|Year : 2021 | Volume
| Issue : 4 | Page : 27-33
A comparison of homocysteine, troponin, cobalamin and folate status in acute myocardial infarction patients and healthy subjects: A case–control study
Abbas Ali Niazi1, Mansour Karajibani2, Keivan Ghassami3, Farzaneh Montazerifar4, Maryam Iranneghad5, Ahmad Bolouri6
1 Department of Pathology, Cellular and Molecular Research Center, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
2 Department of Nutrition, Health Promotion Research Center, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
3 Department of Neurology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
4 Department of Nutrition, Pregnancy Health Research Center, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
5 Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
6 Department of Cardiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
|Date of Submission||24-Feb-2021|
|Date of Decision||11-Apr-2021|
|Date of Acceptance||05-May-2021|
|Date of Web Publication||16-Oct-2021|
Department of Nutrition, Health Promotion Research Center, School of Medicine, Zahedan University of Medical Sciences, Zahedan
Source of Support: None, Conflict of Interest: None
Introduction: Homocysteine (HCY), troponin, cardiac markers, folic acid and Vitamin B12 are known as the potential biomarkers for acute myocardial infarction (AMI) diagnosis. This study was designed to evaluate these markers as candidate biomarkers in the diagnosis, prognosis and prevention of AMI. Materials and Methods: This study was carried out on 40 AMI patients and 40 healthy subjects. After taking blood, HCY level was measured by an enzymatic, troponin and Vitamin B12, while the level of folic acid was determined by the radioimmunoassay method. In addition, the cardiac enzyme markers and lipid profile were measured by commercial kits and spectrophotometric method. Results: The results showed that patients' HCY levels were significantly more than the control group. Furthermore, the level of troponin was significantly different in the two groups (P = 0.0001), while serum levels of cardiac enzyme markers were significantly higher in patients (P < 0.01). Moreover, serum folic acid and Vitamin B12 levels differed between the two groups (P > 0.05). A positive correlation was identified between HCY with cholesterol (r = 0.32, P < 0.04) and low-density lipoprotein cholesterol (LDL-C) (r = 0.38, P < 0.02) in the patients. Conclusion: Elevated fasting HCY and troponin concentration are related to the lower circulation of folate and Vitamin B12 levels in the patients. The deficiency of these vitamins plays a role as an independent factor in HCY metabolism. As our findings revealed, despite a decrease in high-density lipoprotein cholesterol, the level of LDL-C increased in the patients. It can be inferred that merging enzymatic and non-enzymatic biomarkers might be more valuable in the diagnosis of AMI.
Keywords: Cobalamin, folate, homocysteine, myocardial infarction, troponin
|How to cite this article:|
Niazi AA, Karajibani M, Ghassami K, Montazerifar F, Iranneghad M, Bolouri A. A comparison of homocysteine, troponin, cobalamin and folate status in acute myocardial infarction patients and healthy subjects: A case–control study. Adv Hum Biol 2021;11:27-33
|How to cite this URL:|
Niazi AA, Karajibani M, Ghassami K, Montazerifar F, Iranneghad M, Bolouri A. A comparison of homocysteine, troponin, cobalamin and folate status in acute myocardial infarction patients and healthy subjects: A case–control study. Adv Hum Biol [serial online] 2021 [cited 2022 Aug 15];11:27-33. Available from: https://www.aihbonline.com/text.asp?2021/11/4/27/328392
| Introduction|| |
Cardiovascular disease (CVD) is the first leading cause of mortality, and disability-adjusted life years accounting for almost 50% of all deaths and 20%–23% of the burden associated with diseases in Iran.,,
Homocysteine (HCY) is an amino acid that serves as a marker for a higher risk of coronary artery disease (CAD), stroke and peripheral vascular disease. HCY is produced during the metabolism of methionine. Troponin is a polypeptide expressed by cardiac myocytes and released in the setting of myocardial injury. HCY and cardiac troponin are biomarkers for diagnosing acute myocardial injury or infarction. There is considerable controversy on the frequency and significance of cardiac troponins in predicting CVD patients., In this regard, many CVD risk factors such as oxidative stress, inflammation, hyperglycaemia and dyslipidaemia are emphasised in parallel to blood HCY. However, the level of HCY in the CVD complications associated with myocardial injury is not clear.
