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Relationship Between Coronary Artery Disease and Epicardial Adipose Tissue Quantification at Cardiac CT

Rationale and Objectives

The aim of this study was to compare the reproducibility of bidimensional and volumetric quantification of epicardial adipose tissue (EAT) on cardiac computed tomography (CT) and evaluate their relationship with the extent of coronary artery disease (CAD).

Materials and Methods

Forty-five individuals underwent cardiac dual-source CT and conventional coronary angiography for suspicion of CAD. Nonenhanced images acquired to assess calcium score were used to quantify EAT. Coronary stenosis grading was performed on conventional coronary angiograms using Gensini scores. Two independent observers manually measured right ventricular EAT thickness at three different levels and in two different planes (four chamber and short axis) to obtain mean values. Additionally, EAT volume was automatically determined using a commercially available software tool.

Results

Conventional coronary angiography demonstrated nonstenotic coronary arteries in 22 subjects and significant coronary artery stenosis in 23. Significant correlations were observed between volumetric estimation of EAT and body mass index, coronary artery calcification, and Gensini score. On automatic volumetry, patients with significant coronary artery stenosis had significantly greater EAT volumes (154.58 ± 58.91 mL) than those without significant CAD (120.94 ± 81.85 mL) ( P = .016). The manual bidimensional approach based on thickness measurements failed to show a significant difference between the two groups. Reproducibility and interobserver agreement for EAT quantification were higher when the automatic volumetric method was used (concordance-correlation coefficient, 0.96) compared to manual measurements (concordance-correlation coefficients, 0.37 for four-chamber EAT, 0.53 for short-axis EAT, and 0.58 for average EAT).

Conclusions

For the quantification of EAT on cardiac CT, automated volumetry is more reproducible and correlates better with the extent of CAD than manual bidimensional measurements.

There is increasing clinical evidence that visceral adipose tissue is an important indicator of cardiovascular risk . There seems to be an association between visceral adipose tissue and cardiovascular risk factors such as dyslipidemia , diabetes , hypertension , and metabolic syndrome . Epicardial adipose tissue (EAT) is visceral fat located between the myocardium and the pericardium, particularly around subepicardial coronary vessels. It is thought to originate from brown adipose tissue . This depot of visceral fat is correlated with insulin resistance , body mass index (BMI) , visceral abdominal adipose tissue and left ventricular mass . Furthermore, EAT may act as an endocrine or paracrine organ as the source of a number of bioactive molecules causing coronary atherosclerosis . Some studies have revealed correlations between EAT, coronary artery calcification (CAC) , obesity, metabolic syndrome , and coronary artery disease (CAD) , which may be due to the contribution of EAT to the local production of inflammatory mediators developing atherosclerosis .

Traditionally, two-dimensional transthoracic echocardiography has been used to quantify epicardial fat. In these studies, the assessment of EAT is performed by measuring the epicardial fat thickness located around the right ventricle . However, the measurement of EAT thickness using transthoracic echocardiography has limitations. The technique is highly dependent on acoustic windows and observer experience and has limited spatial resolution, which may make it difficult to differentiate between epicardial and pericardial fat . Moreover, the sole quantification of EAT thickness around the right ventricular free wall may be insufficient, because the distribution of this fat depot around the heart is not uniform, and there may exist interindividual differences . In recent studies, the role of magnetic resonance imaging and computed tomography (CT) to detect and quantify EAT has been emphasized . These techniques, in contrast to transthoracic echocardiography, also allow the volumetric quantification of EAT, which may be more exact and reproducible compared to simple thickness measurement at the right ventricular free wall.

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Materials and methods

Study Population

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Computed Tomographic Image Acquisition Protocol

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Coronary Angiography

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Measurements

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EAT Measurements

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Measurement of EAT thickness

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Figure 1, Epicardial adipose tissue (EAT) thickness measurement at the right ventricular free wall. In each plane, EAT thickness was estimated at the base of the heart, mid ventricle, and apex. (a) Four-chamber view. (b) Representative short-axis view.

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Volumetric assessment of EAT

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Figure 2, Epicardial adipose tissue volume quantification using a commercially available software tool based on attenuation-dependent segmentation methods and allowing the quantification of epicardial adipose tissue.

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CAC Scoring

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Severity of CAD

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Statistical Analysis

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Results

Reproducibility and Interobserver Agreement

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Figure 3, Pearson's correlations for interobserver correlation for epicardial adipose tissue (EAT) measurements: (a) four-chamber (4CH) EAT, (b) short-axis (SA) EAT, (c) average EAT, and (d) volume quantification. Obs, observer.

