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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 6  |  Issue : 1  |  Page : 61-67

Correlation of epicardial adipose tissue thickness by echocardiography with waist circumference, lipid profile, and severity of lesion by coronary angiography in patients with acute coronary syndrome


Department of Cardiology, Osmania General Hospital, Hyderabad, Telangana, India

Date of Submission22-Nov-2019
Date of Decision21-Jan-2020
Date of Acceptance14-Feb-2020
Date of Web Publication17-Apr-2020

Correspondence Address:
Nagula Praveen
Department of Cardiology, First Floor, Quli Qutubshah Building, Osmania General Hospital, Afzalgunj, Hyderabad - 500 012, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcs.jpcs_74_19

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  Abstract 


Context: Epicardial adipose tissue (EAT) thickness on echocardiography can be a promising marker for risk stratification in patients with coronary artery disease (CAD). Aim: To correlate EAT with waist circumference (WC), lipid profile, severity of coronary artery disease on angiography in patients with acute coronary syndrome(ACS). Subjects and Methods: Patients with acute coronary syndrome (ACS) with age >18 years were studied. Their demographic, clinical, biochemical, and angiographic profile was assessed. The correlation of EAT with WC, lipid profile, and the severity of lesion by coronary angiography was assessed. Results: A total of 120 consecutive patients with ACS were studied. The male: female ratio was 4:1. The mean age of presentation was 56.43 ± 11.39 years. Dyslipidemia was seen in 70 (58.33%) patients, whereas hypertension was seen in 58 (48.3%) patients. The syntax score (SS) was low in 34 (28.3%) and high in 50 (41.67%) patients. Mean EAT was high in patients with high SS compared to those with intermediate and low SS (9.66 ± 0.33 vs. 6.08 ± 0.10 vs. 5.90 ± 0.24 mm, P < 0.001). A significant correlation of EAT was seen with WC r = 0.749, total cholesterol r = 0.934, and high-density cholesterol r = 0.674, P < 0.001. The cutoff value of EAT on echocardiography to diagnose significant CAD (SS >23) was 6.23 mm on receiver operating characteristic curve analysis with an area under the curve being 0.953 and sensitivity of 100% and specificity of 70%. Conclusions: EAT thickness, can be a reliable, easy, noninvasive marker in risk stratification of patients at risk of CAD.

Keywords: Coronary artery disease, echocardiography, epicardial adipose tissue, syntax score


How to cite this article:
Pruthvi G, Naidu OA, Praveen N, Srinivas R, Reddy PK. Correlation of epicardial adipose tissue thickness by echocardiography with waist circumference, lipid profile, and severity of lesion by coronary angiography in patients with acute coronary syndrome. J Pract Cardiovasc Sci 2020;6:61-7

How to cite this URL:
Pruthvi G, Naidu OA, Praveen N, Srinivas R, Reddy PK. Correlation of epicardial adipose tissue thickness by echocardiography with waist circumference, lipid profile, and severity of lesion by coronary angiography in patients with acute coronary syndrome. J Pract Cardiovasc Sci [serial online] 2020 [cited 2020 May 27];6:61-7. Available from: http://www.j-pcs.org/text.asp?2020/6/1/61/282812




  Introduction Top


The rising prevalence of cardiovascular disease (CVD) worldwide has necessitated the development of simple effective tools that permit accurate risk stratification of individuals requiring primary prevention of CVD. A variety of clinical and biochemical risk markers, risk algorithms, and imaging tests have been developed for this purpose but with variable success. Visceral adiposity is one such marker that is associated with increased CVD risk.[1],[2] Traditionally, visceral adiposity is measured either in the form of waist circumference (WC) or by quantifying hepatic fat using the imaging modalities. Unfortunately, while WC provides only an indirect estimation of visceral adiposity, ultrasound and computed tomography (CT) are only qualitative and magnetic resonance imaging (MRI) is limited by expense and availability issues.

Epicardial adipose tissue (EAT) is a specialized adipose tissue between the visceral pericardium and the myocardium embedding the coronaries. The lack of an anatomic barrier between EAT and the myocardium enables them to share the same microcirculation. It produces numerous proinflammatory and proatherogenic mediators that might promote the initiation and progression of coronary atherosclerosis.[3]

Echocardiography, CT, and MRI are the three commonly utilized imaging modalities for quantification of epicardial fat. Each of these techniques has both advantages and disadvantages.

