European Journal of Cardiovascular Medicine

Globally, ACS is the leading cause of death. Oxidative stress and inflammation are the key contributor for atherosclerotic plaque formation which can eventually rupture and opens the way for the propagation of blood clot. The coronaries become blocked as a result of this clot, which impedes blood flow to the myocardium [1].

Three primary factors determine the prognosis in ACS patients:1. Myocardial damage 2. ACS severity 3. disease's instability and resistance to treatment [2].

The ubiquitous enzyme known as GGT is essential in metabolising glutathione (G-SH), a vital antioxidant in human body. Measuring GGT activity is commonly performed in diagnosing obstructive biliary illnesses and liver disorders, as well as an indication of alcohol intake. Increased levels of GGT activity are linked to systemic inflammation, oxidative stress, and metabolic syndrome. High levels of GGT are found in atherosclerotic plaques and it is also a risk factor for plaque rupture [3].

The terms "ACS" refers to NSTEMI, UA, and STEMI. Presently troponins are used for detecting myocardial necrosis in the diagnosis of ACS [4].

The present study aims to determine the relationship between GGT and ACS in addition to the utilization of a traditional set of biomarkers, including troponin-I, to improve their application by making it easier to reclassify patients into high- and low-risk groups and create appropriate treatment regimens. The study also ascertained to know if there was any association between serum GGT levels with MACE

BLDE (Deemed to be University) Shri B. M. Patil Medical College Hospital and Research Centre, Vijayapura was the site of a cross-sectional study from December 2023 to August 2024. A 10% accuracy level and a 95% confidence range were used to determine the sample size.

Age greater than eighteen years and a myocardial infarction confirmed by laboratory and clinical means were prerequisites for inclusion. Exclusion criteria were history of alcohol intake in <24 hours, hepatobiliary disorders, drug intake like barbiturates, phenytoin, anti-tubercular drugs. A sample size of 80 were included in this study. A complete detailed examination along with electrocardiography (ECG), biochemical evaluation including complete blood picture, kidney and hepatic function tests, GGT, troponin I were done. Other tests like echocardiography, coronary angiography (CAG) was also done. The enzymatic calorimetric test was used to assess the serum GGT levels at 37°C. The Auto-analyser was used to detect the reagent L-gammaglutamyl-3-carboxy-4-nitroanilide. For the research purpose serum GGT levels of >70 IU/L were considered elevated [5]. Upon admission to the hospital, STEMI was defined as an ST-elevation of ≥1mm in two contiguous leads except anterior wall leads (V2, V3), where ST elevation of ≥1.5mm, 2mm and 2.5mm in females of all age groups, males>40years and males<40years respectively was considered.The  absence of ST elevations allowed for the diagnosis of either UA or NSTEMI, which were distinguished by the presence of cardiac enzymes. Those with flat T waves, pseudo-normalisation of T waves, persistent or transitory ST segment depression or T wave inversion, or no ECG alterations at presentation with elevated cardiac enzymes were classified as NSTEMI; those without elevated cardiac enzymes were classified as UA [6]. After performing CAG patients were divided into single, double and triple vessel disease and GGT levels were correlated with them respectively.

Spearman's correlation was used to calculate the correlation between the variables. Every test was two-tailed, and a statistical significance was derived when p-value was less than 0.05.

The study sample showed maximum patients in the age group of 60-79 years i.e.,45 (56.25%).

Table 1: Age: Frequency and percentage distribution

Table 2: Gender: Frequency and percentage distribution

The study consisted of sample size of 80 with 52(65%) males and 28(35%) females.

Table 3: Comorbidities: Frequency and percentage distribution

Majority (61.25%) of the people at presentation had at-least one of the comorbidities at the time of presentation.

Table 4: Statistical variables of GGT

The mean, median and standard deviation of gamma glutamyl transferase were 78.3IU/L, 68IU/L and 45.592IU/L respectively.

