Correlation between plasma homocysteine and ischemic heart disease in young Adults

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Ischemic heart disease is a major cause of morbidity and mortality. Lack of blood supply to the brain can cause tissue death if any of the cerebral veins, carotid arteries, or vertebral arteries are blocked. An ischemic stroke describes this type of event. One of the byproducts of methionine metabolism, the demethylation of methionine, is homocysteine, an amino acid that contains sulfur. During myocardial ischemia, the plasma level of homocysteine (Hcy) increases and plays a role in many methylation processes. Hyperhomocysteinemia has only recently been recognized as a major contributor to the increased risk of cardiovascular disease (CVD) owing to its effects on atherothrombosis and improvement of oxidative stress-induced endothelial dysfunction, joining the ranks of other known risk factors such as hyperlipidemia, hypertension, diabetes, and advanced age. Objective The purpose of this study was to determine whether there is a relationship between elevated serum total homocysteine (tHcy) levels and an increased risk of coronary artery disease (CAD) in an Iraqi population of patients with ischemic heart disease. Methods This study was conducted at Madinat al-Imamain Al Kadhmain Hospital’s Cardiology Department in Baghdad, Iraq. The study lasted for six months and was designed as an observational case-control study from November 1, 2023, to April 1, 2024. Results Cases and controls had similar characteristics but differed significantly in serum homocysteine concentration. The mean homocysteine level in case group was 40.21±14.47 mmol/L and 9.23±2.41 mmol/L in control group with p value <0.001. Conclusion In young individuals, hyperhomocysteinemia is positively associated with coronary artery, even when other traditional risk factors are not present. 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F1000Research 2024, 13 :1477 ( https://doi.org/10.12688/f1000research.158499.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Correlation between plasma homocysteine and ischemic heart disease in young Adults [version 1; peer review: awaiting peer review] Zainab Hassan Muslem https://orcid.org/0009-0002-4307-087X 1 , Samara M.Ali https://orcid.org/0000-0001-7105-6966 2 , Amal Noori Al Marayati 3 Zainab Hassan Muslem https://orcid.org/0009-0002-4307-087X 1 , Samara M.Ali https://orcid.org/0000-0001-7105-6966 2 , Amal Noori Al Marayati 3 PUBLISHED 04 Dec 2024 Author details Author details 1 Department of Pharmacology, College of Medicine, University of Baghdad, Baghdad, Iraq 2 Department of Pharmacology, College of Medicine, University of Baghdad, Baghdad, Iraq 3 Iraqi Center for Heart Diseases, Baghdad, Iraq Zainab Hassan Muslem Roles: Conceptualization, Investigation, Methodology, Resources, Software, Visualization Samara M.Ali Roles: Investigation, Methodology, Project Administration, Supervision, Visualization Amal Noori Al Marayati Roles: Methodology, Project Administration, Supervision OPEN PEER REVIEW REVIEWER STATUS AWAITING PEER REVIEW Abstract Background Cardiovascular disease (CVD) is a leading cause of death worldwide. Ischemic heart disease is a major cause of morbidity and mortality. Lack of blood supply to the brain can cause tissue death if any of the cerebral veins, carotid arteries, or vertebral arteries are blocked. An ischemic stroke describes this type of event. One of the byproducts of methionine metabolism, the demethylation of methionine, is homocysteine, an amino acid that contains sulfur. During myocardial ischemia, the plasma level of homocysteine (Hcy) increases and plays a role in many methylation processes. Hyperhomocysteinemia has only recently been recognized as a major contributor to the increased risk of cardiovascular disease (CVD) owing to its effects on atherothrombosis and improvement of oxidative stress-induced endothelial dysfunction, joining the ranks of other known risk factors such as hyperlipidemia, hypertension, diabetes, and advanced age. Objective The purpose of this study was to determine whether there is a relationship between elevated serum total homocysteine (tHcy) levels and an increased risk of coronary artery disease (CAD) in an Iraqi population of patients with ischemic heart disease. Methods This study was conducted at Madinat al-Imamain Al Kadhmain Hospital’s Cardiology Department in Baghdad, Iraq. The study lasted for six months and was designed as an observational case-control study from November 1, 2023, to April 1, 2024. Results Cases and controls had similar characteristics but differed significantly in serum homocysteine concentration. The mean homocysteine level in case group was 40.21±14.47 mmol/L and 9.23±2.41 mmol/L in control group with p value <0.001. Conclusion In young individuals, hyperhomocysteinemia is