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CORRELATION OF CARDIAC MARKERS WITH THYROID STIMULATING HORMONE IN SUBCLINICAL HYPOTHYROIDELDERLY

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Abstract

Cardiac markers (CPK-MB and TroponinT (TnT)) are often used to differentiate between cardiac and non cardiac chest pain. Subclinical hypothyroidism (SCH) has increased incidence of cardiovascular risk factors and disease. Elderly have an increased incidence of SCH. However, no study has specifically examined the association between cardiac markers and SCH in elderly population. Aims and Objectives: To determine the association of cardiac markers with thyroid stimulating hormone (TSH) in elderly patientswith subclinical hypothyroids and euthyroid. Method: The present study was designed as a retrospective cross-sectional study conducted in Biochemistry department of Adesh institute of medical sciences and research (AIMSR) Bathinda from a period of May 2023 to April 2024.The data was obtained from the lab computers and the subjects were divided into four groups. Group 1 included patients who had MI and SCH. Group 2 consisted of patients who had MI and were euthyroid. Group 3 were those who presented with chest pain only (no MI) and SCH. Group 4 were those who had acute chest pain (no MI) and were found to be euthyroid. Results:Our study showed significant correlation of TSH with CPK-MB (r=0.69, p=0.001)and Troponin T ( r=0.201, p= 0.04) in Group 1 while a non significant correlation was found in Group 2, CPK-MB (r=0.06, p=0.67) and Troponin T (r= 0.156, p= 0.57). There was a significant correlation of TSH with CPK-MB (r=0.71, p=0.02) and Troponin T (r=0.84, p= 0.001) in Group 3. A nonsignificant correlation was found in Group 4, between TSH and CPK-MB (r=0.116, p=0.68) and Troponin T (r= 0.001, p= 0.99). Conclusion: Elevations of TSH levels may cause a significant rise in the cardiac markers in SCH elderly as compared to euthyroid.
ISSN: 2320-5407 Int. J. Adv. Res. 12(05), 25-29
25
Journal Homepage: -www.journalijar.com
Article DOI:10.21474/IJAR01/18679
DOI URL: http://dx.doi.org/10.21474/IJAR01/18679
RESEARCH ARTICLE
CORRELATION OF CARDIAC MARKERS WITH THYROID STIMULATING HORMONE IN
SUBCLINICAL HYPOTHYROIDELDERLY
Dr. Premjeet Kaur1 and Dr. Amandeep Birdi2
1. Assistant Professor, Biochemistry Department, Adesh Institute of Medical Sciences and Research, Bathinda,
Punjab. India.
2. Assistant Professor, Biochemistry Department, Adesh Institute of Medical Sciences and Research, Bathinda,
Punjab. India.
……………………………………………………………………………………………………....
Manuscript Info Abstract
……………………. ………………………………………………………………
Manuscript History
Received: 05 March 2024
Final Accepted: 09 April 2024
Published: May 2024
Key words:-
Cardiac Markers, Subclinical
Hypothyroidism, Elderly
Cardiac markers (CPK-MB and TroponinT (TnT)) are often used to
differentiate between cardiac and non cardiac chest pain. Subclinical
hypothyroidism (SCH) has increased incidence of cardiovascular risk
factors and disease. Elderly have an increased incidence of SCH.
However, no study has specifically examined the association between
cardiac markers and SCH in elderly population.
Aims and Objectives: To determine the association of cardiac markers
with thyroid stimulating hormone (TSH) in elderly patientswith
subclinical hypothyroids and euthyroid.
Method: The present study was designed as a retrospective cross-
sectional study conducted in Biochemistry department of Adesh
institute of medical sciences and research (AIMSR) Bathinda from a
period of May 2023 to April 2024.The data was obtained from the lab
computers and the subjects were divided into four groups. Group 1
included patients who had MI and SCH. Group 2 consisted of patients
who had MI and were euthyroid. Group 3 were those who presented
with chest pain only (no MI) and SCH. Group 4 were those who had
acute chest pain (no MI) and were found to be euthyroid. Results:Our
study showed significant correlation of TSH with CPK-MB (r=0.69,
p=0.001)and Troponin T ( r=0.201, p= 0.04) in Group 1 while a non
significant correlation was found in Group 2, CPK-MB (r=0.06,
p=0.67) and Troponin T (r= 0.156, p= 0.57). There was a significant
correlation of TSH with CPK-MB (r=0.71, p=0.02) and Troponin T
(r=0.84, p= 0.001) in Group 3. A nonsignificant correlation was found
in Group 4, between TSH and CPK-MB (r=0.116, p=0.68) and
Troponin T (r= 0.001, p= 0.99).
