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1.  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
2.  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
coronary artery bypass surgery; epicardial adipose tissue; dual source computed tomography
3.  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
4.  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
5.  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
6.  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
7.  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
8.  Multi-Detector Computed Tomography Angiography for Coronary Artery Disease 
Executive Summary
Computed tomography (CT) scanning continues to be an important modality for the diagnosis of injury and disease, most notably for indications of the head and abdomen. (1) According to a recent report published by the Canadian Institutes of Health Information, (1) there were about 10.3 scanners per million people in Canada as of January 2004. Ontario had the fewest number of CT scanners per million compared to the other provinces (8 CT scanners per million). The wait time for CT in Ontario of 5 weeks approaches the Canadian median of 6 weeks.
This health technology and policy appraisal systematically reviews the published literature on multidetector CT (MDCT) angiography as a diagnostic tool for the newest indication for CT, coronary artery disease (CAD), and will apply the results of the review to current health care practices in Ontario. This review does not evaluate MDCT to detect coronary calcification without contrast medium for CAD screening purposes.
The Technology
Compared with conventional CT scanning, MDCT can provide smaller pieces of information and can cover a larger area faster. (2) Advancing MDCT technology (8, 16, 32, 64 slice systems) is capable of producing more images in less time. For general CT scanning, this faster capability can reduce the time that patients must stay still during the procedure, thereby reducing potential movement artefact. However, the additional clinical utility of images obtained from faster scanners compared to the images obtained from conventional CT scanners for current CT indications (i.e., non-moving body parts) is not known.
There are suggestions that the new fast scanners can reduce wait times for general CT. MDCT angiography that utilizes a contrast medium, has been proposed as a minimally invasive replacement to coronary angiography to detect coronary artery disease. MDCT may take between 15 to 45 minutes; coronary angiography may take up to 1 hour.
Although 16-slice and 32-slice CT scanners have been available for a few years, 64-slice CT scanners were released only at the end of 2004.
Review Strategy
There are many proven, evidence-based indications for conventional CT. It is not clear how MDCT will add to the clinical utility and management of patients for established CT indications. Therefore, because cardiac imaging, specifically MDCT angiography, is a new indication for CT, this literature review focused on the safety, effectiveness, and cost-effectiveness of MDCT angiography compared with coronary angiography in the diagnosis and management of people with CAD.
This review asked the following questions:
Is the most recent MDCT angiography effective in the imaging of the coronary arteries compared with conventional angiography to correctly diagnose of significant (> 50% lumen reduction) CAD?
What is the utility of MDCT angiography in the management and treatment of patients with CAD?
How does MDCT angiography in the management and treatment of patients with CAD affect longterm outcomes?
The published literature from January 2003 to January 31, 2005 was searched for articles that focused on the detection of coronary artery disease using 16-slice CT or faster, compared with coronary angiography. The search yielded 138 articles; however, 125 were excluded because they did not meet the inclusion criteria (comparison with coronary angiography, diagnostic accuracy measures calculated, and a sample size of 20 or more). As screening for CAD is not advised, studies that utilized MDCT for this purpose or studies that utilized MDCT without contrast media were also excluded. Overall, 13 studies were included in this review.
Summary of Findings
The published literature focused on 16-slice CT angiography for the detection of CAD. Two abstracts that were presented at the 2005 European Congress of Radiology meeting in Vienna compared 64-slice CT angiography with coronary angiography.
The 13 studies focussing on 16-slice CT angiography were stratified into 2 groups: Group 1 included 9 studies that focused on the detection of CAD in symptomatic patients, and Group 2 included 4 studies that examined the use of 16-slice CT angiography to detect disease progression after cardiac interventions. The 2 abstracts on 64-slice CT angiography were presented separately, but were not critically appraised due to the lack of information provided in the abstracts.
16-Slice Computed Tomography Angiography
The STARD initiative to evaluate the reporting quality of studies that focus on diagnostic tests was used. Overall the studies were relatively small (fewer than 100 people), and only about one-half recruited consecutive patients. Most studies reported inclusion criteria, but 5 did not report exclusion criteria. In these 5, the patients were highly selected; therefore, how representative they are of the general population of people with suspicion if CAD or those with disease progression after cardiac intervention is questionable. In most studies, patients were either already taking, or were given, β-blockers to reduce their heart rates to improve image quality sufficiently. Only 6 of the 13 studies reported interobserver reliability quantitatively. The studies typically assessed the quality of the images obtained from 16-slice CT angiography, excluded those of poor quality, and compared the rest with the gold standard, coronary angiography. This practice necessarily inflated the diagnostic accuracy measures. Only 3 studies reported confidence intervals around their measures.