positively associated with coronary artery, even when other traditional risk factors are not present. READ ALL READ LESS Keywords Homocysteine, ischemic heart disease, adult Corresponding Author(s) Zainab Hassan Muslem ( [email protected] ) Close Corresponding author: Zainab Hassan Muslem Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2024 Hassan Muslem Z et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Hassan Muslem Z, M.Ali S and Al Marayati AN. Correlation between plasma homocysteine and ischemic heart disease in young Adults [version 1; peer review: awaiting peer review] . F1000Research 2024, 13 :1477 ( https://doi.org/10.12688/f1000research.158499.1 ) First published: 04 Dec 2024, 13 :1477 ( https://doi.org/10.12688/f1000research.158499.1 ) Latest published: 04 Dec 2024, 13 :1477 ( https://doi.org/10.12688/f1000research.158499.1 ) Introduction Cardiovascular events account for one-third of all the fatalities worldwide. Heart disease and stroke kill more than 600,000 people per year in industrialized nations, such as the US. Deaths caused by cardiovascular diseases are most often caused by ischemic heart disease. 1 Atherosclerosis, the hardening and constriction of the coronary arteries that carry blood and oxygen to the heart, is a defining characteristic of ischemic heart disease. Coronary angiography is the most reliable method for diagnosing coronary artery disease is coronary angiography. 2 Figure 1 shows the diseases associated with ischemic heart disease. The etiology and course of atherosclerotic cardiovascular disease remain unexplained by established risk factors according to recent observational studies. Furthermore, 30% of individuals who present with myocardial infarction do not exhibit any of these risk factors. 3 An increasing number of studies point to atherosclerosis as an inflammatory disease and blood inflammatory biomarkers as potential cardiovascular disease CVD predictors. 4 By lowering the levels of antithrombotic factors and endothelial-derived nitric oxide and boosting the levels of prothrombotic factors XII and V, homocysteine accelerates atherosclerosis. Since its discovery in 1932, homocysteine has been a subject of much speculation. The term homocysteine comes from the fact that its chemical characteristics are comparable to those of cysteine as shown in Figure 2 . 5 People naturally possess the amino acid homocysteine (Hcy), which is a thiol group containing amino acids. Two metabolic processes break down Hcy in the body, and the kidneys remove a small amount as waste. Folic acid and vitamins B6 and B12 are required for the chemical processes that break down Hcy. Therefore, the presence or absence of these vitamins affects serum total Hcy levels. Several medical conditions, including occlusive artery disease (particularly in the brain, heart, and kidney), venous thrombosis, megaloblastic anemia, osteoporosis, depression, Alzheimer’s disease, and pregnancy complications are associated with hyperhomocysteinemia (HHcy) and homocystinuria. High HCY levels are associated with a range of diseases in both children and adults. 6 Deficits in vitamin B6, folate, and B12, or by administering foods rich in Met. Furthermore, many medicines, including lipid-lowering and anti-Parkinsonian medications, might increase Hcy levels when used in clinical practice. Folate, vitamin B6, and vitamin B12 supplementation have been demonstrated to lower Hcy levels in studies, but whether they also reduce some related diseases is still under debate. 7 In 1933, Vincent du Vigneaud was the first to isolate Hcy from urinary bladder stones (s). At about the same time, a 4-day evaluation was conducted on an 8-year-old child of Irish-American descent hospitalized at Mass General Hospital for symptoms such as headache, vomiting, lethargy, indicators of abnormal mental development, and dislocated lenses in both eyes. There was a marked decline in the health, and he showed symptoms of stroke, including left-sided paralysis and aberrant reflexes. In addition, the boy’s temperature and blood pressure increased, but there were no outward symptoms of infection. He died from the disease a few days later. This case was published in the New England Journal of Medicine in 1933 as case 19,471. The cause of death was arteriosclerosis of the carotid artery with cerebral infarction. 8 Over the past 20 years, there has been heated discussion between academics and doctors regarding the significance and consequences of increased plasma Hcy levels in pathology. The traditional view of folate’s causative function in pathogenesis has been cast into doubt by the finding that its treatment reduces plasma Hcy levels, but has no discernible effect on the course or outcome of illness. Research into homocysteine homeostasis is ongoing on a global scale because of its potential role as a cause, mediator, biomarker, and innocent bystander in neurological and cardiovascular illnesses. 