|Year : 2017 | Volume
| Issue : 3 | Page : 842-849
Association of echocardiographic epicardial fat with the extent of coronary artery disease
Walaa F Abd El-Aziz, Mahmoud K Ahmed, Wael A Badr MBBCH
Department of cardiology, Faculty of Medicine, Menoufia University, Menofia Governorate, Egypt
|Date of Submission||12-Aug-2016|
|Date of Acceptance||02-Dec-2016|
|Date of Web Publication||15-Nov-2017|
Wael A Badr
Department of Cardiology, Faculty of Medicine, Menoufia University, Shebin el-Kom, 32511, Menoufia
Source of Support: None, Conflict of Interest: None
Epicardial adipose tissue is a metabolically active tissue that accumulates around the coronary arteries and is associated with presence of atherosclerotic coronary artery disease (CAD).
The aim of the study was to evaluate the association of echocardiographic epicardial fat with the presence and severity of CAD.
Patients and methods
The present study was conducted on 140 patients, with 59 male and 81 female patients, and their mean age was 58.19 ± 9.98 years. Patients were admitted for coronary angiography and were divided into two groups (group 1 included 30 patients with normal coronary arteries and group 2 included 110 patients with CAD). The patients underwent transthoracic echocardiography and measurement of epicardial fat thickness in parasternal long-axis view and short-axis view. These echocardiographic measurements were compared with angiographic findings.
The epicardial fat thickness was significantly higher in patients with CAD (6.9 ± 1.5) compared with patients with normal coronary arteries (4.4 ± 0.8) (P < 0.001). Gensini score was significantly correlated with epicardial fat thickness (r = 0.6, P < 0.001). Epicardial fat thickness of greater than or equal to 5.2 mm had an 85% sensitivity and an 81% specificity (receiver operating characteristic area: 0.914, P < 0.001, 95% confidence interval: 0.86–0.96) for predicting CAD.
Epicardial fat thickness is significantly correlated with the presence and severity of CAD.
Keywords: coronary artery disease, echocardiography, epicardial adipose tissue
|How to cite this article:|
Abd El-Aziz WF, Ahmed MK, Badr WA. Association of echocardiographic epicardial fat with the extent of coronary artery disease. Menoufia Med J 2017;30:842-9
|How to cite this URL:|
Abd El-Aziz WF, Ahmed MK, Badr WA. Association of echocardiographic epicardial fat with the extent of coronary artery disease. Menoufia Med J [serial online] 2017 [cited 2018 Sep 25];30:842-9. Available from: http://www.mmj.eg.net/text.asp?2017/30/3/842/218278
| Introduction|| |
The coronary artery disease (CAD) is a major cause of cardiovascular morbidity and mortality; there are several risk factors for developing CAD, including obesity, hypertension, diabetes mellitus, smoking, and dyslipidemia. For the prevention and treatment of CAD, we need early detection, control of the risk factors, and treatment of the sequences of these risk factors. Although the role of classic risk factors has been well established for cardiovascular disease, several emergent conditions have not had their association definitely demonstrated. Studies are necessary to understand the actual role they have in this scenario and whether they can actually be of value in the early identification of individuals at risk of developing cardiovascular diseases .
The scientific and clinical interest in epicardial adipose tissue (EAT), which is situated between the visceral layer of the pericardium and the myocardium, is growing .
Epicardial fat is a metabolically active organ and source of several bioactive molecules that can affect cardiac morphology and function. Because of the close anatomical relationship to the heart, and the absence of fascial boundaries, EAT may locally interact and modulate the coronary arteries and myocardium through paracrine and direct secretion of proatherogenic and proinflammatory hormones and cytokines, which may induce initiation and progression of CAD .
Epicardial fat is clinically related to atherosclerosis and major anthropometric and metabolic predictors of increased cardiovascular risk .
Echocardiography is now less costly, is almost available, and is the most common technique used in cardiology for diagnosis and follow-up of cardiac diseases; therefore, assessment of echocardiographic EAT may serve as a new index of cardiac and visceral adiposity, with the as a diagnostic tool and therapeutic target .
| Patients and Methods|| |
This study was conducted on 140 patients from February 2015 to June 2016 and was approved by the Ethics Committee of Menoufia University Hospital. Written informed consent was obtained from all patients.
Patients who had an indication for coronary angiography, assessed by chest pain and/or a positive stress test, were included in the study.
