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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 2  |  Issue : 1  |  Page : 19-23

Prognostic value of endothelin-1 level in diabetic patients with coronary artery disease


1 Department of Cardiology, Shibin Elkom Teaching Hospital, General Organization of Teaching Hospitals and Institutes, Ministry of Health, Minoufia, Egypt
2 Department of Cardiology, Faculty of Medicine, Menoufia University, Shibin El-Kom, Minoufia, Egypt
3 Department of Biochemistry, Faculty of Medicine, Menoufia University, Shibin El-Kom, Minoufia, Egypt
4 Department of Cardiology, Police Academic Hospital, Ministry of Interior, Cairo, Egypt

Date of Submission08-Mar-2020
Date of Decision14-Mar-2020
Date of Acceptance31-Mar-2020
Date of Web Publication16-Jun-2020

Correspondence Address:
Dr. Mostafa Attia Eldegwi
Asem Street, Shibin El-Kom, Minoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ACCJ.ACCJ_2_20

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  Abstract 


Background and Objectives: ET-1 has been demonstrated to play a role in endothelial dysfunction and inflammation, both of which are actively involved in the pathophysiology of the onset and progression of CAD. Diabetes mellitus (DM) increases the risk of CAD and has unfavorable effects on the vascular endothelium, hence, the importance of assessing this plasma marker and its relation to the severity of CAD in diabetic patients. The aim of this work is to study the prognostic value of the plasma level of the new marker, endothelin-1 (ET-1), in diabetic patients with coronary artery disease (CAD). Methods: Seventy patients with coronary artery lesions of not < 50% in at least one main coronary artery were randomized into 35 diabetics (Group I) and 35 nondiabetics (Group II). Twenty patients with normal coronaries as a control group (Group III) were also enrolled. The severity of coronary artery lesions was assessed by GINSINI score (GS) and SYNTAX score, and then, the relationship between them and ET-1 level was evaluated. Results: The ET-1 levels were significantly higher in Group I with higher GS values of 34.29 ± 11.7 points and SYNTAX scores of 18.4 ± 11.17 points than in Group II with lower GS values of 23.23 ± 8.14 points and SYNTAX of scores 12.06 ± 12.11 points (ET-1 was 187.93 ± 146.61 ng/L in Group I vs. 76.30 ± 91.83 ng/L in Group II, P = 0.001). ET-1 levels were significantly higher in Group I than in Group III (187.93 ± 146.61 ng/L vs. 26.16 ± 7.32 ng/L, P = 0.001). ET-1 levels were significantly higher in Group II than in Group III (76.30 ± 91.83 ng/L vs. 26.16 ± 7.32 ng/L, P = 0.001). Conclusion: There is a positive correlation between DM and both ET-1 levels and the severity of coronary artery lesions, P = 0.001.

Keywords: Coronary artery disease, plasma endothelin-1, risk factors


How to cite this article:
Eldegwi MA, Ibrahim WA, Elmadbouh IS, Mostafa AA, Kamal AM. Prognostic value of endothelin-1 level in diabetic patients with coronary artery disease. Ann Clin Cardiol 2020;2:19-23

How to cite this URL:
Eldegwi MA, Ibrahim WA, Elmadbouh IS, Mostafa AA, Kamal AM. Prognostic value of endothelin-1 level in diabetic patients with coronary artery disease. Ann Clin Cardiol [serial online] 2020 [cited 2020 Jul 3];2:19-23. Available from: http://www.onlineacc.org/text.asp?2020/2/1/19/286472




  Introduction Top


Coronary artery disease (CAD) is recognized as a health threat worldwide and remains a leading cause of both morbidity and mortality.[1] Hence, understanding its predictors would greatly aid in disease prevention and treatment, and the possible relationship between various plasma markers and CAD had intensively been investigated.[2]

Among these markers, endothelin-1 (ET-1) has been demonstrated to play a role in endothelial dysfunction and inflammation,[3] both of which are actively involved in the pathophysiology of the onset and progression of CAD, from the formation of acute coronary syndrome (ACS) and heart failure following myocardial infarction.[4]

Moreover, it has been reported that the baseline plasma ET-1 level can be used to predict the short-term or long-term outcomes in patients with ACS and/or acute heart failure.[5] More importantly, very few studies focusing on the diagnostic value of the plasma ET-1 level for discriminating the severity of CAD have been conducted.