Evaluation of the studies in Group 1 reported variable sensitivity, from just over 60% to 96%, but a more stable specificity, at more than 95%. The false positive rate ranged from 5% to 8%, but the false negative rate was at best under 10% and at worst about 30%. This means that up to one-third of patients who have disease may be missed. These patients may therefore progress to a more severe level of disease and require more invasive procedures. The calculated positive and negative likelihood ratios across the studies suggested that 16-slice CT angiography may be useful to detect disease, but it is not useful to rule out disease. The prevalence of disease, measured by conventional coronoary angiography, was from 50% to 80% across the studies in this review. Overall, 16-slice CT angiography may be useful, but there is no conclusive evidence to suggest that it is equivalent to or better than coronary angiography to detect CAD in symptomatic patients.
In the 4 studies in Group 2, sensitivity and specificity were both reported at more than 95% (except for 1 that reported sensitivity of about 80%). The positive and negative likelihood ratios suggested that the test might be useful to detect disease progression in patients who had cardiac interventions. However, 2 of the 4 studies recruited patients who had been asymptomatic since their intervention. As many of the patients studied were not symptomatic, the relevance of performing MDCT angiography in the patient population may be in question.
64-Slice Computed Tomography Angiography
An analysis from the interim results based on 2 abstracts revealed that 64-slice CT angiography was insufficient compared to coronary angiography and may not be better than 16-slice CT angiography to detect CAD.
Cardiac imaging is a relatively new indication for CT. A systematic review of the literature was performed from 2003 to January 2005 to determine the effectiveness of MDCT angiography (16-slice and 64-slice) compared to coronary angiography to detect CAD. At the time of this report, there was no published literature on 64-slice CT for any indications.
Based on this review, the Medical Advisory Secretariat concluded that there is insufficient evidence to suggest that 16-slice or 64-slice CT angiography is equal to or better than coronary angiography to diagnose CAD in people with symptoms or to detect disease progression in patients who had previous cardiac interventions. An analysis of the evidence suggested that in investigating suspicion of CAD, a substantial number of patients would be missed. This means that these people would not be appropriately treated. These patients might progress to more severe disease and possibly more adverse events. Overall, the clinical utility of MDCT in patient management and long-term outcomes is unknown.
Based on the current evidence, it is unlikely that CT angiography will replace coronary angiography completely, but will probably be used adjunctively with other cardiac diagnostic tests until more definitive evidence is published.
If multi-slice CT scanners are used for coronary angiography in Ontario, access to the current compliment of CT scanners will necessarily increase wait times for general CT scanning. It is unlikely that these newer-generation scanners will improve patient throughput, despite the claim that they are faster.
Screening for CAD in asymptomatic patients and who have no history of ischemic heart disease using any modality is not advised, based on the World Health Organization criteria for screening. Therefore, this review did not examine the use of multi-slice CT for this purpose.
PMCID: PMC3382628  PMID: 23074474
9.  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
10.  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
11.  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
12.  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
13.  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
14.  Receipt of Cardiac Medications Upon Discharge among Men and Women with Acute Coronary Syndrome and Non-Obstructive Coronary Artery Disease 
Clinical cardiology  2010;33(1):36-41.
Management of acute coronary syndrome (ACS) patients with non-obstructive epicardial coronary artery disease (CAD) remains poorly understood.
ACS patients with non-obstructive CAD are less likely to receive effective cardiac medications upon discharge from the hospital.
We identified patients hospitalized with ACS that underwent coronary angiography and had 6-month follow-up. Patients were grouped by CAD severity: non-obstructive CAD (<50% blockage in all vessels) or obstructive CAD (≥50% blockage in ≥1 vessels). Data were collected on demographics, medications at discharge, and adverse outcomes at 6 months, for all patients.