This study is to assess the relation between EAT thickness, WC, lipid profile, and the severity of coronary artery disease (CAD) by syntax score (SS) in patients with acute coronary syndrome (ACS).

On echocardiography, parasternal long-axis or parasternal short-axis view (mid-ventricular level) is the best view to visualize and quantify epicardial fat.[4] Epicardial fat is seen as a relatively hypoechoic layer anterior to the right ventricle, just adjacent to the right ventricular wall. Paracardiac fat is visualized more anteriorly. Intervening echo dense fibrous pericardium helps in distinguishing between the two, though sometimes it is difficult. Pericardial fluid is generally completely echolucent and collects predominantly posterior to the left ventricle. Echocardiographic epicardial fat thickness or EAT measurement has been shown to have good reproducibility, with intraclass correlation coefficients being >0.90 for interobserver and intraobserver agreements.[5]

Echocardiography offers the advantages of being simple, readily available, and less expensive and completely radiation free. A major limitation with echocardiography is that only thickness can be measured and not the volume. Despite it, echocardiography provides a reasonably accurate estimation of the epicardial fat and has a good correlation with CT or MRI.

There are no guidelines regarding the normal limits of epicardial fat thickness. The available evidence suggests that on echocardiography, 6–7 mm is the upper limit and anything >7 mm definitely indicates excess epicardial fat deposition.[5],[6]

A strong relationship has been demonstrated between the epicardial fat and the intra-abdominal fat quantity as estimated by the MRI.[5],[7] More importantly, this relationship is stronger than with the WC suggesting that epicardial fat is a superior marker of visceral adiposity. The thickness and volume of EAT are related to the severity and extent of atherosclerotic CAD;[8] however, some investigators have found no significant association between them.[9] Although the relationship between EAT and the severity and extent of CAD has been extensively investigated, only a few studies of the association of EAT with the complexity of CAD have been there.[10]

Epicardial fat also has a significant relationship with the presence of metabolic syndrome,[11] blood pressure,[11] insulin resistance,[5] fasting blood glucose,[12] low-density lipoprotein (LDL) cholesterol,[11] and inflammatory markers such as C-reactive protein and plasminogen activator inhibitor-1.[13] These relationships are independent of other CVD risk factors, including adiposity.

Aims and objectives

  • To calculate the anterior EAT thickness by two-dimensional (2D) echocardiography
  • To calculate the severity of coronary atherosclerosis by SS on coronary angiogram
  • To correlate the EAT with the SS, WC, and lipid profile.



  Subjects and Methods Top


Study subjects

The present study is a hospital-based observational study. A total of 120 consecutive patients with a diagnosis of ACS were studied between June 2016 and November 2017. All patients have given informed consent for the assessment and inclusion in the study. The Ethical Committee of the institute approved the study (Id no. SS15070804).

Inclusion criteria

Patients diagnosed with ACS during the study period undergoing coronary angiography with age >18 years were included.

Exclusion criteria

Patients with a history of prior coronary intervention, coronary artery bypass grafting, previous chest irradiation, chest deformities, poor echo window, pericardial effusion, pregnancy, and chronic kidney disease (estimated glomerular filtration rate <30 ml/min/1.73 m2) were excluded.

Diagnosis of ACS was done according to the latest criteria with clinical features, ECG changes, 2D-echo, cardiac biomarkers, and coronary angiography findings suggestive of atherosclerosis.

Baseline evaluation included smoking habits (including ex- and current smokers) or tobacco in any other form, alcohol habits, and family history of CAD. Body mass index (BMI) or Quetelet index was calculated with body weight (kg) divided by the square of height in meter. According to the current WHO classification, the normal range of BMI was considered between 18.5 and 24.9 and preobese or overweight was defined as BMI ≥25 and obese as ≥30. Hypertension (HTN) was defined as a blood pressure ≥140 mmHg or current use of antihypertensive drugs. Type 2 diabetes mellitus was defined as fasting blood glucose level ≥126 mg/dL or the use of glucose-lowering drugs.

