|Year : 2017 | Volume
| Issue : 4 | Page : 263-266
Evaluation of the Role of Creatine Phosphokinase as a Biomarker in Acute Myocardial Infarction Patients
Priyal Agrawal, Tushar Phulambrikar, Siddharth K Singh, Anjali Gupta
Department of Oral Medicine and Radiology, Sri Aurobindo College of Dentistry, Indore, Madhya Pradesh, India
|Date of Submission||21-Jul-2017|
|Date of Acceptance||28-Jan-2018|
|Date of Web Publication||15-Feb-2018|
Siddharth K Singh
Department of Oral Medicine and Radiology, Sri Aurobindo College of Dentistry, Indore, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: The study hypothesized that salivary creatine phosphokinase (CPK) can act as a biomarker in diagnosing acute myocardial infarction (AMI) as an alternative to serum CPK, which is a contributory effort towards noninvasive procedures to detect the disease. Aims and Objectives: The main aim of our study was to propose the normal range of salivary CPK in patients with AMI, and to explore the relationship between serum and saliva levels of CPK with comparison of salivary CPK as a biomarker between healthy individuals and patients with AMI. Materials and Methods: A case-control study was carried out including 144 participants who were divided in two main groups – 72 normal healthy individuals and 72 with AMI. CPK levels were assayed in serum and unstimulated whole saliva of AMI and controls by International Federation of Clinical Chemistry (IFCC) method. Statistical Analysis: Statistical analysis was performed using unpaired t-test and Pearson correlation coefficient test. Results: The normal proposed range of salivary CPK of patients with AMI was found to range from 11.30 to 184.50 U/L in males and 20.17 to 69.00 U/L in females. The mean salivary and serum CPK was significantly higher in patients with AMI as compared to healthy individuals with P < 0.001. Saliva CPK concentration correlated significantly with serum CPK of AMI and healthy individuals with r = 0.247. Conclusion: Salivary CPK can be used as an alternative to serum CPK in patients with AMI.
Keywords: Acute myocardial infarction, saliva, salivary CPK, serum CPK
|How to cite this article:|
Agrawal P, Phulambrikar T, Singh SK, Gupta A. Evaluation of the Role of Creatine Phosphokinase as a Biomarker in Acute Myocardial Infarction Patients. J Indian Acad Oral Med Radiol 2017;29:263-6
|How to cite this URL:|
Agrawal P, Phulambrikar T, Singh SK, Gupta A. Evaluation of the Role of Creatine Phosphokinase as a Biomarker in Acute Myocardial Infarction Patients. J Indian Acad Oral Med Radiol [serial online] 2017 [cited 2019 Aug 21];29:263-6. Available from: http://www.jiaomr.in/text.asp?2017/29/4/263/225565
| Introduction|| |
Dawn of the 21st century has witnessed the emergence of cardiovascular disorders as the leading cause of death globally, which entails a spectrum of disorders such as coronary or ischemic heart diseases, strokes, hypertensive heart diseases, inflammatory heart diseases, and rheumatic heart diseases. Ischemic heart diseases are a group of diseases including myocardial infarction (MI) and stable and unstable angina. Over the past few decades, drastic changes in lifestyle such as lack of physical activity, stress, and obesity have led to life threatening conditions such as acute myocardial infarction (AMI) as a major cause of death in industrialized nations as well as in the developing world. Myocardial necrosis is accompanied by the release of structural proteins and other intracellular macromolecules when the integrity of the cellular membranes is compromised, and then these biomarkers such as creatine phosphokinase (CPK), Creatine Kinase (CK)-MB, Cardiac-specific troponin T (cTnT), and cardiac-specific troponin I (cTnI) enter the blood stream and are measured in serum aiding in the detection of MI.
These biomarkers can now be analyzed for the primary observation of AMI using advance biochemistry approaches. Nevertheless, there are certain obstacles in using serum for detecting biomarkers to diagnose AMI. Concerning this predicament of using serum for detection of AMI, it has been determined that a number of markers are also present in saliva for the analysis of AMI; therefore, its use as a diagnostic fluid could have significant diagnostic and logistical advantages when compared with serum. The aim of this study was to explore the relationship between serum and saliva levels of CPK and compare salivary CPK as a biomarker between healthy individuals and patients with AMI.
| Materials and Methods|| |
A case control study was designed in the Department of General Medicine, Sri Aurobindo College of Medical Sciences, Indore (MP) to investigate the correlation between serum and salivary levels of CPK in patients with AMI and apparently healthy individuals. A total of 144 patients were examined to determine the correlation, out of which 72 patients with a typical ischemic chest pain, electrocardiographic ST segment elevation, and a rise in serum CPK biomarker were considered as a case group within the age group of 18 and 89 years. Seventy-two patients age and sex-matched to the case group with no documented heart disease were considered as the control group. These patients reported for routine check-up of anemia, diabetes, and had no cardiovascular history. Exclusion criteria included patients with muscular trauma, lesions in their mouth, and smokers.
