Ischemia-modified albumin: Is it a promising marker in acute coronary syndrome?

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Udaya Ralapanawa, Ramiah Sivakanesan, Sampath Tennakoon, Parackrama Karunathilake This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4120076/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Aug, 2024 Read the published version in BMC Cardiovascular Disorders → Version 1 posted 13 You are reading this latest preprint version Abstract Background Acute coronary syndrome (ACS) is a type of coronary heart disease (CHD), which is responsible for one-third of total deaths in people older than 35 years. Even though cardiac troponin is the gold standard for myocardial necrosis it is blind for ischemia without necrosis. Studies demonstrate that IMA is more sensitive in diagnosing ischemic chest pain compared to cardiac troponin T and electrocardiogram, and its combination with these tests significantly increases the sensitivity for diagnosing unstable angina, NSTEMI, or STEMI, with high positive and negative predictive values, making it a valuable tool for ruling out ACS in patients with inconclusive diagnoses in the emergency department. Methods and Findings This prospective cohort study, conducted at the Teaching Hospital, Peradeniya, Sri Lanka, from 2015 to 2019, investigated ischemia-modified albumin (IMA) levels in 330 acute coronary syndrome (ACS) patients. Excluding those with various chronic conditions and those on specific medications, serum IMA was analysed using a colorimetric assay based on cobalt (II) binding to human serum albumin affected by myocardial ischemia. The study found a significant right skew in IMA distribution, confirming its non-normality. No overall significant gender-based difference in IMA levels was observed, though within the younger age group (< 59 years), males exhibited higher IMA concentrations than females. Ethnicity and age appeared to have limited impact on IMA levels. Notably, a significant gender difference in IMA levels was found in obese patients, suggesting physiological differences in response to obesity. The study also revealed higher IMA concentrations in NSTEMI and STEMI patients compared to those with unstable angina. A significant positive correlation between serum IMA levels and lipid profiles, particularly LDL-cholesterol, was established, indicating a link with dyslipidaemia. Conclusion The findings suggest the potential of IMA as a multifaceted biomarker in ACS diagnosis and prognosis, emphasizing the need for personalized medicine approaches and highlighting the role of lipid management in ACS risk reduction. Ischemia-Modified Albumin (IMA) Acute Coronary Syndrome (ACS) Biomarkers Myocardial Ischemia Lipid Profile Gender Differences Dyslipidaemia Figures Figure 1 INTRODUCTION Acute coronary syndrome (ACS) refers to a range of cardiac conditions, including ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina. This syndrome falls under the category of ischemic heart disease (IHD), also known as coronary heart disease (CHD). It is responsible for one-third of all deaths in individuals over the age of 35 ( 1 ). The economic burden of ACS is significant, encompassing expenses related to hospitalizations, treatments, interventional procedures, follow-up clinic appointments, emergency visits, and prescribed medications ( 2 ). In the United States, IHD accounts for roughly 1-1.5% of the Gross Domestic Product (GDP). In contrast, in low and middle-income countries, the per capita health expenditure specific to IHD care constitutes 10% of the total healthcare expenditure in each respective country ( 2 ). Evaluation of patients presenting with symptoms suggestive of ACS remains a diagnostic challenge at the emergency department (ED). Most of the patients presenting to the ED have symptoms related to non-cardiac and often mild ailment that does not require emergency treatment or hospitalization ( 2 ). Much research has focused on the search for ideal biological markers for the rapid detection of cardiac cell injuries. Currently, the biomarker most widely used for diagnosing acute coronary syndrome is cardiac troponin. Even though cardiac troponin is the gold standard for myocardial necrosis it is blind for ischemia without necrosis ( 3 ). The appearance of symptomatic cardiac ischemia occurs before myocardial necrosis, and a biomarker that reflects ischemia, rather than necrosis itself, would be conceptually appealing and could provide added value to troponin testing. Several candidate biomarkers to detect cardiac ischemia have recently been evaluated. Ischaemia Modified Albumin (IMA), B-type natriuretic peptide, N-terminal pro-BNP, whole blood choline, unesterified free fatty acids, malondialdehyde, low-density lipoprotein, and myeloperoxidase were experimented as cardiac ischemia biomarkers ( 3 ). Arriving at a conclusive diagnosis for individuals with chest pain or other indicators hinting at ACS is frequently a lengthy, challenging, and costly process. Recent studies have pinpointed IMA as a valuable biomarker for detecting ischemia, not infarction ( 4 ). Furthermore, the US Food and Drug Administration has already approved the use of IMA in diagnosing suspected myocardial ischemia ( 5 ). Ischaemia Modified Albumin IMA is a form of human serum albumin in which the N-terminal amino acids have been modified by ischemia ( 4 ). Because of this modification, the affinity of plasma albumin to bind to heavy metal ions like cobalt, nickel, and copper is reduced ( 4 ). IMA is approximately 1–2% of the circulating albumin and increases to 6–8% in patients experiencing ischemia ( 4 ). The estimation of IMA is simple and can be even done in laboratories with very basic facilities or say even at the bedside helping emergency physicians to decide ( 4 ). When interpreting IMA results, it is important to remember that increased IMA reading can be seen in patients with stroke, end-stage renal failure, liver disease, some neoplasms, sepsis and patients who have undergone direct current cardioversion; therefore, it is not specific to cardiac ischemia ( 4 ). However, IMA can be used for early diagnosis of ACS, exclusion of ACS, and risk stratification of ACS ( 4 ). It is detected within 6–10 minutes after the onset of cardiac ischemia, remains elevated for up to several hours, and returns to normal 8–12 hours after the onset of cardiac ischemia ( 4 ). This study aims to further elucidate the role of IMA as a rapid, reliable biomarker in the early detection of Acute Coronary Syndrome, potentially revolutionizing the diagnostic process in emergency medical settings. METHODOLOGY Study Design This prospective cohort study was conducted among ACS patients admitted to Teaching Hospital, Peradeniya (THP), Sri Lanka. The study population included all ACS patients presenting to the Professorial Medical Unit at THP from 2015 to 2019. Inclusion Criteria All patients clinically diagnosed with ACS after a detailed history and examination at the time of presentation were enrolled upon obtaining informed written consent. Typical chest pain associated with ACS was defined as squeezing pain over the precordial area radiating to the neck, arm, back, or epigastric region, accompanied by sweating, nausea, vomiting, or syncope, unresponsive to rest and sublingual nitro-glycerine. Exclusion Criteria Excluded from the study were patients who did not provide consent, as well as those with diabetes mellitus, neoplastic diseases, concomitant inflammatory diseases (such as infections and autoimmune disorders), major depression, liver and kidney diseases, recent major surgical procedures, myocardial infarction or angina episodes within the 48 hours before hospitalization, individuals who had undergone coronary angioplasty or bypass surgery, and those with valvular, myocardial, or pericardial diseases. Patients taking antioxidant drugs such as beta-blocking agents (carvedilol, nebivolol), angiotensin-converting-enzyme inhibitors (captopril), statins, diuretics, vitamins, alcohol, and smoking were also excluded from the study. Data and Sample Collection All patients presenting with ACS symptoms to the Professorial Medical Unit at THP between December 1, 2015, and December 1, 2019, underwent comprehensive assessments by investigators, including detailed history-taking, blood pressure measurement, body mass index (BMI) assessment, ECG, and routine blood tests. Blood samples were collected from ACS patients upon arrival at the preliminary care unit of the Professorial Medical Unit, THP. Serum samples were obtained after clotting, within 30 minutes, by centrifugation of the blood samples. These samples were stored at -80º C until analysis. All serum samples were analysed at the Department of Biochemistry, Faculty of Medicine, University of Peradeniya, Peradeniya. Sample Analysis Serum samples separated from blood samples were analysed for IMA. The assay is based on the premise that myocardial ischemia causes changes in human serum albumin (HSA), leading to a reduction in the binding of exogenous cobalt (II). Ischemia Modified Albumin Assay Principle The assay is based on the premise that myocardial ischemia causes changes in human serum albumin (HSA) causing a reduction in binding of exogenous cobalt (II). The concentration of ischemia-modified albumin can be determined by the addition of a known amount of Cobalt (II) to serum and measurement of the unbound cobalt (II) by colorimetric assay using dithiothreitol (DTT). An inverse relationship thus exists between the level of albumin-bound cobalt and the intensity of the colour formation. Reagents Cobalt chloride 1 g/L Dithiothreitol 1.5 g/L Normal saline Procedure 1. Serum (200 µL) was mixed with 50 µL of a solution of cobalt chloride (1 g/L), followed by 10 minutes of vigorous mixing. 2. DTT (50 µl, 1.5 g/L) was added and mixed. 3. After 2 minutes of incubation, 1.0 ml of saline was added. 