The WHO STEPS protocol for measuring WC instructs that the measurement be made at the approximate midpoint between the lower margin of the last palpable rib and the top of the iliac crest, using a stretch-resistant tape that provides a constant 100 g tension. The participant should stand with feet close together, arms at the side and body weight evenly distributed, and should wear little clothing. The participant should be relaxed, and the measurements should be taken at the end of a normal expiration. Each measurement should be repeated twice; if the measurements are within 1 cm of one another, the average should be calculated.[14]

Biochemical assessment

Blood specimens were obtained after a 12- to 14-h fast (8 pm–9.30 am) to reduce the influence of circadian variation. The concentrations of triglycerides (TGs) were measured using standard enzyme methods (Liquixx Triglycerides GPO-Trinder Method). Total cholesterol (CHOD-PAP) and high-density lipoprotein (HDL) cholesterol were assessed after very LDL (VLDL) with phosphotungstic acid precipitation, and LDL was calculated using the Friedewald formula. Fasting glucose levels were enzymatically examined by the hexokinase method.

After selecting the cases, the purpose of this study was discussed with all study participants. All the participants provided written informed consent. After confirming the diagnosis of ACS, patients who are willing for coronary angiography underwent measurement of EAT thickness on 2D echo (Philips iE33).

Epicardial adipose tissue assessment on echocardiography

For quantification, it is recommended that in the parasternal long-axis view, EAT thickness should be measured perpendicular to the ultrasound beam, anterior to the right ventricle, and in line with the aortic annulus.[18] Moving the measurement plane rightward can lead to significant overestimation as the steep posterior deflection of the right ventricular wall in this region rapidly increases the fat tissue thickness. The measurement should be performed at the end of ventricular systole to avoid any deformation of the fat tissue by the expanded ventricle. It is also important to perform measurements in three cardiac cycles and average them for an accurate assessment.

The EAT thickness was assessed on echocardiography by a cardiologist who is blinded to the study protocol. The echocardiography was done within 48 h of the patient admission.

Coronary angiography

Coronary angiography was performed in the catheterization laboratory (Siemens Axiom Artis, Munich, Germany), equipped with quantitative coronary analysis software. Coronary angiograms were interpreted visually and were analyzed in two orthogonal views and scored by computer-assisted SYNTAX scoring algorithm.[15] Patients were divided into three groups based on SS, i.e., score up to 22 as low, between 23 and 32 as intermediate, and ≥33 as high SS.

Statistical analysis

All the data were collected and Microsoft Word and Excel were used to generate tables and graphs. Data analysis was performed with IBM Statistical Package for the Social Sciences (SPSS) for Windows version 20 (SPSS Inc., Chicago, USA). Patient characteristics were summarized as mean ± standard deviation for continuous variables and percentages for categorical variables. A comparison of three or more than three means was done by analysis of variance and comparison of two means by student's t-test. Correlation between the two parameters was assessed by Pearson correlation coefficient. Cutoff value of EAT for diagnosis of significant CAD was assessed using receiver operating characteristic (ROC) curve analysis and area under the curve (AUC).

All results were considered statistically significant at the level of P < 0.05.

Study population

Out of 120 acute coronary syndrome patients, males were predominant compared to females with a ratio of 4:1 (n = 96:24). The mean age of presentation was 56.45 years ± 11.39 years. On analysis of the risk factors for CAD, dyslipidemia was most commonly seen in 70 patients, HTN was the second most commonly seen in 58 patients, smoking in 44 patients, and diabetes in 38 patients. On analysis of the lesion on coronary angiography, 34 patients had low SS, 36 patients had intermediate SS, and 50 patients had high SS. Baseline characteristics are depicted in [Table 1].
Table 1: Baseline characteristics of the study population

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Epicardial adipose tissue thickness

The EAT thickness among the patients according to the SS was significantly high in patients with high SS compared to low SS (9.66 ± 0.33 vs. 6.08 ± 0.10 vs. 5.9 ± 0.24, P < 0.001) [Table 2] and [Figure 1].
Table 2: Mean epicardial adipose tissue thickness among the groups categorized based on syntax score

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Figure 1: Mean epicardial adipose tissue between the study population groups

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There was a significant difference in the EAT when compared among patients with normal and abnormal WC (6.42 ± 1.16 vs. 9.68 ± 0.32, P < 0.0001) [Table 3].
Table 3: Epicardial adipose tissue in patients with normal and abnormal waist circumference

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There was no significant EAT difference between different age groups and between males and females in the study (males vs. females: 7.46 ± 1.83 vs. 7.84 ± 1.87, P = 0.49).