Conclusion: Elevations of TSH levels may cause a significant rise in
the cardiac markers in SCH elderly as compared to euthyroid.
Copy Right, IJAR, 2024. All rights reserved.
……………………………………………………………………………………………………....
Introduction:-
SCH is biochemically defined as a TSH level above the upper limit of the reference range with normal thyroid
hormone levels. (1) SCH is associated with an increased risk of coronary heart disease (CHD) and mortality. (2)
Corresponding Author:- Dr. Premjeet Kaur
Address:- Assistant Professor, Biochemistry Department, Adesh Institute of
Medical Sciences and Research, Bathinda, Punjab. India.
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26
Incidence of cardiovascular disease increases with age. At the same time TSH values are found higher with
advancing age. (1). Thus, Subclinical hypothyroidism (SCH) is a common condition present in the geriatric age
group that significantly affects the cardiovascular system.(3)The sensitivity and specificity of ECG are low in
diagnosing acute myocardial infarction (AMI), hence the criteria for AMI were decided by the European Society of
Cardiology (ESC) and the American College of Cardiology (ACC). Accordingly, a patient has to have at least two
of the following: typical symptoms, a characteristic elevation pattern in cardiac markers (eg, CK-MB izoenzymes),
preferably serum troponins (cTnI or cTnT), or a typical ECG trace with Q waves that indicate a diagnosis of
AMI.(4) The present study tried to find association between TSH and cardiac markers in elderly subclinical
hypothyroid patients presenting with chest pain and myocardial infarction.
Objectives of the study:-
Material and Methods:-
Study design:
The study was designed as hospital-based retrospective cross-sectional study conducted in Central Clinical
Laboratory of Adesh Institute of Medical Sciences and Research, Bathinda, a tertiary care teaching hospital in
Punjab, India, from a period of May 2023 to April 20234. All participants were in the age group of >60 years. The
average age group of the subjects came out to be 70±8 years. Hence serum TSH reference rangein relation to age for
the present study was 0.48 IU/L to 4.59 IU/L. (5) Subjects were divided into four groups. Group 1 consisted of 100
patients presenting with chest pain and MI and were found to have subclinical hypothyroidism. Group 2 consisted of
subjectspresenting with chest pain and MI but were euthyroid. Group 3 included patients presenting with chest pain
only and were having SCH. Group 4 consisted of subjects who presented with chest pain only and were found
euthyroid. Both emergency and outdoor patients were included in this study.
Sample size:
The sample size was calculated based on the average prevalence rate of hypothyroidism (18%) (3) by using
Cochran’s formula.
Z2 PQ/e2
Where Z is Z score.
It was increased to 100 to have adequate number and to draw significant conclusion. Hence, we included 100
subjects for each group.
Data collection:
The data was collected from the previous one-year data (May 2023 to April 2024) maintained in the laboratory
computer.
Sampling procedure:
Patients presenting with acute chest pain and MI with SCH or euthyroidswhose cardiac markers and TSH available
in the records were enrolled for study analysis.
Sample estimations:
Cardiac markers were analysed by pocttechnique. The thyroid function tests were estimated by chemiluminescence
assay (Maglumi 2000 Fully automated analyzer).
Inclusion Criteria:
Patients >60 years of age presenting with acute chest pain or MI or both, having SCH OR euthyroid.
Exclusion criteria:
Patients with history of myocarditis, cardiomyopathies, arrhythmias, valvular heart disease cardiac contusion,
renalfailure, sepsis, anemia, hypotension, hypoxia, andnoncardiac surgery were excluded.