Several factors including age, sex, smoking, high cholesterol level, genetic background, diet and lifestyle can affect plasma HCY level., HCY levels increase with age and are higher in men than women due to high muscle mass. Alterations in the proportion of lean body mass (LBM) to fat mass may contribute to hyperhomocysteinemia. Hyperhomocysteinemia can lead to smooth muscle proliferation, lipid metabolism disorder and oxidation of low-density lipoprotein cholesterol (LDL-C). HCY can cause endothelial dysfunction by reducing the bioavailability of nitric oxide and increasing oxidative stress in the patients. Hyperhomocysteinemia affects the mechanism of the coagulation and fibrinolytic systems. There is an association between HCY level and thrombosis activation in CVD. This enhances HCY concentration which, in turn, increases the damage to myocardial tissue.
Troponin tests measure the level of cardiac-specific troponin in the blood to help detect heart injury. Troponin is a protein complex composed of three subunits such as troponin T, troponin I (TnI) and troponin C (TnC) that affects the function of skeletal and cardiac muscle. TnC can be found both in cardiac and skeletal muscles. When heart damage occurs, the troponin levels of serum can be used as a surrogate marker of myocardial tissue damage. The level of troponin seldom increases in the subgroups of the general population. The reason for such a rare increase is unknown, but the elevations seem to show a worse prognosis. Troponin levels increase within 3–4 h after the beginning of heart damage and stop rising in up to 4–7 days (cTnI) or 10–14 days (cTnT). Increasing troponin may also indicate hidden myocardial tissue damage in individuals without obvious cardiovascular symptoms.
Several enzymes such as alanine aminotransferase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and troponins have been used as indicators for the diagnosis of acute myocardial infarction (AMI). Besides, delays in the diagnosis of AMI may affect the assessment of other diseases. Nevertheless, there is no agreement on an ideal cardiac biomarker, so no single biomarker is recommended in this case. It should be mentioned that cardiac biomarkers do not make for a diagnosis but do support in reaching one. On the other hand, CK and CK-MB enzymes keep on as valuable factors in the diagnosis of AMI.,
At present, cardiac troponin is regarded as a major biomarker, which has specificity and sensitivity compared with other biomarkers that have been routinely used in clinical diagnoses. The release of troponin into the blood circulation is the main cause of the necrosis of cells. Measurement of troponin in blood has become faster even in lower concentrations while having higher accuracy. Troponin levels are not completely increased in AMI. Increasing troponin concentration can be seen as a multifactorial process.
Folic acid and Vitamin B12 are essential for the main metabolic pathway to decrease HCY levels: Plasma folate and Vitamin B12 impact HCY metabolism as substrate and cofactor, respectively. HCY levels may also increase due to a decrease in methionine metabolism, which is due to mutations in the codons of genes associated with HCY metabolism or deficiency of some vitamins., HCY concentration can be altered through diets containing methionine or lacking folic acid, Vitamin B12 and B6. Several studies have shown that the intake of a high protein diet and dairy products can lead to increased circulating levels of HCY., HCY can injure tissues of arteries by stimulating the release of cytokines, cyclins and other mediators of inflammation. It may lead to the oxidation of LDL (LDL-Ox) and the formation of plaques in arterioles.
They have revealed a decrease in HCY levels after the consumption of folic acid and B-complex vitamins but have not proved any reduction in the pathology status of the CVD patients. However, these findings have led to the adoption of different approaches in the treatment. Plasma HCY concentration is inversely related to these vitamins. Insufficient levels of these vitamins play a significant role in health that may be independent of their role in HCY metabolism.
