Peri-coronary Epicardial Adipose Tissue Research Articles

Single-Nucleus Transcriptomic Atlas of Human Pericoronary Epicardial Adipose Tissue in Normal and Pathological Conditions.

Pericoronary epicardial adipose tissue (EAT) is a unique visceral fat depot that surrounds the adventitia of the coronary arteries without any anatomic barrier. Clinical studies have demonstrated the association between EAT volume and increased risks for coronary artery disease (CAD). However, the cellular and molecular mechanisms underlying the association remain elusive. We performed single-nucleus RNA sequencing on pericoronary EAT samples collected from 3 groups of subjects: patients undergoing coronary bypass surgery for severe CAD (n=8), patients with CAD with concomitant type 2 diabetes (n=8), and patients with valvular diseases but without concomitant CAD and type 2 diabetes as the control group (n=8). Comparative analyses were performed among groups, including cellular compositional analysis, cell type-resolved transcriptomic changes, gene coexpression network analysis, and intercellular communication analysis. Immunofluorescence staining was performed to confirm the presence of CAD-associated subclusters. Unsupervised clustering of 73 386 nuclei identified 15 clusters, encompassing all known cell types in the adipose tissue. Distinct subpopulations were identified within primary cell types, including adipocytes, adipose stem and progenitor cells, and macrophages. CD83high macrophages and FOSBhigh adipocytes were significantly expanded in CAD. In comparison to normal controls, both disease groups exhibited dysregulated pathways and altered secretome in the primary cell types. Nevertheless, minimal differences were noted between the disease groups in terms of cellular composition and transcriptome. In addition, our data highlight a potential interplay between dysregulated circadian clock and altered physiological functions in adipocytes of pericoronary EAT. ANXA1 (annexin A1) and SEMA3B (semaphorin 3B) were identified as important adipokines potentially involved in functional changes of pericoronary EAT and CAD pathogenesis. We built a complete single-nucleus transcriptomic atlas of human pericoronary EAT in normal and diseased conditions of CAD. Our study lays the foundation for developing novel therapeutic strategies for treating CAD by targeting and modifying pericoronary EAT functions.

Relationship Between Coronary Atheroma, Epicardial Adipose Tissue Inflammation, and Adipocyte Differentiation Across the Human Myocardial Bridge.

BackgroundInflammation in epicardial adipose tissue (EAT) may contribute to coronary atherosclerosis. Myocardial bridge is a congenital anomaly in which the left anterior descending coronary artery takes a “tunneled” course under a bridge of myocardium: while atherosclerosis develops in the proximal left anterior descending coronary artery, the bridged portion is spared, highlighting the possibility that geographic separation from inflamed EAT is protective. We tested the hypothesis that inflammation in EAT was related to atherosclerosis by comparing EAT from proximal and bridge depots in individuals with myocardial bridge and varying degrees of atherosclerotic plaque.Methods and ResultsMaximal plaque burden was quantified by intravascular ultrasound, and inflammation was quantified by pericoronary EAT signal attenuation (pericoronary adipose tissue attenuation) from cardiac computed tomography scans. EAT overlying the proximal left anterior descending coronary artery and myocardial bridge was harvested for measurement of mRNA and microRNA (miRNA) using custom chips by Nanostring; inflammatory cytokines were measured in tissue culture supernatants. Pericoronary adipose tissue attenuation was increased, indicating inflammation, in proximal versus bridge EAT, in proportion to atherosclerotic plaque. Individuals with moderate‐high versus low plaque burden exhibited greater expression of inflammation and hypoxia genes, and lower expression of adipogenesis genes. Comparison of gene expression in proximal versus bridge depots revealed differences only in participants with moderate‐high plaque: inflammation was higher in proximal and adipogenesis lower in bridge EAT. Secreted inflammatory cytokines tended to be higher in proximal EAT. Hypoxia‐inducible factor 1a was highly associated with inflammatory gene expression. Seven miRNAs were differentially expressed by depot: 3192‐5P, 518D‐3P, and 532‐5P were upregulated in proximal EAT, whereas miR 630, 575, 16‐5P, and 320E were upregulated in bridge EAT. miR 630 correlated directly with plaque burden and inversely with adipogenesis genes. miR 3192‐5P, 518D‐3P, and 532‐5P correlated inversely with hypoxia/oxidative stress, peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PCG1a), adipogenesis, and angiogenesis genes.ConclusionsInflammation is specifically elevated in EAT overlying atherosclerotic plaque, suggesting that EAT inflammation is caused by atherogenic molecular signals, including hypoxia‐inducible factor 1a and/or miRNAs in an “inside‐to‐out” relationship. Adipogenesis was suppressed in the bridge EAT, but only in the presence of atherosclerotic plaque, supporting cross talk between the vasculature and EAT. miR 630 in EAT, expressed differentially according to burden of atherosclerotic plaque, and 3 other miRNAs appear to inhibit key genes related to adipogenesis, angiogenesis, hypoxia/oxidative stress, and thermogenesis in EAT, highlighting a role for miRNA in mediating cross talk between the coronary vasculature and EAT.