4. The absorbance of the assay mixture was measured at 470 nm. The blank was prepared similarly, excluding DTT. The IMA activity was calculated as the absorbance value obtained by subtracting the blank from the test. An inverse relationship thus exists between the level of albumin-bound cobalt and the intensity of the colour formation, which was used in the quantification of the IMA level. RESULTS Serum Ischemia Modified Albumin (IMA) Distribution The IMA concentration in 330 patients presenting with ACS was found to be non-normally distributed, exhibiting a pronounced right skew (skewness statistic: 0.496). The Shapiro-Wilk test confirmed the non-normality with a p-value of less than 0.001. The average serum IMA concentration across the cohort was 0.252 absorbance units (AU) with a standard deviation of 0.123 AU, and the values ranged from a minimum of 0.008 AU to a maximum of 0.67 AU. The distribution's skewness is both visually depicted in Fig. 1 and statistically corroborated, with slight deviations from normality observed in the Q-Q plot and the presence of three significant outliers. IMA Concentration: Age and Gender Interaction Table 1 displays the summary of IMA concentrations stratified by age and gender, presenting mean values, standard deviations, and ranges. Overall, 330 patients were evaluated, with no significant difference in IMA concentrations between the total male and female cohorts (p = 0.063). When stratifying by age, there was no significant difference in IMA levels between the younger group (age < 59 years) and the older group (age ≥ 59 years) (p = 0.829). However, a gender-based analysis within the younger age group revealed that males had significantly higher IMA concentrations compared to females (p = 0.033). Table 1 Summary of IMA concentrations, dissected by age and gender, highlighting mean, standard deviation, and range Age (years) Total Males Females N Mean ± SD (Absorbance units) N Mean ± SD (Absorbance units) N Mean ± SD (Absorbance units) P value* Total 330 0.252 ± 0.123 (0.008–0.67) 170 0.262 ± 0.120 (0.039–0.58) 160 0.236 ± 0.127 (0.008–0.67) 0.063 < 59 160 0.253 ± 0.129 (0.008–0.67) 100 0.270 ± 0.128 (0.008–0.67) 60 0.225 ± 0.129 (0.042–0.62) 0.033 ≥ 59 170 0.251 ± 0.117 (0.039–0.58) 107 0.254 ± 0.113 (0.047–0.49) 63 0.245 ± 0.126 (0.039–0.58) 0.66 *p values in the column are between genders Ischemia-Modified Albumin Concentrations Across Ethnicities The study found no significant variance in IMA concentrations among the Sinhalese, Tamils, and Moors, with p = 0.217, indicating comparable mean levels across these groups. However, the distribution characteristics differed, particularly for Sinhalese patients, who exhibited a distinct skewness in their results. Outlier analysis revealed minimal ethnic disparities, with Sinhalese having a slightly higher percentage (1.1%) compared to Tamils (3.6%) and none in Moors. Ischemia-Modified Albumin Concentrations Across Different BMI Categories Table 2 presents the IMA concentration in ACS patients stratified by BMI categories and gender. In the underweight category, males (N = 5) exhibited a mean IMA concentration of 0.221 ± 0.063 AU, while females (N = 4) showed a mean of 0.273 ± 0.180 AU, with no significant difference between genders (p = 0.562). Normal-weight males (N = 71) had a mean IMA level of 0.261 ± 0.114 AU compared to 0.281 ± 0.142 AU in females (N = 37), which was not statistically significant (p = 0.443). The overweight male group (N = 97) showed a mean of 0.256 ± 0.133 AU, while the female group (N = 50) had a mean of 0.214 ± 0.112 AU; this difference approached but did not reach, statistical significance (p = 0.056). Notably, in the obese category, a significant gender difference was observed with males (N = 34) having a mean IMA concentration of 0.284 ± 0.1 AU and females (N = 32) having a mean of 0.213 ± 0.115 AU (p = 0.009). Table 2 Ischemia modified albumin concentration of patients according to Body Mass Index and gender BMI categories Ischemia-modified albumin concentration (Absorbance units) P value Males Females N Mean ± SD N Mean ± SD Underweight 5 0.221 ± 0.063 (0.122–0.279) 4 0.273 ± 0.180 (0.104–0.49) 0.562 Normal weight 71 0.261 ± 0.114 (0.067–0.67) 37 0.281 ± 0.142 (0.039–0.62) 0.443 Overweight 97 0.256 ± 0.133 (0.008–0.64) 50 0.214 ± 0.112 (0.079–0.554) 0.056 Obesity 34 0.284 ± 0.1 (0.066–0.463) 32 0.213 ± 0.115 (0.042–0.405) 0.009* Values in parentheses are minimum and maximum; P values are for mean comparison between genders Clinical Conditions and IMA Concentrations Table 3 details the IMA concentrations with different clinical presentations of ACS. For patients with Unstable Angina (N = 137), the mean IMA concentration was 0.221 ± 0.119 AU, with a 95% Confidence Interval (CI) for the mean ranging from 0.201 to 0.242 AU, and values spanning from 0.039 AU to 0.64 AU. In the NSTEMI group (N = 100), the mean IMA level was higher at 0.284 ± 0.115 AU, with a 95% CI of 0.261 AU to 0.306 AU, and a range from 0.051 AU to 0.67 AU. Patients with STEMI (N = 93) had a mean IMA concentration of 0.263 ± 0.129 AU, with a 95% CI from 0.236 to 0.289 AU, and values ranging between 0.008 AU and 0.64 AU. According to Table 3 results STEMI and NSTEMI patients show significantly higher IMA concentrations compared to the Unstable Angina group. Table 3. Ischemia modified albumin concentration of patients according to the clinical conditions Ischemia-Modified Albumin Concentration in ACS Patients Versus Control Subjects The study demonstrated a statistically significant increase in Ischemia Modified Albumin (IMA) concentrations among ACS patients compared to control subjects, with mean levels of 0.252 ± 0.123 AU and 0.164 ± 0.101 AU, respectively (p < 0.001). Correlations of IMA Concentrations with Lipid Profile Our study investigated the relationship between serum IMA levels and lipid profile components, which include Total Cholesterol, LDL cholesterol, HDL cholesterol, and VLDL cholesterol. The bivariate correlation analysis indicated significant findings as shown in Table 4 . For the total population (N = 97), serum IMA showed a significant positive correlation with Total Cholesterol (r = 0.262, p = 0.009) and LDL-Cholesterol (r = 0.280, p = 0.006), suggesting that higher levels of these lipids are associated with increased modifications to albumin, potentially due to ischemic events. However, the correlations with HDL-Cholesterol and VLDL-Cholesterol were not significant (r = 0.103, p = 0.33 and r = 0.184, p = 0.124, respectively). When stratified by gender, different patterns emerged. In females (N = 45), the correlation between IMA levels and Total Cholesterol remained significant (r = 0.401, p = 0.002), but no significant correlation was found with LDL-cholesterol (r = 0.171, p = 0.278). For males (N = 52), significant correlations were found with both Total Cholesterol (r = 0.317, p = 0.018) and LDL-Cholesterol (r = 0.361, p = 0.009), while the correlations with HDL-Cholesterol and VLDL-Cholesterol remained non-significant. Table 4 Bivariate correlation analysis between serum concentrations of Ischemia modified albumin and Lipids Lipids Bivariate correlation Serum Ischemia Modified Albumin and Lipids Total Females Males N r p N r p N r p Total cholesterol 97 0.262 0.009 42 0.201 0.202 55 0.317 0.018 LDL- Cholesterol 94 0.28 0.006 42 0.171 0.278 52 0.361 0.009 HDL- Cholesterol 91 -0.103 0.33 39 -0.128 0.439 52 -0.056 0.692 VLDL- Cholesterol 71 0.184 0.124 28 0.253 0.194 43 0.144 0.357 N = Number of patients, r = Pearson’s correlation, p = p value A multiple linear regression analysis was run to predict serum IMA concentration from age, gender, ethnicity, BMI, TC, LDL-C, VLDL-C, and HDL-C. The most significant predictor of serum IMA concentrations was low-density lipoprotein cholesterol (LDL-C), as substantiated by multiple linear regression analysis (Beta coefficient = 0.393, p = 0.001). The model accounted for 15.5% of the variance in IMA levels, emphasizing LDL-C's role in ischemic stress. DISCUSSION The distribution of IMA concentrations in this cohort of 330 ACS patients suggests a pattern that deviates from normality, indicated by a significant right skew. This finding is consistent with the notion that IMA levels increase in response to ischemic stress, which may not be uniformly experienced across the patient population ( 6 ). The variability in IMA concentrations could reflect the heterogeneous nature of ACS presentations, ranging from unstable angina to various forms of myocardial infarctions. The analysis of IMA concentrations across different age and gender demographics within our ACS patient cohort presents intriguing findings. The lack of a significant difference in IMA levels between the aggregated male and female groups suggests that, overall, gender may not play a decisive role in IMA variability among ACS patients. However, the observed gender disparity in IMA levels within the younger age group (< 59 years) is of particular interest. The higher IMA concentrations in males compared to females in this age bracket may be indicative of biological differences in the pathophysiology of ACS or differences in the acute response to ischemic stress ( 7 ). Anyhow this contrasts the findings of Stea et al. where men aged 45 years showed significantly lower IMA concentrations compared to women aged 45 and fertile and menopausal women ( 8 ). This could also reflect gender-specific variations in myocardial damage or differences in risk factors prevalence such as smoking, physical inactivity, or occupational stress, which are known to be more common among younger males ( 9 ). The absence of a significant age-based difference in IMA levels could suggest that the process of ischemia-related albumin modification is not substantially affected by age. Alternatively, it could be that the compensatory mechanisms against ischemia in albumin are preserved across age groups. Prior studies have indicated that age may not be a major determinant in the levels of IMA which appears to align with our findings ( 8 ). The significant gender difference in the younger age group but not in the older group may also raise questions about the influence of hormones, such as oestrogen, which has been found to have cardioprotective effects and may influence biomarker levels ( 10 ). The analysis of IMA concentrations across BMI categories within this ACS patient cohort revealed gender-specific variations, particularly within the obese group. The significant difference in IMA levels between obese males and