Of the 2,264 ACS patients included in the study: 123 patients had non-obstructive CAD and 2,141 had obstructive CAD. Cardiac risk factors including hypertension and diabetes were common among patients with non-obstructive CAD. Men and women with non-obstructive CAD were less likely to receive cardiac medications compared to patients with obstructive CAD including aspirin (87.8% vs. 95.0%, p=0.001), beta-blockers (74.0% vs. 89.2%, p<0.001), or statins (69.1% vs. 81.2%, p=0.001). No gender-related differences in discharge medications were observed for patients with nonobstructive CAD. However women with non-obstructive CAD had similar rates of cardiac-related rehospitalization as men with obstructive CAD (23.3% and 25.9%, respectively).
Patients with non-obstructive CAD are less likely to receive evidence-based medications compared to patients with obstructive CAD, despite the presence of CAD risk factors and occurrence of an ACS event. Further research is warranted to determine if receipt of effective cardiac medications among patients with non-obstructive CAD would reduce cardiac related events.
PMCID: PMC2935808  PMID: 20063300
Non-obstructive coronary artery disease; Acute Coronary Syndrome; Prevention
15.  Relationship between epicardial adipose tissue, coronary artery disease and adiponectin in a Mexican population 
The amount of epicardial adipose tissue (EAT) around the heart has been identified as an independent predictor of coronary artery disease (CAD), potentially through local release of inflammatory cytokines. Ethnic differences have been observed, but no studies have investigated this relationship in the Mexican population. The objective of the present study was to evaluate whether a relationship exist between EAT thickness assessed via echocardiography with CAD and adiponectin levels in a Mexican population.
We studied 153 consecutive patients who underwent coronary angiography and transthoracic echocardiography (TTE). EAT thickness on the free wall of the right ventricle was measured at the end of systole from parasternal long and short axis views of three consecutive cardiac cycles. Coronary angiograms were analyzed for the presence, extent and severity of CAD. Serum adiponectin, lipids, glucose, C-reactive protein and fibrinogen were determined.
EAT thickness was greater in patients with CAD than in those without CAD from both parasternal long (5.39 ± 1.75 mm vs 4.00 ± 1.67 mm p < 0.0001) and short-axis views (5.23 ± 1.67 vs 4.12 ± 1.77, p = 0.001). EAT thickness measured from parasternal long and short-axis showed a statistically significant positive correlation with age (r = 0.354, p < 0.001; r = 0.286, p < 0.001 respectively), and waist circumference (r = 0.189, p = 0.019; r = 0.217, p = 0.007 respectively). A significant negative correlation between EAT thickness from the parasternal long axis with cholesterol-HDL was observed (r = -0.163, p = 0.045). No significant correlation was found between epicardial fat thickness and serum adiponectin or with the severity of CAD.
EAT thickness was greater in patients with CAD. However, no correlation was observed with the severity of the disease or with serum adiponectin levels. EAT thickness measured by echocardiography might provide additional information for risk assessment and prediction of CAD.
PMCID: PMC4163040  PMID: 25200587
Epicardial adipose tissue; Coronary artery disease; Echocardiography; Adiponectin
16.  Cardiac Magnetic Resonance Imaging for the Diagnosis of Coronary Artery Disease 
Executive Summary
In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease (CAD), an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.
After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD. Evidence-based analyses have been prepared for each of these five imaging modalities: cardiac magnetic resonance imaging, single photon emission computed tomography, 64-slice computed tomographic angiography, stress echocardiography, and stress echocardiography with contrast. For each technology, an economic analysis was also completed (where appropriate). A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).
The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports, which can be publicly accessed at the MAS website at: or at
Single Photon Emission Computed Tomography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Stress Echocardiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Stress Echocardiography with Contrast for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Cardiac Magnetic Resonance Imaging for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Pease note that two related evidence-based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website:
Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis
Magnetic Resonance Imaging for the Assessment of Myocardial Viability: an Evidence-Based Analysis
The Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled:
The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [Internet]. Available from:
The objective of this analysis was to determine the diagnostic accuracy of cardiac magnetic resonance imaging (MRI) for the diagnosis of patients with known/suspected coronary artery disease (CAD) compared to coronary angiography.