The exclusion criteria include the following: history of either surgical or percutaneous prior revascularization, Pericardial effusion, more than mild valvular pathology, endocrinal diseases other than diabetes mellitus, or poor echocardiographic imaging.
All patients included in this study were subjected to a full history taking, including age, sex, and risk factors for CAD such as hypertension, diabetes mellitus, smoking, dyslipidemia, and family history of CAD.
All patients underwent thorough clinical examination: general examination with regarding patient appearance, blood pressure, and pulse; anthropometric measurements (Height, weight, BMI, and waist circumference); waist circumference measurement, which was measured at the iliac crest by a tape; BMI, which was calculated with BMI = body weight/height2 (kg/m2); and local cardiac examination for cardiomegaly, pulsations, thrills, and heart sounds.
Standard resting surface 12-lead ECG was performed for detection of any ischemic changes. The ECG was recorded on the paper at an adjusted speed of 25 mm/s with a calibration of 10 mm.
All patients underwent thorough laboratory investigations including the following: lipid profile that include fasting levels of total cholesterol, high-density lipoproteins (HDL) cholesterol, low-density lipoproteins cholesterol, and triglycerides (TG).
Diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association as following: HbA1c greater than or equal to 6.5%, fasting plasma glucose greater than or equal to 126 mg/dl, 2-h postprandial plasma glucose greater than or equal to 200 mg/dl, or random plasma glucose greater than or equal to 200 mg/dl .
A detailed transthoracic echocardiography scan was performed on all patients at the Menoufia University Hospital using General Electric System Vivid-9 (del Rio Yorba Linda, CA, USA) machine ultrasound with a 1.7–4 MHz transducer. The echocardiogram was performed with the patient breathing quietly and lying in the supine or left lateral position.
The echocardiographic evaluation was performed with two-dimensional, M-mode and Doppler echocardiography according to the recommendations of the American Society of Echocardiography to assess the following data.
Left ventricle dimensions were measured with conventional M-mode from parasternal long-axis view, including the following: left ventricular end-diastolic diameter, left ventricular end-systolic diameter, ejection fraction, fractional shortening, posterior wall thickness, and interventricular septal thickness, aortic root diameter and cusp opening, left atrium diameter, and left ventricle diastolic function. The Doppler inflow at the mitral valve was recorded for the assessment of E/A ratio and evaluation of the left ventricular diastolic function. The mitral inflow velocities were obtained by the pulsed Doppler technique from the apical four-chamber view by placing the sample volume between the tips of the mitral leaflets. Varying degree of diastolic dysfunction had been detected by the pulsed Doppler:
- Grade 1 diastolic dysfunction:mitral E deceleration time greater than 220 ms and E/A ratio less than 1, representing impaired relaxation filling pattern
- Grade 2 diastolic dysfunction: deceleration time between 150 and220 ms and E/A ratio greater than 1, suggesting a pseudonormal filling pattern
- Grade 3 diastolic dysfunction: deceleration time less than 150 ms and E/A ratio greater than 2, suggesting restrictive filling pattern.
Epicardial fat thickness measurement
The maximum epicardial fat thickness is measured from a two-dimensional long-axis view on the right ventricular free wall parallel to the aortic annulus and in the parasternal short-axis view at the tip of the papillary muscle, and then the parasternal long-axis and short-axis measurements were averaged to obtain the mean thickness.
A standard view normally displays the epicardial fat thickness in the right ventricular free wall during normal systolic and diastolic functions, and epicardial fat appears as an echo-free space between the outer wall of the right ventricle myocardium and the visceral layer of the pericardium during diastole.
It was performed for all patients using a cardiac angiography system (Siemens AG, Medical Solutions, Erlangen, Germany), by the standard Judkin's method, through the femoral artery approach, and at least five projections were performed in all patients to completely expose different segments of coronary artery. If necessary, nitroglycerin was injected into the coronary artery to relieve coronary spasm. The images with the most severe stenosis were captured, and the severity of coronary stenosis was evaluated by Gensini scoring system to examine the coronary arterial stenosis of each segment; scoring was done according to the severity of stenosis and its significance :
Score 1: if there is 1–25% stenosis.
Score 2: if there is 26–50% stenosis.
Score 4: if there is 51–75% stenosis.
Score 8: if there is 76–90% stenosis.
Score 16: if there is 91–99% stenosis.
