|Year : 2022 | Volume
| Issue : 1 | Page : 14-19
The evaluation of serum zinc level in patients with acute coronary syndrome and its correlation with cardiac enzymes
Wessam ElDin Hadad El-Shafey, Walaa Mosa, Mina Boktor, Ahmed El-Kersh
Department of Cardiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||20-Sep-2020|
|Date of Decision||06-Jan-2021|
|Date of Acceptance||18-Jan-2021|
|Date of Web Publication||18-Apr-2022|
Wessam ElDin Hadad El-Shafey
32511, Shebein El Kom, Menoufia
Source of Support: None, Conflict of Interest: None
To assess serum zinc level in patients presented with acute coronary syndrome and its relation to cardiac enzymes in acute myocardial infarction (AMI).
Atherosclerosis is a well-known cause of myocardial infarction owing to accumulation of lipids and fibrous elements in arteries. It was found that there are highly efficient protective mechanisms in the cell, including metal-binding proteins as antioxidants and manganese superoxide dismutase and copper–zinc superoxide dismutase as enzymes. Zinc deficiency can reduce activity of superoxide dismutase linked to atherosclerosis.
Patients and methods
Our study was carried out in cardiac care units, Menoufia University Hospital, on 100 patients who presented with acute coronary syndrome and 100 other healthy participants. Routine electric-cardiogram, ECG, and full laboratory workup were done including serum zinc level.
There was a statistically significant inverse correlation between serum zinc levels and cardiac biomarkers used, that is, creatine kinase, MB fraction of creatine kinase, and troponin I (cardiac troponin T) in the studied groups, where serum zinc levels were less than 57.38 μg/dl (26%), 57.38–69.70 μg/dl (24%), 69.70–79.73 μg/dl (26%), and more than or equal to 79.73 μg/dl (24%), respectively, when divided into four quartile groups, with a remarkable increase in the AMI prevalence.
Serum zinc levels were significantly negatively correlated with cardiac biomarkers. The AMI prevalence rate decreased with increasing zinc quartiles.
Keywords: acute coronary syndrome, acute myocardial infarction, atherosclerosis, cardiac enzymes, trace elements, zinc
|How to cite this article:|
El-Shafey WE, Mosa W, Boktor M, El-Kersh A. The evaluation of serum zinc level in patients with acute coronary syndrome and its correlation with cardiac enzymes. Menoufia Med J 2022;35:14-9
|How to cite this URL:|
El-Shafey WE, Mosa W, Boktor M, El-Kersh A. The evaluation of serum zinc level in patients with acute coronary syndrome and its correlation with cardiac enzymes. Menoufia Med J [serial online] 2022 [cited 2022 Aug 11];35:14-9. Available from: http://www.mmj.eg.net/text.asp?2022/35/1/14/343117
| Introduction|| |
Acute coronary syndrome (ACS) comprises a clinical condition that is initiated by rupture of an atherosclerotic coronary plaque with overlying acute thrombosis .
Zinc is a trace element and one of the major micronutrients . In acute organ injury, there is a rapid decrease in serum zinc concentration at the beginning of the acute phase response . Accompanied by an increase in inflammatory cytokines derived from the organ injury, those factors lead to reduction of serum zinc concentration .
The aim of this work was to assess serum zinc level in patients presented with ACS and its relation to cardiac enzymes in acute myocardial infarction (AMI).
| Patients and methods|| |
This study involved 100 patients who presented with ACS at cardiac care units, to evaluate the serum zinc level and its correlation with cardiac enzymes. In addition, another 100 apparently healthy participants were included as a control group. Before our study, the participants gave informed consent after understating our study procedures according to the ethical standards of the Menoufia University Hospital (no ethical number/ID was required at the time of this study).
The study inclusion criteria were patients with clinical history of acute and persistent chest pain for more than 20 min and patients with ECG changes in the form of ST-segment elevation within 12 h of symptoms onset and/or new or presumed new left bundle branch block (LBBB). The patients with AMI were defined as patients complaining of typical continuous chest pain for more than 30 min: ST-segment elevation of more than 0.1 mV in two or more successive leads or ST-segment depression of more than 0.1 mV in two or more successive leads monitored by a standard 12-lead ECG and rise of either creatine kinase (CK) or MB fraction of creatine kinase (CKMB) to greater than twice the normal level or elevation of troponin I [cardiac troponin T (cTnT)] more than or equal to 0.1 ng/ml. Patients without AMI were defined as individuals without any symptoms or criteria aforementioned and were also enrolled in the current study as a control group.
