Coronary artery disease, in which atherosclerotic plaque builds up inside the coronary arteries and restricts the flow of blood (and therefore the delivery of oxygen) to the heart, continues to be the number-one killer of Americans. Coronary artery disease can cause acute coronary syndrome (ACS), a condition characterized by signs of rapid myocardial ischemia, or an abrupt reduction in the heart's blood flow. The acronym ACS was chosen because it was believed to better describe the progression of the condition associated with myocardial ischemia. Unstable angina and myocardial infarction (MI) both come under the ACS. The signs and symptoms of ACS can vary greatly, ranging from unstable angina to non-ST segment elevation MI (NSTEMI) to ST-segment elevation MI (STEMI). Unstable angina and NSTEMI are generally caused by a partly or intermittently obstructed coronary artery, whereas STEMI is caused by a totally occluded coronary artery ⁽¹⁾. According to the World Health Organisation (WHO), the leading cause of death worldwide is cardiovascular disease, specifically acute coronary syndrome (ACS). In 2022, CVDs were predicted to have killed 19.8 million people or nearly 32% of all deaths globally. 85% of these deaths were from heart attacks and strokes ⁽²⁾.

The sensitivity of admission ECGs is typically around 50%. As a result, a way to identify ischemia before necrosis appears and perform prompt revascularization is needed. Utilizing additional quantitative risk categorization methods as possible ischemia biomarkers presents a difficulty. To date, three markers have been proposed: ischemia modified albumin (IMA), free fatty acids, and choline ⁽³⁾.

Ischemia episodes are preceded by IMA, a modified version of HAS (human serum albumin). IMA's sensitivity to ischemia conditions justifies its use. Albumin's structure changes as a result of ischemia's impact on the metabolic environment. The N-terminal portion of human serum albumin has the amino acid sequence N-(Aspartate) Asp-(Alanine) Ala-(Histidine) His-(Lysin) Lys. Transition metals such as cobalt (Co+2), copper (Cu+2), and nickel (Ni+2) bond to this area. When reactive oxygen species (ROS) are produced during ischemia, highly reactive hydroxyl free radicals are produced, which damage the N-terminal region of albumin.

This significantly alters albumin's ability to bind transition metals, particularly cobalt. This type of albumin was known as Ischemia Modified Albumin (IMA). IMA levels have been shown to increase within two minutes of the onset of ischemia, remain elevated for twelve hours, and then return to normal within twenty-four hours. Therefore, if IMA assessment is reliable and fast, it could be a potential marker for ACS patient identification. It might provide a more effective screening method for determining whether a person has acute myocardial ischemia when paired with standard practice.⁽⁴⁾

The Gensini score is an effective method for evaluating the extent and severity of atherosclerotic lesions in the coronary arteries. The Gensini score is an effective method for evaluating the extent and severity of atherosclerotic lesions in the coronary arteries.In this system, three main parameters need to be evaluated for each coronary lesion; severity score, segment multiplication factor and collateral correction factor.2 Severity scores are as; 1 score for 1–25% stenosis, 2 score for 26–50% stenosis, 4 score for 51–75% stenosis, 8 score for 76–90% stenosis, 16 score for 91–99% stenosis, and 32 score for total (100%) occlusion ⁽⁵⁾.

The relationship between the Gensini Score and acute coronary syndrome (ACS) has been extensively investigated, as the score provides a reliable estimate of coronary artery disease (CAD) burden and severity, which directly influences ACS presentation and prognosis.⁽⁶⁾

METERIAL AND METHODS

100 Patient’s diagnosed with ACS, Visiting the in Patients Department (IPD) of Cardiology Fulfilling the inclusion and exclusion criteria were enrolled for the study. The control Group consisted of 100 age and sex matched healthy subjects. The study was conducted after taking approval from the Institutional Ethics Committee and obtaining consent from the willing participants. Inclusion criteria for the study was Patients with chest pain, Shortness of breath, Epigastric pain, Age above 18 year and who were interested in taking part in the study. Patients with hypoalbunemia, Chronic inflammatory disorder, Liver disorder, Renal disorder, Brain ischemia, Pregnant & lactating females, Age below 18 year, Patient declined to participate were excluded from the study. Standard aseptic techniques were used to collect blood samples, and the Coronary angiography was used to calculate the Gensini score for assessing the severity of coronary artery disease, while serum Ischemia Modified Albumin (IMA) levels were measured using the ELISA method.

RESULTS

A total of 200 participants were studied, including 100 ACS patients (75 males, 25 females) and 100 controls (58 males, 42 females). The mean IMA level was significantly higher in ACS patients (13.31 ± 6.41 ng/mL) compared to controls (2.76 ± 0.99 ng/mL, P < 0.0001). Based on Gensini scores, mean IMA levels increased with disease severity: 7.26 ± 2.37 ng/mL (score 0–24), 13.74 ± 4.12 ng/mL (score 25–53), and 18.88 ± 5.18 ng/mL (score >53), showing a highly significant difference (P < 0.0001).

Table no:1 Distribution of the subject on the basis of gender

Table no:2 Comparison of mean IMA levels between Cases and Controls groups.

Table no: 3 Distribution of IMA on the basis of Gensini Score

Fig:1 Distribution of the subject on the basis of gender

Fig:2 Comparison of mean IMA levels between Cases and Controls groups.

Fig:3 Distribution of IMA on the basis of Gensini Score

In the present study, the mean age was comparable between ACS patients and the control group. Serum IMA levels were significantly higher in ACS patients compared to controls. When analyzed according to Gensini score, IMA levels increased progressively with the severity of coronary artery disease, showing strong statistical significance. This suggests that higher IMA levels are associated with more severe coronary artery involvement, indicating that IMA can be a useful marker not only for early detection of ACS but also for assessing the extent of coronary artery disease.