Cardiac MRI
Stress cardiac MRI is a non-invasive, x-ray free imaging technique that takes approximately 30 to 45 minutes to complete and can be performed using to two different methods, a) perfusion imaging following a first pass of an intravenous bolus of gadolinium contrast, or b) wall motion imaging. Stress is induced pharmacologically with either dobutamine, dipyridamole, or adenosine, as physical exercise is difficult to perform within the magnet bore and often induces motion artifacts. Alternatives to stress cardiac perfusion MRI include stress single-photon emission computed tomography (SPECT) and stress echocardiography (ECHO). The advantage of cardiac MRI is that it does not pose the radiation burden associated with SPECT. During the same sitting, cardiac MRI can also assess left and right ventricular dimensions, viability, and cardiac mass. It may also mitigate the need for invasive diagnostic coronary angiography in patients with intermediate risk factors for CAD.
Evidence-Based Analysis
Literature Search
A literature search was performed on October 9, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2005 to October 9, 2008. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Given the large amount of clinical heterogeneity of the articles meeting the inclusion criteria, as well as suggestions from an Expert Advisory Panel Meeting held on October 5, 2009, the inclusion criteria were revised to examine the effectiveness of cardiac MRI for the detection of CAD.
Heath technology assessments, systematic reviews, randomized controlled trials, observational studies
≥20 adult patients enrolled.
Published 2004-2009
Licensed by Health Canada
For diagnosis of CAD:
Reference standard is coronary angiography
Significant CAD defined as ≥ 50% coronary stenosis
Patients with suspected or known CAD
Reported results by patient, not segment
Non-English studies
Grey literature
Planar imaging
Patients with recent MI (i.e., within 1 month)
Patients with non-ischemic heart disease
Studies done exclusively in special populations (e.g., women, diabetics)
Outcomes of Interest
Sensitivity and specificity
Area under the curve (AUC)
Diagnostic odds ratio (DOR)
Summary of Findings
Stress cardiac MRI using perfusion analysis yielded a pooled sensitivity of 0.91 (95% CI: 0.89 to 0.92) and specificity of 0.79 (95% CI: 0.76 to 0.82) for the detection of CAD.
Stress cardiac MRI using wall motion analysis yielded a pooled sensitivity of 0.81 (95% CI: 0.77 to 0.84) and specificity of 0.85 (95% CI: 0.81 to 0.89) for the detection of CAD.
Based on DORs, there was no significant difference between pooled stress cardiac MRI using perfusion analysis and pooled stress cardiac MRI using wall motion analysis (P=0.26) for the detection of CAD.
Pooled subgroup analysis of stress cardiac MRI using perfusion analysis showed no significant difference in the DORs between 1.5T and 3T MRI (P=0.72) for the detection of CAD.
One study (N=60) was identified that examined stress cardiac MRI using wall motion analysis with a 3T MRI. The sensitivity and specificity of 3T MRI were 0.64 (95% CI: 0.44 to 0.81) and 1.00 (95% CI: 0.89 to 1.00), respectively, for the detection of CAD.
The effectiveness of stress cardiac MRI for the detection of CAD in unstable patients with acute coronary syndrome was reported in only one study (N=35). Using perfusion analysis, the sensitivity and specificity were 0.72 (95% CI: 0.53 to 0.87) and 1.00 (95% CI: 0.54 to 1.00), respectively, for the detection of CAD.
Ontario Health System Impact Analysis
According to an expert consultant, in Ontario:
Stress first pass perfusion is currently performed in small numbers in London (London Health Sciences Centre) and Toronto (University Health Network at the Toronto General Hospital site and Sunnybrook Health Sciences Centre).
Stress wall motion is only performed as part of research protocols and not very often.
Cardiac MRI machines use 1.5T almost exclusively, with 3T used in research for first pass perfusion.
On November 25 2009, the Cardiac Imaging Expert Advisory Panel met and made the following comments about stress cardiac MRI for perfusion analysis:
Accessibility to cardiac MRI is limited and generally used to assess structural abnormalities. Most MRIs in Ontario are already in 24–hour, constant use and it would thus be difficult to add cardiac MRI for CAD diagnosis as an additional indication.
The performance of cardiac MRI for the diagnosis of CAD can be technically challenging.
GRADE Quality of Evidence for Cardiac MRI in the Diagnosis of CAD
The quality of the body of evidence was assessed according to the GRADE Working Group criteria for diagnostic tests. For perfusion analysis, the overall quality was determined to be low and for wall motion analysis the overall quality was very low.
