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1.  Epicardial fat volume is correlated with coronary lesion and its severity 
Objective: To evaluate the correlation of epicardial adipose tissue volume (EATV) with the coronary artery lesion and its severity. Methods: Inpatients with suspicious stable angina of coronary heart lesion were recruited. For patients with coronary artery lesions in CTA, further coronary angiography (CAG) was performed to evaluate the coronary artery lesion. Gensini scoring system was employed to assess the severity of coronary artery lesions. Results: Patients were classified as coronary heart disease (CHD) group (n = 160). Results showed the mean EATV was 192.57 ± 30.32 cm3 in CHD group, which was significantly larger than that in control group (138.56 ± 23.18 cm3; P < 0.01). The coronary artery stenosis was classified as mild, moderate and severe stenosis according to the extent of coronary artery lesions, and results showed marked difference in the EATV among patients with different severities of coronary artery stenosis (P < 0.005). The Gensini score was positively related to EATV (r = 0.285, P = 0.000). The EATV increased with the increase in the number of affected coronary arteries. Multivariate Logistic regression analysis showed EATV was an independent risk factor of CHD after adjusting other confounding factors (OR = 1.023, P = 0.013). Conclusion: EATV is closely related to the severity of coronary artery lesions: the larger the EATV, the more severe the coronary artery lesions. Moreover, EATV is an independent risk factor of CHD.
PMCID: PMC4443183  PMID: 26064349
Volume of epicardial adipose tissue; coronary artery lesion; coronary arteriography; computer-assisted tomography
2.  Association between increased epicardial adipose tissue volume and coronary plaque composition 
Heart and Vessels  2013;29(5):569-577.
To assess the relationship between epicardial adipose tissue volume (EATV) and plaque vulnerability in significant coronary stenosis using a 40-MHz intravascular ultrasound (IVUS) imaging system (iMap-IVUS), we analyzed 130 consecutive patients with coronary stenosis who underwent dual-source computed tomography (CT) and cardiac catheterization. Culprit lesions were imaged by iMap-IVUS before stenting. The iMAP-IVUS system classified coronary plaque components as fibrous, lipid, necrotic, or calcified tissue, based on the radiofrequency spectrum. Epicardial adipose tissue was measured as the tissue ranging from −190 to −30 Hounsfield units. EATV, calculated as the sum of the fat areas on short-axis images, was 85.0 ± 34.0 cm3. There was a positive correlation between EATV and the percentage of necrotic plaque tissue (R2 = 0.34, P < 0.01), while there was a negative correlation between EATV and the percentage of fibrous tissue (R2 = 0.24, P < 0.01). Multivariate analysis revealed that an increased low-density lipoprotein cholesterol level (β = 0.15, P = 0.03) and EATV (β = 0.14, P = 0.02) were independently associated with the percentage of necrotic plaque tissue. An increase in EATV was associated with the development of coronary atherosclerosis and, potentially, with the most dangerous type of plaque.
PMCID: PMC4160569  PMID: 23982316
Adipose tissue; Coronary artery disease; Percutaneous coronary intervention
3.  Epicardial Adipose Tissue is Associated with Extensive Coronary Artery Lesions in Patients Undergoing Coronary Artery Bypass Grafting: an Observational Study 
Mædica  2014;9(2):135-143.
To investigate the relationship between the epicardial adipose tissue (EAT) volume measured by 256-slice dual source computed tomography (DSCT) and the complexity with the presence of significant coronary artery disease (CAD) in patients undergoing coronary artery bypass graft surgery (CABG).
Material and methods:
Study subjects were enrolled as they were undergoing DSCT for coronary evaluation. Two subgroups were formed according to coronary artery bypass history: Group A (patients with significant CAD), Group B (patients with normal coronary arteries). In both groups, EAT volume was measured by DSCT with the same technique. The complexity of CAD was assessed by using Syntax score (SxS). Group A patients were subdivided into two groups according to these results (Group A1, A2).
Ninety-three patients (53 male, 40 female) with a mean age of 55.1 years were enrolled in the study (48 in group A and 45 in Group B). The serum levels of fasting plasma glucose (FPG), total cholesterol (TC) and low-density lipoprotein (LDL) were found statistically higher in Group A. In Group A, mean EAT volume was 44.87±21.28 cm3 while it was in normal range (32.37±17.50 cm3) in control group (p=0.003). Higher EAT volume was found to be related to FPG (r=0.242, p=0.015) and body surface area (BSA) (r =0.268, p=0.009) and also correlated positively with CAD. On the other hand, there was no significant difference between subgroups when considering the complexity of CAD.
Our data shows that increased EAT volume is associated with significant CAD. EAT volume contributes to the development of coronary lesions, but it does not affect the complexity of the lesions.
PMCID: PMC4296755  PMID: 25705268
coronary artery bypass surgery; epicardial adipose tissue; dual source computed tomography
4.  Comparison of Epicardial Adipose Tissue Volume and Coronary Artery Disease Severity in Asymptomatic Adults with versus without Diabetes Mellitus 
The American journal of cardiology  2014;114(5):686-691.
Epicardial adipose tissue (EAT) has been shown to have important effects on the development of coronary artery disease (CAD) via local paracrine influences on the vascular bed. We compared a cohort of asymptomatic patients with Type II Diabetes (DM) without known CAD to an age and gender matched group of asymptomatic patients without DM from the CTRAD study in which patients underwent a cardiac computed tomography angiogram (CTA), for early detection of CAD. Mean EAT volumes of 118.6 ± 43.0 and 70.0 ± 44.0 cm3 were found in the DM and non-DM groups respectively. When stratified by presence and severity of CAD, it was found that in the DM (p=0.003) and non-DM groups (p<0.001) there was a statistically significant increase in EAT volume as the patients were found to have increasingly severe CAD. After adjusting for age, race, gender, DM, hypertension, insulin use, BMI, and coronary artery calcium (CAC) score, the presence of >120 cm3 of EAT was found to be highly correlated with the presence of significant CAD (Adjusted Odds Ratio 4.47, 95% CI (1.35–14.82)). We found that not only is EAT volume an independent predictor of CAD, but that an increasing volume of EAT predicted increasing severity of CAD even after adjustment for CAC score.