Correlation between Peri-Coronary Epicardial Adipose Tissue Volume, Cardiac Calcification and the Severity of Coronary Artery Disease by Multi Slice Computed Tomography

ABSTRACT The authors in that article addressed a very important and relevant issue. Background Epicardial adipose tissue (EAT) is a complex endocrine organ that plays an important role in the development of unfavorable metabolic and cardiovascular risk profile. EAT may express a variety of inflammatory mediators which may contribute to the pathogenesis of coronary artery disease (CAD). Aortic and mitral valve calcification may reflect generalized atherosclerosis in the elderly and may be a marker of high prevalence and severity of CAD. There is a direct correlation (extent, severity and the future CV events) between the coronary artery calcium and the CAD. Aim and Objectives To correlate peri-coronary epicardial adipose tissue and coronary artery calcification and valvular (aortic and mitral) calcification with the severity of the coronary artery disease. Patients and Methods The study recruited 200 patients with suspected coronary artery disease. The amount of EAT surrounding the left main and the three main coronary arteries was quantified in axial cuts with the most distinct layer of EAT. The amount of calcium in the aortic and mitral valve and the coronaries were quantified with multi-detector computed tomography MDCT using dedicated software for measuring calcium score that is based on Agatson score. Coronary artery disease severity was assessed in terms of number of vessels affected and the severity of coronary stenosis by multi-planner reformation technique. Results Based on the finding of the MDCT and according to the presence of calcification in the aortic or the mitral valves, and the significance of the coronary artery disease, patients were classified into two groups, group (I): 115 patients with normal coronaries or with non significant lesions in their coronaries, and group (II): 85 patients with significant coronary artery disease. The Mean ± SD (in millimeters) of EAT for the entire study cohort in various coronary artery locations were as follows: LM EAT 9.82 ± 2.67, proximal LAD EAT 10.06 ± 2.80, mid LAD EAT 9.15 ± 2.41, distal LAD EAT 6.46 ± 1.87, proximal LCX EAT 8.10 ± 1.90, distal LCX EAT 6.83 ± 1.79, proximal RCA EAT 10.23 ± 2.42, mid RCA EAT 9.26 ± 2.72, distal RCA EAT 7.25 ± 2.58. Statistically highly significant difference was observed between the two groups with regards to LM EAT, proximal, mid and distal LAD EAT, proximal and distal LCX EAT, proximal, mid and distal RCA EAT (8.38 ± 2.18 Vs 11.77 ± 1.94 P: 0.000, 8.49 ± 2.21 Vs 12.18 ± 2.00, 7.93 ± 1.77 Vs 10.81 ± 2.16, 5.45 ± 1.26 Vs 7.82 ± 1.68 P: 0.000, 7.08 ± 1.34 Vs 9.46 ± 1.67, 6.05 ± 1.50 Vs 7.89 ± 1.61 P: 0.000, 9.01 ± 1.94 Vs 11.88 ± 1.99, 8.07 ± 2.32 Vs 10.86 ± 2.39, 6.31 ± 2.26 Vs 8.51 ± 2.45 P: 0.000; respectively). Statistically highly significant difference was observed between the two groups with regards calcium score and the severity of CAD in the three major vessels (LAD, LCX and RCA) and the total calcium score in all vessels (35 (16 – 85.5) Vs 179.5 (59.5 – 243) P: 0.000, 20.5 (7 – 50.5) Vs 56 (33 – 95) P: 0.000, 31 (9 – 54) Vs 97 (54 – 199) P: 0.000, 12 (0 – 84) Vs 286 (106 – 511) P:0.000; respectively) while calcium score in the LM was not statistically significant with the severity of CAD (4 (3 – 26) Vs 12 (9 – 16) P: 0.360). As regards aortic valve calcification there was statistically highly significant difference between the two groups; P value 0.000, while mitral valve calcification was found to be not statistically significant between the two groups P: 0.272. Conclusion The present study demonstrated a significant correlation between the peri-coronary epicardial adipose tissue, coronary calcification and aortic valve calcification and the severity of the coronary artery disease.