Several studies have reported the relationship between HCY and troponin changes in AMI patients, but none seem well established. The present study is designed to describe the status of HCY, troponin, folate and Vitamin B12 concentrations; cardiac enzymes and lipid profile in AMI patients and healthy subjects. Discussing these indices will yield a better understanding of the role of these markers in the health of AMI patients.
| Methods|| |
Study design and subjects
This case–control, analytical study was performed on 40 AMI patients, including 16 (40%) males and 24 (60%) females (mean age = 58.3 ± 14.7 years), admitted to the coronary care unit (CCU) wards at Emam-Ali Hospital of Zahedan University of Medical Science (ZAUMS) in 2019. Written informed consent was obtained from all participants in accordance with the Helsinki Declaration. The diagnosis of AMI patients admitted to the CCU was established according to three clinical criteria including cardiac troponins and creatine phosphokinase (CPK) activity, echocardiography (ECG) changes and symptoms. The patients showed symptoms or were confirmed by a specialist physician. They were followed up by a cardiologist and allowed to take their regular medication. The control group included 40 healthy subjects, including 23 (57.5%) males and 17 (24.5%) females (63.6 ± 13.3 yrs). The age-matched subjects were with normal electrocardiograph and without any history of hypertension, heart disease, diabetes mellitus, renal or liver disease malignancy, endocrine disorders, pregnancy, operation or any acute medical condition. Exclusion criteria for both the groups were body mass index (BMI) ≥40 kg/m2, age <18 years and absence of any systemic disease. The study excluded patients who had taken any medication containing B Vitamin supplementation (Vitamin B12, B6 and folic acid) in recent 3 months, N-acetyl cysteine supplements, medication with metformin, trimethoprim and omeprazole, smoking, and also those suffering from hypothyroidism, or having any features of chronic renal failure. Some information was collected by interview and a questionnaire covering all general demographic and medical history. All patients were of the same age and lived in the same community as the control subjects. The second source of data included laboratory tests which were performed for HCY, troponin, folic acid and Vitamin B12; lipid profile including triglyceride (TG) and total cholesterol (TC); LDL-C and high-density lipoprotein cholesterol (HDL-C) levels and levels of enzymatic markers such as CK, CK-MB and LDH.
The study protocol was approved by the ethics board of Zahedan University of Medical Sciences (Code number; IR: ZAUMS.REC. NO: 1396.300; 6 May 2018). All aims of the protocol were clearly elucidated to patients and healthy individuals.
Blood samples were withdrawn from patients after an overnight fast. The serum was separated from the blood sample by centrifugation (20 min, RT, at 2000 RPM). Serum samples were divided into multiple aliquots, and aliquots were stored at −70°C until the day of analysis.
Serum HCY level was measured by an enzymatic method on the instrument Hitachi 912, HCY reagent, Version no: 2016/01: Axis-Shield Enzymatic. Axis-Shield HCY enzyme immunoassay (EIA) is an EIA for the determination of HCY in serum. In the Axis-Shield Enzymatic HCY assay, bound or dimerised HCY (oxidised form) is reduced to free HCY, which then reacts with serine catalysed by cystathionine beta-synthase to form L-cystathionine.
Serum Vitamin B12 and folic acid levels were determined in two groups. Serum level of folic acid and Vitamin B12 were determined by radioimmunoassay (RIA). Serum Vitamin B12 analysis was performed using Cobas E411, 741-0050 (Roche kit, Germany). The principle of this method is based on competitive protein binding, electrochemiluminescence detection in Roche Cobas E411 and 741-0050 chemiluminescence detection produced from the enzymatic reaction.
Folate and Vitamin B12 deficiency was defined as serum folate level <1.5 ng/mL and Vitamin B12 concentration <160 pg/ml.
Analysis of cardiac markers
TnI concentration in serum was measured by microparticle EIAs RIA on a routine, Tosoh AIA-360; 16155807, Japan. TnI values of higher than 1.3 ng/mL were considered positive, and the assay sensitivity was 0.030 ng/mL. Concentrations of various cardiac enzymes including CPK, CK-MB, LDH and AST levels were measured by commercial kits (Parsazmun, Tehran, Iran) using an auto-analyzer (BT-3500, Italy).