PMCID: PMC4216806  PMID: 25037677
Coronary Artery Disease; Epicardial Adipose Tissue; Diabetes
5.  Differential associations of angiographic extent and severity of coronary artery disease with asymmetric dimethylarginine but not insulin resistance in non-diabetic men with stable angina: a cross-sectional study 
Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthesis inhibitor, and insulin resistance (IR) have been implicated in atherogenesis. Our aim was to estimate relations between ADMA, the magnitude of IR and angiographic indices of extent and severity of coronary atherosclerosis in non-diabetic men with stable coronary artery disease (CAD).
We studied 151 non-diabetic men (mean age 57 ± 11 years) with stable angina, obstructive CAD (at least 1 luminal diameter stenosis of ≥70% in major coronary segments) and without heart failure, and 34 age-matched controls free of ≥50% coronary narrowings. The following CAD indices were computed: the number of major epicardial vessels with ≥70% stenosis, Sullivan extent score representing a proportion of the visible coronary tree with vessel wall irregularities, and Gensini score which reflects both CAD severity and extent, yet assigning a heavier weight to proximal segments and to the more severe narrowings by a non-linear point system. An estimate of IR was derived by homeostasis model assessment (HOMA-IR) from fasting insulin and glucose.
Among the CAD patients, the proportions of subjects with 1-vessel, 2- vessel and 3-vessel CAD were 26%, 25% and 49%, respectively. ADMA levels were higher in patients with obstructive CAD compared to the controls (0.51 ± 0.10 vs. 0.46 ± 0.09 μmol/L [SD], P = 0.01), whereas HOMA-IR was similar (median, 3.2 [interquartile range: 2.4–4.9] vs. 2.9 [2.3–4.7], P = 0.2). Within the CAD group, ADMA increased across ascending quartiles of Sullivan score (Spearman’s rho = 0.23, P = 0.004), but not with Gensini score (rho = 0.12, P = 0.15) or the number of vessels involved (rho = 0.08, P = 0.3). ADMA correlated to log-transformed Sullivan score (Pearson's r = 0.21, P = 0.008), which was only slightly attenuated upon multivariate adjustment (β = 0.19 ± 0.08 [SEM], P = 0.015). HOMA-IR did not differ according to any measure of angiographic CAD (P ≥ 0.2). ADMA and log (HOMA-IR) were mutually unrelated (r = 0.07, P = 0.4).
ADMA is associated with diffuse but not focal coronary atherosclerosis in non-diabetic men with stable CAD irrespectively of the degree of IR. The independent relationship between ADMA and coronary atherosclerotic burden may contribute to the well-recognized prognostic effect of ADMA in CAD.
PMCID: PMC3852014  PMID: 24103320
ADMA; Coronary artery disease; Insulin resistance
6.  Visceral adipose tissue influences on coronary artery calcification at young and middle-age groups using computed tomography angiography 
Avicenna Journal of Medicine  2015;5(3):83-88.
The purpose of the study was to evaluate the impact of excessive visceral adipose tissue (VAT) on subclinical coronary atherosclerosis and coronary artery calcifications (CAC) in young and middle-age groups using multislice computed tomography.
This study is a single center, cross-sectional study. Eligible patients (n = 159), who under the age of 61 years, with chest pain and mild to moderate probability to have coronary artery disease (CAD) were enrolled. Coronary calcium score and epicardial adipose tissue (EAT) were measured at the level of the left main coronary artery while VAT was measured at the level of the iliac crest.
The average age was (48 ± 8 years). The mean VAT was (38 ± 21 cm2) with no significant difference between men and women (38 ± 22 vs. 37 ± 19 P = 0.8) respectively. Student's t-test analysis showed significantly higher VAT in patients with detectable CAC than patients with no CAC (48 ± 24 vs. 33 ± 18 P = 0.00002), respectively. Univariate regression analysis showed that VAT and EAT, are strong predictor for CAC (hazard ratio [HR] 1.034, 95% confidence interval [CI: 1.016–1.052]. P <0.001 and [HR] 1.344, 95% CI: [1.129–1.601] P = 0.001), respectively.
Excessive VAT is significantly associated with positive CAC. VAT can strongly predict subclinical CAD in individuals at young and middle-age groups.
PMCID: PMC4510826  PMID: 26229760
Computed tomography-angiography; coronary artery calcifications; visceral adipose tissue
7.  The impact of obesity on the relationship between epicardial adipose tissue, left ventricular mass and coronary microvascular function 
Epicardial adipose tissue (EAT) has been linked to coronary artery disease (CAD) and coronary microvascular dysfunction. However, its injurious effect may also impact the underlying myocardium. This study aimed to determine the impact of obesity on the quantitative relationship between left ventricular mass (LVM), EAT and coronary microvascular function.
A total of 208 (94 men, 45 %) patients evaluated for CAD but free of coronary obstructions underwent quantitative [15O]H2O hybrid positron emission tomography (PET)/CT imaging. Coronary microvascular resistance (CMVR) was calculated as the ratio of mean arterial pressure to hyperaemic myocardial blood flow.
Obese patients [body mass index (BMI) > 25, n = 133, 64 % of total] had more EAT (125.3 ± 47.6 vs 93.5 ± 42.1 cc, p < 0.001), a higher LVM (130.1 ± 30.4 vs 114.2 ± 29.3 g, p < 0.001) and an increased CMVR (26.6 ± 9.1 vs 22.3 ± 8.6 mmHg×ml−1×min−1×g−1, p < 0.01) as compared to nonobese patients. Male gender (β = 40.7, p < 0.001), BMI (β = 1.61, p < 0.001), smoking (β = 6.29, p = 0.03) and EAT volume (β = 0.10, p < 0.01) were identified as independent predictors of LVM. When grouped according to BMI status, EAT was only independently associated with LVM in nonobese patients. LVM, hypercholesterolaemia and coronary artery calcium score were independent predictors of CMVR.
