:A cross-sectional study on risk factors for Type 2 diabetes mellitus in rural population of Davangere.
Topics:

Terms of use | Privacy policy | Copyright © 2018 Farlex, Inc. | Feedback | For webmasters