Evaluation of cardiovascular parameters
The serum level of lipid profile was determined by the calorimetric method. Plasma lipids concentrations; cholesterol, TG and HDL-C levels were determined in serum by enzymatic method, commercial kits, Parsazmun, Tehran, Iran, RA-1000 auto-analyzer). LDL-C value was calculated by Friedewald formula., LDL-C/HDL-C was calculated in two groups as well.
All data were analysed statistically through SPSS software under windows (version 18 for windows, Chicago, Illinois, USA). The results were represented as mean ± standard deviation. T-test was used to compare the groups. The relationship between variables was determined by Pearson's correlation coefficient. The difference was considered significant at P < 0.05.
| Results|| |
Demographic and biochemical characteristics of patients and healthy subjects are summarised in [Table 1]. The results showed that there was no statistically significant difference between the two groups in terms of age and BMI and the levels of serum cholesterol, TG, LDL-C and LDL-C/HDL-C (P > 0.05) [Table 1]. However, the levels of lipid profile with the exception of HDL-C in the case group were more than the control group. Compared to the control group, serum levels of CPK, CK-MB, LDH and SGOT were significantly higher in patients (P < 0. 01). In addition, serum folic acid and Vitamin B12 levels differed between the two groups, but this difference was not significant (P > 0.05) [Table 1].
The findings also indicated that there was no statistically significant difference regarding HCY level between the two groups (P = 0.38). However, a statistically significant difference was observed in troponin levels between the two groups (P = 0.0001) [Table 2].
In general, the results showed that there was no statistically significant difference according to folate (P = 0.13) and Vitamin B12 (P = 0.21) levels between two groups [Table 3].
Furthermore, no statistically significant difference was seen in folate and Vitamin B12 levels between the two groups, including subjects whose age was classified as <50 years and more (P > 0.05) [Table 4] and [Table 5].
|Table 4: Mean serum folic acid and vitamin B12 levels based on age in case group|
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|Table 5: Mean serum folic acid and vitamin B12 levels based on age in control group|
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In general, 4 (10%) and 2 (5%) of all subjects in case and control groups were folate deficient (folate <1.5 ng/ml) and 7 (17.5%) and 5 (12.5%) had low Vitamin B12 level (Vitamin B12 < 160 pg/mL) in both groups, respectively, according to the manufacturer's reference range (It has not been showed).
[Table 4] and [Table 5] show the mean serum folate and Vitamin B12 levels of studied groups and frequency of case and control groups separately in terms of folate and Vitamin B12 deficiency with different cut-off points in the age groups. There was no statistically significant difference based on the following vitamins level between the two groups.
There was only a positive correlation between HCY with cholesterol (r = 0.32, P < 0.04) and LDL-C levels (r = 0.38, P < 0.02) in the patients.
| Discussion|| |
This study showed that the age range of those suffering from the MI problems in the study population included young, middle-aged and old patients (20–90 years old). The results revealed that patients' HCY and troponin levels were more than healthy subjects. The findings of the current study are consistent with Alam et al.'s study, which reported an increase in cardiac troponin and HCY levels in AMI patients. Nonetheless, this increase was not significant either. Sadeghian et al. also reported no statistically significant difference in HCY level of females with and without CAD, while the level of HCY measured in the male participants was significantly great. High total HCY concentration is seen as an independent risk factor for CVD. HCY affords cardiomyocyte dysfunction and apoptosis through increased oxidative stress. Hyperhomocysteinemia damages cardiac relaxation, contractile function, platelets and affects mechanisms of the coagulation and fibrinolytic systems.
In the present study, the mean serum levels of folic acid and Vitamin B12 of the AMI patients were less than healthy subjects. According to these findings, 21.6% had folate and 35.4% suffered from Vitamin B12 deficiency compared to the control group, which were less and more than 50 years old. Similar to our study, it has been reported that folic acid and Vitamin B12 levels can be lower in CAD. Compared to the control group, the mean serum levels of folic acid and Vitamin B12 in the study group decreased. Hence, 10.7% and 26.6% of the patients had folate and Vitamin B12 deficiency, respectively. Folate and Vitamin B12 are the main nutritional factors influencing HCY levels. The relationship of lower levels of folate and Vitamin B12 with higher levels of HCY can indicate poor dietary habits in coronary heart disease.