EAT volume is associated with LVM independently of BMI and might therefore be a better predictor of cardiovascular risk than BMI. However, EAT volume was not related to coronary microvascular function after adjustments for LVM and traditional risk factors.
Electronic supplementary material
The online version of this article (doi:10.1007/s00259-015-3087-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4521095  PMID: 26054890
Coronary microvascular function; Epicardial adipose tissue; Left ventricular mass; Obesity; [15O]H2O Positron emission tomography
8.  Comparison of the diagnostic performance of 64-slice computed tomography coronary angiography in diabetic and non-diabetic patients with suspected coronary artery disease 
Diabetics have high prevalence of subclinical coronary artery disease (CAD) with typical characteristics (diffuse disease, large calcifications). Although 64-slice multidetector computed tomography (MDCT) coronary angiography has high diagnostic accuracy to detect CAD, its diagnostic performance in diabetics with suspected CAD is unknown. To compare the diagnostic performance of 64-slice MDCT between diabetics and non-diabetics with suspected CAD scheduled for invasive coronary angiography (ICA).
We enrolled one hundred and five diabetic patients (92 men, age 65 +/- 9 years, Group 1) and 105 non-diabetic patients (63 men, age 63+/-5 years, Group 2) with indication to ICA for suspected CAD undergoing coronary 64-slice MDCT before ICA.
In Group 1, the overall feasibility of coronary artery visualization was 93.8%. The most frequent artifact was blooming due to large coronary calcifications (54 artifacts, 67%). In Group 2, the overall feasibility was significantly higher vs. Group 1 (97%, p < 0.0001). In Group 1, the segment-based analysis showed a MDCT sensibility, specificity, positive predictive value, negative predictive value and accuracy for the detection of ≥50% luminal narrowing of 77%, 90%, 70%, 93% and 87%, respectively. In Group 2, all these parameters were significantly higher vs. Group 1. In the patient-based analysis, specificity, negative predictive value and accuracy were significantly lower in Group 1 vs. Group 2.
Although MDCT has high sensitivity for early identification of significant CAD in diabetics, its diagnostic performance is significantly reduced in these patients as compared to non-diabetics with similar clinical characteristics.
PMCID: PMC3006364  PMID: 21114858
9.  Epicardial Adipose Tissue Thickness Correlates with the Presence and Severity of Angiographic Coronary Artery Disease in Stable Patients with Chest Pain 
PLoS ONE  2014;9(10):e110005.
Epicardial adipose tissue (EAT) is suggested to correlate with metabolic risk factors and to promote plaque development in the coronary arteries. We sought to determine whether EAT thickness was associated or not with the presence and extent of angiographic coronary artery disease (CAD).
We measured epicardial fat thickness by computed tomography and assessed the presence and extent of CAD by coronary angiography in participants from the prospective EVASCAN study. The association of EAT thickness with cardiovascular risk factors, coronary artery calcification scoring and angiographic CAD was assessed using multivariate regression analysis.
Of 970 patients (age 60.9 years, 71% male), 75% (n = 731) had CAD. Patients with angiographic CAD had thicker EAT on the left ventricle lateral wall when compared with patients without CAD (2.74±2.4 mm vs. 2.08±2.1 mm; p = 0.0001). The adjusted odds ratio (OR) for a patient with a LVLW EAT value ≥2.8 mm to have CAD was OR = 1.46 [1.03–2.08], p = 0.0326 after adjusting for risk factors. EAT also correlated with the number of diseased vessels (p = 0.0001 for trend). By receiver operating characteristic curve analysis, an EAT value ≥2.8 mm best predicted the presence of>50% diameter coronary artery stenosis, with a sensitivity and specificity of 46.1% and 66.5% respectively (AUC:0.58). Coronary artery calcium scoring had an AUC of 0.76.
Although left ventricle lateral wall EAT thickness correlated with the presence and extent of angiographic CAD, it has a low performance for the diagnosis of CAD.
PMCID: PMC4204866  PMID: 25335187
10.  An Intravascular Ultrasound Analysis in Women Experiencing Chest Pain in the Absence of Obstructive Coronary Artery Disease 
Using intravascular ultrasound (IVUS), we sought to characterize coronary morphology in women with chest pain without major epicardial obstructive coronary artery disease (CAD). We have previously observed an unexpectedly high rate of adverse outcomes among women with chest pain and normal or insignificant obstructive CAD. Information about the presence and characteristics of coronary atherosclerosis in these women could provide insight into the mechanisms related to increased risk, as well as improved diagnosis, prevention, and treatment.
Women (n=100) with suspected ischemia without obstructive CAD (>50% stenosis) underwent IVUS of a left coronary segment with measurements by a core lab masked to clinical and angiographic findings.
Angiograhic core lab analysis found 69.6% of patients had no (≤20%) and 30.4% had minimal (20–<50%) CAD. IVUS segmental images were interpretable by the core lab in 92 women, with 19 (21%) having no atherosclerosis (intimal-medial thickness <0.5 mm). In the remaining 73 women (79%), percent atheroma volume was 27±8% and mean maximum plaque thickness was 0.53±0.22 mm. Thirty-eight women with atherosclerosis (53%) had >30% of interrogated vessel involved. The average vessel involvement was 40%, and the maximum plaque thickness was 1.27 mm. The number of risk factors strongly correlated with percent atheroma volume (r=0.53, p<0.0001) and percent vessel involvement (r=0.51, p<0.0001), with the strongest independent predictor of both being age. Remodeling was assessed in 59/73 women (81%), and 73% had evidence of positive remodeling.
In symptomatic women without significant luminal obstructive CAD, we observed a very high prevalence of atherosclerosis with positive remodeling and preserved lumen size. These findings may help explain increased risk and emphasize need for improved diagnostic and treatment options for women with concealed CAD.