Saliva and serum collection
The patients and controls were explained about the complete study in his/her own language and his/her willingness to participate was recorded in the consent form, which was duly signed by him/her. The blood of AMI patients was collected randomly from IV units inserted in patient's median cubital vein. The blood sample for the controls was collected to investigate for other pathologies such as anemia, diabetes and other infections in the controls. Venous blood (1 ml) was collected in a test tube using a 5-ml syringe.
Cases and controls were asked to avoid eating, drinking, and brushing teeth at least 2 hours before obtaining the saliva sample. All participants were asked to swallow all their oral fluids, followed by rinsing their mouth with tap water and holding for 1 minute, and thereafter, 1 ml of resting whole saliva was collected in a plastic tube by the spitting method. Immediately after collecting the sample, the samples were sent for analysis; two samples were analyzed at the same time.
Analysis of saliva
The blood and saliva were centrifuged in a test tube at 3800 rpm for 10 minutes using a centrifugal machine (REMI R#4CDX), and then supernatants were discarded while serum was isolated and divided into aliquots and kept in test tube stands. Machine parameters were set according to the instructions given in the International Federation of Clinical Chemistry (IFCC) CK-NAAC kit for the CPK concentration to be analyzed in the colorimeter (ERBA-CHEM-5PLUS). CPK concentration was determined by pipetting 200 μL of reagent (L1), 50 μL of reagent (L2), and 0.005 μL of sample collected in fresh aliquots, as per the sequence given in the kit. These aliquots were immediately transferred to colorimeter in biochemistry central laboratory of college, and readings were recorded in the case proforma.
| Results|| |
Out of the 144 samples, 72 were cases of AMI while the remaining 72 were normal individuals with no documented heart disease who were selected purposively as participants for the present study. Participants were distributed into two groups of equal size, and for further statistical analysis were treated as case group (n1 =72) and control group (n2 =72). Out of a population of 144, 102 (70.83%) were males and 42 (29.1%) were females.
The age of all the cases and controls were found to be in the range of 18 to 89 years. The scatter of mean age for the case group and control group was similar, which ranged 59.86 ± 15.19 years. Approximately half of the individuals (51.3%) in case and control groups were observed frequently in the age group of 58–78 years followed by 31.9% of patients and controls noted in the age group of 38–58 years. Few (9.7%) patients in case and control groups were noted within a lower age range of 18–38 years. Very few (6.9%) patients and controls comprised higher age group of more than or equal to 78 years.
Most patients (70.8%) in the case and control groups were males. Rest (29.1%) of the patients and controls were females. The range (minimum–maximum) of whole saliva level of CPK among male patients was noted with a wide spread from 11.30 to 184.50 U/L, while in female patients with a squeezed scatter from 20.17 to 69.00 U/L [Table 1]. The average (mean ± SD) unstimulated whole saliva concentration of CPK among patients (47.14 ± 30.28 U/L) of case group was high compared to average unstimulated whole saliva concentration of CPK among individuals (22.67 ± 16.33 U/L) of the control group. These differences in mean unstimulated whole saliva concentration of CPK (24.46 U/L) between cases and controls were strongly significant (P < 0.001), which was confirmed statistically [Table 2] and [Figure 1]a,[Figure 1]b.
|Figure 1: (a) Box and whisker diagram showing the distribution of serum creatine phosphokinase among all patients with myocardial infarction and individual controls by using median, quartiles and error bars (95% confidence interval of mean) in groups: case group and control group (b) Box and whisker diagram showing the distribution of unstimulated whole saliva concentration of creatine phosphokinase among all patients with myocardial infarction and all individual controls by using median, quartiles and error bars (95% confidence interval of mean) in groups: case group and control group|
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|Table 1: Identification of the range of unstimulated whole saliva level of creatine phosphokinase for patients with acute myocardial infarction|
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|Table 2: Comparison of serum creatine phosphokinase concentration and unstimulated whole saliva concentration of creatine phosphokinase between cases of acute myocardial infarction and controls|
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We found a positive relationship of serum CPK and unstimulated whole saliva level of CPK in cases with r = 0.235 of CPK in blood and saliva, respectively, which was statistically significant. In controls, the relationship between serum CPK and unstimulated whole saliva level of CPK was positive with r = 0.247, which was statistically significant [Table 3].