A new approach to cardiac fat volume assessment and the correlation with coronary artery calcification.

Coronary artery disease (CAD) is the foremost cause of death in the most developed societies. Plaque formation in epicardial coronary arteries and ensuing inflammation are a known pathophysiologic factor of CAD. We aimed to separately and simultaneously evaluate the correlation between pericardial fat pad volume and overall peri-coronary epicardial adipose tissue (EAT) thickness with coronary calcium score (CCS) to improve risk stratification of CAD. We retrospectively reviewed patients who underwent a non-invasive contrast-enhanced coronary multidetector CT (MDCT) angiography. Peri-coronary EAT thickness, pericardial fat pad volume and CCS were obtained by an expert radiologist from the patients coronary multidetector CT (MDCT) angiography. We included 141 symptomatic patients (86 men, 55 women) with an average age of 53.53 ± 12.92. An increment of overall peri-coronary EAT thickness (1/3 × (left anterior descending artery (LAD) + left circumflex artery (LCx) + right coronary artery (RCA)) was associated with a 49% increase in the odds for the presence of coronary artery calcification (CAC) (P = 0.004). Significant predictability of peri-coronary EAT-average was seen in diagnosing calcified plaque. Pericardial fat pad volume was positively correlated with overall peri-coronary EAT thickness in age and body mass index (BMI)-adjusted linear regression models, (P < 0.001). Our results amplify previous idea that peri-coronary EAT and pericardial fat pad volume might act as useful markers and better indicators of CCS based on Agatston score in comparison with BMI or body weight in order to reveal subsequent CADs.

Relation between quantity and quality of peri-coronary epicardial adipose tissue and its underlying hemodynamically significant coronary stenosis

BackgroundWe aimed to investigate the association of lesion-specific epicardial adipose tissue (EAT) volume and density with the presence of myocardial ischemia.MethodsWe enrolled 45 patients (55 lesions) with known or suspected coronary artery disease who underwent coronary computed tomography angiography (CTA) followed by invasive fractional flow reserve (FFR) assessment within 30 days. EAT volume (index) and density in patient-, vessel- and lesion-level were measured on CTA images. Lesion-specific ischemia was defined as a lesion with stenosis diameter > 90% or FFR ≤0.80. Multivariate analysis determined the independent association of EAT parameters with lesion-specific ischemia.ResultsMean age of the patients was 60 years, and 75% were male. Overall, 55.6% of patients had ischemic lesions and a mean FFR baseline value of 0.82 ± 0.10. Total EAT volume index was significantly higher in patients with functionally or anatomically significant stenosis. Specifically, peri-lesion EAT volume index, not the density, was positively correlated with lesion-specific ischemia independent of luminal stenosis and plaque characteristics (hazard ratio 1.56, 95% confidence interval 1.04–2.33, P = 0.032; per 0.1 ml/m2 increase). Moreover, peri-lesion EAT volume was negatively correlated with lesion FFR values, whereas total EAT volume was positively correlated with fat accumulation and glucose metabolism. In addition, there was no association of EAT volume or density with myocardial ischemia in vessel-level analysis.ConclusionsLesion-specific EAT volume index, but not density, seems positively and independently associated with myocardial ischemia, while its incremental diagnostic value of lesion-specific ischemia should be further investigated.