PMCID: PMC3019081  PMID: 21029178
chest pain in women; intravascular ultrasound; atherosclerosis; coronary artery disease
11.  Epicardial Fat is Associated with Duration of Antiretroviral Therapy and Coronary Atherosclerosis: The Multicenter AIDS Cohort Study 
AIDS (London, England)  2014;28(11):1635-1644.
Cytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and anti-retroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine if HIV infection is associated with greater epicardial fat and if epicardial fat is associated with subclinical coronary atherosclerosis.
We studied 579 HIV-infected and 353 HIV-uninfected men age 40 to 70 years with non-contrast computed tomography (CT) to measure epicardial adipose tissue volume (EAT) and coronary artery calcium (CAC). Total plaque score (TPS), and plaque subtypes (non-calcified, calcified and mixed) were measured by coronary CT angiography in 706 men.
We evaluated the association between EAT and HIV serostatus, and the association of EAT with subclinical atherosclerosis, adjusting for age, race and serostatus and with additional cardiovascular (CV) risk factors and tested for modifying effects of HIV serostatus.
HIV-infected men had greater EAT than HIV-uninfected men (p=0.001). EAT was positively associated with duration of antiretroviral therapy (p=0.02), specifically AZT (p<0.05). EAT was associated with presence of any coronary artery plaque (p=0.006) and non-calcified plaque (p=0.001), adjusting for age, race, serostatus and CV risk factors. Among men with CAC, EAT was associated with CAC extent (p=0.006). HIV serostatus did not modify associations between EAT and either CAC extent or presence of plaque.
Greater epicardial fat volume in HIV-infected men and its association with coronary plaque and antiretroviral therapy duration suggest potential mechanisms that might lead to increased risk for cardiovascular disease in HIV.
PMCID: PMC4169787  PMID: 24809732
Imaging; plaque; risk factors; HIV; ART
12.  The relation of location-specific epicardial adipose tissue thickness and obstructive coronary artery disease: systemic review and meta-analysis of observational studies 
There is growing evidence about the importance of epicardial adiposity on cardiometabolic risk. However, the relation of location-specific epicardial adipose tissue (EAT) thickness to coronary atherosclerotic burden is still unclear.
This meta-analysis was used to study the relations between location-specific EAT thickness and obstructive coronary artery disease (CAD). A systemic literature search to identify eligible studies that met the inclusion criteria from the beginning until January 2014 was made. We conducted the meta-analysis of all included 10 published studies. Pre-specified subgroup analyses were performed according to ethnicity, body mass index, diagnostic tools for CAD, and measurement tool if presence of high heterogeneity between studies. Potential publication bias was also assessed.
We identified ten observed studies with a total of 1625 subjects for planned comparison. With regard to the association between obstructive CAD and location-specific EAT thickness at the right ventricular free wall, caution is warranted. The pooled estimate showed that location-specific EAT thickness at the right ventricular free wall was significantly higher in the CAD group than non-CAD group (standardized mean difference (SMD): 0.70 mm, 95% CI: 0.26-1.13, P = 0.002), although heterogeneity was high (I2 = 93%). It should be clear that only the result of echocardiography-based studies showed a significant association (SMD: 0.98 mm, 95% CI: 0.43-1.53, P = 0.0005), and the result of all included CT-based studies showed a non-significant association (SMD: 0.06 mm, 95% CI: -0.12-0.25, P = 0.50). In the subgroup analysis, the “diagnostic tools for CAD” or “measurement tool of EAT thickness” are potential major sources of heterogeneity between studies. With regard to location-specific EAT thickness at the left atrioventricular (AV) groove, it was significantly higher in the CAD group than non-CAD group (SMD: 0.74 mm, 95% CI: 0.55-0.92, P <0.00001; I2 = 0%).
Our meta-analysis suggests that significantly elevated location-specific EAT thickness at the left AV groove is associated with obstructive CAD. Based on the current evidence, the location-specific EAT thickness at the left AV groove appears to be a good predictor in obstructive CAD, especially in Asian populations. Furthermore well-designed studies are warranted because of the current limited number of studies.
PMCID: PMC4101835  PMID: 24884458
Coronary artery disease; Location-specific epicardial adipose tissue thickness; Meta-analysis
13.  Epicardial Adipose Tissue Is Associated with Plaque Burden and Composition and Provides Incremental Value for the Prediction of Cardiac Outcome. A Clinical Cardiac Computed Tomography Angiography Study 
PLoS ONE  2016;11(5):e0155120.
We sought to investigate the association of epicardial adipose tissue (eCAT) volume with plaque burden, circulating biomarkers and cardiac outcomes in patients with intermediate risk for coronary artery disease (CAD).
Methods and Results
177 consecutive outpatients at intermediate risk for CAD and completed biomarker analysis including high-sensitive Troponin T (hs-TnT) and hs-CRP underwent 256-slice cardiac computed tomography angiography (CCTA) between June 2008 and October 2011. Patients with lumen narrowing ≥50% exhibited significantly higher eCAT volume than patients without any CAD or lumen narrowing <50% (median (interquartile range, IQR): 108 (73–167) cm3 vs. 119 (82–196) cm3, p = 0.04). Multivariate regression analysis demonstrated an independent association eCAT volume with plaque burden by number of lesions (R2 = 0.22, rpartial = 0.29, p = 0.026) and CAD severity by lumen narrowing (R2 = 0.22, rpartial = 0.23, p = 0.038) after adjustment for age, diabetes mellitus, hyperlidipemia, body-mass-index (BMI), hs-CRP and hs-TnT. Univariate Cox proportional hazards regression analysis identified a significant association for both increased eCAT volume and maximal lumen narrowing with all cardiac events. Multivariate Cox proportional hazards regression analysis revealed an independent association of increased eCAT volume with all cardiac events after adjustment for age, >3 risk factors, presence of CAD, hs-CRP and hs-TnT.
Epicardial adipose tissue volume is independently associated with plaque burden and maximum luminal narrowing by CCTA and may serve as an independent predictor for cardiac outcomes in patients at intermediate risk for CAD.