Score 32: if there is 100% stenosis.
The aforementioned score was multiplied by different coefficients depending on the site of stenosis:
Left main artery: 5.
Proximal left anterior descending artery and proximal left circumflex artery: 2.5.
Middle left anterior descending artery: 1.5.
Proximal, middle, and distal right coronary artery; distal left anterior descending artery; the first diagonal branch; obtuse marginal branch; distal left circumflex artery; and posterior descending artery: 1.
The remaining segments: 0.5.
The total score was used as the final score of a specific patient. The sites of lesions included left main artery, left anterior descending artery, left circumflex artery, and right coronary artery.
All data were collected, tabulated, and statistically analyzed using statistical package for the social sciences for Windows (version 19.0; SPSS Inc., Chicago, Illinois, USA). Continuous variables are expressed as mean ± SD. A t-test was used to assess differences among groups, and categorical variables were compared with a χ2-test. P value less than 0.05 was considered statistically significant, and a 95% confidence interval was used. The cut-off value of EAT thickness for predicting CAD with corresponding specificity and sensitivity was estimated by receiver operating characteristic (ROC) curve analysis.
| Results|| |
The present study was conducted on 140 patients. There were 59 males and 81 females, and their mean age 58.19 ± 9.98 years. The clinical and laboratory characteristics of the two study groups showed that the incidence of smoking, diabetes mellitus, hypertension, and dyslipidemia was increased in CAD group more than normal coronary arteries group [Table 1].
|Table 1: The clinical and laboratory characteristics of the two study groups|
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The echocardiographic characteristics of the two study groups showed that the left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricle mass, left atrium diameters, and aortic root diameters were increased in CAD group more than normal coronary arteries group. Moreover, the systolic and diastolic functions were more negatively affected in CAD group more than normal coronary arteries group [Table 2].
Association of epicardial fat thickness with the severity of coronary artery disease
The average epicardial fat thickness was significantly higher in patients with CAD (6.9 ± 1.5) compared with patients with normal coronary arteries (4.4 ± 0.8), (P < 0.001) [Table 3].
|Table 3: Comparison of epicardial fat thickness between coronary artery disease and noncoronary artery disease groups|
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Furthermore, epicardial fat thickness increased significantly with the degree of CAD (P < 0.001, 95% confidence interval). Gensini score was significantly correlated with EAT thickness (r = 0.6, P < 0.001).
ANOVA test showed the significant difference of Gensini score between the groups according to the quartile of epicardial fat thickness. The first quartile of epicardial fat thickness is 1.10–4.48 mm, the second quartile is 4.49–6.23 mm, the third quartile is 6.24–7.59 mm, and the fourth quartile is 7.60–16.55 mm. An increasing trend in Gensini score was seen according to quartiles of EAT (P < 0.001) [Figure 1].
|Figure 1: Association of Gensini score with epicardial fat thickness. An increasing trend in Gensini score was seen according to quartiles of epicardial adipose tissue (EAT) thickness (*P < 0.001).|
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EAT of greater than or equal to 5.2 mm had an 85% sensitivity and an 81% specificity (ROC area: 0.914, P < 0.001, 95% confidence interval: 0.86–0.96) for predicting CAD [Figure 2].
|Figure 2: Receiver operating characteristic curve of the epicardial adipose tissue thickness for predicting angiographic coronary artery disease.|
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Furthermore, from the ROC curve of the EAT thickness, the patients clinical and laboratory characteristics were classified according to the cut-off value of EAT thickness and showed that the CAD incidences, male sex, diabetes mellitus, hypertension, smoking, TG, and waist circumference were increased and HDL cholesterol was decreased in patients with EAT thickness greater than or equal to 5.2 mm in comparison with patients with EAT thickness less than 5.2 mm [Table 4].
|Table 4: Clinical and laboratory characteristics according to epicardial adipose tissue thickness|
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Correlation between epicardial fat thickness and other parameters
There was a significant correlation between EAT and waist circumference (r = 0.3, P < 0.01). However, there were no significant correlations between EAT thickness and lipid profile and other parameters [Table 5].
|Table 5: Correlation between epicardial adipose tissue thickness and other variables|
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Multivariate analysis revealed that epicardial fat thickness was found to be an independent and powerful predictor of CAD in the multivariate regression model, including well-known risk factors such as age, hypertension, diabetes mellitus, smoking, dyslipidemia, and family history of CAD [Table 6].
|Table 6: Multivariate analysis using the logistic regression method for prediction of coronary artery disease|
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| Discussion|| |
Epicardial fat, in which coronary arteries are embedded, is a specialized visceral adipose tissue around the heart located between the visceral pericardium and myocardium. There is no anatomical barrier between epicardial fat and myocardium, and they share the same microcirculation; therefore, epicardial fat, which is a component of visceral adiposity, may contribute to the progression of coronary atherosclerosis .