females (p = 0.009) might suggest that gender-related physiological differences in adiposity and inflammatory responses to obesity could contribute to divergent IMA concentrations. It is well-documented that obesity is associated with a chronic low-grade inflammatory state, which could potentially influence the modification of albumin in response to ischemic stress and thus alter IMA levels ( 11 ). The absence of significant differences in the underweight and normal weight categories might indicate that at these BMI levels, other factors such as acute illness severity, the extent of myocardial ischemia, or individual patient management practices have a more pronounced impact on IMA levels than adiposity. The near-significant difference observed in the overweight category suggests a possible trend that warrants further investigation with a larger sample size to confirm if overweight status has a differential impact on IMA levels between genders. The pronounced gender difference in the obese category raises questions about the role of sex hormones, differential fat distribution patterns, and metabolic profiles that are known to vary between obese men and women ( 12 ). The clinical implications of these observations are particularly relevant when considering the use of IMA for diagnostic or prognostic purposes in ACS. The significant gender difference in IMA concentrations among obese patients suggests that gender-specific reference ranges might be necessary to improve the biomarker's diagnostic accuracy. Moreover, these findings reinforce the need for personalized medicine approaches considering patient demographics and comorbidities when interpreting biomarker levels. Future studies should aim to explore these relationships in more diverse populations and investigate the mechanisms underlying the gender differences in IMA levels among obese individuals. The assessment of IMA concentrations across varying clinical conditions of ACS provides valuable insights into its potential as a differential biomarker. The elevated IMA levels in NSTEMI and STEMI patients, compared to those with Unstable Angina, are particularly noteworthy. This could imply a more pronounced ischemic insult in NSTEMI and STEMI, as these conditions are typically associated with more substantial myocardial damage ( 13 ). The clinical application of these findings could be significant. Elevated IMA concentrations in NSTEMI and STEMI patients might facilitate early and more accurate diagnosis, particularly in ambiguous cases. It could also aid in distinguishing between NSTEMI and Unstable Angina, potentially influencing the urgency and type of intervention. The present study's findings corroborate previous research indicating elevated levels of IMA in ACS patients, supporting its potential as a diagnostic biomarker. Comparable to Hazini et al. (2015) who investigated IMA levels in Turkey, our study observed a significant increase in serum IMA concentration in ACS patients compared to healthy controls. While Hazini et al. reported mean serum IMA levels of 0.527 ± 0.08 in patients and 0.347 ± 0.05 in controls, the direct comparison is hindered by unspecified units ( 14 ). Nonetheless, the trend of elevated IMA in patient populations aligns with our observations, suggesting a consistent biomarker presence across different cohorts. Furthermore, Bhagavan et al. (2003) identified a notable differentiation in absorbance units between myocardial ischemic individuals and non-myocardial ischemic ones, with means of 0.63 ± 0.25 and 0.43 ± 0.10, respectively, a finding that is echoed in our results ( 15 ). This consistency across studies conducted over different periods and populations underscores the reliability of IMA as a biomarker for myocardial ischemia. The prognostic value of IMA extends beyond diagnosis, as illustrated by Dominguez-Rodriguez et al. (2009), who demonstrated a significant association between serum IMA levels and ST-segment resolution post-mechanical reperfusion in STEMI patients ( 16 ). Moreover, they found that IMA levels could serve as a predictor of left ventricular dysfunction, as further supported by their 2008 study which linked higher IMA concentrations with severe left ventricular impairment indicated by higher Killip classes ( 16 ). Cumulatively, these studies bolster the proposition that IMA serves as a sensitive marker for oxidative stress and myocardial injury ( 14 , 15 ). Given the predictive value of IMA concerning ST-segment resolution and its correlation with left ventricular function, it emerges as a multifaceted biomarker with potential utility in both the diagnosis and prognosis of ACS ( 16 ). Considering these findings, it becomes imperative to conduct further research on the role of IMA in ACS within the global population. Such studies could solidify the role of IMA as an oxidative stress marker and its effectiveness in the early detection of ACS. Moreover, considering the hereditary aspects of myocardial infarction, screening for IMA levels in individuals with a family history of cardiac events may prove to be a valuable preventive measure. The relationship between IMA and lipid fractions has been a subject of research with variable results. In the current study, the significant positive correlation found between IMA and total cholesterol, as well as LDL-cholesterol, aligns with previous findings suggesting that elevated IMA levels may be associated with dyslipidaemia, which is a recognized risk factor for atherosclerosis and subsequently ACS ( 17 , 18 ). Interestingly, the correlation seems to be more pronounced in the male subgroup, which could suggest a gender-specific interaction between lipid metabolism and ischemic modifications to albumin. This is particularly notable in the context of LDL-cholesterol, known to be atherogenic, and its higher correlation with IMA in males could point towards a more substantial role of LDL-related oxidative stress in men ( 19 ). Our analysis revealed a significant association between LDL-C and serum IMA concentrations, underscoring the pivotal role of lipids in ischemic stress. The Beta coefficient of 0.393 with a p-value of 0.001 in our multiple linear regression model indicates that LDL-C is a robust predictor of IMA levels. This is consistent with the hypothesis that atherogenic lipoproteins contribute to endothelial dysfunction and subsequent ischemic events, a relationship that has been corroborated by other studies ( 20 , 21 ). Our findings bear clinical implications. They suggest that monitoring serum IMA concentrations could be an adjunct strategy in assessing the ischemic risk associated with dyslipidaemia. This is particularly relevant considering that current guidelines emphasize LDL-C management as a primary target for cardiovascular risk reduction ( 22 ). Conclusion This study on IMA levels in ACS patients reveals that IMA concentrations are influenced by various demographic factors, but not uniformly across patients. While gender does not significantly impact IMA levels overall, notable differences are observed in specific subgroups, such as higher levels in younger males. This suggests potential biological and lifestyle influences on IMA variability. Age appears to have a limited effect on IMA levels, indicating possible consistency in ischemia-related albumin modification across age groups. Furthermore, the study highlights significant gender-specific differences in IMA levels in obese patients, implying the influence of physiological differences in response to obesity. These findings underscore the potential of IMA as a diagnostic and prognostic biomarker in ACS, suggesting the need for personalized approaches considering patient demographics and comorbidities. Additionally, the study's correlation between IMA levels and lipid profiles, particularly LDL-cholesterol, highlights the importance of lipid management in ACS risk reduction, pointing to the multifaceted role of IMA in ACS management. Declarations Ethics approval and consent to participate The ethical approval was obtained from the Ethical Review Committee, Faculty of Medicine, University of Peradeniya, Sri Lanka. The Committee granted approval for the research protocol. In compliance with the Declaration of Helsinki, all participants provided written informed consent. Consent for Publication Not applicable Availability of Data and Materials The datasets generated and analyzed during the current study are under the control of the authors and can be made available upon reasonable request. Requests for access to the data should be directed to Prof. Udaya Ralapanawa, who will ensure that any data released does not compromise participant confidentiality. Competing Interests The authors declare that there are no competing interests in relation to this work. Funding This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contributions UR and RS were instrumental in conceptualizing and designing the study. UR, RS, and PK conducted the data collection, while ST was responsible for data analysis. UR, RS, and PK took an active role in drafting the manuscript and critically revising it to enhance its intellectual content. 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Correlations between Oxidative Stress and Blood Lipids Are Stronger in Men than Women. Vol. 170. 2020. Adams MR, Kinlay S, Blake GJ, Orford JL, Ganz P, Selwyn AP. Atherogenic Lipids and Endothelial Dysfunction: Mechanisms in the Genesis of Ischemic Syndromes. https://doi.org/101146/annurev.med511149 [Internet]. 2003 Nov 28 [cited 2023 Nov 13];51:149–67. Available from: https://www.annualreviews.org/doi/abs/10.1146/annurev.med.51.1.149 Stancu CS, Toma L, Sima A V. Dual role of lipoproteins in endothelial cell dysfunction in atherosclerosis. Cell and Tissue Research 2012 349:2 [Internet]. 2012 May 18 [cited 2023 Nov 13];349(2):433–46. Available from: https://link.springer.com/article/10.1007/s00441-012-1437-1 Aygun S, Tokgozoglu L. Comparison of Current International Guidelines for the Management of Dyslipidemia. J Clin Med [Internet]. 