PMCID: PMC4871366  PMID: 27187590
14.  Correlation between Aortic Wall Thickness and Coronary Artery Disease by 64 Slice Multidetector Computed Tomography 
Introduction: Atherosclerotic cardiovascular disease is a dispersed pathology involving the coronary arteries, carotid arteries, aorta and peripheral arteries. It has been previously suggested that coronary and aortic atherosclerosis may be associated. Imaging of the aorta and the aortic wall can be performed by various imaging modalities including state-of-the-art multidetector computer tomography (MDCT). This study aimed to investigate a possible association between the MDCT-measured thickness of the thoracic aorta and the presence of coronary artery disease (CAD) as well as its severity.
Methods: Three hundred and fifty candidates of coronary computer tomography angiography (CTA) with signs and symptoms suggestive of CAD were recruited in Tabriz Parsian and Iran CTA Centers. Contrast-enhanced MDCT examinations were performed using a 64 detector scanner. Maximum aortic wall thickness in the mid-portion of descending thoracic aorta (region of pulmonary trunk to diaphragm) was measured perpendicular to the center of the vessel.
Results: CAD was confirmed in 189 cases (54%) and the remaining 161 cases served as controls. The mean age of the cases, as well as the percentage of male subjects was significantly higher in the CAD group. The mean aortic wall thickness was also significantly higher in the patient group (2.21±0.63 mm vs. 1.88±0.58 mm; P<0.001). In multivariate analysis, however, the two groups turned up comparable as to the aortic wall thickness (P=0.31). The optimal cut-off point of aortic wall thickness was ≥2 mm in discriminating between CAD+ and CAD- groups, with a corresponding sensitivity and specificity of 65% and 57%, respectively. There was no significant association between aortic wall thickness and the severity of CAD (the number of significantly occluded coronary arteries).
Conclusion: Aortic wall thickness is apparently neither an independent predictor of CAD nor is it associated with the severity of CAD in candidates of CTA.
PMCID: PMC3825395  PMID: 24252983
Coronary Artery Disease; Multidetector Computer; Tomography; Aortic Wall Thickness
15.  Epicardial Adipose Tissue Volume as a Marker of Coronary Artery Disease Severity in Patients with Diabetes Independent of Coronary Artery Calcium: Findings from the CTRAD study 
The association between epicardial adipose tissue (EAT) volume and coronary artery disease (CAD) severity was evaluated, independent of traditional risk factors and coronary artery calcium (CAC) scores, in patients with diabetes type 2 (DM-2) using cardiac computed tomography angiography (CTA).
A multivariate analysis was utilized to assess for an independent association after calculating EAT volume, CAD severity, and calcium scores in 92 patients with DM-II from the CTRAD study. We graded CAD severity as none (normal coronaries), mild-moderate (<70% stenosis), and severe (70% or greater stenosis).
A total of 39 (42.3 %) asymptomatic patients with diabetes did not have CAD; 30.4% had mild/moderate CAD; and 27.1% had severe CAD. Mean EAT volume was highest in patients with severe CAD (143.14 cm3) as compared to mild/moderate CAD (112.7 cm3), and no CAD (107.5 cm3) (p= 0.003). After adjustment of clinical risk factors, notably, CAC score, multivariate regression analysis showed EAT volume was an independent predictor of CAD severity in this sample (odds ratio 11.2, 95% confidence interval 1.7 –73.8, p =0.01).
Increasing EAT volume in asymptomatic patients with DM-II is associated with presence of severe CAD, independent of BMI and CAC, as well as traditional risk factors.
PMCID: PMC4261017  PMID: 25262111
EAT; Pericardial fat; Coronary Artery Disease; Multi-detector Computed Tomography; Computed Tomography Angiography; Diabetes; Metabolic Syndrome
16.  Epicardial adipose tissue and pericoronary fat thickness measured with 64-multidetector computed tomography: potential predictors of the severity of coronary artery disease 
Clinics  2014;69(6):388-392.
The aim of the present study was to investigate the relationship between pericoronary fat and the severity and extent of atherosclerosis, quantified using 64-multidetector computed tomography, in patients with suspected coronary artery disease.
The study population consisted of 131 patients who were clinically referred for noninvasive multislice computed tomography coronary angiography for the evaluation of coronary artery disease. Patients were classified as follows: no atherosclerosis, Group 1; nonobstructive atherosclerosis (luminal narrowing <50% in diameter), Group 2; and obstructive atherosclerosis (luminal narrowing ≥50%) in a single vessel or obstructive atherosclerosis in the left main coronary artery and/or multiple vessels, Group 3. Epicardial adipose tissue was defined as the adipose tissue between the surface of the heart and the visceral layer of the pericardium (visceral epicardium). Epicardial adipose tissue thickness (mm) was determined in the right ventricular anterior free wall. The mean thickness of the pericoronary fat surrounding the three coronary arteries was used for the analyses.
The average thickness over all three regions was 13.2 ± 2.1 mm. The pericoronary fat thickness was significantly increased in Group 3 compared with Groups 2 and 1. The epicardial adipose tissue thickness was significantly increased in Group 3 compared with Groups 2 and 1. A receiver operating characteristic curve for obstructive coronary artery disease was assessed to verify the optimum cut-off point for pericoronary fat thickness, which was 13.8 mm. A receiver operating characteristic curve for obstructive coronary artery disease was also assessed to verify the optimum cut-off point for epicardial adipose tissue, which was 6.8 cm.
We showed that the epicardial adipose tissue and pericoronary fat thickness scores were higher in patients with obstructive coronary artery diseases.
PMCID: PMC4050325  PMID: 24964302
Epicardial Adipose Tissue; Pericoronary Fat Thickness; 64-Multidetector Computed Tomography; Severity of Coronary Artery Disease
17.  Assosiation of Epicardial and Pericardial Fat Thickness with Coronary Artery Disease 
Electronic Physician  2016;8(9):2982-2989.
Visceral adipose tissue is a known important risk factor for coronary artery disease (CAD). While some studies have suggested relationship between epicardial fat thickness (EFT) and CAD, there are no adequate studies for pericardial fat thickness (PFT). The aim of this study was to determine the association of EFT and PFT with CAD.