PMCID: PMC3377522  PMID: 23074389
17.  Multidetector Computed Tomography for Coronary Artery Disease Screening in Asymptomatic Populations 
Executive Summary
This evidence-based health technology assessment systematically reviewed the published literature on multidetector computed tomography (MDCT) angiography (with contrast) as a diagnostic tool for coronary artery disease (CAD), and applied the results of the assessment to health care practices in Ontario.
Clinical Need
Coronary artery disease is the leading cause of death in the western world. Occlusion of coronary arteries reduces coronary blood flow and oxygen delivery to the myocardium (heart muscle). The rupture of an unstable atherosclerotic plaque may result in myocardial infarction. If left untreated, CAD can result in heart failure and, subsequently, death. According to the Heart and Stroke Foundation of Canada, 54% of all cardiovascular deaths are due to CAD. Patient characteristics (e.g., age, sex, and genetics), underlying clinical conditions that predispose to cardiac conditions (e.g., diabetes, hypertension, and elevated cholesterol), lifestyle characteristics, (e.g., obesity, smoking, and physical inactivity), and, more recently, determinants of health (e.g., socioeconomic status) may predict the risk of getting CAD.
In 2004/2005, The Ontario government funded approximately 15,400 percutaneous (through the skin) coronary interventions and 7,840 coronary bypass procedures for the treatment of CAD. These numbers are expected to reach 22,355 for percutaneous coronary interventions and 12,323 for coronary bypass procedures in 2006/2007. It was noted that more than one-half of all first coronary events occur in people without symptoms of CAD. In Ontario in 2000/2001, $457.9 million (Cdn) was spent on invasive ($237.4 million) and noninvasive ($220.5 million) cardiac services. The use of noninvasive cardiac tests, in particular, is rising rapidly.
The Technology
Computed tomography (CT) is a medical imaging method employing tomography where digital geometry processing is used to generate a 3-dimensional image of the internals of an object from a large series of 2-dimensional X-ray images taken around a single axis of rotation. Multidetector computed tomography is performed for noninvasive imaging of the coronary arteries. Computer software quantifies the amount of calcium within the coronary arteries and calculates a coronary artery calcium score.
Compared with conventional CT scanning, MDCT can provide smaller pieces of information and cover a larger area faster. Advanced MDCT technology (that is, 8-, 16-, 32-, and 64-slice systems) can produce more images in less time. For general CT scanning, this faster capability can reduce the length of time people are required to be still during the procedure and thereby reduce potential movement artifact. However, the additional clinical utility of images obtained from faster scanners compared with the images obtained from conventional CT scanners for current CT indications (i.e., nonmoving body parts) is unknown.
Review Strategy
The Medical Advisory Secretariat completed a computer-aided search limited to English-language studies in humans from 1998 to 2007 in multiple medical literature databases, including MEDLINE, EMBASE, The Cochrane Library, and INAHTA/CRD. Case reports, letters, editorials, nonsystematic reviews, and comments were excluded. Additional studies that met the inclusion and exclusion criteria were obtained from reference lists of included studies. Inclusion and exclusion criteria were applied to the results according to the criteria listed below.
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the overall quality of the body of evidence (defined as 1 or more studies) supporting the research questions explored in this systematic review.
Summary of Findings and Conclusions
Screening the asymptomatic population for CAD using MDCT does not meet World Health Organization criteria for screening; hence, it is not justifiable. Coronary artery calcification measured by MDCT is a good predictor of future cardiovascular events. However, MDCT exhibits only moderately high sensitivity and specificity for detection of CAD in an asymptomatic population. If population-based screening were implemented, a high rate of false positives would result in increased downstream costs and interventions. Additionally, some cases of CAD would be missed, as they may not be developed, or not yet have progressed to detectable levels. There is no evidence for the impact of screening on patient management. Cardiovascular risk factors are positively associated with the presence of coronary artery calcification and cardiovascular events; however, risk factor stratification to identify high-risk asymptomatic individuals is unclear given the current evidence-base.
Safety of MDCT screening is also an issue because of the introduction of increased radiation doses for the initial screening scan and possible follow-up interventions.
No large randomized controlled trials of MDCT screening have been published, which indicates an important area of future research.