2022 Dec 1 [cited 2023 Nov 13];11(23). Available from: /pmc/articles/PMC9737468/ Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 22 Aug, 2024 Read the published version in BMC Cardiovascular Disorders → Version 1 posted Editorial decision: Revision requested 17 Jul, 2024 Reviews received at journal 16 Jul, 2024 Reviews received at journal 13 Jul, 2024 Reviews received at journal 13 Jul, 2024 Reviewers agreed at journal 13 Jul, 2024 Reviewers agreed at journal 08 Jul, 2024 Reviewers agreed at journal 07 Jul, 2024 Reviewers agreed at journal 05 Jul, 2024 Reviewers invited by journal 05 Jul, 2024 Editor invited by journal 19 Jun, 2024 Editor assigned by journal 18 Jun, 2024 Submission checks completed at journal 18 Jun, 2024 First submitted to journal 18 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4120076","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":318147265,"identity":"9d6e131b-9c88-46b7-9247-a89393be6b15","order_by":0,"name":"Udaya Ralapanawa","email":"","orcid":"","institution":"University of Peradeniya","correspondingAuthor":false,"prefix":"","firstName":"Udaya","middleName":"","lastName":"Ralapanawa","suffix":""},{"id":318147266,"identity":"8076874d-1d89-457f-9412-e60fc0003c23","order_by":1,"name":"Ramiah Sivakanesan","email":"","orcid":"","institution":"University of Peradeniya","correspondingAuthor":false,"prefix":"","firstName":"Ramiah","middleName":"","lastName":"Sivakanesan","suffix":""},{"id":318147267,"identity":"b534f708-475b-492a-a8d1-477297559ba9","order_by":2,"name":"Sampath Tennakoon","email":"","orcid":"","institution":"University of Peradeniya","correspondingAuthor":false,"prefix":"","firstName":"Sampath","middleName":"","lastName":"Tennakoon","suffix":""},{"id":318147268,"identity":"98c7470c-6610-42a9-a33f-f65ecc38a19d","order_by":3,"name":"Parackrama Karunathilake","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIie3RsarCMBSA4VMKdRG6Vhx8AqHSoZSL+CqRQFysS3cRBO/Su/sehcyBgFOkayapSyfFgEtBEK3gIhg7Cjf/EBrIR04ogMn0tbHHaoMCQI/PgjUk1vpJUFNit5uQsLXdq0rsev1fEQTDFZ9BixeAxHsSpZOgk8pkQMU0wPGKJ9AmPiD5nviMQBcUsiiLMx5TPl7A9D6Y0pC8tC93MqL5MeNRTdzDByKJ0wWJxlTGGbZq4tW3aAaL1qUTpQJhKk/nwd91kjhe6TPd80OX2LLaoCHNCfYq8TNzXbwv1EYz2Mt+CQ48/1NDMtcdNplMpn/aDYW1XWdVXRZ1AAAAAElFTkSuQmCC","orcid":"","institution":"Wayamba University of Sri Lanka","correspondingAuthor":true,"prefix":"","firstName":"Parackrama","middleName":"","lastName":"Karunathilake","suffix":""}],"badges":[],"createdAt":"2024-03-18 05:15:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4120076/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4120076/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12872-024-04108-2","type":"published","date":"2024-08-22T15:57:27+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60443331,"identity":"bb4b80c2-a213-4509-8d1c-349d7f3f2074","added_by":"auto","created_at":"2024-07-16 20:21:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":169323,"visible":true,"origin":"","legend":"\u003cp\u003eVisual representation of IMA concentration distribution, showcasing histogram\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4120076/v1/d5293cf8f1e79b7b6fac8de0.png"},{"id":63300193,"identity":"095dfbed-1e20-4ef2-ae5a-9cdcf108669e","added_by":"auto","created_at":"2024-08-26 16:12:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":878421,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4120076/v1/b27136e0-687b-4126-ba6b-377319692e85.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ischemia-modified albumin: Is it a promising marker in acute coronary syndrome?","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAcute coronary syndrome (ACS) refers to a range of cardiac conditions, including ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina. This syndrome falls under the category of ischemic heart disease (IHD), also known as coronary heart disease (CHD). It is responsible for one-third of all deaths in individuals over the age of 35 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The economic burden of ACS is significant, encompassing expenses related to hospitalizations, treatments, interventional procedures, follow-up clinic appointments, emergency visits, and prescribed medications (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In the United States, IHD accounts for roughly 1-1.5% of the Gross Domestic Product (GDP). In contrast, in low and middle-income countries, the per capita health expenditure specific to IHD care constitutes 10% of the total healthcare expenditure in each respective country (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEvaluation of patients presenting with symptoms suggestive of ACS remains a diagnostic challenge at the emergency department (ED). Most of the patients presenting to the ED have symptoms related to non-cardiac and often mild ailment that does not require emergency treatment or hospitalization (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Much research has focused on the search for ideal biological markers for the rapid detection of cardiac cell injuries. Currently, the biomarker most widely used for diagnosing acute coronary syndrome is cardiac troponin. Even though cardiac troponin is the gold standard for myocardial necrosis it is blind for ischemia without necrosis (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The appearance of symptomatic cardiac ischemia occurs before myocardial necrosis, and a biomarker that reflects ischemia, rather than necrosis itself, would be conceptually appealing and could provide added value to troponin testing.\u003c/p\u003e \u003cp\u003eSeveral candidate biomarkers to detect cardiac ischemia have recently been evaluated. Ischaemia Modified Albumin (IMA), B-type natriuretic peptide, N-terminal pro-BNP, whole blood choline, unesterified free fatty acids, malondialdehyde, low-density lipoprotein, and myeloperoxidase were experimented as cardiac ischemia biomarkers (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Arriving at a conclusive diagnosis for individuals with chest pain or other indicators hinting at ACS is frequently a lengthy, challenging, and costly process. Recent studies have pinpointed IMA as a valuable biomarker for detecting ischemia, not infarction (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Furthermore, the US Food and Drug Administration has already approved the use of IMA in diagnosing suspected myocardial ischemia (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eIschaemia Modified Albumin\u003c/h3\u003e\n\u003cp\u003eIMA is a form of human serum albumin in which the N-terminal amino acids have been modified by ischemia (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Because of this modification, the affinity of plasma albumin to bind to heavy metal ions like cobalt, nickel, and copper is reduced (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). IMA is approximately 1\u0026ndash;2% of the circulating albumin and increases to 6\u0026ndash;8% in patients experiencing ischemia (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The estimation of IMA is simple and can be even done in laboratories with very basic facilities or say even at the bedside helping emergency physicians to decide (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). When interpreting IMA results, it is important to remember that increased IMA reading can be seen in patients with stroke, end-stage renal failure, liver disease, some neoplasms, sepsis and patients who have undergone direct current cardioversion; therefore, it is not specific to cardiac ischemia (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). However, IMA can be used for early diagnosis of ACS, exclusion of ACS, and risk stratification of ACS (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). It is detected within 6\u0026ndash;10 minutes after the onset of cardiac ischemia, remains elevated for up to several hours, and returns to normal 8\u0026ndash;12 hours after the onset of cardiac ischemia (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). This study aims to further elucidate the role of IMA as a rapid, reliable biomarker in the early detection of Acute Coronary Syndrome, potentially revolutionizing the diagnostic process in emergency medical settings.\u003c/p\u003e"},{"header":"METHODOLOGY","content":"\u003cdiv id=\"Sec4\"\u003e\n \u003ch2\u003eStudy Design\u003c/h2\u003e\n \u003cp\u003eThis prospective cohort study was conducted among ACS patients admitted to Teaching Hospital, Peradeniya (THP), Sri Lanka. The study population included all ACS patients presenting to the Professorial Medical Unit at THP from 2015 to 2019.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\"\u003e\n \u003ch2\u003eInclusion Criteria\u003c/h2\u003e\n \u003cp\u003eAll patients clinically diagnosed with ACS after a detailed history and examination at the time of presentation were enrolled upon obtaining informed written consent. Typical chest pain associated with ACS was defined as squeezing pain over the precordial area radiating to the neck, arm, back, or epigastric region, accompanied by sweating, nausea, vomiting, or syncope, unresponsive to rest and sublingual nitro-glycerine.\u003c/p\u003e\n \u003cdiv id=\"Sec6\"\u003e\n \u003ch2\u003eExclusion Criteria\u003c/h2\u003e\n \u003cp\u003eExcluded from the study were patients who did not provide consent, as well as those with diabetes mellitus, neoplastic diseases, concomitant inflammatory diseases (such as infections and autoimmune disorders), major depression, liver and kidney diseases, recent major surgical procedures, myocardial infarction or angina episodes within the 48 hours before hospitalization, individuals who had undergone coronary angioplasty or bypass surgery, and those with valvular, myocardial, or pericardial diseases. Patients taking antioxidant drugs such as beta-blocking agents (carvedilol, nebivolol), angiotensin-converting-enzyme inhibitors (captopril), statins, diuretics, vitamins, alcohol, and smoking were also excluded from the study.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec7\"\u003e\n \u003ch2\u003eData and Sample Collection\u003c/h2\u003e\n \u003cp\u003eAll patients presenting with ACS symptoms to the Professorial Medical Unit at THP between December 1, 2015, and December 1, 2019, underwent comprehensive assessments by investigators, including detailed history-taking, blood pressure measurement, body mass index (BMI) assessment, ECG, and routine blood tests.