This cross-sectional study was conducted on patients who were candidates for elective coronary artery angiography, referred to Emam Reza Hospital, Mashhad, Iran during Jan 2014–2016. Demographic and laboratory data were collected. Transthoracic echocardiography was performed to determine average EFT and PFT at the standard parasternal long-axis view at end-systole for 3 cardiac cycles. SCA was performed on the same day. The patients were divided into two groups: CAD (n=59) and non-CAD (n=41) based on presence or absence of epicardial coronary artery stenosis of > 50%. Chi-square, independent T-test, and receiver operating characteristic (ROC) curve were used by SPSS Version 16 for data analysis.
One hundred patients (44 women and 56 men) with an average age of 56.4 ± 9.9 years were studied. The two groups were not significantly different in demographic profile and cronary risk factors. While PFT was not significantly different between the two groups, EFT was significantly higher in CAD group (3.0 ± 3.69 vs. 1.2 ± 3.6, p <0.0001). Moreover, with the increase of the affected coronary arteries, EFT increased (p <0.0001). Gensini score had a strong correlation with amount of EFT (r = 0.765, p <0.0001). EFT with a cutoff value of 4.25 mm (sensitivity=79%, specificity=68%) was specified in predicting CAD.
EFT measured by echocardiography can be used as an independent marker to predict CAD. More studies are needed to determine the predictive role of PFT for CAD.
PMCID: PMC5074760  PMID: 27790354
Epicardial fat thickness; Pericardial fat thickness; Coronary artery disease; Echocardiography
18.  Association between omentin-1 expression in human epicardial adipose tissue and coronary atherosclerosis 
Omentin-1, a novel adipocytokine mainly expressed in visceral adipose tissue, has been found to inhibit the inflammatory response and improve insulin resistance as well as other obesity-related disorders. This study investigated the association between omentin-1 expression in human epicardial adipose tissue (EAT) and coronary atherosclerosis.
Serum samples, and paired biopsies from EAT and subcutaneous adipose tissue (SAT), were obtained from patients with and without coronary artery disease (CAD, n = 28 and NCAD, n = 12, respectively) during elective cardiac surgery. Coronary angiography was performed to identify CAD presence. Serum omentin-1 and adiponectin levels were measured by ELISA. mRNA expression of omentin-1 and adiponectin was detected in adipose tissue by quantitative real-time PCR, and omentin-1 protein expression was evaluated by immunohistochemistry. Correlation and multivariate linear regression analyses were performed to determine the association between omentin-1 expression and clinical risk factors.
mRNA and protein expression of omentin-1 were higher in EAT than paired SAT in patients with CAD and NCAD. Compared with NCAD patients, CAD patients had lower omentin-1 and adiponectin mRNA levels in EAT and serum levels as well as lower omentin-1 protein levels. Among patients with CAD, omentin-1 expression was lower in EAT surrounding coronary segments with stenosis than those without stenosis, in terms of mRNA and protein, whereas adiponectin mRNA level in EAT did not seem to differ between stenotic and non-stenotic coronary segments in CAD patients. In multivariate linear regression analysis, CAD was an independent predictor of EAT omentin-1 mRNA expression (beta = −0.57, 95 % CI −0.89 to −0.24; P = 0.001) and serum omentin-1 levels (beta = −0.35, 95 % CI −0.67 to −0.03; P = 0.036).
Circulating and EAT-derived omentin-1 levels were reduced in patients with CAD. Omentin-1 expression in patients with CAD was lower in EAT adjacent to coronary stenotic segments than non-stenotic segments.
PMCID: PMC4924240  PMID: 27352781
Epicardial adipose tissue; Omentin-1; Atherosclerosis; Coronary artery disease
19.  Quantification of epicardial fat: Which method can predict significant coronary artery disease? 
World Journal of Cardiology  2015;7(5):287-292.
AIM: To compare the predictive value of three methods of epicardial fat (EF) assessment for presence of significant coronary artery disease (CAD) [i.e., epicardial fat volume (EFV), EFV indexed with body surface area (EFV/BSA) and EFV indexed with body mass index (EFV/BMI)].
METHODS: The study was performed on 170 patients (85 women and 85 men) with clinical suspicion of CAD. They aged 26-89 years with a median age of 54 years. The patients were classified into three groups: Group 1: 58 patients with normal coronary arteries; group 2: 48 patients with non-significant CAD and group 3: 64 patients with significant CAD. The three methods for assessment of epicardial fat were retrospectively studied to determine the best method to predict the presence of significant CAD.
RESULTS: The three methods for epicardial fat quantification and measurements, i.e., EFV, EFV/BSA and EFV/BMI with post- hoc analysis showed a significant difference between patients with significant coronary artery disease compared to the normal group. Receiver operating characteristic curve analysis showed no significant difference between the three methods of epicardial fat measurements, the area under curve ranging between 0.6 and 0.62. The optimal cut-off was 80.3 cm3 for EFV, 2.4 cm3/m2 for EFV indexed with BMI and 41.7 cm3/(kg/m2) for EFV indexed with BSA. For this cut-off the sensitivity ranged between 0.92 and 0.94, while specificity varied from 0.31 to 0.35.
CONCLUSION: Any one of the three methods for assessment of epicardial fat can be used to predict significant CAD since all have the same equivalent predictive value.
PMCID: PMC4438468  PMID: 26015859
Quantification of epicardial fat; Coronary heart disease; Epicardial fat volume
20.  Coronary Microvascular Dysfunction is Related to Abnormalities in Myocardial Structure and Function in Cardiac Amyloidosis 
JACC. Heart failure  2014;2(4):358-367.
We sought to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis.
Effort angina is common in subjects with cardiac amyloidosis even in the absence of epicardial coronary artery disease (CAD).
Thirty one subjects were prospectively enrolled in this study including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2D echocardiography. Global LV myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF / rest MBF) adjusting for rest rate pressure product.