9 Methionine was heated with sulfuric acid to produce the desired amino acids. An increase in homocysteine levels has been associated with an increase in inflammation and oxidative stress in vascular endothelial cells as well as a decrease in endothelial nitric oxide production and bioavailability. Strong evidence suggests that oxidation plays a role in the process linking increased Hcy levels to atherosclerosis. To highlight the significance of this finding, it is necessary to mention that Vincent du Vigneaud was awarded the Nobel Prize in Chemistry in 1955 “For his work on biochemically important sulfur compounds, especially for the first synthesis of a polypeptide hormone”. 10 In addition to causing occlusion or constriction of capillaries, hyperhomocysteinemia inculcates direct damage to endothelial cells, which in turn causes hyperplasia of smooth muscle cells. Elevated homocysteine levels in the blood are positively associated with hypertension and an increased risk of cardiac complications. Higher blood homocysteine levels are associated with an increased risk of aspirin resistance. Because of this, many people believe that homocysteine is its own risk factor for coronary artery disease. While the vascular toxicity of hyperhomocysteinemia is well established, there is a lack of data on how it alone affects coronary artery disease in younger people, devoid of the combined and synergistic effects of other traditional risk factors. 11 Figure 1. Ischemic heart disease: a schematic depicting the pathophysiological mechanisms. 12 Figure 2. Structure of homocysteine. 13 Methods A total of 80 people were involved, with 40 serving as patients and 40 as controls. We included all cases and controls in the study who were either younger than 40 years or older than 25 years. Forty people served as controls and had no ischemic heart disease. The 40 patients served as cases with coronary angiographic evidence of moderate-to-severe stenosis in one or more main coronary arteries. A Performa was framed, and all relevant information of each performa was recorded. The procedure was described to the patient and written consent was obtained. A universal sampling technique is used for this purpose. To create a control group for comparison with the patient group, members were randomly selected from the general community. Both groups included patients of varying sex, ethnicity, geographical location, and socioeconomic status in their respective studies. Criteria for exclusion: Patients who were chosen for the study did not have any history of diabetes, myocardial infarction, angina, or autoimmune diseases, and they did not take any steroidal anti-inflammatory drugs or receive treatment for cancer. The two sets of patients were as follows. 1- The control group of forty patients with no ischemic heart disease. 2- The case group of forty patients with ischemic heart disease. Extraction was performed immediately after venous blood was collected from the participants’ forearms. Separated from the cycles of freezing and thawing, the specimens were kept at -20°C. Before centrifuging the mixture for 20 min, serum was left to coagulate. Ther liquid was then collected. Statistical Package for the Social Sciences (SPSS) was used for statistical analysis. Version 23 was updated. Data are presented as mean values with or without standard deviation (mean ± SD). The T test was used to compare parameters across the various study groups. In this study, to be considered statistically significant, the p-value must be less than or equal to 0.05. This study utilized the Human Homocysteine (Hcy) ELISA Kit. Result The participants in the case group had a mean age of 31.12±4 years and 40 participants in the control group had a mean age of 33.35±4.5 years. In the case group, there were 24(60%) males and 16(40%) females, while in the control group, there were 26(65%) males and 14(35%) females with a significant association between case and control and sex. Regarding age distribution, the majority of cases in group 17(42.5%) were between 25-29 years, 15(37.5) were between 30-34 years, and 8(20%) were between 35-39 years. In the control group, 17 patients (42.5%) were between 35-39 years, 12(30%) between 30-34 years, 8(20%) between 25-29 years, 2(5%) ≥ 40 years, and only 1(2.5%) between 20-24 years as shown in Table 1 . Table 1. Basic characteristics of case and control. Variable Frequency Percentage % Gender Case Male 24 60 Female 16 40 Control Male 26 65 Female 14 35 Age Case 20-24 0 0 25-29 17 42.5 30-34 15 37.5 35-39 8 20 ≥40 0 0 Control 20-24 1 2.5 25-29 8 20 30-34 12 30 35-39 17 42.5 ≥40 2 5 The mean homocysteine level in case group was 40.21±14.47 mmol/L and 9.23±2.41 mmol/L in control group with p value <0.001 as it shown in Table 2 . Table 2. The mean homocysteine difference between case