A NOVEL 3-DIMENSIONAL TECHNIQUE IN MEASURING PERICORONARY EPICARDIAL ADIPOSE TISSUE

Pericoronary epicardial adipose tissue radiodensity (PCATrd) is of emerging interest as a risk factor for coronary artery disease (CAD), but can be difficult to measure. This study aims to investigate a novel semi automated three-dimensional quantification of PCATrd. Fifty-five patients with suspected CAD were retrospectively identified. PCATrd was measured in contrast CT data-set using image analysis software (ITK-SNAP, Version 3.6.0). We applied a thresholding map, using in-house MatLab code with range of (-190,-3) Hounsfield unit derived from previous work, to the contrast CT data-set. The cursor was probed in the center of the short axis of the coronary arteries in the coronal, sagittal and axial images simultaneously. Then the 3D round brush segmented the epicardial adipose tissue with the orthogonal distance from the coronary vessel wall equal to the coronary radius and, the segmentation followed the path of 4 major coronary arteries from proximal to the distal terminal (Figure 1 A & B). The PCATrd of each coronary artery was automatically computed. We compared this 3D segmenting method (3D_PCATrd) with a 7-segment segmentation method (7S_PCATrd) published by the Society of Cardiovascular Computed Tomography. We further compared both PCATrd estimates with coronary artery disease severity (non-obstructive, obstructive and extensive obstructive) by using ordered logistic regression. The 3D_PCATrd was substantially different from the 7S_PCATrd in the general_PCATrd, LM, LAD and RCA, but similar in LCX (Table 1 & Figure 1C). Standard deviations around 3D_PCATrd estimates were significantly smaller than estimates from 7S_PCATrd. The 3D_PCATrd, but not 7S_PCATrd, was independently associated with severity of coronary lesions (multivariable odds ratio 0.86 for per 1 HU increase, p=0.017). Our novel 3-dimension quantified PCATrd technique produced estimates that were significantly different than estimates derived from the SCCT published technique, was more precise than the 7-segment quantified PCATrd and was better associated with coronary artery disease severity.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Coronary Plaque Geometry and Thoracic Fat Distribution in Patients with Acute Chest Pain – a CT Angiography Study

Abstract The aim of our study was to investigate the correlation between volumes of thoracic fat distributed in different compartments and the geometry of vulnerable coronary plaques assessed by coronary computed tomography angiography (CCTA), in patients with acute chest pain. Methods: This was a non-randomized, observational, single-center study, including 50 patients who presented in the emergency department with acute chest pain who underwent 128-slice single-source CCTA. Plaque geometry was evaluated in transversal and longitudinal planes, and the assessment of adipose tissue was performed using the Syngo.via Frontier (Siemens AG, Healthcare Sector, Forchheim, Germany) research platform. Results: Eccentric plaques presented a significantly higher incidence of spotty calcification (40% vs. 22%, p = 0.018), whereas positive remodeling, volume of low attenuation plaque, and incidence of napkin-ring sign were not significantly different between the study groups or in ascending versus descending plaques. The volume of pericoronary fat around the plaque was significantly larger near eccentric lesions (707.68 ± 454.08 mm3 vs. 483.25 ± 306.98 mm3, p = 0.046) and descendent plaques (778.26 ± 479.37 mm3 vs. 473.60 ± 285.27 mm3, p = 0.016). Compared to ascending lesions, descendent ones presented a significantly larger volume of thoracic fat (1,599.25 ± 589.12 mL vs. 1,240.71 ± 291.50 mL), while there was no significant correlation between thoracic fat and cross-sectional eccentricity. Conclusions: The phenotype of plaque distribution and geometry seems to be associated with a higher vulnerability of coronary lesions and may be influenced by the local accumulation of inflammatory mediators released by the pericoronary epicardial adipose tissue.

Regional coronary endothelial dysfunction is related to the degree of local epicardial fat in people with HIV

Background and aimsCoronary artery disease (CAD) is now an important cause of premature death in people with HIV but the causes of accelerated CAD are poorly understood. Epicardial adipose tissue (EAT) is metabolically-active and thought to contribute to CAD development. We tested the hypothesis that abnormal coronary endothelial function (CEF), an early marker and mediator of atherosclerosis, is related to the amount of local pericoronary EAT in HIV. MethodsWe studied 36 participants with HIV and no CAD (HIV+ CAD-), 15 participants with HIV and known CAD (HIV+ CAD+), and 14 age-matched, healthy participants without HIV (HIV-CAD-). To measure CEF, coronary MRI was performed before and during isometric handgrip exercise (IHE), an endothelial-dependent stressor. EAT was measured with MRI at the same imaging plane as CEF. ResultsCEF was significantly depressed, as measured by IHE-induced % coronary cross sectional area (CSA) change, in HIV+ CAD- and HIV+ CAD+ as compared to HIV-CAD-participants (p<0.0001). EAT thickness was significantly greater in HIV+ CAD- and HIV+ CAD+ participants as compared to HIV-CAD-participants (p=0.001). There was a significant inverse relationship between CEF and local EAT thickness and area (R = −0.48 and R = −0.51 respectively, p<0.0001 for both) among participants with HIV even after adjustment for cardiovascular risk factors. In participants with multiple CEF measures, CEF was lower in segments with higher EAT, other factors being equivalent. ConclusionsThere is a significant relationship between increased metabolically-active EAT and depressed local CEF in people with HIV, consistent with the hypothesis that increased epicardial fat contributes to accelerated CAD in persons with HIV.