Elevated fasting HCY level is related to lower circulating level and intake of folate and Vitamin B12. There are many factors that increase HCY concentration in AMI patients, for example, environmental and ethnic differences, oxidative stress, inadequate intake of B-complex and folate and fortification of grain products with folic acid., Folic acid can be used as a supplement therapy in cardiovascular alterations caused by HCY. The preservation of folate concentration in different foods highly depends on the type of foods and the process of cooking.,
It was also found that serum troponin levels elevated significantly in patients with AMI compared to healthy subjects. The findings from the present study are consistent with those reported in a recent article, indicating that the level of troponin increased significantly during AMI. In the first steps of AMI, pathological changes occur rapidly, which can be followed by the release of necrotic products such as cardiac troponins and CK into the bloodstream. When heart disease occurs, serum troponin can be used as an alternative indicator to evaluate it in CVD patients. In this study, a positive correlation was found between serum HCY with TC and LDL-C levels. Regarding the risk factor of CVD, the levels of BMI, TC, TG and LDL-C were higher, whereas HDL-C was lower in patients compared to the control group. These findings are consistent with the reports of Sadeghian et al., which showed higher dyslipidaemia in CAD patients. It has also been shown that inhibition of apo A-I synthesis and improved acetylated-LDL uptake might be induced by HCY as a subsequent mechanism in atherosclerosis progress.
HCY alterations are sometimes linked to alteration in LBM and body fat. Nevertheless, BMI or weight alteration does not predict a change in HCY levels. Changes in the ratio of LBM to total body fat mass may take part in hyperhomocysteinemia.
It has been reported that folate and Vitamin B12 deficiencies are involved in total Hcy concentrations of serum., It seems that these patients need a high dose of Vitamin B12 and folic acid supplements for treatment. However, a mega dose of folic acid can delay the syndrome of anaemia but cannot relieve neurological symptoms.
Our results confirm that elevated HCY levels are possibly attributable to a low level of the above-mentioned vitamin concentrations as folate is an established predictor of HCY level. In this case, it would be suitable to investigate the effect of folate enrichment of foods on HCY concentration in the Iranian population. Elevated fasting HCY level is generally regulated by treatment with folic acid and Vitamin B12 supplements. However, Vitamin B12 deficiency in the elderly can be caused by its malabsorption in the gastrointestinal tract.,
The results showed that concentrations of the lipid profile of patients were insignificantly more than healthy subjects, although most of these patients used to take lipid-lowering drugs. Besides, dyslipidaemia was not significantly related to increased serum troponin in our study. Along with other risk factors, dyslipidaemia can lead to high blood pressure and other adverse outcomes. As our findings revealed, the level of LDL-C increased in patients, while a decrease was observed in HDL-C level. Dyslipidaemia can develop atherosclerosis. Several studies have shown a significant elevation of cholesterol, TG and LDL-C levels and a significant reduction of HDL-C level in AMI patients as compared with healthy subjects.,
The present study demonstrated a significant increase in the enzymatic cardiac markers such as CPK, CK-MB, LDH and AST. Ischaemia is usually caused by decreased blood flow to the coronary artery and impaired ventricular function and myocardial necrosis. Several markers such as CK, CK-MB, ALT, AST and LDH are used in the diagnosis of AMI.