When patients were assessed regarding lipid profile according to the SS on the angiography, patients with high SS had more levels of lipid (total cholesterol, LDL, VLDL, and TG), less HDL, and increased WC, though the difference among the three groups was not statistically not significant (P = 0.75) [Table 4].
Table 4: Lipid profile of the patients according to the syntax score

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Of the 120 patients, 28 patients were on statins before the enrollment. All patients who were on statins were diabetics (22/38 = 57%, statins were prescribed by their primary physician).

When compared the EAT among the patients who were on statins and off statins, there was a significant decrease (6.23 ± 1.5 vs. 9.71 ± 0.32, P < 0.0001), and the other parameters were also significant [Table 5].
Table 5: Comparison of lipid profile and epicardial adipose tissue thickness in patients on and off statins

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Correlation of epicardial adipose tissue with other parameters

A significant correlation was seen between EAT and LDL, VLDL, TG, and WC whereas negative correlation with HDL [Table 6].
Table 6: Correlation of epicardial adipose tissue with anthropometric and biochemical parameters

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Cutoff value for diagnosing significant coronary artery disease

On ROC curve analysis, the value of EAT was 6.25 to diagnose significant CAD, with AUC being 0.953 (95% confidence interval [CI]: 0.864–1.000), sensitivity of 100%, and specificity of 70%, P < 0.0001.


  Discussion Top


This study compared EAT thickness measured by 2D echo with CAD burden assessed through the SS. A comparison of EAT with WC and lipid profile was also done.

A EAT value of >6.23 mm on ROC curve analysis with a sensitivity of 100% and a specificity of 70% predicted significant CAD. EAT had a positive correlation with WC, total cholesterol and negative correlation with high-density cholesterol.

EAT correlated well with atherosclerosis and can be used as a surrogate marker for risk stratification of patients; however, there is a considerable variation in the studies as per the literature.[16]

Numerous studies have demonstrated that epicardial fat directly contributes to coronary atherogenesis. Local ischemia produced by coronary stenosis may lead to the activation of inflammatory pathways in the surrounding epicardial fat tissue, initiating a vicious cycle. Conversely, the adiponectin level is markedly low in the epicardial fat of such patients.[17] Furthermore, the location of atherosclerotic plaques, when eccentric, also seems to correlate with the site of epicardial fat deposition,[18] providing another evidence of a direct pathogenic role of epicardial fat in causation of coronary atherosclerosis. Data from the Framingham Heart Study showed that epicardial fat is more closely related to major adverse cardiovascular events (MACE), whereas abdominal visceral fat has a stronger relationship with stroke.[19] These findings suggest a differential impact of various visceral fat depots on systemic atherogenesis.

In a study by Erkan et al., mean EAT was 4.3 ± 0.9, 5.2 ± 1.5, and 7.5 ± 1.9 mm in the patients with normal coronary arteries, minimal CAD, and significant CAD groups, respectively (P < 0.001). Multivariate analysis and ROC analysis revealed that EAT can be used as an independent predictor of significant CAD. Cutoff EAT value to predict significant CAD was identified as 5.8 mm (ROC analysis: 0.875; P < 0.001, 95% CI: 0.825–0.926).[20] In the present study, EAT cutoff value to predict significant CAD was identified as 6.25 mm (ROC analysis: 0.953, P = 0.001, 95% CI: 0.864–1.000) with a sensitivity of 100% and a specificity of 70%, respectively [Figure 2]. In the Framingham Heart Study, epicardial fat was predictive of MACE events than the presence of excess abdominal visceral fat.[21]
Figure 2: Receiver operating characteristic curve analysis for epicardial adipose tissue.

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Studies have shown that epicardial fat is independently associated with the risk, the severity, and also the outcomes after ablation of atrial fibrillation.[22] Posterior left atrial epicardial fat pad thickness measured between the left atrium and the esophagus may have a greater association with atrial fibrillation than epicardial fat deposited around other cardiac structures.[22] Similarly, epicardial fat is linked to the risk of ventricular tachyarrhythmias.[23]

Gökdeniz et al.[24] studied the relationship of EAT thickness to the complexity of CAD in nondiabetic participants. They found EAT thickness to be significantly correlated to the SS (r = 0.629; P < 0.001). However, those investigators studied nondiabetic patients only, whereas we identified the relationship of EAT thickness with CAD complexity in a diabetic and nondiabetic population. The patients who were on statins were found to be having lesser epicardial fat thickness compared to those off statins and less SS.