Epicardial Adipose Tissue Removal Potentiates Outward Remodeling and Arrests Coronary Atherogenesis

Pericoronary epicardial adipose tissue (cEAT) serves as a metabolic and paracrine organ thatcontributes to inflammation and is associated with macrovascular coronary artery disease (CAD) development. Although there is a strong correlation in humans between cEAT volume and CAD severity, there remains a paucity of experimental data demonstrating a causal link of cEAT to CAD. The current study tested the hypothesis that surgical resection ofcEAT attenuates inflammation and CAD progression. Female Ossabaw miniature swine (n= 12) were fed an atherogenic diet for 8 months and randomly allocated into sham (n= 5) or adipectomy (n= 7) groups. Both groups underwent a thoracotomy, opening of the pericardial sac, and placement of radioopaque clips to mark the proximal left anterior descending artery. Adipectomy swine underwent removal of 1 to 1.5 cm2 of cEAT from the proximal artery. After sham or adipectomy, CAD severity was assessed with intravascular ultrasonography. Swine recovered for an additional 3 months on an atherogenic diet, and CAD was assessed immediately before euthanasia. Artery sections were processed for histologic and immunohistochemical analysis. Severity of CAD as assessed by percent stenosis was reduced in the adipectomy cohort compared with shams; however, plaque size remained unaltered, whereas larger plaque sizes developed in sham-operated swine. Adipectomy resulted in an expanded arterial diameter, similar to the Glagov phenomenon of positive outward remodeling. No differences in inflammatory marker expression were observed. These data indicate that cEAT resection did not alter inflammatory marker expression, but arrested CAD progression through increased positive outward remodeling and arrest of atherogenesis.

Correlation of Pericoronary Epicardial Adipose Tissue with Coronary Artery Calcification, and Coronary Atherosclerosis in Egyptian Post-Menopausal Women

Background and rationale: Previous data demonstrated that regional fat distribution plays an important role in the development of an unfavorable metabolic and cardiovascular risk profile. Epicardial adipose mass reflects intra-abdominal visceral fat, is related to leftventricular mass and other features of the metabolic syndrome, such as concentrations of LDL cholesterol, fasting insulin and adiponectin, and arterial blood pressure.Aim of the study: To examine the relation of peri-coronary epicardial adipose tissue (EAT) to coronary artery calcification and atherosclerosis in Egyptian post-menopausal women.Patients and methods: The study enrolled 100 post-menopausal women with suspected coronary artery disease. The amount of EAT surrounding the left main and three main coronary arteries was quantified in axial cuts with the most distinct layer of EAT.The amount of calcium in the coronary arteries was quantified with multidetector-row computed tomography (MDCT) using dedicated software for calcium scoring that is based on the Agatston score. Coronary artery disease severity was assessed in terms of numberof vessels affected and severity of coronary stenosis by multiplanner reformation (MPR) technique. Results: Sixty patients had proven coronary artery disease (CAD) of varying severity (Group I), whereas forty patients showed normal coronaries (Group II). The mean ± SD (in millimeters) epicardial adipose tissue thickness (EAT) for the entire study cohort in variouscoronary artery locations were as follows: Left Main (LM-EAT) 12.95 ± 7.86 mm, Left Anterior Descending (LAD-EAT) 8.2 ± 2.3 mm, Left Circumflex (LCX-EAT) 7.4 ± 2; and Right Coronary Artery (RCAEAT) 8.5 ± 1.9. Statistically significant differences were observed between groups I and II with regards to LM-EAT: LAD-EAT; LCXEAT; and RCA-EAT (15.7 ± 8.5 versus 9.11 ± 1.72, p=0.006; 9.1 ± 2 versus 6.88 ± 1.98, p=0.001; 8.27 ± 1.72 versus 6.19 ± 1.79, p=0.004; and 9.23 ± 1.65 versus 7.5 ± 1.9, p=0.005; respectively).Statistically significant differences in LM-EAT: LAD-EAT; LCXEAT; and RCA-EAT values were observed between patients with coronary artery calcium (CAC) scores lower than 400 Hounsfield Units (HU) and those with (CAC) scores equal to or higher than 400 HU (8.99 ± 5.99 versus 13.15 ± 1.94, p=0.001; 8.7 ± 2.1 versus 10.4 ± 2.6, p=0.003, 7.6 ± 1.8 versus 8.9 ± 2.2, p=0.005, and 8.02 ± 1.6 versus 9.48 ± 1.95, p=0.008). Conclusion: The present study demonstrated a significant correlation between peri-coronary epicardial adipose tissue and coronary artery calcification and atherosclerosis.