and control. Clinical characteristics Mean±SD P value Homocysteine Mean (mmol/L) Case 40.21±14.47 <0.001 Control 9.23±2.41 The mean serum triglyceride levels in the case group were 118.42±14.145 mg/dl while 121.11±14.616 mg/dl in the control group (p = 0.412), as shown in Table 3 . Table 3. Serum Triglyceride mean difference between case and control. Clinical characteristics Mean±SD P value Triglyceride mg/dl Case 118.42±14.145 0.412 Control 121.11±14.616 The mean serum cholesterol level in the case group was 141.47±24.565 mg/dl, while in the control group was 156.31±19.017 mg/dl (p = 0.004), as shown in Table 4 . Table 4. Serum Cholesterol mean difference between case and control. Clinical characteristics Mean±SD P value Cholesterol mg/dl Case 141.47±24.565 0.004 Control 156.31±19.017 Regarding the homocysteine level and its association with sex, 20(50%) of male and 10(25%) of female had intermediate homocysteine levels, while 4(10%) of male and 6(15%) of female had mild homocysteine levels, as shown in Table 5 . Table 5. Severity of homocysteine level and its association with gender in case group. Gender Plasma homocysteine concentration mmol/L Mild (15-30) Intermediate (30-100) Sever >100 P value Male 4 (10%) 20 (50%) 0 24 0.136 Female 6 (15%) 10 (25%) 0 16 Total 10 30 0 40 Discussion The primary goal of the current investigation was to determine the function of homocysteine in cardiovascular disease. Although there have been significant attempts to lower the mortality rate of cardiovascular illnesses in recent decades, effective prevention and treatment strategies have not met expectations, especially for high-risk individuals. 14 Consequently, new risk factors for coronary artery disease (CAD) and their prevention have become the primary focus of contemporary research. Myocardial infarction (MI), heart failure, and stroke are outcomes of atherosclerosis, the most prevalent underlying pathology. When the arterial intima is continuously damaged by inflammation, it leads to arteriosclerosis, which is characterized by increased permeability to plasma, fibrosis, calcification of plaques, and deposition of plasma lipids. The idea that atherosclerotic disease is linked to high homocysteine levels was originally proposed more than 40 years ago because of the atherothrombotic mechanism that causes endothelial dysfunction. According to multiple studies, patients’ risks of cardiovascular disease and death are enhanced by 10% when their homocysteine levels are high. The main conclusion of this study was that hyperhomocysteinemia increases the risk of coronary artery disease (CAD) and myocardial infarction (MI) in the adult Iraqi population. Our findings demonstrated a markedly elevated homocysteine concentration in patients with myocardial infarction compared to healthy controls, suggesting a robust correlation between hyperhomocysteinemia and cardiovascular disease and its consequences, such as myocardial infarction. This confirms previous research linking elevated homocysteine levels to an increased risk of coronary heart disease in individuals who have suffered acute myocardial infarction. Further evidence linking homocysteine levels to an increased risk of coronary artery disease was found in research conducted by Schaffer and Al-Obaidi. 15 , 16 There is substantial evidence that increases in homocysteine cause damage to endothelial cells, decrease vascular flexibility, and alter the hemostasis process. Research has shown that high homocysteine levels are a cause of coronary artery disease (CAD), and other studies have shown that this new atherogenic risk factor might be a consequence of preclinical vascular illnesses. Traditional risk factors for coronary artery disease (CAD), such as hyperlipidemia, smoking, hypertension, and inflammation, may be amplified by high homocysteine levels. Research 17 found no association between hyperhomocysteinemia and coronary artery disease (CAD) in individuals devoid of hypertension, diabetes, and dyslipidemia. Recent research in the Middle East, particularly in the Kurdistan region and Iraq, has examined the association between blood total homocysteine levels and coronary artery disease (CAD), but has failed to identify any effects on other risk factors for cardiovascular disease. A study conducted by Al-Gazally et al. corroborated these findings 18 by investigating the prevalence of homocysteine in the Iraqi population and found that it was significantly higher in the groups affected by ischemic stroke and myocardial infarction, suggesting that it may serve as a standalone risk factor for coronary artery disease (CAD). Multiple Iranian studies 19 demonstrated that elevated homocysteine levels are a distinct determinant of an increased risk of coronary artery disease (CAD), as greater serum homocysteine levels were detected in patients with abnormal angiography than in the