Recently, big ET-1, the biological precursor of ET-1, with a longer half-life, has been reported to be a more accurate indicator. Therefore, in this study, we tried to explain the usefulness of the plasma high ET-1 level in predicting the severity of CAD in diabetic patients.


  Methods Top


This is a cross-sectional study in which the data were collected from January 2019 to December 2019 from patients who were selected from the Cardiology Department, Faculty of Medicine, Menoufia University Hospital, Egypt. The current study included 90 patients who were divided, according to the presence or absence of diabetes mellitus (DM) and CAD, into three groups: Group I: 35 diabetic patients with CAD, Group II: 35 nondiabetic patients with CAD, and Group III (control group): 20 nondiabetic patients with normal coronary angiography.

The study group was chosen by the convenient sample technique. Written informed consent was obtained from all participants who were submitted to the following: full history taking, clinical examination, electrocardiography, fasting and postprandial blood sugar, glycosylated hemoglobin, and lipid profile measurement. Echocardiography was performed using VIVID S5 machine stressing on ejection fraction (EF), regional wall motion abnormalities and scoring of the 16 left ventricular (LV) segments according to the American Society of Echocardiography as follows: normokinesia will be given a score of 1 point which means normal wall thickening and endocardial excursion, hypokinesia will be given a score of 2 points, which means reduced wall thickening and endocardial excursion, akinesia will be given a score of 3 points, which means the absence of wall thickening and endocardial excursion and dyskinesia will be given a score of 4 points, which means systolic outward stretching or thinning. Then, the wall motion scoring index (WMSI) was calculated by dividing the total points obtained over the number of LV wall segments, 16, where WMSI of 1 is normal, scores of 1.5, 2, and 2.5 are for mild, moderate, and severe hypokinesia, respectively, and finally, a score of 3 is for akinesia.[6]

Serum level of ET-1 was measured before coronary angiography using a highly sensitive and specific commercial sandwich-enzyme immunoassay and was correlated with scoring assessment of coronary arteries. Coronary angiography was performed using the PHILIPS catheterization device together with scoring of coronary artery lesions using SYNTAX and GINSINI score (GS) systems for each patient.

Statistical analysis

Data were statistically analyzed by an IBM compatible personal computer with the SPSS Statistical Package for the Social Sciences version 23 (SPSS Inc., Released 2015. IBM SPSS statistics for Windows, version 23.0, Armnok, NY, USA: IBM Corp.). Categorical data were expressed as number and percentage. Continuous data were expressed as mean and standard deviation. Suitable tests of significance were calculated. A comparison between the groups was done using the Chi-square test or Fishers' exact test for categorical data and Student's t-test or ANOVA (F) test when suitable for continuous data. The accepted level of significance in this work was P = 0.05.


  Results Top


This study included 59 male patients (65.6%) and 31 female patients (34.4%) with 32–75 (mean: 58.21 ± 8.46 and median 59) years of age. Analysis of anginal symptoms showed that 74 patients (82.2%) had chest pain, and 16 patients (17.8%) had exertional dyspnea, as shown in [Table 1].
Table 1: Demographics and complaints of studied groups

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Patients were divided into three groups and were compared regarding sex, age, risk factors, and their complaints, as shown in [Table 2].
Table 2: Comparison of demographic data, risk factors, and complaints of the studied groups

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Group I included 35 diabetic patients, of whom 24 patients (68.6%) were male and 11 patients (31.4%) were female with 47–75 years (mean: 61 ± 6.27 and median age of 63 years). Eight patients (22.9%) had dyslipidemia, 26 patients (74.3%) had exertional chest pain, and 9 patients (25.7%) had exertional dyspnea.

Group II included 35 patients, of whom 18 patients (51.4%) were male and 17 patients (48.6%) were female with 42–74 (mean: 59.03 ± 8.8 and median age of 59) years of age. Twenty-six patients (74.3%) had systemic arterial hypertension (HTN), eight patients (22.9%) were smokers, and 18 patients (51.4%) had dyslipidemia. Twenty-eight patients (80%) had exertional chest pain and seven patients (20%) had exertional dyspnea.

Group III included 20 patients, of whom 15 patients (75%) were male and 5 patients (25%) were female with 32–70 (mean: 58.9 ± 8.1 and the median age of 57 years). Thirteen patients (65%) had HTN and seven patients (35%) were smokers. These patients had exertional chest pain.