In general, increasing or decreasing levels of cardiac markers such as CK-MB isoenzymes, preferably troponin, and abnormal ECG waves are typical symptoms of AMI., Cardiac enzymes are superior to ECG in the diagnosis of AMI. Recently, cardiac enzymes have been substituted by another marker, including troponins, myoglobin, glycogen phosphorylase isoenzyme BB and calcium-binding protein in the diagnosis of AMI. In our study, cardiac markers such as HCY, troponin, ECG changes and CK-MB were used in diagnosing AMI. However, there are several main candidate biomarkers that may be applicable in diagnosing AMI. It seems that merging enzymatic and non-enzymatic biomarkers and other biomarkers can be more valuable for the AMI diagnosis.
| Conclusion|| |
Elevated fasting HCY and troponin levels are related to lower circulating folate and Vitamin B12 concentration in the patients. Although there was no association between HCY and troponin levels, the deficiency of these vitamins may have a role as an independent factor in HCY metabolism. While HDL-C decreased in the patients, LDL-C level increased. The study found a statistically significant difference between the two groups in terms of troponin levels and cardiac enzyme. However, there was no statistically significant difference based on serum folic acid and Vitamin B12 levels between the two groups. According to these results, each of these biomarkers has an important role in determining the history of the disease and diagnosis and analysis of AMI.
The present study was subject to some limitations including the small size of the study population and high charge of the commercial kits, which led to a decrease in our sample size. This research is also a cross-sectional study which has its own inherent limitations. Therefore, the present study cannot determine any causal relationships between the markers based on priority. Hence, the findings of our research need confirmation in long-term follow-up studies to check whether HCY causes such manifestations of subclinical myocardial injury.
We would like to our thank the patients and healthy subjects for their conscientious collaboration and gratefully acknowledge the colleagues who willingly cooperate in this study.
Financial support and sponsorship
This study was carried out by grant of Deputy Research in Zahedan University of Medical Science, Zahedan, Iran, with financial assistance registration grant No: 8609: 6 May 2018.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sarrafzadegan N, Mohammmadifard N. Cardiovascular disease in iran in the last 40 years: Prevalence, mortality, morbidity, challenges and strategies for cardiovascular prevention. Arch Iran Med 2019;22:204-10.
Naghavi M, Shahraz S, Sepanlou SG, Dicker D, Naghavi P, Pourmalek F, et al.
Health transition in Iran toward chronic diseases based on results of Global Burden of Disease 2010. Arch Iran Med 2014;17:321-35.
Namazi Shabestari A, Saeedi Moghaddam S, Sharifi F, Fadayevatan R, Nabavizadeh F, Delavari A, et al.
The most prevalent causes of deaths, DALYs, and geriatric syndromes in Iranian elderly people between 1990 and 2010: Findings from the global burden of disease study 2010. Arch Iran Med 2015;18:462-79.
Cao R, Bai Y, Xu R, Ye P. Homocysteine is associated with plasma high-sensitivity cardiac troponin T levels in a community-dwelling population. Clin Interv Aging 2014;9:79-84.
Taheri S, Pilehvarian AA, Akbari N, Musavi S, Naeini AE. Association between troponin I level and cardiovascular risk factors in asymptomatic hemodialysis patients. J Res Pharm Pract 2016;5:101-5.
] [Full text]
Alfthan G, Aro A, Gey KF. Plasma homocysteine and cardiovascular disease mortality. Lancet 1997;349:397.
Nygård O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, et al.
Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA 1995;274:1526-33.
Park SB, Georgiades A. Changes in body composition predict homocysteine changes and hyperhomocysteinemia in Korea. J Korean Med Sci 2013;28:1015-20.
Hayashi T, Honda G, Suzuki K. An atherogenic stimulus homocysteine inhibits cofactor activity of thrombomodulin and enhances thrombomodulin expression in human umbilical vein endothelial cells. Blood 1992;79:2930-6.
Wang X, Cui L, Joseph J, Jiang B, Pimental D, Handy DE, et al.
Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress. J Mol Cell Cardiol 2012;52:753-60.
Durand P, Prost M, Loreau N, Lussier-Cacan S, Blache D. Impaired homocysteine metabolism and atherothrombotic disease. Lab Invest 2001;81:645-72.
Al-Obaidi MK, Stubbs PJ, Collinson P, Conroy R, Graham I, Noble MI. Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes. J Am Coll Cardiol 2000;36:1217-22.
Members NW, Morrow DA, Cannon CP, Jesse RL, Newby LK, Ravkilde J, et al.