Table 5: ACS: Frequency and percentage distribution

The study consisted mainly of STEMI patients i.e., 49 (61.3%) followed by NSTEMI (25%) and unstable angina (13.8%).

Table 6: Association of GGT with ACS

 Majority of the people with STEMI had serum GGT levels more than 70IU/L.

The study showed significant correlation between serum GGT and acute coronary syndrome with p-value of 0.005.

Table 7: Association of GGT with MACE

 The major adverse cardiovascular outcomes were found in 8 patients (10%). Death (37.5%) was the predominant adverse cardiovascular outcome among them.

The study showed significant correlation between serum GGT and major adverse cardiovascular event with the majority of MACE occurring in patients who had serum GGT levels above 70IU/L, with a p-value of 0.02.The increment in levels of GGT and troponin-I was directly proportional.Additionally, the study also showed significant correlation between GGT and CAG where maximum patients in both double and triple vessel disease had GGT levels above 70IU/L.

Current investigation intended to determine association of GGT with ACS and its correlation with MACE. We identified the risk factors pertaining to ACS like hypertension, diabetes, valvular heart disease. A total of 80 patients were categorised into UA, NSTEMI, STEMI.Serum GGT levels were estimated,

and MACE were noted if occurred during hospital stay. Results demonstrated statistically significant correlation between serum GGT with both ACS and MACE.

Other studies based on GGT had both consistent and conflicting data in relation to our present study are as follows., research by Tanler ulus et al., concluded patients with MACE had considerably higher serum GGT activity than patients without MACE, suggesting that GGT was a predictor of the onset of MACE-CCU on its own (P=0.001) [7]. In a study by Mustafa Duran et al., patients with ACS who had higher serum GGT levels at admission have a higher burden of atherosclerosis [8].In a study by Amina Valjevac et al., when assessing risk in individuals who have chest discomfort and are suspected of having ACS, GGT may be employed as an additional measure [9].

In an observation by M. Sheikh et al., the GGT's diagnostic accuracy was 74.9%. In young, the existence of premature CAD might be predicted by GGT levels in those with typical chest discomfort or positive results from non-invasive testing [10]. In study research by Dr. G. Methun senthur et al., ACS patients have considerably higher than normal levels of gamma-glutamyl transferase. GGT levels did not link with unstable angina, but they did independently correlate with STEMI and NSTEMI. These findings did not correlate with our study because even in unstable angina our study showed elevation of GGT [11]. In a study by K. Rajani kumari et al., patients who arrive with acute coronary syndrome have much higher than normal levels of gamma glutamyl transferase. GGT levels did not link with unstable angina, but they did correlate independently with STEMI and NSTEMI which contradicted with the present research [12].

Research by Siavash Arasteh et al., patients with more than 50% obstruction in coronaries exhibited greater levels of GGT [13] which strongly relates with our study. Selami Demirelli et al., showed a fairly strong correlation between troponin-positive and GGT activity in their investigation. GGT activity may be used in conjunction with other diagnostic markers to predict troponin positivity in patients who presented with chest pain [14]. These were in line with our research. In a study by Sujesh kumar N et al., GGT is helpful in assessing ACS severity in troponin positive patients, and this is further enhanced by the high association that exists between GGT and Troponin-I [15].

Thus, our study concluded that serum GGT can be used as a valuable inexpensive tool in ACS severity assessment and also to predict MACE in the hospital.

LIMITATIONS

Increased multi-centric research with bigger sample sizes will contribute to the correctness of the study. This study's single-centre design presented challenges. Follow up of the patients was not done to identify further MACE.

Current study found a significant positive correlation with levels of GGT with severity of ACS. In this study even in UA there was an increase in the levels of GGT which can predict the development of further complications and can also aid in the early initiation of treatment. Thus, GGT can be used as a valuable and inexpensive marker in predicting the severity of ACS, initiating early treatment and to predict MACE during the hospital stay.