The exclusion criteria included patients with insufficient clinical information, passed time MI (if patients presented with symptoms that lasted >24 h), cardiogenic shock, chronic kidney disease, chronic liver cell failure, significant valvular heart disease, hematological disease, malignancy, severe liver or renal disease, systemic inflammatory disease, active infection, autoimmune disease, and patients on steroids whatever the cause is. Those were excluded as they will have unreliable results owing to inaccurate serum zinc level ,.
All patients in the study were subjected to careful history taking, careful clinical assessment including general and local examination, cardiac examination for murmurs or additional sounds, and chest examination for detection of fine bilateral basal crepitations.
Resting ECG was done including a 12-lead resting ECG that was performed on admission. Serial ECG tracing was recorded, and continuous ECG monitoring was conducted during their stay in the cardiac care unit.
Blood samples were taken to measure the troponin I level on admission and repeated after 12 h in case of a negative result. CK and CKMB mass levels were also measured on admission and repeated every 4 h. On admission of the patients at cardiac care unit, serum zinc level was measured using inductively coupled plasma-optical emission spectrometry . Moreover, lipid profile, kidney function tests, and uric acid levels were measured.
Transthoracic echocardiography was done for all patients during their cardiac care unit stay including two-dimensional and color Doppler echocardiography studies. It was performed in the left lateral position using the parasternal and apical transducer positions. All studies were technically adequate for scoring endocardial regional wall motion. The following views were obtained: long-axis parasternal, short-axis parasternal, apical four chamber, apical two-chamber and apical five-chamber views. All the measurements taken were according to the criteria of the American Society of Echocardiography .
Recorded data were analyzed using the statistical package for social sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed in mean ± SD, whereas qualitative data were expressed as frequency and percentage.
The following tests were done: a one-way analysis of variance when comparing between more than two means, Kruskal–Wallis test was used when data are not normally distributed, χ2 test of significance was in order to compare proportions between qualitative parameters, Pearson's correlation coefficient (r) test was used to assess the degree of association between two sets of continuous variables (for normally distributed data), Spearman rank correlation coefficient was used to assess the degree of association between two sets of continuous variables (for not normally distributed data), and finally, linear regression is used to test and estimate the dependence of a quantitative variable based on its relationship to one or more independent variables.
The confidence interval was set to 95%, and the margin of error accepted was set to 5%. So, P value less than 0.05 was considered significant.
| Results|| |
In our study, there were 43 males and 57 females, and their age ranged from 39 to 69 years, with a mean of 56.84 years. Demographic data collected among the studied group showed that 40% were smoker, and concerning comorbidities, 59 and 42% had comorbid hypertension and diabetes, respectively [Table 1].
|Table 1: Comparison between the studied groups regarding demographic data|
Click here to view
Laboratory cardiac biomarkers showed that CK level among the studied patients ranged from 224 to 2960 U/l, with a mean of 1521.8 U/l. Regarding CKMB, the mean was 237.82 U/l. cTnT ranged from 0.001 to 0.29 ng/ml, with a mean of 0.027 ng/ml [Table 2].
|Table 2 Creatine kinase, MB fraction of creatine kinase, cardiac troponin T and UA data descriptive of the study group|
Click here to view
Moreover, CKMB mass level being accurate in diagnosis of myocardial damage, we assessed its correlation with our studied parameters, and it shows that there is a statistically significant negative correlation between CKMB mass and systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and serum creatinine. On the contrary, there is a significant positive correlation between it and age. There is a nonsignificant correlation between CKMB mass and either waist circumference, BMI, diastolic blood pressure, high-density lipoprotein cholesterol, triglycerides, or troponin [Table 3].