control group. Our findings demonstrate that pure hyperhomocysteinemia, in the absence of traditional risk factors, can have a harmful effect on the cardiovascular system, even in the absence of other risk factors. The results demonstrated that regardless of whether the patient had one or more main coronary arteries narrowed to a moderate to severe degree, all young patients with coronary artery disease had elevated homocysteine levels in their blood. It is critical to address hyperhomocysteinemia immediately, because it is a controllable risk factor. Reducing cardiovascular morbidity and mortality can be achieved through primary and secondary prevention efforts by focusing on this area. Conclusion Hyperhomocysteinemia increases the risk of cardiovascular thrombosis in younger patients with coronary artery disease. Recent evidence points to increased homocysteine plasma concentration as a novel, preventable risk factor for atherosclerotic vascular disease. There are several ways in which an increase in homocysteine concentration can cause vascular alterations, according to the available experimental data. More research is needed to put these results into context. Ethical considerations and consent The study was conducted based on the declaration of Baghdad University’s Ethical Committee, College of Medicine, and according to the Ministry of Health Ethical Policy (ethical permission letter No. 03-35 in 2024/9/17). Written informed consent was obtained from all participants before inclusion in the study. The study was conducted in accordance with the Helsinki Treaty. Data availability Underlying data Zenodo: Data of patients, https://doi.org/10.5281/zenodo.14012546 . 20 This project contains the following underlying data: • Data of patients.case.xlsx • Data of patients.control.xlsx Zenodo: Result of the correlation between plasma homocysteine and ischemic heart disease in young adult, https://doi.org/10.5281/zenodo.14171516 . 21 • Basic characteristics of patients.xlsx • Deference means of homocysteine between case and control.xlsx • Triglyceride.xlsx • cholestrole.xlsx • severity of homocysteine.xlsx Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). References 1. Sadeq A, Al Saffar H, Alabdali S: Inflammatory markers in patients who presented with acute coronary syndrome and history of COVID-19 infection: a cross-sectional study. F1000Res. 2022; 11 : 987. Publisher Full Text 2. Shah H, Jan MU, Altaf A, et al. : Correlation of hyper-homocysteinemia with coronary artery disease in absence of conventional risk factors among young adults. J. Saudi Heart Assoc. 2018; 30 (4): 305–310. PubMed Abstract | Publisher Full Text | Free Full Text 3. Amen SO, Baban ST: Association of Hyperhomocysteinemia with Acute Myocardial Infarction in Kurdish Patients. IOP Conference Series: Materials Science and Engineering. IOP Publishing; 2019. 4. Altaei OA, Al-Sharifi AN: Prevalence of peripheral arterial disease among patients with acute coronary syndrome, a sample of Iraqi patients in Al-Yarmook Teaching Hospital 2016. J. Fac. Med. Baghdad. 2021; 63 (2): 50–56. Publisher Full Text 5. Nedelcu C, Ionescu M, Pantea-Stoian A, et al. : Correlation between plasma homocysteine and first myocardial infarction in young patients: Case-control study in Constanta County, Romania. Exp. Ther. Med. 2021; 21 (1): 101. PubMed Abstract | Publisher Full Text 6. Zaric BL, Obradovic M, Bajic V, et al. : Homocysteine and hyperhomocysteinaemia. Curr. Med. Chem. 2019; 26 (16): 2948–2961. Publisher Full Text 7. Kumar A, Palfrey HA, Pathak R, et al. : The metabolism and significance of homocysteine in nutrition and health. Nutr. Metab. 2017; 14 : 1–12. 8. Azzini E, Ruggeri S, Polito A: Homocysteine: its possible emerging role in at-risk population groups. Int. J. Mol. Sci. 2020; 21 (4): 1421. PubMed Abstract | Publisher Full Text | Free Full Text 9. Hannibal L, Blom HJ: Homocysteine and disease: causal associations or epiphenomenons? Mol. Asp. Med. 2017; 53 : 36–42. Publisher Full Text 10. Dawood AS, Mohammed AJ: Relationship between Folate, B12 and Homocysteine levels and Obstetrical Outcomes in Preterm Premature Rupture of Membrane. J. Fac. Med. Baghdad. 2024; 66 (1): 18–25. Publisher Full Text 11. Poddar R: Hyperhomocysteinemia is an emerging comorbidity in ischemic stroke. Exp. Neurol. 2021; 336 : 113541. PubMed Abstract | Publisher Full Text | Free Full Text 12. Severino P, et al. : Ischemic heart disease pathophysiology paradigms overview: from plaque activation to microvascular dysfunction. Int. J. Mol. Sci. 2020; 21 (21):8118. PubMed Abstract | Publisher Full Text | Free Full Text 13. Xiao Q, et al. : High performance liquid chromatography assay of cysteine and homocysteine using fluorosurfactant functionalized gold nanoparticles as postcolumn resonance light scattering reagents. J. Chromatogr. A. 2013; 1274 :145–150. PubMed Abstract | Publisher Full Text 14. Hussein BJ, Abdul-Qahar ZH, Abbas NN: Evaluation of serum apelin in acute coronary syndrome patients. J. Fac. Med. Baghdad. 