Statistical analysis:
Data was analyzed using SPSS software. Pearson’s correlation was calculated. The data was presented as mean ±
SD. A p value of < 0.05 was taken as statistically significant.
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Results:-
There was no significant difference between age and gender of the groups. Average age group of the subjects was 70
±8 years.The present study showed a non significantly high (r=0.268, p=0.03) levels of TSH in cases (Group 1&3)
(90.9 ± 6.6 uIU/ml) as compared to the controls Group 2&4) (1.6 ± 0.8 uIU/ml).Our study showed significant
correlation of TSH withCPK-MB (r=0.69, p=0.001)and Troponin T ( r=0.201, p= 0.04) in Group 1 while a non
significant correlation was found in Group 2, CPK-MB (r=0.06, p=0.67) and Troponin T (r= 0.156, p= 0.57). There
was a significant correlation of TSH with CPK-MB (r=0.71, p=0.02) and Troponin T (r=0.84, p= 0.001) in Group 3.
A nonsignificant correlation was found in Group 4, between TSH and CPK-MB (r=0.116, p=0.68) and Troponin T
(r= 0.001, p= 0.99). (Table 1 and 2)
Table 1:- Correlates the levels of CPK-MB, TnT and BNPin Group 1and2.
Variables
TSH in Group 1
TSH in Group 2
CPK-MB
r
0.69
0.06
p
0.001
0.67
TnT
r
0.21
0.15
p
0.04
0.57
BNP
r
0.64
0.01
p
0.001
0.62
r is the correlation coefficient, p is the values obtained from Spearman correlation analysis, p<0.05 is considered
statistically significant.
Table 2:- Correlates the levels of CPK-MB, TnT and BNPin Group 3 and 4.
Variables
TSH in Group 3
TSH in Group 4
CPK-MB
r
0.71
0.11
p
0.02
0.68
TnT
r
0.84
0.001
p
0.001
0.99
BNP
r
0.13
0.08
p
0.58
0.55
r is the correlation coefficient, p is the values obtained from Spearman correlation analysis, p<0.05 is considered
statistically significant. Figure 1:-
Discussion:-
There was no significant difference in age and gender ratio in cases and controls. The present study showed a
nonsignificant (r=0.04, p=0.65) elevation in the levels of TSH in subclinical hypothyroid patients (7.9 ± 1.9 uIU/ml)
8.66
1.41
11.5
1.51
1.629
0.009
1.067
0.025
1
2
3
4
Figure 1 : Correlation of CPK-MB and TnT with TSH in Group
1, 2, 3 and 4
Series1
Series2
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as compared to euthyroid subjects (2.0 ± 1.0 uIU/ml). Similar results were found byC.Baumgartner et. Al (6).
Reference range for TSH is 0.48 IU/L to 4.59 IU/L. (5). Our study showed significant correlation of TSHwith CPK-
MB (r=0.69,p=0.001) Troponin T ( r=0.201, p= 0.04)and BNP (r= 0.64, p=0.001) in Group 1 while a non
significant correlation was found in Group 2, CPK-MB (r=0.06, p=0.67) Troponin T (r= 0.156, p= 0.57) and BNP
(r= 0.07, p=0.62). This shows that slight elevations of TSH levels causes a significant rise in the cardiac markers in
SCH as compared to euthyroid.
Though a large amount of data is available which gives an explanation on the association of the cardiac functions
and subclinical hypothyroidism. (1,5,7,8) Another viewpoint of our study can be, despite the nonsignificant
difference in the levels of TSH in pairs of group 1& group 2 and group 3 & 4, there exists a significant rise in the
levels of the cardiac markers. These results may point towards a need for revised reference ranges for the cardiac
markers with respect to SCH in elderly in cases of acute chest pain or MI in order to reduce the over diagnosis of MI
patients based on cardiac markers.