|Table 3: Correlation between MB fraction of creatine kinase mass and the studied parameters among the studied patients|
Click here to view
Among the studied group, serum zinc level ranged from 23.99 to 108.95 μg/dl, with a mean 68.099 μg/dl. To help us to investigate the relation between serum zinc with risk factors and its correlation with cardiac biomarkers, we divided the result of serum zinc levels to four quartiles according to their zinc concentrations. The results showed that zinc level less than 57.386 μg/dl was prevalent in 26% of patients, 24% had zinc level ranged from 57.386 to 69.706 μg/dl (24%), 26% had zinc level from 69.706 to 79.738 μg/dl, whereas levels more than or equal to 79.738 μg/dl were noticed in 24% of the studied patients. Further assessment of the relation between serum zinc quartiles and both demographic and clinical data shows that there is a statistically highly significant relation between zinc quartile of patients and presence of diabetes. Lower zinc quartiles were highly prevalent among diabetics. Lowest levels (70.8%) of patients within lowest zinc quartiles were diabetics versus 16.7% among those within highest quartile. However, there is a statistically nonsignificant relation between zinc quartiles and either hypertension and smoking of the studied patients. Moreover, there is a statistically nonsignificant relation between zinc quartiles and sex of the studied patients [Table 4].
|Table 4: Comparison between the studied groups regarding zinc level and zinc quartile distribution of the studied patients|
Click here to view
Using Pearson correlation coefficient method to assess the correlation between zinc and cardiac biomarker CK, CKMB, cTnT, and CKMB mass, it shows that there is a statistically significant negative correlation between serum zinc and CKMB, troponin, and CKMB mass (P < 0.001) among the studied patients, whereas there is a nonsignificant positive correlation between zinc and CK-total. Moreover, serum zinc was found to be independently significantly associated with serum CKMB mass when using linear stepwise regression analysis (unstandardized β=−0.251, P < 0.001). When we assessed the relation between CKMB mass results and serum zinc level in our four quartiles, it was found that there is a statistically significant relation between zinc quartiles and CKMB mass. Higher CKMB mass was present among patients with lower zinc quartiles, with a mean 25.46 in the lowest quartile compared with 10.488 among the highest quartile [Table 5].
|Table 5: Relation between zinc quartile and both demographic and clinical data|
Click here to view
A scattered dot plot shows a significant negative correlation between CKMB (U/l) and CKMB mass and zinc level [Figure 1].
|Figure 1: Scatter dot plot showing significant negative correlation between serum zinc and CKMB (U/l) and CKMB mass among the studied patients. CKMB, MB fraction of creatine kinase.|
Click here to view
| Discussion|| |
Trace elements are being increasingly recognized as essential mediators for the development and progression of cardiovascular diseases (CVD). Zinc serves many biological functions, being an integral component of many metallo-enzymes. Zinc acts as a stabilizer for cell membrane by protecting its integrity through reducing free radical formation and preventing lipid peroxidation. Furthermore, it is required for immune system function and for the activity of more than 1000 transcription factors and more than 300 enzymes .
According to previous studies , the lower the plasma zinc level, the higher the prevalence rate of CVD. Moreover, new advances in cardiac pathophysiology have recognized the important contribution of perturbations in zinc homeostasis to myocardial ischemia and reperfusion injury and the role zinc plays in cardio-protection against these injuries, and it was indicated that there is a significant association between zinc deficiency and MI .
As there is a direct relation between AMI and underlying risk factors such as diabetes mellitus, hypertension, smoking, and dyslipidemia in our study, the prevalence of such risk factors was statistically significant among patients group, and this was in accordance with previous studies .
It was proven that the levels of biochemical markers, that is, CK, CKMB, and cTnT, increase with any heart muscle damage (including any physical damage to the heart such as trauma, surgery, inflammation, and ischemia); therefore, they play essential roles in the diagnosis, prognosis, monitoring, and risk stratification in AMI .
Although several authors investigated the prognostic relationship between serum zinc and AMI, the assessment of a change in serum zinc levels in association with biomarkers previously established, such as CK, CKMB mass, and cTnT, has been rarely reported or unexplored. Moreover, the evaluation of different zinc quartiles in the assessment of AMI prevalence has not been explored thoroughly, and the conflicting results among the findings reported in several studies prevent definitive recommendations at present, so we tried in the current study to find direct relations between serum zinc and cardiac markers in such cohort of patients with ACS.