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Circulation 2007;115:e356-75.
Alam N, Khan HI, Chowdhury AW, Haque MS, Ali MS, Sabah KM, et al.
Elevated serum homocysteine level has a positive correlation with serum cardiac troponin I in patients with acute myocardial infarction. Bangladesh Med Res Counc Bull 2012;38:9-13.
Wallace TW, Abdullah SM, Drazner MH, Das SR, Khera A, McGuire DK, et al.
Prevalence and determinants of troponin T elevation in the general population. Circulation 2006;113:1958-65.
Otsuka T, Kawada T, Ibuki C, Seino Y. Association between high-sensitivity cardiac troponin T levels and the predicted cardiovascular risk in middle-aged men without overt cardiovascular disease. Am Heart J 2010;159:972-8.
Aydin S, Ugur K, Aydin S, Sahin İ, Yardim M. Biomarkers in acute myocardial infarction: Current perspectives. Vasc Health Risk Manag 2019;15:1-10.
Danese E, Montagnana M. An historical approach to the diagnostic biomarkers of acute coronary syndrome. Ann Transl Med 2016;4:194.
Mythili S, Malathi N. Diagnostic markers of acute myocardial infarction. Biomed Rep 2015;3:743-8.
Thygesen K, Mair J, Giannitsis E, Mueller C, Lindahl B, Blankenberg S, et al.
How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 2012;33:2252-7.
Westermann D, Neumann JT, Soerensen NA, Blankenberg S. High-sensitivity assays for troponin in patients with cardiac disease. Nat Rev Cardiol 2017;14:47.
Giannitsis E, Katus HA. Cardiac troponin level elevations not related to acute coronary syndromes. Nat Rev Cardiol 2013;10:623-34.
Kumar A, Palfrey HA, Pathak R, Kadowitz PJ, Gettys TW, Murthy SN. The metabolism and significance of homocysteine in nutrition and health. Nutr Metab (Lond) 2017;14:78.
Tsai MY, Hanson NQ, Bignell MK, Schwichtenberg KA. Simultaneous detection and screening of T833C and G919A mutations of the cystathionine β-synthase gene by single-strand conformational polymorphism. Clin Biochem 1996;29:473-7.
Stabler SP. Vitamins, homocysteine, and cognition. Am J Clin Nutr 2003;78:359-60.
Morita H, Kurihara H, Yoshida S, Saito Y, Shindo T, Oh-Hashi Y, et al.
Diet-induced hyperhomocysteinemia exacerbates neointima formation in rat carotid arteries after balloon injury. Circulation 2001;103:133-9.
Xiao Y, Zhang Y, Wang M, Li X, Xia M, Ling W. Dietary protein and plasma total homocysteine, cysteine concentrations in coronary angiographic subjects. Nutr J 2013;12:144.
Chambers JC, Obeid OA, Kooner JS. Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects. Arterioscler Thromb Vasc Biol 1999;19:2922-7.
McCully K. Homocysteine theory of arteriosclerosi Development and current status. Atherosclerosis 1983;11:157-246.
Loscalzo J. The oxidant stress of hyperhomocyst(e)inemia. J Clin Invest 1996;98:5-7.
Smulders YM, Blom HJ. The homocysteine controversy. J Inherit Metab Dis 2011;34:93-9.
Fakhrzadeh H, Ghotbi S, Pourebrahim R, Nouri M, Heshmat R, Bandarian F, et al.
Total plasma homocysteine, folate, and vitamin B12 status in healthy Iranian adults: The Tehran homocysteine survey (2003-2004)/a cross-sectional population based study. BMC Public Health 2006;6:29.
Shams M, Homayouni K, Omrani GR. Serum folate and vitamin B12 status in healthy Iranian adults. East Mediterr Health J 2009;15:1285-92.
Mortazavi MM, Ganjpour Sales J, Nouri-Vaskeh M, Parish M, Abdolhosseynzadeh S. Perioperative cardiac troponin i levels in patients undergoing total hip and total knee arthroplasty: A single center study. Anesth Pain Med 2018;8:e84228.