Compared to the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 vs. 0.88 ± 0.23 ml/g/min, P = 0.004), stress MBF (0.85 ± 0.29 vs. 1.85 ± 0.45 vs. ml/min/g, P < 0.0001), CFR (1.19 ± 0.38 vs. 2.23 ± 0.88, P < 0.0001), and higher minimal coronary vascular resistance (111 ± 40 vs. 70 ± 19 mm Hg/mL/g/min, P = 0.004). Of note, almost all amyloid subjects (> 95%) demonstrated significantly reduced peak stress MBF (< 1.3 mL/g/min). In multivariable linear regression analyses, a diagnosis of amyloidosis, increased LV mass and age were the only independent predictors of impaired coronary vasodilator function.
Coronary microvascular dysfunction is highly prevalent in subjects with cardiac amyloidosis even in the absence of epicardial CAD, and may explain their anginal symptoms. Further study is required to understand whether specific therapy directed at amyloidosis may improve coronary vasomotion in amyloidosis.
PMCID: PMC4127145  PMID: 25023822
Amyloidosis; myocardial blood flow; coronary microvascular function; PET; strain
21.  Assessment of Epicardial Fat Volume With Threshold-Based 3-Dimensional Segmentation in CT: Comparison With the 2-Dimensional Short Axis-Based Method 
Korean Circulation Journal  2010;40(7):328-333.
Background and Objectives
We aimed to assess the usefulness of a threshold-based, 3-dimensional (3D) segmentation in comparison with the traditional 2-dimensional (2D) short axis-based method for measurement of epicardial fat volume with 64-slice multidetector computed tomography (MDCT).
Subjects and Methods
One hundred patients (52 males; mean age, 58.36±11.0 years) who underwent coronary CT angiography were enrolled in this study. The epicardial fat volume was measured using the two methods. The existing method was the 2D short axis-based method and the new method was the threshold-based 3D segmentation. Pearson's correlation was used to compare the two measurement methods. We also assessed the relationship between the epicardial fat volume and coronary artery disease (CAD).
There were a strong correlation between the epicardial fat volumes determined using the two methods (r=0.956, p<0.001). The mean overestimation of epicardial fat volume by the threshold-based 3D method was 59.89±12.00% compared to the 2D short-axis based method. Using the 3D method, the epicardial fat volume was significantly higher in the CAD group than in the controls (165.07±48.22 cm3 vs. 108.39±48.03 cm3, p<0.001).
Threshold-based 3D segmentation is another easy and useful tool for measuring the epicardial fat volume.
PMCID: PMC2910289  PMID: 20664741
Pericardium; Tomography, X-ray computed; Visceral fats; Coronary artery disease
22.  Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis 
Growing evidence suggests that epicardial adipose tissue (EAT) may play a key role in the pathogenesis and development of coronary artery disease (CAD) by producing several inflammatory adipokines. Chemerin, a novel adipokine, has been reported to be involved in regulating immune responses and glucolipid metabolism. Given these properties, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis. In this study, we sought to determine the relationship of chemerin expression in EAT and the severity of coronary atherosclerosis in Han Chinese patients.
Serums and adipose tissue biopsies (epicardial and thoracic subcutaneous) were obtained from CAD (n = 37) and NCAD (n = 16) patients undergoing elective cardiac surgery. Gensini score was used to assess the severity of CAD. Serum levels of chemerin, adiponectin and insulin were measured by ELISA. Chemerin protein expression in adipose tissue was detected by immunohistochemistry. The mRNA levels of chemerin, chemR23, adiponectin and TNF-alpha in adipose tissue were detected by RT-PCR.
We found that EAT of CAD group showed significantly higher levels of chemerin and TNF-alpha mRNA, and significantly lower level of adiponectin mRNA than that of NCAD patients. In CAD group, significantly higher levels of chemerin mRNA and protein were observed in EAT than in paired subcutaneous adipose tissue (SAT), whereas such significant difference was not found in NCAD group. Chemerin mRNA expression in EAT was positively correlated with Gensini score (r = 0.365, P < 0.05), moreover, this correlation remained statistically significant (r = 0.357, P < 0.05) after adjusting for age, gender, BMI and waist circumference. Chemerin mRNA expression in EAT was also positively correlated with BMI (r = 0.305, P < 0.05), waist circumference (r = 0.384, P < 0.01), fasting blood glucose (r = 0.334, P < 0.05) and negatively correlated with adiponectin mRNA expression in EAT (r = -0.322, P < 0.05). However, there were no significant differences in the serum levels of chemerin or adiponectin between the two groups. Likewise, neither serum chemerin nor serum adiponectin was associated with Gensini score (P > 0.05).
The expressions of chemerin mRNA and protein are significantly higher in EAT from patients with CAD in Han Chinese patients. Furthermore, the severity of coronary atherosclerosis is positive correlated with the level of chemerin mRNA in EAT rather than its circulating level.
PMCID: PMC3198902  PMID: 21981776
Epicardial adipose tissue; Chemerin; Adipokine; Atherosclerosis
23.  Differential impacts of cardiac and abdominal ectopic fat deposits on cardiometabolic risk stratification 
Previous studies have shown that excessive abdominal visceral adipose tissue (AVAT) and epicardial adipose tissue (EAT) are risk factors of cardiometabolic disease; we hypothesized there is differential contribution of abdominal and cardiac fat deposits to the cardiometabolic profiles.
Two hundred eight consecutive subjects with clinical suspicion of coronary artery disease (CAD) who underwent cardiac and abdominal CT for Agatston score and abdominal visceral fat measurement were retrospectively analyzed. Regional thickness of EAT (EATth), total volume of EAT, total volume of paracardial adipose tissue (PAT) and total volume of AVAT from L2 to L5 level were measured. The relationships between abdominal and cardiac adipose tissue measurements, the number of components of metabolic syndrome, and the severity of Agatston score on a four ranking scale (0, 1–10,11–100, 101–400, >400) were investigated.