Notably, there is a statistical difference within the studied groups regarding zinc level when divided into four quartiles according to zinc concentration [<57.386 μg/dl (26%), 57.386–69.706 μg/dl (24%), 69.706–79.738 μg/dl (26%), and ≥79.738 μg/dl (22%)]. When we investigated the relation between the patients' risk factors in the four quartiles, we observed a statistically highly significant relation between serum zinc and diabetes; lower zinc quartiles were highly prevalent among diabetics, where the lowest levels (70.8%) of patients within lowest zinc quartiles were diabetics compared with those of the highest quartiles, who only represented 16.7%.
Previous investigations showed that there is a relationship between zinc and cardiac markers, and the risk of AMI by zinc quartiles; they divided the participants into four groups according to their concentrations of zinc by quartile. It was reported that there was no statistically significant difference between the four groups regarding age, sex, smoking, and the presence of other risk factors such diabetes or hypertension. The prevalence of risk for AMI showed a statistically significance difference between the highest and lowest quartile .
In our study, we provided novel insights into the complex relationship between zinc and biochemical myocardial damage markers and the relationship between zinc and the prevalence of AMI. Within the past several years, the preferred cardiac biochemical markers are CK, CKMB mass, and cTnT, due to their presence in relatively high concentrations in the myocardium . So, we investigated the relation and found that there is a statistically significant inverse relation between zinc quartile and those cardiac biochemical markers.
El-Adawy et al.  reported regarding the correlation between cardiac enzymes and Zn that there were significant positive correlations between Zn versus Tn, CK, and CKMB. In patients with positive Tn, the mean ± SD value of Zn was 104.09 ± 32.32 compared with 113.00 ± 38.69 in patients with negative Tn. The difference was found to be statistically significant (P < 0.001). In patients with high CK, the mean ± SD value of Zn was 100.00 ± 30.77 compared with 114.76 ± 38.88 in patients with low CK. The difference was found to be statistically significant (P < 0.001). In patients with high CKMB, the mean ± SD value of Zn was 107.06 ± 31.02 compared with 112.77 ± 39.98 in patients with low CKMB. The difference was found to be statistically significant (P < 0.001).
El-Adawy et al.  showed no significant difference in serum zinc level between patients and control. Patients with AMI showed significant decrease in serum zinc level than patients with unstable angina (UA) and those who received reperfusion therapy (P = 0.033 and 0.002, respectively). These results were in agreement with the studies of Giannoglou et al.  and Cebi et al. , which showed that serum Zn was not significantly associated with CHD risk and severity (P = 0.320). In contrast, a study by Islamoglu et al.  found that serum Zn was significantly lower in patients than in healthy control (P < 0.010). Moreover, in the study of Bayir et al. , serum Zn concentration was significantly less in the CHD group compared with the control group (P < 0.010). Moreover, a meta-analysis study by Liu et al.  indicated that patients with MI had lower Zn levels than healthy controls (SMD=−1.848, 95% confidence interval=−2.365, −1.331). However, other study suggested that the occurrence of lower serum Zn in patients with MI may be an acute phase response rather than a cause of CVD.
A multivariate binary logistic regression analysis of the incidence of ACS versus 10 independent factors by El-Mahdy et al.  indicated that total cholesterol, zinc, the presence of diabetes mellitus, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were the independent predictors of ACS. Distant studies have shown that zinc has a direct relationship with the incidence of CVDs, so that patients whose zinc is in the lowest quartiles of zinc levels are more at risk of CHD than those in highest quartiles of zinc levels ,,.
In our study, there was a statistically significant difference between the studied groups regarding zinc level (lower in case group).
Yousif and Abdalla  found that serum zinc levels were significantly lower in patients with AMI when compared with control group (0.351 ± 0.08 vs. 0.531 ± 0.09, P = 0.000). According to age groups of the test group there is insignificant difference in serum zinc and troponin T levels (P > 0.05). The study observed insignificantly inversely correlated between serum zinc level with AST and LDH (P > 0.05). However, a significant inversely correlation with serum CKMB and troponin T was found (r=−0.28. P = 0.03, and r = 0.34, P = 0.001, respectively).