The dimeric enzyme, consisting of two subunits, M and B, has three isoenzymes: CK-BB (CK1), CK-MB (CK2),
and CK-MM (CK3). CK-MB can be found in the heart, skeletal muscle, small intestine, diaphragm, uterus, tongue,
and prostate.Therefore, its increasing level during trauma and inflammation reduces its specificity. Moreover, it
cannot detect minor myocardial damage, due to its high molecular weight. (4)
One of the conditions in which CK-MB is false positive in diagnosis of AMI is hypothyroidism. It can cause false-
positive results in CK-MB measurements. Therefore, this condition should be considered when using CK-MB as a
biomarker in the diagnosis of AMI. (9)
There are many proteins released into the circulation by the cardiac system, such as myoglobin, BNP, TnI (blocking
actinmyosin interaction), and TnT (bound to tropomyosin). cTn has many isoforms specific to tissue. (4)
The amount of cTnpresent in the cytosolic pool is similar to the amount of CK-MB, but there is also a significant
amount of cTn in the contractile apparatus. Therefore, the amount of cTn per gram of myocardium is 1315 times
greater than the amount of CK-MB. This explains the higher sensitivity of cTn compared with CK-MB in the early
period and the elevated level of cTn in peripheral blood despite the normal level of CK-MB after myocardial tissue
damage. The reason for the long-lasting elevation is the continuation of the release of cTn from the contractile
apparatus in the late period. (10) (11)
Elevated cardiac troponin (representing true myocardial injury) is present in several cardiac and noncardiac
conditions in the absence of acute MI. Heterophile antibodies are widely accepted to be risk factors for true false
positive troponin results in the absolute absence of myocardial injury. In addition to interfering with troponin assays,
heterophile antibodies can also interfere with thyroid function tests, hormones, and tumor markers. Therefore,
elevation of troponins should not always be interpreted in favor of coronary ischemia. (12,13)
Limitations of the study:
Our study is just a proposed conclusion on the findings obtained, morelarge-scale detailed studies may be required
to prove the facts.
Conclusion:-
Our study is a significant reminder of the importance behind consideration of impact of high TSH levels in elderly
SCH on cardiac markers.
Conflict of interest:
Nil.
Ethical clearance:
The approval from the institutional ethical committee was not required.
Source of funding:
Nil.
ISSN: 2320-5407 Int. J. Adv. Res. 12(05), 25-29
29
Data Availability:
Data included within this article.
Authors’ Contributions:
Dr Premjeet Kaur: Designed the study, retrieved literature, extracted data and wrote article.
References:-
1.Maja Udovic, Raul Herrera Peña, BhargaviPatham. Hypothyroidism and the heart. MDCVJ.2017, XIII (2):55-59.
2.Jing Sun, Liang Yao, Yuan Fang et al. Relationship between Subclinical Thyroid Dysfunction and the Risk of
Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies. Int J Endocrinol.
2017:2017:8130796. doi: 10.1155/2017/8130796
3.PriyankaPandey, Ana ParchiaFranchini et at. Subclinical hypothyroidism in geriatric population and its association
with heart failure. Cerus. 2021.13(4)e14296.
4.Suleyman Aydin, KaderUgur, SunaAydin, İbrahimSahin, MeltemYardim. Biomarkers in acute myocardial
infarction: current perspectives. Vasc Health and Risk Manag. 2019,15:1-10.
5.OwainLeng and Salman Razvi. Hypothyroidism in the older population. Thyroid Research. 2019.12;2:1-10.
://doi.org/10.1186/s13044-019-0063
6.Christine Baumgartner, Bruno R da Costa, Tinh-Hai Collet, Martin Feller, Carmen Floriani, Douglas C Bauer
et.al. Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.
Circulation. 2017 Nov 28;136(22):2100-2116
7.Meng Y, Zhao T, Zhang ZY, Zhang DK. Chin. Association between sub-clinical hypothyroidism and heart failure
with preserved ejection fraction. Med J (Engl) 2020; 133:364366.
8. Razvi S, Jabbar A, Pingitore A, Danzi S, Biondi B, Klein I, et al. Thyroid hormones and cardiovascular function
and diseases. J Am Coll Cardiol. 2018; 71:178196. https://doi.org/10.1016/j.jacc.2018.02.045.
9.Kim S, Um TH, Cho CR, Jeon JS. False-positive elevation of creatine kinase MB mass concentrations caused by
macromolecules in a patient who underwent nephrectomy for renal cell carcinoma. Ann Lab Med. 2014;34(5):405
407.