In our study, we compared EF, laboratory investigations, and scoring systems of CAD among the three groups, as shown in [Table 3].
Table 3: Comparison of investigations, ejection fraction %, wall motion scoring index, endothelin-1, coronary angiographic scoring among studied groups

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There was no significant difference regarding the EF between Group I and Group II (43.69% ± 5.38% vs. 45.29% ± 5.09%, P = 0.194), whereas there was a significant difference between Group I and Group III regarding the EF (43.69 ± 5.38 vs. 63.5 + 4.65, P < 0.001). There was also a significant difference between Group II and Group III regarding the EF (45.29% +5.09% vs. 63.5 ± 4.65, P = 0.001).

There was no major difference regarding the WMSI between Group I and Group II (P = 0.194), whereas there was a high significant difference between Group I and Group III regarding the EF (P = 0.001) and between Group II and Group III (P < 0.001), as shown in [Figure 1].
Figure 1: Comparison of wall-motion scoring index among studied groups

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More importantly, the ET-1 levels were significantly higher in Group I with high GS values of 34.29 ± 11.7 points and SYNTAX scores of 18.4 ± 11.17 points than in Group II with lower GS values of 23.23 ± 8.14 points and SYNTAX of scores 12.06 ± 12.11 points (187.93 ± 146.61 ng/L in GI vs. 76.30 ± 91.83 ng/L, P = 0.001).

ET-1 levels were significantly higher in Group I than in Group III (187.93 ± 146.61 ng/L vs. 26.16 ± 7.32 ng/L, P = 0.001). ET-1 levels were significantly higher in Group II than in Group III (76.30 ± 91.83 ng/L vs. 26.16 ± 7.32 ng/L, P = 0.001). ET-1 levels were significantly higher in Group II than in Group III (76.30 ± 91.83 ng/L vs. 26.16 ± 7.32 ng/L, P = 0.001).

This means that there is a positive correlation between DM and both the severity of coronary artery lesions and ET-1 levels.

There was a positive correlation between the plasma levels of ET-1 and the number of coronary arteries affected (P = 0.001), as its levels were the highest among patients with multivessel CAD (219.34 ± 14.65 ng/L). This correlation was followed by left main artery (LM) lesions (172.87 ± 17.2 ng/L), then two vessel CAD (157.31 ± 16.79 ng/L), after that chronic total occlusion lesions (113.16 ± 12.13 ng/L), and finally, one vessel CAD (69.28 ± 7.77 ng/L), as shown in [Table 4].
Table 4: Relationship between coronary artery lesion and endothelin-1

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The plasma ET-1 level indicated a strong discriminatory power for predicting a high GS; the optimal cutoff value of the plasma ET-1 level for predicting a high GS was 48.36 ng/L, with a sensitivity of 77.1% and specificity of 80%. Higher levels of ET-1 were detected in diabetic patients with CAD, GI, compared to nondiabetic patients with CAD, GII, as shown in [Table 5].
Table 5: Validity of endothelin-1 as a predictor of the severity of coronary artery disease in diabetic patients

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  Discussion Top


The endothelium plays an integral role in the regulation of vascular tone, platelet activity, leukocyte adhesion, and thrombosis and is intimately involved in the development of atherosclerosis. Endothelial dysfunction has been observed in patients with established CAD or coronary risk factors, both in the coronary and peripheral vasculature.[7] Coronary endothelial dysfunction, in epicardial or resistance vessels, is typically accompanied by myocardial perfusion defects suggestive of ischemia. In patients with dysfunctional endothelium, the loss of flow-mediated and catecholamine-stimulated nitric oxide (NO) release and increased production of ET-1 permits unopposed constriction to catecholamines. Thus, the loss of NO and increased levels of ET-1 may contribute to impaired dilation or constriction of epicardial and resistance vessels.