2015; 57 (4): 325–327. Publisher Full Text 15. Schaffer A, Verdoia M, Cassetti E, et al. : Relationship between homocysteine and coronary artery disease. Results from a large prospective cohort study. Thromb. Res. 2014; 134 (2): 288–293. PubMed Abstract | Publisher Full Text 16. Al-Obaidi MK, Stubbs PJ, Collinson P, et al. : Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes. J. Am. Coll. Cardiol. 2000; 36 (4): 1217–1222. PubMed Abstract | Publisher Full Text 17. Donner MG, Klein GK, Mathes PB, et al. : Plasma total homocysteine levels in patients with early-onset coronary heart disease and a low cardiovascular risk profile. Metabolism. 1998; 47 (3): 273–279. PubMed Abstract | Publisher Full Text 18. Al-Gazally ME, Al-Saadi AH, Radeef AH: Effect of homocysteine on ischemic stroke and myocardial infarction in Iraqi population. Int. J. Pharmtech Res. 2015; 8 (10): 139–145. 19. Mirdamadi A, Farzamnia H, Varzandeh P, et al. : Association between serum homocysteine concentration with coronary artery disease in Iranian patients. ARYA Atheroscler. 2011; 7 (2): 63–67. PubMed Abstract 20. H.M pz: Data of Patients. zenodo. 2024. Publisher Full Text 21. H.M pz: Result of correlation between plasma homocysteine and ischemic heart disease in young adult. zenodo. 2024. Publisher Full Text Comments on this article Comments (1) Version 1 VERSION 1 PUBLISHED 04 Dec 2024 Reader Comment 30 Oct 2025 huda Majeed , Biology, Mustansiriyah University, Baghdad, Iraq 30 Oct 2025 Reader Comment "I would like to express my deepest gratitude and profound admiration for the outstanding research conducted by Zainab Hassan Muslem, Samara M. Ali, and Amal Noori Al Marayati on "Correlation ... Continue reading "I would like to express my deepest gratitude and profound admiration for the outstanding research conducted by Zainab Hassan Muslem, Samara M. Ali, and Amal Noori Al Marayati on "Correlation between plasma homocysteine and ischemic heart disease in young adults." This work is a groundbreaking contribution to our understanding of non-traditional risk factors driving ischemic heart disease, particularly in young adults. What makes this research truly remarkable is its unique focus on the link between elevated homocysteine levels and coronary artery disease in young adults, filling a critical gap in existing data. The study's conclusive finding that hyperhomocysteinemia is positively associated with coronary artery disease, even in the absence of traditional risk factors, strongly supports the notion of homocysteine as an independent risk factor. The high methodological quality of the research, demonstrated through its case-control design and careful exclusion of patients with other traditional risk factors, significantly enhances the credibility of its findings. In summary, this research is meticulously executed and highly compelling, offering an important clinical perspective on the need to screen and monitor homocysteine levels as an emerging and independent risk factor, particularly in cardiac risk assessment for young individuals. I commend the researchers for their exceptional work and dedication. This achievement is a testament to their expertise and commitment to advancing our understanding "I would like to express my deepest gratitude and profound admiration for the outstanding research conducted by Zainab Hassan Muslem, Samara M. Ali, and Amal Noori Al Marayati on "Correlation between plasma homocysteine and ischemic heart disease in young adults." This work is a groundbreaking contribution to our understanding of non-traditional risk factors driving ischemic heart disease, particularly in young adults. What makes this research truly remarkable is its unique focus on the link between elevated homocysteine levels and coronary artery disease in young adults, filling a critical gap in existing data. The study's conclusive finding that hyperhomocysteinemia is positively associated with coronary artery disease, even in the absence of traditional risk factors, strongly supports the notion of homocysteine as an independent risk factor. The high methodological quality of the research, demonstrated through its case-control design and careful exclusion of patients with other traditional risk factors, significantly enhances the credibility of its findings. In summary, this research is meticulously executed and highly compelling, offering an important clinical perspective on the need to screen and monitor homocysteine levels as an emerging and independent risk factor, particularly in cardiac risk assessment for young individuals. I commend the researchers for their exceptional work and dedication. This achievement is a testament to their expertise and commitment to advancing our understanding