The most prominent physiologic function of epicardial fat is to protect the coronary arteries against torsion induced by arterial pulsation and cardiac contraction as well as protect them against trauma. Second, it serves as a buffering system against toxic effects of high levels of circulatory free fatty acids by its ability to scavenge excess fatty acids. Third, the increased lipolytic activity of epicardial fat suggests that this fat deposit may serve as a local energy source by producing free fatty acids under high metabolic demands during ischemia .
On the contrary, epicardial fat can secrete numerous bioactive molecules, including adiponectin, resistin, and inflammatory cytokines. Inflammatory mediators originating outside the coronary artery can also induce compositional changes in the inner layer of intima. Therefore, increased epicardial fat thickness might act as an inflammatory organ, which affects vascular function.
This study included 140 patients who were divided into two groups: the first group included patients who had normal coronary angiography findings and the second group included patients who had CAD.
Regarding the demographic and laboratory characteristics of the two study groups, the incidence of diabetes mellitus was significantly higher in CAD group than normal coronary arteries group, as it is well known that diabetes mellitus is a major risk factor for CAD. There is no significant difference between the two groups regarding other variables.
The echocardiographic characteristics of the two study groups showed that the left ventricle dimensions, left atrium, and aortic root diameters were significantly higher in the CAD group, whereas the ejection fraction was significantly lower in the CAD group than in the normal coronary arteries group. These echocardiographic changes are most probably the result of ischemic heart disease changes in CAD group, which leads to reduction of ejection fraction and higher left ventricular dimensions.
In our study, the average epicardial fat thickness was significantly higher in patients with CAD (6.9 ± 1.5) compared with patients with normal coronary arteries (4.4 ± 0.8) (P = 0.001).
Epicardial fat thickness increased significantly with the severity of CAD (P < 0.001), as there were significant differences between the groups regarding epicardial fat thickness quartiles in relation to the Gensini score. The first quartile of epicardial fat thickness (1.1–4.48 mm) has Gensini score of 3.4, the second quartile (4.49–6.23 mm) has Gensini score of 18, the third quartile (6.24–7.59 mm) has Gensini score of 43.7, and the fourth quartile (7.60–16.55 mm) has Gensini score of 49. As noted, an increasing trend in Gensini score was seen according to quartiles of measured epicardial fat thickness (P < 0.001).
Many studies ,,, have used different techniques such as echocardiography, multislice computed tomography (MSCT), and cardiac magnetic resonance while examining the relation between CAD and epicardial fat thickness and have reported controversial results, probably owing to differences in measurement methods and study populations. Ahn et al.  measured the epicardial fat thickness using two-dimensional echocardiography in 527 patients undergoing their first coronary angiography. They found that epicardial fat was thicker in patients with CAD (7 ± 1.6) compared with patients with normal coronary arteries (4.6 ± 0.9) (P = 0.001). Also, they found that patients with unstable angina had thicker epicardial fat measurements than those with stable angina or atypical chest pain (P = 0.001).
Eroǧlu et al.  assessed the association between epicardial fat thickness and CAD using two-dimensional echocardiography in 150 patients (100 patients with CAD and 50 patients with normal coronary arteries diagnosed by coronary angiography). Epicardial fat thickness was measured at parasternal long-axis and short-axis views at end diastole.
Eroǧlu et al.  found that epicardial fat thickness was significantly higher in patients with CAD (7.1 ± 1.8) compared with patients with normal coronary arteries (4.3 ± 0.7) (P = 0.001). Furthermore, epicardial fat thickness increased with severity of CAD (multivessel vs. single vessel, P < 0.001).
Djaberi et al.  aimed at investigating the relation between epicardial fat volume, assessed by MSCT, and presence of coronary atherosclerosis. Their results showed a significantly larger mean epicardial fat volume in patients with coronary artery calcium and/or coronary atherosclerosis on MSCT angiogram compared with those with a coronary artery calcium score less than 10 and/or angiographically normal coronaries. Interestingly, epicardial fat volume was revealed to be an independent predictor for CAD.