Endothelial dysfunction and reduced NO with increased levels of ET-1, in particular, may play an important role in destabilizing atherosclerotic plaques as well. Endothelial dysfunction, increased production of ET-1, and deficiency of NO exacerbate myocardial ischemia in patients with stable angina or acute-ischemic syndromes. In addition, endothelial dysfunction may predispose to a transition from stable-to-unstable ischemic syndromes.[8] The aim of this work was to study the prognostic value of a new marker, ET-1, level in diabetic patients with CAD and to determine its relation to the clinical presentation, cardiovascular risk factors, and the extent, severity, and angiographic lesion morphology of coronary atherosclerosis. Seventy patients with CAD were included, 35 with DM Group I and 35 without DM (Group II), versus 20 patients with normal coronary arteries as a control group (Group III). This study showed that plasma ET-1 levels are significantly elevated in patients with DM and CAD as compared to those without DM.[9],[10]

There was a significant association between plasma ET-1 levels and the number of arteries affected by atheroma in humans. In the present study, the demonstration of significantly higher levels of plasma ET-1 in patients with DM and CAD than in normal persons (187.93 ± 146.61 vs. 26.16 ± 7.32 ng/L, P = 0.001) suggests a role for this peptide in the pathophysiology of coronary atheroma.

Therefore, the trend toward an association between elevated plasma ET-1 levels and severity of CAD observed in this study may reflect the degree of associated endothelial dysfunction. The present study demonstrates a positive correlation between the plasma ET-1 level and the severity and number of diseased coronary segments.

In our study, we examined the relation between plasma ET-1 and the angiographic equivalent of diabetic patients with CAD. The plasma ET-1 level was significantly elevated in patients with DM and CAD when compared with healthy controls (187.93 ± 146.61 vs. 26.16 ± 7.32 ng/L, P = 0.001) and patients without DM but with CAD (76.30 ± 91.83 ng/L, P = 0.001). This observation indicates that ET-1 has a good predictive value for the severity of CAD in diabetic patients.


  Conclusion Top


Plasma ET-1 levels were significantly higher in diabetic patients with CAD compared to Group III. Plasma ET-1 levels were significantly higher in nondiabetic patients with CAD compared to Group III.

Plasma ET-1 levels were significantly higher in diabetic patients with CAD compared to nondiabetic patients with CAD. A positive correlation between the plasma ET-1 level and the severity of CAD as assessed by SYNTAX and GS scoring systems had been identified.

Recommendations

Plasma ET-1 may be used as a surrogate marker for the severity of CAD in diabetic patients with evidence of ischemic heart disease.



Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Roger VL. Epidemiology of myocardial infarction. Med Clin North Am 2007;91:537-52.  Back to cited text no. 1
    
2.
Hong LF, Li XL, Luo SH, Guo YL, Zhu CG, Qing P, et al. Association of fibrinogen with severity of stable coronary artery disease in patients with type 2 diabetic mellitus. Dis Markers 2014;2014:485687.  Back to cited text no. 2
    
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Kolettis TM, Barton M, Langleben D. Endothelin in coronary artery disease and myocardial infarction. CardioL Rev 2013;21:249-56.  Back to cited text no. 3
    
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Khimji AK, Rockey DC. Review: Endothelin-biology and disease. Cell Signal 2010;22:1615-25.  Back to cited text no. 4
    
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Freixa X, Heras M, Ortiz JT, Argiró S, Guasch E, Doltra A, et al. Usefulness of endothelin-1 assessment in acute myocardial infarction. Rev Esp Cardiol 2011;64:105-10.  Back to cited text no. 5
    
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Lebeau R, Serri K, Lorenzo MD, Sauvé C, Le VH, Soulières V, et al. Assessment of LVEF using a new 16-segment wall motion score in echocardiography. Echo Res Pract 2018;5:63-9.  Back to cited text no. 6
    
7.
Wesson DE, Simoni J, Green DF. Reduced extracellular pH increases endothelin-1 secretion by human renal microvascular endothelial cells. J Clin Invest 1998;101:578-83.  Back to cited text no. 7
    
8.
Zeiher AM, Goebel H, Schächinger V, Ihling C. Tissue endothelin-1 immunoreactivity in the active coronary atherosclerotic plaque. A clue to the mechanism of increased vasoreactivity of the culprit lesion in unstable angina. Circulation 1995;91:941-7.  Back to cited text no. 8
    
9.
Vanhoutte PM. How to assess endothelial function in human blood vessels. J Hypertens 1999;17:1047-58.  Back to cited text no. 9
    
10.
Zeiher AM, Drexler H, Wollschlager H. Modulation of coronary vasomotor tone in humans: Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 2009;83:391-401.  Back to cited text no. 10
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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