Competing Interests: no competing interests Close Report a concern Comment ADD YOUR COMMENT Author details Author details 1 Department of Pharmacology, College of Medicine, University of Baghdad, Baghdad, Iraq 2 Department of Pharmacology, College of Medicine, University of Baghdad, Baghdad, Iraq 3 Iraqi Center for Heart Diseases, Baghdad, Iraq Zainab Hassan Muslem Roles: Conceptualization, Investigation, Methodology, Resources, Software, Visualization Samara M.Ali Roles: Investigation, Methodology, Project Administration, Supervision, Visualization Amal Noori Al Marayati Roles: Methodology, Project Administration, Supervision Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 04 Dec 2024, 13:1477 https://doi.org/10.12688/f1000research.158499.1 Copyright © 2024 Hassan Muslem Z et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Hassan Muslem Z, M.Ali S and Al Marayati AN. Correlation between plasma homocysteine and ischemic heart disease in young Adults [version 1; peer review: awaiting peer review] . 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Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Comments on this article Comments (1) Version 1 VERSION 1 PUBLISHED 04 Dec 2024 Reader Comment 30 Oct 2025 huda Majeed , Biology, Mustansiriyah University, Baghdad, Iraq 30 Oct 2025 Reader Comment "I would like to express my deepest gratitude and profound admiration for the outstanding research conducted by Zainab Hassan Muslem, Samara M. Ali, and Amal Noori Al Marayati on "Correlation ... Continue reading "I would like to express my deepest gratitude and profound admiration for the outstanding research conducted by Zainab Hassan Muslem, Samara M. Ali, and Amal Noori Al Marayati on "Correlation between plasma homocysteine and ischemic heart disease in young adults." This work is a groundbreaking contribution to our understanding of non-traditional risk factors driving ischemic heart disease, particularly in young adults. What makes this research truly remarkable is its unique focus on the link between elevated homocysteine levels and coronary artery disease in young adults, filling a critical gap in existing data. The study's conclusive finding that hyperhomocysteinemia is positively associated with coronary artery disease, even in the absence of traditional risk factors, strongly supports the notion of homocysteine as an independent risk factor. The high methodological quality of the research, demonstrated through its case-control design and careful exclusion of patients with other traditional risk factors, significantly enhances the credibility of its findings. In summary, this research is meticulously executed and highly compelling, offering an important clinical perspective on the need to screen and monitor homocysteine levels as an emerging and independent risk factor, particularly in cardiac risk assessment for young individuals. I commend the researchers for their exceptional work and dedication. This achievement is a testament to their expertise and commitment to advancing our understanding "I would like to express my deepest gratitude and profound admiration for the outstanding research conducted by Zainab Hassan Muslem, Samara M. Ali, and Amal Noori Al Marayati on "Correlation between plasma homocysteine and ischemic heart disease in young adults." This work is a groundbreaking contribution to our understanding of non-traditional risk factors driving ischemic heart disease, particularly in young adults. What makes this research truly remarkable is its unique focus on the link between elevated homocysteine levels and coronary artery disease in young adults, filling a critical gap in existing data. The study's conclusive finding that hyperhomocysteinemia is positively associated with coronary artery disease, even in the absence of traditional risk factors, strongly supports the notion of homocysteine as an independent risk factor. The high methodological quality of the research, demonstrated through its case-control design and careful exclusion of patients with other traditional risk factors, significantly enhances the credibility of its findings. In summary, this research is meticulously executed and highly compelling, offering an important clinical perspective on the need to screen and monitor homocysteine levels as an emerging and independent risk factor, particularly in cardiac risk assessment for young individuals. I commend the researchers for their exceptional work and dedication. This achievement is a testament to their expertise and commitment to advancing our understanding Competing Interests: no competing interests Close Report a concern Comment ADD YOUR COMMENT keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status AWAITING PEER REVIEW Comments on this article All Comments (1) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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