The amounts of AVAT, EAT, PAT and EATth-LAVG showed a significant linear trend with increasing number (0–5) of components in metabolic syndrome (AVAT, EAT and PAT P for trend <0.0001; EATth-LVAG P for trend <0.001). EATth at left atrioventricular groove (EATth-LAVG) showed significant linear trend with the severity of Agatston score on a four ranking scale (P for trend <0.0001). In multivariate binary regression analysis, total volume of AVAT was the sole adiposity predictor for metabolic syndrome independent to age, gender, and waist circumference (odds ratio of 1.20, 95 % CI 1.08–1.32, p < 0.001) while total volume of EAT, PAT, and EATth-LAVG were not. In contrary, EATth-LAVG was the sole adiposity predictor for Agatston score >400 (odds ratio of 1.11, 95 % CI 1.034–1.184, p = 0.004).
Excessive total volume of AVAT appears to be preferentially associated with metabolic syndrome; while EAT, esp. EATth-LAVG is preferentially associated with coronary artery disease. This differential effect of the two adiposities deserves a large-scale cohort study for further investigation.
PMCID: PMC4724070  PMID: 26800881
Ectopic fat deposits; Cardiometabolic risks
24.  Gender differences in the prevalence, severity, and composition of coronary artery disease in the young: a study of 1635 individuals undergoing coronary CT angiography from the prospective, multinational confirm registry 
Prior studies examining coronary atherosclerosis in the young have been limited by retrospective analyses in small cohorts. We examined the relationship between cardiovascular risk factors (RFs) and prevalence and severity of coronary atherosclerosis in a large, prospective, multinational registry of consecutive young individuals undergoing coronary computerized tomographic angiography (CCTA).
Method and results
Of 27 125 patients undergoing CCTA, 1635 young (<45 years) individuals without known coronary artery disease (CAD) or coronary anomalies were identified. Coronary plaque was assessed for any CAD, obstructive CAD (≥50% stenosis), and presence of calcified plaque (CP) and non-calcified plaque (NCP). Among 1635 subjects (70% men, age 38 ± 6 years), any CAD, obstructive CAD, CP, and NCP were observed in 19, 4, 5, and 8%, respectively. Compared with women, men demonstrated higher rates of any CAD (21 vs. 12%, P < 0.001), CP (6 vs. 3%, P = 0.01), and NCP (9 vs. 5%, P = 0.008), although no difference was observed for rates of obstructive CAD (5 vs. 4%, P = 0.46). Any CAD, obstructive CAD, and NCP were higher for young individuals with diabetes, hypertension, dyslipidaemia, current smoking, or family history of CAD; while only diabetes and dyslipidaemia were associated with CP. Increasing cardiovascular RFs was associated with a greater prevalence and extent and severity of CAD, with individuals with 0, 1, 2, ≥3 RFs manifesting a dose–response increase in any CAD (P < 0.001, for trend), obstructive CAD (P < 0.001, for trend), NCP (P < 0.001, for trend), and CP (P < 0.001, for trend). In multivariable analysis adjusting for sex and cardiovascular RFs, male sex was the strongest predictor for any CAD (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.43–2.66, P < 0.001), CP (OR = 1.46, 95% CI = 1.08–1.98, P = 0.01), and NCP (OR = 1.33, 95% CI = 1.06–1.67, P = 0.01); family history of CAD was the strongest predictor for obstructive CAD (OR = 2.71, 95% CI = 1.65–4.45, P < 0.001).
Any and obstructive CAD is present in 1 in 5 and 1 in 20 young individuals, respectively, with family history associated with the greatest risk of obstructive CAD.
PMCID: PMC4447773  PMID: 25539786
young adults; coronary artery disease; coronary risk factors; coronary CT angiography
25.  Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men 
AIDS (London, England)  2010;24(2):243-253.
The degree of subclinical coronary atherosclerosis in HIV-infected patients is unknown. We investigated the degree of subclinical atherosclerosis and the relationship of traditional and nontraditional risk factors to early atherosclerotic disease using coronary computed tomography angiography.
Design and methods
Seventy-eight HIV-infected men (age 46.5 ± 6.5 years and duration of HIV 13.5 ± 6.1 years, CD4 T lymphocytes 523 ± 282; 81% undetectable viral load), and 32 HIV-negative men (age 45.4 ± 7.2 years) with similar demographic and coronary artery disease (CAD) risk factors, without history or symptoms of CAD, were prospectively recruited. 64-slice multidetector row computed tomography coronary angiography was performed to determine prevalence of coronary atherosclerosis, coronary stenosis, and quantitative plaque burden.
HIV-infected men demonstrated higher prevalence of coronary atherosclerosis than non-HIV-infected men (59 vs. 34%; P = 0.02), higher coronary plaque volume [55.9 (0–207.7); median (IQR) vs. 0 (0–80.5) μl; P = 0.02], greater number of coronary segments with plaque [1 (0–3) vs. 0 (0–1) segments; P = 0.03], and higher prevalence of Agatston calcium score more than 0 (46 vs. 25%, P = 0.04), despite similar Framingham 10-year risk for myocardial infarction, family history of CAD, and smoking status. Among HIV-infected patients, Framingham score, total cholesterol, low-density lipoprotein, CD4/CD8 ratio, and monocyte chemoattractant protein 1 were significantly associated with plaque burden. Duration of HIV infection was significantly associated with plaque volume (P = 0.002) and segments with plaque (P = 0.0009) and these relationships remained significant after adjustment for age, traditional risk factors, or duration of antiretroviral therapy. A total of 6.5% (95% confidence interval 2–15%) of our study population demonstrated angiographic evidence of obstructive CAD (>70% luminal narrowing) as compared with 0% in controls.
Young, asymptomatic, HIV-infected men with long-standing HIV disease demonstrate an increased prevalence and degree of coronary atherosclerosis compared with non-HIV-infected patients. Both traditional and nontraditional risk factors contribute to atherosclerotic disease in HIV-infected patients.
PMCID: PMC3154841  PMID: 19996940
atherosclerosis; cardiovascular risk factors; coronary artery disease; coronary computed tomography angiography; HIV

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