\u003c/p\u003e\n \u003cp\u003eBlood samples were collected from ACS patients upon arrival at the preliminary care unit of the Professorial Medical Unit, THP. Serum samples were obtained after clotting, within 30 minutes, by centrifugation of the blood samples. These samples were stored at -80\u0026ordm; C until analysis. All serum samples were analysed at the Department of Biochemistry, Faculty of Medicine, University of Peradeniya, Peradeniya.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003eSample Analysis\u003c/h2\u003e\n \u003cp\u003eSerum samples separated from blood samples were analysed for IMA. The assay is based on the premise that myocardial ischemia causes changes in human serum albumin (HSA), leading to a reduction in the binding of exogenous cobalt (II).\u003c/p\u003e\n \u003cdiv id=\"Sec9\"\u003e\n \u003ch2\u003eIschemia Modified Albumin Assay\u003c/h2\u003e\n \u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003ePrinciple\u003c/h2\u003e\n \u003cp\u003eThe assay is based on the premise that myocardial ischemia causes changes in human serum albumin (HSA) causing a reduction in binding of exogenous cobalt (II). The concentration of ischemia-modified albumin can be determined by the addition of a known amount of Cobalt (II) to serum and measurement of the unbound cobalt (II) by colorimetric assay using dithiothreitol (DTT). An inverse relationship thus exists between the level of albumin-bound cobalt and the intensity of the colour formation.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003eReagents\u003c/h2\u003e\n \u003cp\u003eCobalt chloride 1 g/L\u003c/p\u003e\n \u003cp\u003eDithiothreitol 1.5 g/L\u003c/p\u003e\n \u003cp\u003eNormal saline\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eProcedure\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cspan\u003e1. Serum (200 \u0026micro;L) was mixed with 50 \u0026micro;L of a solution of cobalt chloride (1 g/L), followed by 10 minutes of vigorous mixing.\u003cbr\u003e\u003c/span\u003e \u003cspan\u003e2. DTT (50 \u0026micro;l, 1.5 g/L) was added and mixed.\u003cbr\u003e\u003c/span\u003e \u003cspan\u003e3. After 2 minutes of incubation, 1.0 ml of saline was added.\u003cbr\u003e\u003c/span\u003e \u003cspan\u003e4. The absorbance of the assay mixture was measured at 470 nm. The blank was prepared similarly, excluding DTT. The IMA activity was calculated as the absorbance value obtained by subtracting the blank from the test.\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp\u003eAn inverse relationship thus exists between the level of albumin-bound cobalt and the intensity of the colour formation, which was used in the quantification of the IMA level.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eSerum Ischemia Modified Albumin (IMA) Distribution\u003c/h2\u003e\n \u003cp\u003eThe IMA concentration in 330 patients presenting with ACS was found to be non-normally distributed, exhibiting a pronounced right skew (skewness statistic: 0.496). The Shapiro-Wilk test confirmed the non-normality with a p-value of less than 0.001. The average serum IMA concentration across the cohort was 0.252 absorbance units (AU) with a standard deviation of 0.123 AU, and the values ranged from a minimum of 0.008 AU to a maximum of 0.67 AU. The distribution\u0026apos;s skewness is both visually depicted in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and statistically corroborated, with slight deviations from normality observed in the Q-Q plot and the presence of three significant outliers.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eIMA Concentration: Age and Gender Interaction\u003c/h2\u003e\n \u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e displays the summary of IMA concentrations stratified by age and gender, presenting mean values, standard deviations, and ranges. Overall, 330 patients were evaluated, with no significant difference in IMA concentrations between the total male and female cohorts (p\u0026thinsp;=\u0026thinsp;0.063). When stratifying by age, there was no significant difference in IMA levels between the younger group (age\u0026thinsp;\u0026lt;\u0026thinsp;59 years) and the older group (age\u0026thinsp;\u0026ge;\u0026thinsp;59 years) (p\u0026thinsp;=\u0026thinsp;0.829). However, a gender-based analysis within the younger age group revealed that males had significantly higher IMA concentrations compared to females (p\u0026thinsp;=\u0026thinsp;0.033).\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSummary of IMA concentrations, dissected by age and gender, highlighting mean, standard deviation, and range\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMales\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eFemales\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003cp\u003e(Absorbance units)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003cp\u003e(Absorbance units)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003cp\u003e(Absorbance\u003c/p\u003e\n \u003cp\u003eunits)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value*\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e330\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.252\u0026thinsp;\u0026plusmn;\u0026thinsp;0.123\u003c/p\u003e\n \u003cp\u003e(0.008\u0026ndash;0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e0.262\u0026thinsp;\u0026plusmn;\u0026thinsp;0.120\u003c/p\u003e\n \u003cp\u003e(0.039\u0026ndash;0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.236\u0026thinsp;\u0026plusmn;\u0026thinsp;0.127\u003c/p\u003e\n \u003cp\u003e(0.008\u0026ndash;0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.063\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.253\u0026thinsp;\u0026plusmn;\u0026thinsp;0.129\u003c/p\u003e\n \u003cp\u003e(0.008\u0026ndash;0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e0.270\u0026thinsp;\u0026plusmn;\u0026thinsp;0.128\u003c/p\u003e\n \u003cp\u003e(0.008\u0026ndash;0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.225\u0026thinsp;\u0026plusmn;\u0026thinsp;0.129\u003c/p\u003e\n \u003cp\u003e(0.042\u0026ndash;0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.251\u0026thinsp;\u0026plusmn;\u0026thinsp;0.117\u003c/p\u003e\n \u003cp\u003e(0.039\u0026ndash;0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e0.254\u0026thinsp;\u0026plusmn;\u0026thinsp;0.113\u003c/p\u003e\n \u003cp\u003e(0.047\u0026ndash;0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.245\u0026thinsp;\u0026plusmn;\u0026thinsp;0.126\u003c/p\u003e\n \u003cp\u003e(0.039\u0026ndash;0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"15\"\u003e*p values in the column are between genders\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003eIschemia-Modified Albumin Concentrations Across Ethnicities\u003c/h2\u003e\n \u003cp\u003eThe study found no significant variance in IMA concentrations among the Sinhalese, Tamils, and Moors, with p\u0026thinsp;=\u0026thinsp;0.217, indicating comparable mean levels across these groups. However, the distribution characteristics differed, particularly for Sinhalese patients, who exhibited a distinct skewness in their results. Outlier analysis revealed minimal ethnic disparities, with Sinhalese having a slightly higher percentage (1.1%) compared to Tamils (3.6%) and none in Moors.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003eIschemia-Modified Albumin Concentrations Across Different BMI Categories\u003c/h2\u003e\n \u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e presents the IMA concentration in ACS patients stratified by BMI categories and gender. In the underweight category, males (N\u0026thinsp;=\u0026thinsp;5) exhibited a mean IMA concentration of 0.221\u0026thinsp;\u0026plusmn;\u0026thinsp;0.063 AU, while females (N\u0026thinsp;=\u0026thinsp;4) showed a mean of 0.273\u0026thinsp;\u0026plusmn;\u0026thinsp;0.180 AU, with no significant difference between genders (p\u0026thinsp;=\u0026thinsp;0.562). Normal-weight males (N\u0026thinsp;=\u0026thinsp;71) had a mean IMA level of 0.261\u0026thinsp;\u0026plusmn;\u0026thinsp;0.114 AU compared to 0.281\u0026thinsp;\u0026plusmn;\u0026thinsp;0.142 AU in females (N\u0026thinsp;=\u0026thinsp;37), which was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.443). The overweight male group (N\u0026thinsp;=\u0026thinsp;97) showed a mean of 0.256\u0026thinsp;\u0026plusmn;\u0026thinsp;0.133 AU, while the female group (N\u0026thinsp;=\u0026thinsp;50) had a mean of 0.214\u0026thinsp;\u0026plusmn;\u0026thinsp;0.112 AU; this difference approached but did not reach, statistical significance (p\u0026thinsp;=\u0026thinsp;0.056). Notably, in the obese category, a significant gender difference was observed with males (N\u0026thinsp;=\u0026thinsp;34) having a mean IMA concentration of 0.284\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 AU and females (N\u0026thinsp;=\u0026thinsp;32) having a mean of 0.213\u0026thinsp;\u0026plusmn;\u0026thinsp;0.115 AU (p\u0026thinsp;=\u0026thinsp;0.009).