1. Benslaimam S J, Garcia U G, Sebal A L et al. Pathophysiology of Atherosclerosis. Int. J. Mol. Sci. 2022; 23(3346): 1-38. 10.3390/ijms23063346.
2. Bugiardini R: Risk stratification in acute coronary syndrome: focus on unstable angina/non-ST segment elevation myocardial infarction. Heart. 2004 ; 90(7): 729–731. 10.1136/hrt.2004.034546.
3. Ndrepepa G, Colleran R, Kastrati A: Gamma-glutamyl transferase and the risk of atherosclerosis and coronary heart disease. Science direct. 2018; 476: 130-138. 10.1016/j.cca.2017.11.026.
4. Danese E, Montagnana M: An historical approach to the diagnostic biomarkers of acute coronary syndrome. ATM. 2016; 4(10): 194. 10.21037/atm.2016.05.19.
5. Rajan B, Velappam P, Salaam A, et al: Association of Serum Gamma Glutamyl Transferase Level with Acute Coronary Syndrome and Its Correlation with Major Adverse Cardiovascular Outcomes - A Single Center Cross Sectional Study from a Tertiary Care Centre in Kerala. Jebmh. 2021; 8(25): 2349-2562. 10.18410/jebmh/202 1 /404.
6. Jyoti J, Verma N, Shashank B, Pradeep D: Gamma Glutamyl Transferase Levels in Patients with Acute Coronary Syndrome: A Cross-Sectional Study. Journal of Cardiovascular Disease Research. 2017; 8(3): 96-100. 10.5530/jcdr.2017.3.22.
7. Ulus T, Yildirir A, Sade L E et al: Serum gamma-glutamyl transferase activity: new high-risk criteria in acute coronary syndrome patients? Coronary Artery disease. 2008; 19(7): 489-495.10.1097/MCA.0b013e32830eab8c.
8. Duran M, Uysal O K et al: Serum gamma-glutamyltransferase and the burden of atherosclerosis in patients with acute coronary syndrome. Arch Turk Soc Cardiol. 2013; 41(4): 275-281. 10.5543/tkda.2013.99896.
9. Valjevac A, Rebic A, Mehmedbasic A H et al: The value of gamma glutamyltransferase in predicting myocardial infarction in patients
10. with acute coronary syndrome. Future Cardiol.2018; 14(1): 37–45. 10.2217/fca-2017-0033.
11. Sheikh M, Tajdini M, Shafiee A et al: Association of serum gamma-glutamyltransferase and premature coronary artery disease. Neth Heart J. 2017; 25: 439–445. 10.1007/s12471-017-0964-5.
12. Senthur M G, Dr. Baburaj K, Dr. Paari N. Estimation of gamma-glutamyl transferase with acute coronary syndrome. International Journal of Advanced Research in Medicine. 2021; 3(2): 477-480. 10.22271/27069567.2021.v3.i2g.292.
13. Kumari K R, Srikanth T, Srinivas B, Sammaiah P. ASSOCIATION OF GAMMA GLUTAMYL TRANSFERASE WITH ACUTE CORONARY SYNDROME AND CORRELATION WITHIN HOSPITAL OUTCOMES. Int J Acad Med Pharm. 2022; 4 (5): 280-284. 10.47009/jamp.2022.4.5.56.
14. Arasteh S, Moohebati M, Avan A et al: Serum level of gamma-glutamyl transferase as a biomarker for predicting stenosis severity in patients with coronary artery disease. Indian Heart Journal 70 (2018) 788–792. 10.1016/j.ihj.2017.11.017.
15. Demirelli S, Firtina S, Askin L, et al. Utility of γ-Glutamyl Transferase in Predicting Troponin Elevation in Emergency Departments. Angiology. 2016;67(8):737-741. 10.1177/0003319715613923.
16. Kumar SN, Krishnan S. Comparison of Gamma-glutamyl Transferase and Troponin-I Levels in Patients Presenting with Acute Coronary Syndrome. Indian J Med Biochem .2018;22(2):114-119. 10.5005/jp-journals-10054-0067.