According to the World Health Organization (WHO), cardiovascular disease, particularly ACS, is the leading cause of death globally. It was estimated that CVDs caused 19.8 million deaths in 2022, accounting for nearly 32% of all fatalities worldwide, with heart attacks and strokes responsible for 85% of these deaths (WHO, 2022) ⁽⁷⁾.

In the present study, 75% of ACS cases were male and 25% were female. Across Unstable Angina, NSTEMI, and STEMI, the majority of patients were male, and the male-to-female ratio was similar to that of the control group. Anthony N et al., 2024⁽⁸⁾ also reported that ACS was more prevalent in males (60%) compared to females (40%).

The study observed that IMA levels were significantly elevated in ACS patients compared to controls. Similar findings were reported by Ralapanawa U et al., 2024⁽⁹⁾ supporting the potential of IMA as a diagnostic biomarker. Aggarwal et al., 2011⁽¹⁰⁾ also found that IMA levels were significantly higher in patients with myocardial ischemia presenting with chest pain compared to controls.

When IMA levels were analyzed according to Gensini score, a statistically significant increase was observed with higher scores, indicating a correlation between IMA and the severity of coronary artery disease. Toklu O et al., 2016⁽¹¹⁾ demonstrated that IMA levels were a strong predictor of the extent and severity of coronary artery disease in patients with unstable angina, as determined by Gensini score. Similarly, Demirtas A et al., 2013⁽¹²⁾ reported that IMA and BNP could predict the extent of coronary artery disease before performing coronary angiography, with Gensini score used to quantify severity and >50% stenosis considered severe.

Overall, these findings indicate that IMA is not only a sensitive marker for early detection of ACS but also correlates with angiographic severity, providing valuable information for risk stratification and management of patients with coronary artery disease.

CONCLUSION

The study findings suggest that serum Ischemia Modified Albumin (IMA) levels are significantly elevated in patients with Acute Coronary Syndrome (ACS) compared to controls. Moreover, IMA levels increase progressively with higher Gensini scores, indicating a strong association between this biomarker and the severity of coronary artery disease. Therefore, IMA can serve as a useful marker not only for early detection of ACS but also for assessing the severity of coronary artery involvement.

REFERENCES

1. Lloyd-Jones D, et al. Heart disease and stroke statistics— 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119(3):e21-e181.
2. Lippi G, Sanchis-Gomar F, Cervellin G. Chest pain, dyspnea and other symptoms in patients with type 1 and 2 myocardial infarction. A literature review. Int J Cardiol2016;215:20-2.
3. Apple, F.S., Wu, AH., Mair, J., Ravkilde, J., Panteghini, M., Tate, J.,Pagani,F.,Christenson,R.H.,Mockel,M.,Danne,O. and Jaffe, A. S.: Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome. Clin. Chem., 51(5): 810–824 (2005).
4. Erenler KA, Yardan T, Kati C, Altantas M, Turedi S. Role of ischemia modified albumin in clinical practice. Laboratoriums Medicine. Vol 39, no. 4, 2015, pp.241-247.
5. Shiga Y, Tashiro K, Miura E, Higashi S, Kawahira Y, Kuwano T, Sugihara M, Miura S. Association between major adverse cardiovascular events and the Gensini score or coronary artery calcification score in hypertensive patients who have undergone coronary computed tomography angiography. Cardiol Res. 2023 Apr;14(2):91-6. doi:10.14740/cr1453.
6. Kurtul A, Ocek AH, Murat SN, Duran M, Kivrak A, Ergun G, et al. The association of Gensini score with SYNTAX score in patients with acute coronary syndrome. Int J Cardiovasc Imaging. 2016 Jul;32(7):1103-10. doi:10.1007/s10554-016-0874-8.
7. Arechkik A, Moussadak N, Assafane T, EL Yousoufi A, ID Ouhazli Y, Baba MA, et al. Acute Coronary Syndrome: A Retrospective Study of the Epidemiological and Evolutionary Profile of Patients Hospitalized at the Agadir Regional Hospital in Southern Morocco. Curr Med Res Opin. 2025;18:e18749445389857. doi:10.2174/0118749445389857250530110431.
8. Anthony N, Hassan A, Ghani U, Rahim O, Ghulam M, James N, Ashfaq Z, Ali S, Siddiqui A. Age-related patterns of symptoms and risk factors in acute coronary syndrome (ACS): a study based on cardiology patients’ records at Rehman Medical Institute, Peshawar. Cureus. 2024 Apr 16;16(4):e58426. doi:10.7759/cureus.58426. PMID: 38765358; PMCID: PMC11098971.
9. Ralapanawa U, Sivakanesan R, Tennakoon S, Karunathilake P. Ischemia-modified albumin: is it a promising marker in acute coronary syndrome? BMC Cardiovasc Disord. 2024;24:436. doi:10.1186/s12872-024-04108-2.
10. Aggarwal K, Seth S, Dahiya K, Aggarwal HK, Aggarwal MK. Ischemia modified albumin in patients of cardiac and non cardiac chest pain. Biomed Res 2011;23:61–5.
11. Toklu O, Akgöl E, Yeşil M, Abusoglu S, et al. Predictive value of ischemia modified albumin in determining the severity of coronary artery disease. Eurasian Clin Anal Med. 2016;5(1).doi:10.4328/AEMED.100.
12. Demirtas A, Karabag T, Sayin M, Akpinar I, Yavuz N, Aydin M. Can Ischemia modified albumin and brain natriuretic peptide levels predict the extension of coronary artery disease in low intermediate risk unstable angina pectoris? J Am Coll Cardiol 2013;62(18_S2), C121–C121.