\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eIschemia modified albumin concentration of patients according to Body Mass Index and gender\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eBMI categories\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eIschemia-modified albumin concentration\u003c/p\u003e\n \u003cp\u003e(Absorbance units)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMales\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eFemales\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnderweight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.221\u0026thinsp;\u0026plusmn;\u0026thinsp;0.063\u003c/p\u003e\n \u003cp\u003e(0.122\u0026ndash;0.279)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.273\u0026thinsp;\u0026plusmn;\u0026thinsp;0.180\u003c/p\u003e\n \u003cp\u003e(0.104\u0026ndash;0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.562\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal weight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.261\u0026thinsp;\u0026plusmn;\u0026thinsp;0.114\u003c/p\u003e\n \u003cp\u003e(0.067\u0026ndash;0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.281\u0026thinsp;\u0026plusmn;\u0026thinsp;0.142 (0.039\u0026ndash;0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.443\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverweight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.256\u0026thinsp;\u0026plusmn;\u0026thinsp;0.133 (0.008\u0026ndash;0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.214\u0026thinsp;\u0026plusmn;\u0026thinsp;0.112 (0.079\u0026ndash;0.554)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObesity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.284\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 (0.066\u0026ndash;0.463)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.213\u0026thinsp;\u0026plusmn;\u0026thinsp;0.115 (0.042\u0026ndash;0.405)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.009*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eValues in parentheses are minimum and maximum; P values are for mean comparison between genders\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003eClinical Conditions and IMA Concentrations\u003c/h2\u003e\n \u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e details the IMA concentrations with different clinical presentations of ACS. For patients with Unstable Angina (N\u0026thinsp;=\u0026thinsp;137), the mean IMA concentration was 0.221\u0026thinsp;\u0026plusmn;\u0026thinsp;0.119 AU, with a 95% Confidence Interval (CI) for the mean ranging from 0.201 to 0.242 AU, and values spanning from 0.039 AU to 0.64 AU. In the NSTEMI group (N\u0026thinsp;=\u0026thinsp;100), the mean IMA level was higher at 0.284\u0026thinsp;\u0026plusmn;\u0026thinsp;0.115 AU, with a 95% CI of 0.261 AU to 0.306 AU, and a range from 0.051 AU to 0.67 AU. Patients with STEMI (N\u0026thinsp;=\u0026thinsp;93) had a mean IMA concentration of 0.263\u0026thinsp;\u0026plusmn;\u0026thinsp;0.129 AU, with a 95% CI from 0.236 to 0.289 AU, and values ranging between 0.008 AU and 0.64 AU. According to Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e results STEMI and NSTEMI patients show significantly higher IMA concentrations compared to the Unstable Angina group.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u003cstrong\u003eIschemia modified albumin concentration of patients according to the\u0026nbsp;\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u003cstrong\u003eclinical conditions\u003c/strong\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1719995471.png\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003eIschemia-Modified Albumin Concentration in ACS Patients Versus Control Subjects\u003c/h2\u003e\n \u003cp\u003eThe study demonstrated a statistically significant increase in Ischemia Modified Albumin (IMA) concentrations among ACS patients compared to control subjects, with mean levels of 0.252\u0026thinsp;\u0026plusmn;\u0026thinsp;0.123 AU and 0.164\u0026thinsp;\u0026plusmn;\u0026thinsp;0.101 AU, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n \u003ch2\u003eCorrelations of IMA Concentrations with Lipid Profile\u003c/h2\u003e\n \u003cp\u003eOur study investigated the relationship between serum IMA levels and lipid profile components, which include Total Cholesterol, LDL cholesterol, HDL cholesterol, and VLDL cholesterol. The bivariate correlation analysis indicated significant findings as shown in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. For the total population (N\u0026thinsp;=\u0026thinsp;97), serum IMA showed a significant positive correlation with Total Cholesterol (r\u0026thinsp;=\u0026thinsp;0.262, p\u0026thinsp;=\u0026thinsp;0.009) and LDL-Cholesterol (r\u0026thinsp;=\u0026thinsp;0.280, p\u0026thinsp;=\u0026thinsp;0.006), suggesting that higher levels of these lipids are associated with increased modifications to albumin, potentially due to ischemic events. However, the correlations with HDL-Cholesterol and VLDL-Cholesterol were not significant (r\u0026thinsp;=\u0026thinsp;0.103, p\u0026thinsp;=\u0026thinsp;0.33 and r\u0026thinsp;=\u0026thinsp;0.184, p\u0026thinsp;=\u0026thinsp;0.124, respectively).\u003c/p\u003e\n \u003cp\u003eWhen stratified by gender, different patterns emerged. In females (N\u0026thinsp;=\u0026thinsp;45), the correlation between IMA levels and Total Cholesterol remained significant (r\u0026thinsp;=\u0026thinsp;0.401, p\u0026thinsp;=\u0026thinsp;0.002), but no significant correlation was found with LDL-cholesterol (r\u0026thinsp;=\u0026thinsp;0.171, p\u0026thinsp;=\u0026thinsp;0.278). For males (N\u0026thinsp;=\u0026thinsp;52), significant correlations were found with both Total Cholesterol (r\u0026thinsp;=\u0026thinsp;0.317, p\u0026thinsp;=\u0026thinsp;0.018) and LDL-Cholesterol (r\u0026thinsp;=\u0026thinsp;0.361, p\u0026thinsp;=\u0026thinsp;0.009), while the correlations with HDL-Cholesterol and VLDL-Cholesterol remained non-significant.\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBivariate correlation analysis between serum concentrations of Ischemia modified albumin and Lipids\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eLipids\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"11\"\u003e\n \u003cp\u003eBivariate correlation\u003c/p\u003e\n \u003cp\u003eSerum Ischemia Modified Albumin and Lipids\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFemales\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMales\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.262\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.317\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLDL- Cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.278\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHDL- Cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.439\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.692\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVLDL- Cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.184\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\"\u003eN\u0026thinsp;=\u0026thinsp;Number of patients, r\u0026thinsp;=\u0026thinsp;Pearson\u0026rsquo;s correlation, p\u0026thinsp;=\u0026thinsp;p value\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eA multiple linear regression analysis was run to predict serum IMA concentration from age, gender, ethnicity, BMI, TC, LDL-C, VLDL-C, and HDL-C. The most significant predictor of serum IMA concentrations was low-density lipoprotein cholesterol (LDL-C), as substantiated by multiple linear regression analysis (Beta coefficient\u0026thinsp;=\u0026thinsp;0.393, p\u0026thinsp;=\u0026thinsp;0.001). The model accounted for 15.5% of the variance in IMA levels, emphasizing LDL-C\u0026apos;s role in ischemic stress.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe distribution of IMA concentrations in this cohort of 330 ACS patients suggests a pattern that deviates from normality, indicated by a significant right skew. This finding is consistent with the notion that IMA levels increase in response to ischemic stress, which may not be uniformly experienced across the patient population (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The variability in IMA concentrations could reflect the heterogeneous nature of ACS presentations, ranging from unstable angina to various forms of myocardial infarctions.\u003c/p\u003e \u003cp\u003eThe analysis of IMA concentrations across different age and gender demographics within our ACS patient cohort presents intriguing findings. The lack of a significant difference in IMA levels between the aggregated male and female groups suggests that, overall, gender may not play a decisive role in IMA variability among ACS patients. However, the observed gender disparity in IMA levels within the younger age group (\u0026lt;\u0026thinsp;59 years) is of particular interest. The higher IMA concentrations in males compared to females in this age bracket may be indicative of biological differences in the pathophysiology of ACS or differences in the acute response to ischemic stress (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Anyhow this contrasts the findings of Stea et al. where men aged 45 years showed significantly lower IMA concentrations compared to women aged 45 and fertile and menopausal women (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This could also reflect gender-specific variations in myocardial damage or differences in risk factors prevalence such as smoking, physical inactivity, or occupational stress, which are known to be more common among younger males (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe absence of a significant age-based difference in IMA levels could suggest that the process of ischemia-related albumin modification is not substantially affected by age. Alternatively, it could be that the compensatory mechanisms against ischemia in albumin are preserved across age groups. Prior studies have indicated that age may not be a major determinant in the levels of IMA which appears to align with our findings (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe significant gender difference in the younger age group but not in the older group may also raise questions about the influence of hormones, such as oestrogen, which has been found to have cardioprotective effects and may influence biomarker levels (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe analysis of IMA concentrations across BMI categories within this ACS patient cohort revealed gender-specific variations, particularly within the obese group. The significant difference in IMA levels between obese males and females (p\u0026thinsp;=\u0026thinsp;0.009) might suggest that gender-related physiological differences in adiposity and inflammatory responses to obesity could contribute to divergent IMA concentrations. It is well-documented that obesity is associated with a chronic low-grade inflammatory state, which could potentially influence the modification of albumin in response to ischemic stress and thus alter IMA levels (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe absence of significant differences in the underweight and normal weight categories might indicate that at these BMI levels, other factors such as acute illness severity, the extent of myocardial ischemia, or individual patient management practices have a more pronounced impact on IMA levels than adiposity. The near-significant difference observed in the overweight category suggests a possible trend that warrants further investigation with a larger sample size to confirm if overweight status has a differential impact on IMA levels between genders. The pronounced gender difference in the obese category raises questions about the role of sex hormones, differential fat distribution patterns, and metabolic profiles that are known to vary between obese men and women (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe clinical implications of these observations are particularly relevant when considering the use of IMA for diagnostic or prognostic purposes in ACS. The significant gender difference in IMA concentrations among obese patients suggests that gender-specific reference ranges might be necessary to improve the biomarker's diagnostic accuracy. Moreover, these findings reinforce the need for personalized medicine approaches considering patient demographics and comorbidities when interpreting biomarker levels. Future studies should aim to explore these relationships in more diverse populations and investigate the mechanisms underlying the gender differences in IMA levels among obese individuals.