|Table 3: Correlation of creatine phosphokinase of serum and saliva in case and control groups|
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| Discussion|| |
Saliva is clinically an informative, biologic fluid (biofluid) that is useful for novel approaches in clinical assessment, laboratory diagnosis, as well as for prognostic values and monitoring of patients. In our study, we have kept a wide spectrum of age range i.e., from 18 to 89 years and the mean age calculated was 61.4 years, as the prevalence of MI is more common in the elder age group, i.e. approximately 60 years and above. Hence, taking a broader age range to encompass all possible age groups who might get affected with MI.
In our study, males were affected more than females by myocardial infarction among the selected population, with 70.8% of males being affected while females affected were 29.1% similar to the study done by Alghani et al. in (2011) where percentages of males affected were 55.6% and females were 30.2%, and this difference in the gender percentage may be due to several factors, including the differences in risk factors such as smoking and tobacco chewing being more prevalent among men in India than women.
In the present study, we have chosen CPK as the biomarker for MI and our reason for using CPK was that it shows similar specificity and sensitivity compared to other specific myocardial biomarkers and also because of its early increase in serum and saliva within 4–8 h after the onset of AMI as compared to other biomarkers which usually rise within 24 h after the onset of AMI.
In the current study, the range calculated for salivary CPK levels in patients of MI in males was from 11.33 to 184.50 U/L while in females it was 20.17 to 69.00 U/L. The mean calculated for serum and salivary CPK levels among myocardial infarction patients was 727.20 U/L and 47.14 U/L, respectively. With respect to above findings, we compared serum and salivary CPK levels of myocardial infarction patients to healthy individuals. It was found that serum and salivary levels of CPK in AMI patients were higher compared to healthy individuals.
To our knowledge, the present study is the only study to propose the range of unstimulated whole saliva level of CPK for patients with AMI. The value for males ranged from 11.33 to 184.50 U/L while in females it ranged from 20.17 to 69.00 U/L. Owing to the results obtained in this specific study design, we propose further studies with a larger sample size to make these proposed ranges of salivary CPK as a standard for early detection of AMI.
Even after certain limitations, with respect to the data we observed it can be concluded that a diagnostic window exists during which saliva has the utility for early and rapid screening of MI as its collection is noninvasive and leads to less discomfort to the patients diagnosed with AMI. A more advance research with a large sample size can be directed at assessing the variations of salivary CPK in AMI patients.
| Conclusion|| |
Further studies can be employed to assess the treatment outcomes in MI patients by directly correlating them with alternation in the intensity of the serum and salivary CPK levels to evaluate the success of medical care.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Shoaibi A, Tavris DR, McNulty S. Gender differences in co-relates of troponin assay in diagnosis of myocardial infarction. Transitional Res 2009;154:250-5.
Chauhan S, Aeri BT. Prevalence of cardiovascular diseases in India and its economic impact- A Review. Int J Sci Res 2013;3:2250-3153.
Thames MD, Sease DR, Damian A. Ischemic heart disease: An overview. Adv Stud Med 2004;4:S794-S802.
Anand IS, Chhabra ST. Ischemic Heart disease. API Text Book of Medicine. 9th
ed. Mumbai: The Association of Physicians of India; 2012. p. 666.
Mirzaii-Dizgah I, Jafari-Sabet M. Unstimulated whole saliva creatine phosphokinase in acute myocardial infarction. Oral Dis 2011;17:597-600.
Alani FA. Significance of total creatine kinase and creatine kinase-MB Levels in patients with acute myocardial infarction. Int J Biol Med Res 2011;2:762-5.
Mirzaii-Dizgah I, Riahi E. Salivary troponin I as an indicator of myocardial infarction. Indian J Med Res 2013;138:861-5.
] [Full text]
Malamud D. Saliva as a diagnostic fluid. Dent Clin North Am 2011;55:159-78.
[Table 1], [Table 2], [Table 3]