10.Shah AS, McAllister DA, Mills R, et al. Sensitive troponin assay and the classification of myocardial infarction.
Am J Med. 2015;128(5):493501.
11.Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardialinfarction (2018). J Am Coll
Cardiol2018; 72:223164.
12.McCarthy CP, Raber I, Chapman AR, et al.Myocardialinjury in the era of highsensitivity cardiac troponin assays:
a practical approach for clinicians. JAMA Cardiol. 2019; 4:1034442.
13.James L. Januzzi, Cian P. McCarthy. Cardiac Troponin and theTrue False Positive. JACC: CASE REPORTS,
VOL. 2, NO. 3,2020:461 3.
... The BTL has published 2024 volume 11 with two issues, the readers are invited to refer the published articles. [1][2][3][4][5][6][7][8][9][10] ...
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Biomedical and Therapeutics Letters ISSN 2394-2274 : A peer reviewed journal for research in Biomedical Sciences, Clinical Reports, Medical Sciences, Molecular Medicine, Molecular Genetics, Medicinal Chemistry, Drug Discovery, Immunology, Pharmaceutical Sciences, Clinical Research, research advances in drug design and development.
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Background Evidence on the association between subclinical thyroid dysfunction and the risk of cardiovascular outcomes are conflicting. Methods and Results PubMed, EMbase, Web of Science, Cochrane Library, and China Biology Medicine (CBM) databases were searched from inception to July 10, 2016. A total of 16 studies were included for meta-analysis. We found that subclinical hypothyroidism was not correlated with coronary heart disease (CHD) (RR = 1.17; 95% CI, 0.91–1.52), total mortality (RR = 1.02; 95% CI, 0.93–1.13), cardiovascular mortality (RR = 1.06; 95% CI, 0.77–1.45), heart failure (RR = 1.17; 95% CI, 0.87–1.57), and atrial fibrillation (RR = 1.05; 95% CI, 0.91–1.21), except CHD mortality (RR = 1.37; 95% CI, 1.03–1.84). Subgroup analysis indicated a higher estimation risk in CHD (RR = 1.54; 95% CI, 1.00–2.39), cardiovascular mortality (RR = 2.14; 95% CI, 1.43–3.22), and CHD mortality (RR = 1.54; 95% CI, 1.11–2.15) among participants < 65 years. Furthermore, subclinical hyperthyroidism was found to be associated with CHD (RR = 1.20; 95% CI, 1.02–1.42), total mortality (RR = 1.27; 95% CI, 1.07–1.51), and CHD mortality (RR = 1.45; 95% CI, 1.12–1.86). Conclusions Subclinical hypothyroidism is likely associated with an increased risk of CHD mortality, and subclinical hyperthyroidism is likely associated with increased risk of CHD, CHD mortality, and total mortality.
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Background: Lowering the diagnostic threshold for troponin is controversial because it may disproportionately increase the diagnosis of myocardial infarction in patients without acute coronary syndrome. We assessed the impact of lowering the diagnostic threshold of troponin on the incidence, management, and outcome of patients with type 2 myocardial infarction or myocardial injury. Methods: Consecutive patients with elevated plasma troponin I concentrations (≥50 ng/L; n = 2929) were classified with type 1 (50%) myocardial infarction, type 2 myocardial infarction or myocardial injury (48%), and type 3 to 5 myocardial infarction (2%) before and after lowering the diagnostic threshold from 200 to 50 ng/L with a sensitive assay. Event-free survival from death and recurrent myocardial infarction was recorded at 1 year. Results: Lowering the threshold increased the diagnosis of type 2 myocardial infarction or myocardial injury more than type 1 myocardial infarction (672 vs 257 additional patients, P < .001). Patients with myocardial injury or type 2 myocardial infarction were at higher risk of death compared with those with type 1 myocardial infarction (37% vs 16%; relative risk [RR], 2.31; 95% confidence interval [CI], 1.98-2.69) but had fewer recurrent myocardial infarctions (4% vs 12%; RR, 0.35; 95% CI, 0.26-0.49). In patients with troponin concentrations 50 to 199 ng/L, lowering the diagnostic threshold was associated with increased healthcare resource use (P < .05) that reduced recurrent myocardial infarction and death for patients with type 1 myocardial infarction (31% vs 20%; RR, 0.64; 95% CI, 0.41-0.99), but not type 2 myocardial infarction or myocardial injury (36% vs 33%; RR, 0.93; 95% CI, 0.75-1.15). Conclusions: After implementation of a sensitive troponin assay, the incidence of type 2 myocardial infarction or myocardial injury disproportionately increased and is now as frequent as type 1 myocardial infarction. Outcomes of patients with type 2 myocardial infarction or myocardial injury are poor and do not seem to be modifiable after reclassification despite substantial increases in healthcare resource use.