Human epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri-coronary location.

Human epicardial adipose tissue (EAT) is a visceral and perivascular fat that has been shown to act locally on myocardium, atria, and coronary arteries. Its abundance has been linked to coronary artery disease (CAD) and atrial fibrillation. However, its physiological function remains highly debated. The aim of this study was to determine a specific EAT transcriptomic signature, depending on its anatomical peri-atrial (PA), peri-ventricular (PV), or peri-coronary location. Samples of EAT and thoracic subcutaneous fat, obtained from 41 patients paired for cardiovascular risk factors, CAD, and atrial fibrillation were analysed using a pangenomic approach. We found 2728 significantly up-regulated genes in the EAT vs. subcutaneous fat with 400 genes being common between PA, PV, and peri-coronary EAT. These common genes were related to extracellular matrix remodelling, inflammation, infection, and thrombosis pathways. Omentin (ITLN1) was the most up-regulated gene and secreted adipokine in EAT (fold-change >12, P < 0.0001). Among EAT-enriched genes, we observed different patterns depending on adipose tissue location. A beige expression phenotype was found in EAT but PV EAT highly expressed uncoupled protein 1 (P = 0.01). Genes overexpressed in peri-coronary EAT were implicated in proliferation, O-N glycan biosynthesis, and sphingolipid metabolism. PA EAT displayed an atypical pattern with genes implicated in cardiac muscle contraction and intracellular calcium signalling pathway. This study opens new perspectives in understanding the physiology of human EAT and its local interaction with neighbouring structures.

The relationship between coronary artery disease and pericoronary epicardial adipose tissue thickness.

A retrospective study to investigate the relationship between epicardial adipose tissue thickness (EATT) and presence of coronary artery plaque, coronary artery disease (CAD) and CAD risk factors. Multidetector computed tomography (MDCT) coronary angiography images were reviewed. Left anterior decending artery, right coronary artery and left circumflex artery pericoronary EATT were measured. Demographic, clinical and CAD risk factor data were obtained from medical records. Patients with CAD (n = 49) had significantly larger mean EATT than those without CAD (n = 101). Pericoronary EATT was significantly correlated with body mass index, total cholesterol level, coronary artery calcium score, hypertension and diabetes mellitus history. There is an association between pericoronary EATT and CAD, as well as CAD risk factors. Pericoronary EATT measurement may become a widely used, easy-to-perform method for determining CAD risk.

Peri-coronary epicardial adipose tissue is related to cardiovascular risk factors and coronary artery calcification in post-menopausal women

To determine whether peri-coronary epicardial adipose tissue (EAT) is associated with vascular risk factors and coronary atherosclerosis. In this study, 573 healthy post-menopausal women underwent a cardiac CT scan to assess coronary calcification. Peri-coronary EAT thickness was measured in the areas of right coronary artery (RCA), left anterior descending (LAD) artery, and left circumflex (LCX) coronary artery. Average EAT thickness was 16.5 +/- 4.3 mm (range 5.9-34.6) in the RCA area, 6.4 +/- 2.2 mm (range 2.0-14.0) in the LAD area, and 10.8 +/- 3.0 mm (range 2.8-29.1) in the LCX area. Overall average thickness was 11.2 +/- 2.2 mm (range 5.4-19.1). EAT was positively related to age (P = 0.002). In age-adjusted linear regression models, EAT was positively related to weight (P< 0.001), waist circumference (P< 0.001), waist-to-hip ratio (P< 0.001), body mass index (P< 0.001), glucose (P< 0.001), triglycerides (P = 0.001), use of anti-hypertensive drugs (P = 0.007), and systolic blood pressure (P = 0.034), and inversely to HDL cholesterol (P = 0.005). In multivariable models, age, weight, waist circumference, smoking, and glucose were the main determinants of EAT. EAT showed a graded relation with coronary calcification (P = 0.026). EAT is strongly related to vascular risk factors and coronary calcification. Our findings support the hypothesis that EAT affects coronary atherosclerosis and possibly coronary risk.