Burtis CA, Ashwood ER, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular DiagnosticsEBook. Saunders : Elsevier Health Sciences; 2012.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
Sadeghian S, Fallahi F, Salarifar M, Davoodi G, Mahmoodian M, Fallah N, et al.
Homocysteine, vitamin B12 and folate levels in premature coronary artery disease. BMC Cardiovasc Disord 2006;6:38.
Guo H, Lee JD, Ueda T, Shan J, Wang J. Plasma homocysteine levels in patients with early coronary artery stenosis and high risk factors. Jpn Heart J 2003;44:865-71.
Genser D, Prachar H, Hauer R, Halbmayer WM, Mlczoch J, Elmadfa I. Homocysteine, folate and vitamin b12 in patients with coronary heart disease. Ann Nutr Metab 2006;50:413-9.
Brattström LE, Israelsson B, Jeppsson JO, Hultberg BL. Folic acid – An innocuous means to reduce plasma homocysteine. Scand J Clin Lab Invest 1988;48:215-21.
Golbahar J, Rezaian G, Bararpour H. Distribution of plasma total homocysteine concentrations in the healthy Iranians. Clin Biochem 2004;37:149-51.
Kolling J, Scherer EB, da Cunha AA, da Cunha MJ, Wyse AT. Homocysteine induces oxidative-nitrative stress in heart of rats: Prevention by folic acid. Cardiovasc Toxicol 2011;11:67-73.
McKillop DJ, Pentieva K, Daly D, McPartlin JM, Hughes J, Strain JJ, et al.
The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet. Br J Nutr 2002;88:681-8.
Li LM, Cai WB, Ye Q, Liu JM, Li X, Liao XX. Comparison of plasma microRNA-1 and cardiac troponin T in early diagnosis of patients with acute myocardial infarction. World J Emerg Med 2014;5:182-6.
Mierzecki A, Kłoda K, Bukowska H, Chełstowski K, Makarewicz-Wujec M, Kozłowska-Wojciechowska M. Association between low-dose folic acid supplementation and blood lipids concentrations in male and female subjects with atherosclerosis risk factors. Med Sci Monit 2013;19:733-9.
Brown NB. Potential of manuka honey as a natural polyelectrolyte to develop biomimetic nanostructured meshes with antimicrobial properties. Front Bioeng Biotechnol 2019;7:344. doi: 10.3389/fbioe.2019.00344.
Tucker KL, Selhub J, Wilson PW, Rosenberg IH. Dietary intake pattern relates to plasma folate and homocysteine concentrations in the Framingham Heart Study. J Nutr 1996;126:3025-31.
Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, et al
. Blood cholesterol and vascular mortality by age, sex, and blood pressure: A meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet (London, England) 2007;370:1829-39.
Hirano T. Pathophysiology of diabetic dyslipidemia. J Atheroscler Thromb 2018;25:771-82.
Serdar Z, Aslan K, Dirican M, Sarandöl E, Yeşilbursa D, Serdar A. Lipid and protein oxidation and antioxidant status in patients with angiographically proven coronary artery disease. Clin Biochem 2006;39:794-803.
Pasupathi P, Rao YY, Farook J, Saravanan G, Bakthavathsalam GJ. Oxidative stress and cardiac biomarkers in patients with acute myocardial infarction. Disease Markers;2009;27:27585.
Aydin S, Aydin S. Irisin Concentrations as a Myocardial Biomarker. In: Patel V., Preedy V. (eds) Biomarkers in Cardiovascular Disease. Biomarkers in Disease: Methods, Discoveries and Applications.. Springer, Dordrecht. 2016. https://doi.org/10.1007/978-94-007-7678-4_3
Martin TN, Groenning BA, Murray HM, Steedman T, Foster JE, Elliot AT, et al.
ST-segment deviation analysis of the admission 12-lead electrocardiogram as an aid to early diagnosis of acute myocardial infarction with a cardiac magnetic resonance imaging gold standard. J Am Coll Cardiol 2007;50:1021-8.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]