| Conclusion|| |
The results of the current study concluded that serum zinc levels were significantly negatively correlated with cardiac enzymes, that is, serum CK, CKMB mass, and troponin levels. Furthermore, the AMI prevalence rates decreased with increasing zinc quartiles.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Huang L, Teng T, Zhao J, Bian B, Yao W, Yu X, et al
. The relationship between serum zinc levels, cardiac markers and the risk of acute myocardial infarction by zinc quartiles. Heart Lung Circ 2018; 27
Plum L, Rink L, Haase H. The essential toxin: impact of zinc on human health. Int J Environ Res Public Health 2010; 7
Lang C, Murgia C, Leong M, Tan LW, Perozzi G, Knight D, et al
. Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. Am J Physiol Lung Cell Mol Physiol 2007; 292
Pannitteri G, Marino B, Campa PP, Martucci R, Testa U, Peschle C. Interleukins 6 and 8 as mediators of acute phase response in acute myocardial infarction. Am J Cardiol 1997; 80
Prasad AS. Zinc deficiency: has been known of for 40 years but ignored by global health organisations. BMJ 2003; 326
El-Adawy AH, Mohamad AT, Rizk EA, Marzouk HF. Linkage of some trace elements and cardiac markers in assessment of acute coronary syndromes. J Cardiovasc Dis Res 2018; 9
Sahn DJ, DeMaria AN, Kisslo JO, Weyman AF. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978; 58
David N, Thomas M. Routine clinical determination of lead, arsenic, zinc, copper, magnesium, cadmium and thalium in urine and whole blood by inductively coupled plasma-mass spectrometry. Spectrochm Acta 1996; 51
Prasad A. Discovery of human zinc deficiency: its impact on human health and disease. Adv Nutr 2013; 4
Little PJ, Bhattacharya R, Moreyra AE, Korichneva IL. Zinc and cardiovascular disease. Nutrition 2010; 26
Liu B, Cai Z, Zhou YM. Deficient zinc levels and myocardial infarction: association between deficient zinc levels and myocardial infarction: a meta-analysis. Biol Trace Elem Res 2015; 165
Mirghani H, Mohammed O, Alyoussuf A. Coronary syndrome and its relation to in-hospital complications. Indian J Appl Res 2015; 5
Firoz CK, Jabir NR, Kamal MA, Alama MN, Damanhouri GA, Khan W, et al
. Neopterin: an immune biomarker of coronary artery disease and its association with other CAD markers. IUBMB Life 2015; 67
Lewandrowski K. Cardiac markers of myocardial necrosis: a history and discussion of milestones and emerging new trends. Clin Lab Med 2014; 34
Giannoglou GD, Konstantinou DM, Kovatsi L, Chatzizisis YS, Mikhailidis DP. Association of reduced zinc status with angiographically severe coronary atherosclerosis: a pilot study. Angiology 2010; 61
Cebi A, Kaya Y, Gungor H, Demir H, Yoruk IH, Soylemez N, et al
. Trace elements, heavy metals and vitamin levels in patients with coronary artery disease. Int J Med Sci 2011; 8
Islamoglu Y, Evliyaoglu O, Tekbas E, Cil H, Elbey MA, Atilgan Z, et al
. The relationship between serum levels of Zn and Cu and severity of coronary atherosclerosis. Biol Trace Elem Res 2011; 144
Bayir A, Kara H, Kiyici A, Ozturk B, Akyurek F. Levels of selenium, zinc, copper and cardiac troponin I in serum of patients with acute coronary syndrome. Biol Trace Elem Res 2013; 154
El-Mahdy RI, Mostafa MM, El-Deen HS. Serum zinc measurement, total antioxidant capacity, and lipid peroxide among acute coronary syndrome patients with and without ST elevation. Appl Biochem Biotechnol 2019; 188
Martin-Moreno JM, Gorgojo L, Riemersma RA, Gomez-Aracen J, Kark JD, Guillen J, et al
. Myocardial infarction risk in relation to zinc concentration in toenails. Br J Nutr 2003; 89
Yu X, Huang L, Zhao J, Wang Z, Yao W, Wu X, et al
. The relationship between serum zinc level and heart failure: a meta-analysis. Biomed Res Int 2018; 2018
Yousif HA, Abdalla AM. Assessment of serum zinc among sudanese patients with acute myocardial infarction. J Adv Med Dent Sci Res 2018; 6
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]