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Importance Traditionally, elevated troponin concentrations were synonymous with myocardial infarction. But with improvements in troponin assays, elevated concentrations without overt myocardial ischemia are now more common; this is referred to as myocardial injury. Physicians may be falsely reassured by the absence of myocardial ischemia; however, recent evidence suggests that myocardial injury is associated with even more detrimental outcomes. Accordingly, this article reviews the definition, epidemiology, differential diagnosis, diagnostic evaluation, and management of myocardial injury. Observations Current epidemiological evidence suggests that myocardial injury without overt ischemia represents about 60% of cases of abnormal troponin concentrations when obtained for clinical indications, and 1 in 8 patients presenting to the hospital will have evidence of myocardial injury. Myocardial injury is a concerning prognosis; the 5-year mortality rate is approximately 70%, with a major adverse cardiovascular event rate of 30% in the same period. The differential diagnosis is broad and can be divided into acute and chronic precipitants. The initial workup involves an assessment for myocardial ischemia. If infarction is ruled out, further evaluation includes a detailed history, physical examination, laboratory testing, a 12-lead electrocardiogram, and (if there is no known history of structural or valvular heart disease) an echocardiogram. Unfortunately, no consensus exists on routine management of patients with myocardial injury. Identifying and treating the underlying precipitant is the most practical approach. Conclusion and Relevance Myocardial injury is the most common cause of abnormal troponin results, and its incidence will likely increase with an aging population, increasing prevalence of cardiovascular comorbidities, and greater sensitivity of troponin assays. Myocardial injury represents a challenge to clinicians; however, given its serious prognosis, it warrants a thorough evaluation of its underlying precipitant. Future strategies to prevent and/or manage myocardial injury are needed.
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Thyroid hormone (TH) receptors are present in the myocardium and vascular tissue, and minor alterations in TH concentration can affect cardiovascular (CV) physiology. The potential mechanisms that link CV disease with thyroid dysfunction are endothelial dysfunction, changes in blood pressure, myocardial systolic and diastolic dysfunction, and dyslipidemia. In addition, cardiac disease itself may lead to alterations in TH concentrations (notably, low triiodothyronine syndrome) that are associated with higher morbidity and mortality. Experimental data and small clinical trials have suggested a beneficial role of TH in ameliorating CV disease. The aim of this review is to provide clinicians dealing with CV conditions with an overview of the current knowledge of TH perturbations in CV disease.
Raul Herrera Peña, BhargaviPatham. Hypothyroidism and the heart
  • Maja Udovic
Maja Udovic, Raul Herrera Peña, BhargaviPatham. Hypothyroidism and the heart. MDCVJ.2017, XIII (2):55-59.
Subclinical hypothyroidism in geriatric population and its association with heart failure
  • Ana Priyankapandey
  • Parchiafranchini
  • At
PriyankaPandey, Ana ParchiaFranchini et at. Subclinical hypothyroidism in geriatric population and its association with heart failure. Cerus. 2021.13(4)e14296.
Biomarkers in acute myocardial infarction: current perspectives. Vasc Health and Risk Manag
  • Suleyman Aydin
  • Kaderugur
  • Sunaaydin
  • Meltemyardim İbrahimsahin
Suleyman Aydin, KaderUgur, SunaAydin, İbrahimSahin, MeltemYardim. Biomarkers in acute myocardial infarction: current perspectives. Vasc Health and Risk Manag. 2019,15:1-10.