Shemirani et al.  classified 315 cases that underwent coronary angiography into two groups including normal and CAD groups. Epicardial fat thickness was quantified by echocardiography. They reported epicardial fat thickness as an independent predictor of CAD among other well-known risk factors.
However, Chaowalit et al.  assessed the association between epicardial fat thickness and coronary atherosclerosis in 180 patients who underwent echocardiography and coronary angiography. Epicardial fat thickness on the free wall of right ventricle was measured at end diastole from parasternal long-axis and short-axis views, and patients were divided into two groups: one group with and the other group without measurable amounts of epicardial fat measured by echocardiography (0–1 vs. >1 mm). This study found that no significant correlation was detected between epicardial fat thickness and any other clinical variables (sex, weight, BMI, hypertension, diabetes mellitus, dyslipidemia, smoking, or family history of CAD).
Chaowalit et al. , also did not find any correlation between epicardial fat thickness and CAD. Their experimental protocol divided patients based on the presence of epicardial fat instead of absolute thickness of epicardial fat.
Our study results are similar to those of Eroǧlu et al.  and Ahn et al. . Specifically, our study showed that epicardial fat is significantly correlated with the presence of CAD (P = 0.001, 95% confidence interval: 1.64–3.64) and severity of CAD, as an increasing trend in Gensini score was seen with higher epicardial fat thickness (P < 0.001).
Our study results showed that epicardial fat thickness of greater than or equal to 5.3 mm had an 85% sensitivity and an 81% specificity (ROC area: 0.914, P < 0.001, 95% confidence interval: 0.86–0.96) for predicting CAD.
When the patients' clinical and laboratory characteristics were classified according to the cut-off value of epicardial fat thickness, our study showed that male sex, incidences of the CAD, diabetes mellitus, hypertension, smoking, TG, and waist circumference were significantly higher, whereas HDL cholesterol was significantly lower in patients with epicardial fat greater than or equal to 5.3 in comparison with patients with epicardial fat thickness less than 5.3 mm.
Eroǧlu et al.  identified 5.2 mm as a cut-off value of epicardial fat thickness measured using two-dimensional echocardiography at end diastole, with 83% sensitivity and 80% specificity (ROC area: 0.813, P < 0.001, 95% CI: 0.84–0.94) for predicting CAD.
Ahn et al.  identified 4.9 mm as a cut-off value of epicardial fat thickness measured at end diastole using two-dimensional echocardiography, with 82% sensitivity and 80% specificity (ROC area: 0.783, P < 0.001, 95% CI: 0.742–0.824).
Regarding other CAD risk factors, our study results are similar to those of Eroǧlu et al. , as both studies showed that diabetes mellitus, hypertension, smoking, CAD incidences, TG, and waist circumference were significantly higher and HDL cholesterol was significantly lower in patients with a larger epicardial fat thickness.
In addition this study found that epicardial fat was thicker in men than in women, consistent with the results of Eroǧlu et al. ; however, Ahn et al. , did not find any difference in epicardial fat thickness between men and women.
Our study showed that there was a significant correlation between epicardial fat thickness and waist circumference (r = 0.3, P = 0.01). However, there were no significant correlations between epicardial fat thickness and other parameters, including BMI.
Eroǧlu et al. , showed similar results as ours, as there were no significant correlations between epicardial fat thickness and BMI, so both studies highlight the importance of epicardial fat in predicting CAD and its severity is independent of BMI.
Multivariate regression analysis found epicardial fat thickness to be an independent and powerful predictor of CAD, which included well-known risk factors such as age, hypertension, diabetes mellitus, smoking, dyslipidemia, and family history of CAD.
| Conclusion|| |
There are several CAD risk factors such as obesity, hypertension, diabetes mellitus, smoking, and high cholesterol level, but among these well-known risk factors, epicardial fat thickness emerged as an independent predictor of CAD and can be categorized as a type of active adipose tissue that mediates coronary circulation through secretion of inflammatory mediators and adipokines.
Quantification of EAT thickness using echocardiography, which is a relatively cheap and readily available tool, is beneficial for choosing patients who would need more aggressive approach in terms of risk reduction and in distinguishing the degree of CAD severity.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]