Table 1

Assessments of Interobserver Variability for Estimation of EAT Volume and EAT Thickness Measurements

Parameter CCC Pearson ρ

(95% Confidence Interval) Bias Correction Factor C b EAT thickness (mm) EAT-4CH 0.37 0.53 (0.29–0.72) 0.69 EAT-SA 0.53 0.76 (0.59–0.86) 0.70 Average-EAT 0.58 0.78 (0.63–0.87) 0.75 EAT volume (ml) 0.96 0.98 (0.97–0.99) 0.98

EAT, epicardial adipose tissue; EAT-4CH, epicardial adipose tissue thickness measured in the four-chamber view; EAT-SA, epicardial adipose tissue thickness measured in the short-chamber view; SD, standard deviation; CCC, concordance correlation coefficient. Pearson ρ indicates precision; Bias correction factor C b indicates accuracy.

Figure 4, Bland-Altman plots of interobserver agreement for epicardial adipose tissue (EAT) measurements: (a) four-chamber (4CH) EAT, (b) short-axis (SA) EAT, (c) average EAT, and (d) volume quantification. Obs, observer; SD, standard deviation.

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Prevalence of Atherosclerotic Disease

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Table 2

Gender-related Differences in Individuals With and Without Significant Coronary Artery Stenosis (SCAS)

Male Female_P_ SCAS Age (years) 60.81 ± 11.48 65 ± 8.64 NS BMI (kg/m 2 ) 30.02 ± 3.13 28.96 ± 5.45 NS CAC Agatston score 394 (0–1870.5) 88 (0–1119) NS Gensini score 48.25 (27.5–156) 36 (27–70.5) NS No SCAS Age (years) 54 ± 9.49 55.93 ± 8.62 NS BMI (kg/m 2 ) 27.49 ± 7.74 29.15 ± 6.86 NS CAC Agatston score 0 (0–34) 0 (0–54) NS Gensini score 14 (3–76) 29 (3–99) NS

BMI, body mass index; CAC, coronary artery calcification; NS, not significant.

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EAT Quantification

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Table 3

Epicardial Adipose Tissue Quantification in Individuals With and Without Significant Coronary Artery Stenosis (SCAS)

Parameter SCAS No SCAS_P_ EAT thickness (mm) EAT-4CH 9.45 ± 4.12 7.77 ± 2.98 NS EAT-SA 8.99 ± 2.19 8.13 ± 3.03 NS Average-EAT 8.57 ± 2.08 7.69 ± 2.68 NS EAT volume (ml) 154.58 ± 58.91 120.94 ± 81.85 .016

EAT, epicardial adipose tissue; EAT-4CH, epicardial adipose tissue thickness measured in the four-chamber view; EAT-SA, epicardial adipose tissue thickness measured in the short-chamber view; NS, not significant.

Table 4

Gender-related Differences in Epicardial Fat Measurements in Individuals With and Without Significant Coronary Artery Stenosis (SCAS)

Male Female_P_ SCAS EAT thickness (mm) EAT-4CH 9.41 ± 4.09 9.53 ± 4.53 NS EAT-SA 8.89 ± 1.93 9.22 ± 2.88 NS Average-EAT 8.48 ± 1.85 8.78 ± 2.70 NS EAT volume (ml) 166.26 ± 64.10 127.89 ± 35.45 NS No SCAS EAT thickness (mm) EAT-4CH 7 ± 1.97 8.12 ± 3.35 NS EAT-SA 7.97 ± 2.33 8.20 ± 3.38 NS Average-EAT 7.48 ± 2.13 7.79 ± 2.97 NS EAT volume (ml) 142.42 ± 71.16 110.93 ± 86.84 NS

EAT, epicardial adipose tissue, EAT-4CH, epicardial adipose tissue thickness measured in the four-chamber view; EAT-SA, epicardial adipose tissue thickness measured in the short-chamber view; NS, not significant.

Table 5

Overall Correlation of Epicardial Adipose Tissue Measurements to Age, BMI, and CAC Agatston Score

Age (years) BMI CAC Agatston Score Gensini Score Parameter_r__P__r__P__r__P__r__P_ EAT thickness (mm) EAT-4CH 0.203 NS 0.325 0.029 0.114 NS 0.384 0.009 EAT-SA 0.148 NS 0.382 0.01 0.123 NS 0.347 0.020 Average-EAT 0.158 NS 0.376 0.011 0.115 NS 0.346 0.020 EAT volume (ml) 0.215 NS 0.432 0.003 0.368 0.013 0.43 0.003

BMI, body mass index; CAC, coronary artery calcification; EAT, epicardial adipose tissue; EAT-4CH, epicardial adipose tissue thickness measured in the four-chamber view; EAT-SA, epicardial adipose tissue thickness measured in the short-chamber view; NS, not significant.

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Discussion

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