In 2014, Yañez-Rivera et al.[25] found no significant relationship between echocardiography EAT thickness and the angiographic severity of CAD. This discrepancy might have resulted from the method used to evaluate CAD severity. Whereas those investigators[25] used the number of stenotic major coronary arteries as the surrogate of CAD severity, we used the SS – a more quantitative method to assess the severity of CAD.

Nasri et al. have evaluated EAT thickness on echocardiography in diabetic patients with CAD and found a positive correlation of EAT with severity of CAD by Gensini score (r = 0.83, P < 0.001).[26]

In a study by Eren et al., EAT thickness was 6.4 ± 2.3 mm in obesity with metabolic syndrome, 6.0 ± 2.0 mm in obesity without metabolic syndrome, and 0.27 ± 0.12 cm in the control group (P < 0.001).[27] EATs was significantly higher in patients with increased WC than in those with normal WC, 4.0 ± 0.8 vs. 2.5 ± 0.9 mm, P < 0.01, respectively.[28] In a study by Iacobellis et al., their participants showed median values of epicardial fat thickness of 9.5 and 7.5 mm (in men and women, respectively), and EAT showed a significant correlation with WC (r = 0.845, P = 0.01).[11]

In the present study, there was a significant correlation between EAT and WC, and mean EAT in patients with abnormal WC and normal WC was 6.42 mm and 9.68 mm (P ≤ 0.001), respectively, which is statistically significant; the similar significant correlation was found in a study by Silaghi et al. (r = 0.55, P ≤ 0.001).[29]

This study compared the correlation of EAT with all lipid molecules, which showed a significant correlation with all parameters contrary to the previous studies. Iacobellis et al. showed a significant correlation with LDL and HDL but not with TG.[11] Pierdomenico et al. showed a significant correlation with HDL and TG but not with LDL.[28] Eren et al. showed a significant correlation with HDL, TG, and total cholesterol but not with LDL.[27] Mazur et al. showed a significant correlation with HDL and TG but not with LDL and TC.[30] Rajkumar showed a significant correlation of epicardial fat thickness with only LDL.[31]

Recently, on meta-analysis of 2306 patients who underwent assessment of EAT thickness either by echocardiography or cardiac CT, EAT correlated well with the clinical and angiographic risk score of acute coronary syndromes, coronary perfusion, and MACE.[32]

Limitations

Main limitation of the study is small sample size. Only patients with acute coronary syndrome were included, which have led to higher EAT values. The finding cannot be extrapolated to all the CAD population. We did not categorize patients concerning clinical presentation. Further studies with large number of patients (of all subsets of CAD population), trends of the EAT in them with long term follow up and its prognostic significance is of high need in the near future.


  Conclusions Top


EAT thickness was significantly higher in patients with a SS of ≥33 when compared with patients having a SS of <33. EAT cutoff value to predict significant CAD was identified as 6.25 mm (ROC analysis: 0.046; P = 0.00, 95% CI: 0.864–1.000). The sensitivity and specificity of EAT cutoff 6.25 mm to predict significant CAD were 100% and 70%, respectively. There was a significant correlation of EAT with WC and lipid profile. There was no significant EAT difference between different age groups and between males and females in the study.


  Summary Top


Epicardial fat plays a significant role in the development and progression of coronary atherosclerosis. Since it is also easy to quantify epicardial fat noninvasively, it has emerged as a potentially useful tool for CVD risk stratification in clinical practice. This study showed that by assessing EAT with 2D echo, one can predict CAD burden in a better way. Quantification of EAT thickness by 2D echo might be beneficial in the early identification of patients who have complex or critical CAD. This knowledge could enable the earlier referral of these patients for diagnostic coronary angiography and timely interventions. Our findings warrant further research in a larger study population.

Ethics clearance

Institutional Ethical Committee has approved for the conduct of the study.

Acknowledgement

We acknowledge the staff of ICCU, echo lab, cath lab, and the biochemistry department for the smooth conduct of the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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