\u003c/p\u003e \u003cp\u003eThe assessment of IMA concentrations across varying clinical conditions of ACS provides valuable insights into its potential as a differential biomarker. The elevated IMA levels in NSTEMI and STEMI patients, compared to those with Unstable Angina, are particularly noteworthy. This could imply a more pronounced ischemic insult in NSTEMI and STEMI, as these conditions are typically associated with more substantial myocardial damage (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe clinical application of these findings could be significant. Elevated IMA concentrations in NSTEMI and STEMI patients might facilitate early and more accurate diagnosis, particularly in ambiguous cases. It could also aid in distinguishing between NSTEMI and Unstable Angina, potentially influencing the urgency and type of intervention.\u003c/p\u003e \u003cp\u003eThe present study's findings corroborate previous research indicating elevated levels of IMA in ACS patients, supporting its potential as a diagnostic biomarker. Comparable to Hazini et al. (2015) who investigated IMA levels in Turkey, our study observed a significant increase in serum IMA concentration in ACS patients compared to healthy controls. While Hazini et al. reported mean serum IMA levels of 0.527\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 in patients and 0.347\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 in controls, the direct comparison is hindered by unspecified units (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Nonetheless, the trend of elevated IMA in patient populations aligns with our observations, suggesting a consistent biomarker presence across different cohorts.\u003c/p\u003e \u003cp\u003eFurthermore, Bhagavan et al. (2003) identified a notable differentiation in absorbance units between myocardial ischemic individuals and non-myocardial ischemic ones, with means of 0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25 and 0.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10, respectively, a finding that is echoed in our results (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). This consistency across studies conducted over different periods and populations underscores the reliability of IMA as a biomarker for myocardial ischemia.\u003c/p\u003e \u003cp\u003eThe prognostic value of IMA extends beyond diagnosis, as illustrated by Dominguez-Rodriguez et al. (2009), who demonstrated a significant association between serum IMA levels and ST-segment resolution post-mechanical reperfusion in STEMI patients (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Moreover, they found that IMA levels could serve as a predictor of left ventricular dysfunction, as further supported by their 2008 study which linked higher IMA concentrations with severe left ventricular impairment indicated by higher Killip classes (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCumulatively, these studies bolster the proposition that IMA serves as a sensitive marker for oxidative stress and myocardial injury (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Given the predictive value of IMA concerning ST-segment resolution and its correlation with left ventricular function, it emerges as a multifaceted biomarker with potential utility in both the diagnosis and prognosis of ACS (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eConsidering these findings, it becomes imperative to conduct further research on the role of IMA in ACS within the global population. Such studies could solidify the role of IMA as an oxidative stress marker and its effectiveness in the early detection of ACS. Moreover, considering the hereditary aspects of myocardial infarction, screening for IMA levels in individuals with a family history of cardiac events may prove to be a valuable preventive measure.\u003c/p\u003e \u003cp\u003eThe relationship between IMA and lipid fractions has been a subject of research with variable results. In the current study, the significant positive correlation found between IMA and total cholesterol, as well as LDL-cholesterol, aligns with previous findings suggesting that elevated IMA levels may be associated with dyslipidaemia, which is a recognized risk factor for atherosclerosis and subsequently ACS (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eInterestingly, the correlation seems to be more pronounced in the male subgroup, which could suggest a gender-specific interaction between lipid metabolism and ischemic modifications to albumin. This is particularly notable in the context of LDL-cholesterol, known to be atherogenic, and its higher correlation with IMA in males could point towards a more substantial role of LDL-related oxidative stress in men (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur analysis revealed a significant association between LDL-C and serum IMA concentrations, underscoring the pivotal role of lipids in ischemic stress. The Beta coefficient of 0.393 with a p-value of 0.001 in our multiple linear regression model indicates that LDL-C is a robust predictor of IMA levels. This is consistent with the hypothesis that atherogenic lipoproteins contribute to endothelial dysfunction and subsequent ischemic events, a relationship that has been corroborated by other studies (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur findings bear clinical implications. They suggest that monitoring serum IMA concentrations could be an adjunct strategy in assessing the ischemic risk associated with dyslipidaemia. This is particularly relevant considering that current guidelines emphasize LDL-C management as a primary target for cardiovascular risk reduction (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study on IMA levels in ACS patients reveals that IMA concentrations are influenced by various demographic factors, but not uniformly across patients. While gender does not significantly impact IMA levels overall, notable differences are observed in specific subgroups, such as higher levels in younger males. This suggests potential biological and lifestyle influences on IMA variability. Age appears to have a limited effect on IMA levels, indicating possible consistency in ischemia-related albumin modification across age groups. Furthermore, the study highlights significant gender-specific differences in IMA levels in obese patients, implying the influence of physiological differences in response to obesity. These findings underscore the potential of IMA as a diagnostic and prognostic biomarker in ACS, suggesting the need for personalized approaches considering patient demographics and comorbidities. Additionally, the study's correlation between IMA levels and lipid profiles, particularly LDL-cholesterol, highlights the importance of lipid management in ACS risk reduction, pointing to the multifaceted role of IMA in ACS management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ethical approval was obtained from the Ethical Review Committee, Faculty of Medicine, University of Peradeniya, Sri Lanka. The Committee granted approval for the research protocol. In compliance with the Declaration of Helsinki, all participants provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are under the control of the authors and can be made available upon reasonable request. Requests for access to the data should be directed to Prof. Udaya Ralapanawa, who will ensure that any data released does not compromise participant confidentiality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no competing interests in relation to this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUR and RS were instrumental in conceptualizing and designing the study. UR, RS, and PK conducted the data collection, while ST was responsible for data analysis. UR, RS, and PK took an active role in drafting the manuscript and critically revising it to enhance its intellectual content. All authors have actively contributed to the revision of the manuscript and have given their approval for the final version to be submitted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe want to express our gratitude to all participants who consented to take part in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAcute Coronary Syndrome - PubMed [Internet]. [cited 2023 Oct 22]. Available from: https://pubmed.ncbi.nlm.nih.gov/29083796/\u003c/li\u003e\n\u003cli\u003eKhan MA, Hashim MJ, Mustafa H, Baniyas MY, Suwaidi SKBM Al, AlKatheeri R, et al. Global Epidemiology of Ischemic Heart Disease: Results from the Global Burden of Disease Study. Cureus [Internet]. 2020 Jul 23 [cited 2023 Dec 15];12(7). Available from: /pmc/articles/PMC7384703/\u003c/li\u003e\n\u003cli\u003eGarg P, Morris P, Fazlanie AL, Vijayan S, Dancso B, Dastidar AG, et al. Cardiac biomarkers of acute coronary syndrome: from history to high-sensitivity cardiac troponin. Intern Emerg Med [Internet]. 2017 Mar 1 [cited 2023 Dec 15];12(2):147. Available from: /pmc/articles/PMC5329082/\u003c/li\u003e\n\u003cli\u003eKumar A. Ischemia-Modified Albumin: Its Diagnostic Implications and Shortfalls. JOURNAL OF BIOMEDICAL SCIENCES [Internet]. 2012;1(2). Available from: http://www.imedpub.com/\u003c/li\u003e\n\u003cli\u003eBhakthavatsala Reddy C, Cyriac C, Desle HB. Role of \u0026ldquo;Ischemia Modified Albumin\u0026rdquo; (IMA) in acute coronary syndromes. Indian Heart J [Internet]. 2014 Nov 1 [cited 2023 Dec 15];66(6):656. Available from: /pmc/articles/PMC4311005/\u003c/li\u003e\n\u003cli\u003eShevtsova A, Gordiienko I, Tkachenko V, Ushakova G. Ischemia-Modified Albumin: Origins and Clinical Implications. Dis Markers [Internet]. 2021 [cited 2023 Nov 13];2021. Available from: /pmc/articles/PMC8315882/\u003c/li\u003e\n\u003cli\u003eSullivan S, Young A, Hammadah M, Lima BB, Levantsevych O, Ko YA, et al. Sex differences in the inflammatory response to stress and risk of adverse cardiovascular outcomes among patients with coronary heart disease. Brain Behav Immun. 2020 Nov 1;90:294\u0026ndash;302. \u003c/li\u003e\n\u003cli\u003eStea S, De Pasquale D, Beraudi A, Catalani S, Amabile M, Bracci G, et al. Ischemia-Modified Albumin Expression: Is there a Difference between Male and Female Subjects? Clin Lab [Internet]. 2019 [cited 2023 Nov 13];65(6). Available from: https://pubmed.ncbi.nlm.nih.gov/31232020/\u003c/li\u003e\n\u003cli\u003eKatulanda P, Wickramasinghe K, Mahesh JG, Rathnapala A, Constantine GR, Sheriff R, et al. Prevalence and Correlates of Tobacco Smoking in Sri Lanka. http://dx.doi.org/101177/1010539509355599 [Internet]. 2010 May 10 [cited 2023 Nov 13];23(6):861\u0026ndash;9. Available from: https://journals.sagepub.com/doi/10.1177/1010539509355599\u003c/li\u003e\n\u003cli\u003eRuberti OM, Rodrigues B. Estrogen Deprivation and Myocardial Infarction: Role of Aerobic Exercise Training, Inflammation and Metabolomics. Curr Cardiol Rev [Internet]. 2020 Jul 30 [cited 2023 Nov 13];16(4):292. Available from: /pmc/articles/PMC7903506/\u003c/li\u003e\n\u003cli\u003eHildebrandt X, Ibrahim M, Peltzer N. Cell death and inflammation during obesity: \u0026ldquo;Know my methods, WAT(son).\u0026rdquo; Cell Death \u0026amp; Differentiation 2022 30:2 [Internet]. 2022 Sep 29 [cited 2023 Nov 13];30(2):279\u0026ndash;92. Available from: https://www.nature.com/articles/s41418-022-01062-4\u003c/li\u003e\n\u003cli\u003eKarastergiou K, Smith SR, Greenberg AS, Fried SK. Sex differences in human adipose tissues \u0026ndash; the biology of pear shape. Biol Sex Differ [Internet]. 2012 [cited 2023 Nov 13];3(1):13. Available from: /pmc/articles/PMC3411490/\u003c/li\u003e\n\u003cli\u003eSarkees ML, Bavry AA. Acute coronary syndrome (unstable angina and non-ST elevation MI). BMJ Clin Evid [Internet]. 2009 [cited 2023 Nov 13];2009. Available from: /pmc/articles/PMC2907796/\u003c/li\u003e\n\u003cli\u003eHazini A, Cemek M, Işildak I, Alpdaʇtaş S, \u0026Ouml;n\u0026uuml;l A, Şenel \u0026Uuml;, et al. Investigation of ischemia modified albumin, oxidant and antioxidant markers in acute myocardial infarction. Postepy Kardiol Interwencyjnej [Internet]. 2015 [cited 2023 Dec 15];11(4):298. Available from: /pmc/articles/PMC4679797/\u003c/li\u003e\n\u003cli\u003eBhagavan N V., Lai EM, Rios PA, Yang J, Ortega-Lopez AM, Shinoda H, et al. Evaluation of human serum albumin cobalt binding assay for the assessment of myocardial ischemia and myocardial infarction. Clin Chem [Internet]. 2003 Apr 1 [cited 2023 Dec 15];49(4):581\u0026ndash;5. Available from: https://pubmed.ncbi.nlm.nih.gov/12651810/\u003c/li\u003e\n\u003cli\u003eDominguez-Rodriguez A, Kaski JC, Abreu-Gonzalez P, Samimi-Fard S. Role of ischemia modified albumin to ST-segment resolution after mechanical reperfusion in patients with ST-segment elevation myocardial infarction. Atherosclerosis [Internet]. 2009 Apr [cited 2023 Dec 15];203(2):576\u0026ndash;80. Available from: https://pubmed.ncbi.nlm.nih.gov/18789442/\u003c/li\u003e\n\u003cli\u003eMajanović SK, Peloza OC, Detel D, Jovanović GK, Bakula M, Rahelic D, et al. Dyslipidemia: Current Perspectives and Implications for Clinical Practice. Management of Dyslipidemia [Internet]. 2021 Jul 5 [cited 2023 Nov 13]; Available from: https://www.intechopen.com/chapters/77410\u003c/li\u003e\n\u003cli\u003eHan K, Jia N, Yang L, Min LQ. Correlation between ischemia-modified albumin and lipid levels in patients with acute cerebrovascular disease. Mol Med Rep. 2012 Sep;6(3):621\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eKochidaira H, Kawakami T, Yura A, Takata K, Inagaki M, Kiuchi Y, et al. Correlations between Oxidative Stress and Blood Lipids Are Stronger in Men than Women. Vol. 170. 2020. \u003c/li\u003e\n\u003cli\u003eAdams MR, Kinlay S, Blake GJ, Orford JL, Ganz P, Selwyn AP. Atherogenic Lipids and Endothelial Dysfunction: Mechanisms in the Genesis of Ischemic Syndromes. https://doi.org/101146/annurev.med511149 [Internet]. 2003 Nov 28 [cited 2023 Nov 13];51:149\u0026ndash;67. Available from: https://www.annualreviews.org/doi/abs/10.1146/annurev.med.51.1.149\u003c/li\u003e\n\u003cli\u003eStancu CS, Toma L, Sima A V. Dual role of lipoproteins in endothelial cell dysfunction in atherosclerosis. Cell and Tissue Research 2012 349:2 [Internet]. 2012 May 18 [cited 2023 Nov 13];349(2):433\u0026ndash;46. Available from: https://link.springer.com/article/10.1007/s00441-012-1437-1\u003c/li\u003e\n\u003cli\u003eAygun S, Tokgozoglu L. Comparison of Current International Guidelines for the Management of Dyslipidemia. J Clin Med [Internet]. 2022 Dec 1 [cited 2023 Nov 13];11(23). Available from: /pmc/articles/PMC9737468/\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ischemia-Modified Albumin (IMA), Acute Coronary Syndrome (ACS), Biomarkers, Myocardial Ischemia, Lipid Profile, Gender Differences, Dyslipidaemia","lastPublishedDoi":"10.21203/rs.3.rs-4120076/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4120076/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAcute coronary syndrome (ACS) is a type of coronary heart disease (CHD), which is responsible for one-third of total deaths in people older than 35 years. Even though cardiac troponin is the gold standard for myocardial necrosis it is blind for ischemia without necrosis. Studies demonstrate that IMA is more sensitive in diagnosing ischemic chest pain compared to cardiac troponin T and electrocardiogram, and its combination with these tests significantly increases the sensitivity for diagnosing unstable angina, NSTEMI, or STEMI, with high positive and negative predictive values, making it a valuable tool for ruling out ACS in patients with inconclusive diagnoses in the emergency department.\u003c/p\u003e\u003ch2\u003eMethods and Findings\u003c/h2\u003e \u003cp\u003eThis prospective cohort study, conducted at the Teaching Hospital, Peradeniya, Sri Lanka, from 2015 to 2019, investigated ischemia-modified albumin (IMA) levels in 330 acute coronary syndrome (ACS) patients. Excluding those with various chronic conditions and those on specific medications, serum IMA was analysed using a colorimetric assay based on cobalt (II) binding to human serum albumin affected by myocardial ischemia. The study found a significant right skew in IMA distribution, confirming its non-normality. No overall significant gender-based difference in IMA levels was observed, though within the younger age group (\u0026lt;\u0026thinsp;59 years), males exhibited higher IMA concentrations than females. Ethnicity and age appeared to have limited impact on IMA levels. Notably, a significant gender difference in IMA levels was found in obese patients, suggesting physiological differences in response to obesity. The study also revealed higher IMA concentrations in NSTEMI and STEMI patients compared to those with unstable angina. A significant positive correlation between serum IMA levels and lipid profiles, particularly LDL-cholesterol, was established, indicating a link with dyslipidaemia.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe findings suggest the potential of IMA as a multifaceted biomarker in ACS diagnosis and prognosis, emphasizing the need for personalized medicine approaches and highlighting the role of lipid management in ACS risk reduction.\u003c/p\u003e","manuscriptTitle":"Ischemia-modified albumin: Is it a promising marker in acute coronary syndrome?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-16 20:20:57","doi":"10.21203/rs.3.rs-4120076/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-17T07:03:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-16T05:24:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-13T12:07:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-13T07:22:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"283053342011700735348585770246271257098","date":"2024-07-13T06:53:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"330513894927752715581794014830104864200","date":"2024-07-08T05:24:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"51916708229959757459672805763078325511","date":"2024-07-07T09:15:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"186498342030485525720561849093459771558","date":"2024-07-06T02:28:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-06T01:49:39+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-19T07:37:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-18T10:22:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-18T10:21:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2024-03-18T05:14:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"178de9f6-7d27-4046-b1ca-b4005df78432","owner":[],"postedDate":"July 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-26T16:02:03+00:00","versionOfRecord":{"articleIdentity":"rs-4120076","link":"https://doi.org/10.1186/s12872-024-04108-2","journal":{"identity":"bmc-cardiovascular-disorders","isVorOnly":false,"title":"BMC Cardiovascular Disorders"},"publishedOn":"2024-08-22 15:57:27","publishedOnDateReadable":"August 22nd, 2024"},"versionCreatedAt":"2024-07-16 20:20:57","video":"","vorDoi":"10.1186/s12872-024-04108-2","vorDoiUrl":"https://doi.org/10.1186/s12872-024-04108-2","workflowStages":[]},"version":"v1","identity":"rs-4120076","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4120076","identity":"rs-4120076","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}