Lastly, the policy implications for MDCT screening for CAD in the asymptomatic population are significant. There is no evidence on the long-term implications of screening, and the potential impact on the resources of the health care system is considerable.
PMCID: PMC3377586  PMID: 23074503
18.  Prediction of coronary artery disease by a systemic atherosclerosis score index derived from whole-body MR angiography 
Whole-body magnetic resonance angiography (WB-MRA) has shown its potential for the non-invasive assessment of nearly the entire arterial vasculature within one examination. Since the presence of extra-cardiac atherosclerosis is associated with an increased risk of coronary events, our goal was to establish the relationship between WB-MRA findings, including a systemic atherosclerosis score index, and the presence of significant coronary artery disease (CAD).
WB-MRA was performed on a 1.5T scanner in 50 patients scheduled to undergo elective cardiac catheterization for suspected CAD. In each patient, 40 extra-cardiac vessel segments were evaluated and assigned scores according to their luminal narrowing. The atherosclerosis score index (ASI) was generated as the ratio of summed scores to analyzable segments.
ASI was higher in patients with significant (> 50% stenosis) CAD (n = 27) vs. patients without CAD (n = 22; 1.56 vs. 1.28, p = 0.004). ASI correlated with PROCAM (R = 0.57, p < 0.001) and Framingham (R = 0.36, p = 0.01) risk scores as estimates of the 10-year risk of coronary events. A ROC derived ASI of > 1.54 predicted significant CAD with a sensitivity of 59%, specificity of 86% and a positive predictive value of 84%. Logistic regression revealed ASI > 1.54 as the strongest independent predictor for CAD with a 11-fold increase in likelihood to suffer from significant coronary disease. On the contrary, while 15/27 (55%) of patients with CAD exhibited at least one extra-cardiac stenosis > 50%, only 3/22 (14%) of those patients without CAD did (p = 0.003). The likelihood for an extra-cardiac stenosis when CAD is present differed between vascular territories and ranged from 15% for a carotid stenosis to 44% for a stenosis in the lower extremities.
This study provides important new evidence for the close association of extra-cardiac and coronary atherosclerosis. The novel findings that a WB-MRA derived systemic atherosclerosis score index is not only associated with established cardiovascular risk scores but is also predictive of significant CAD suggest its potential prognostic implications and underline the importance to screen for coronary disease in patients with extra-cardiac manifestations of atherosclerosis.
PMCID: PMC2758875  PMID: 19761595
19.  Normal Thoracic Aorta Diameter on Cardiac Computed Tomography in Healthy Asymptomatic Adult; Impact of Age and Gender 
Academic radiology  2008;15(7):827-834.
To establish the normal criterion of ascending aortic diameter (AAOD) measured by 64 Multi-Detector Computed Tomography (MDCT) and Electron Beam Computed Tomography (EBT) based on gender and age.
1442 consecutive subjects who were referred for evaluation of possible coronary artery disease underwent coronary CT angiography (CTA) and coronary artery calcium scanning (CACS) (55+11 years, 65% male) without known coronary heart disease, hypertension, chronic pulmonary and renal disease, diabetes and severe aortic calcification. The ascending aortic diameter, descending aortic diameter (DAOD), pulmonary artery (PAD) and chest anterioposterior diameter (CAPD), posterior border of sternal bone to anterior border of spine, were measured at the slice level of mid right pulmonary artery by using end systolic trigger image. The volume of four chambers, ejection fraction of left ventricle, and cardiac output were measured in 56% of the patients. Patients demographic information, age, gender, weight, height and body surface area (BSA), were recorded. The mean value and age specific and gender adjusted upper normal limits (mean + 2 standard deviations) were calculated. The linear correlation analysis was done between AAOD and all parameters. The reproducibility, wall thickness and difference between end systole and diastole were calculated.
AAOD has significant linear association with age, gender, descending aortic diameter and pulmonary artery diameter (P<0.05). There is no significant correlation between AAOD and body surface area, four chamber volume, LVEF, CO and CAPD. The mean Intra-luminal AAOD was 31.1 ± 3.9mm and 33.6 ± 4.1 mm in females and males respectively. The upper normal limits (mean + 2 standard deviations) of Intra-luminal AAOD, mean+ standard deviation, was 35.6, 38.3 and 40 mm for females and 37.8, 40.5 and 42.6 mm for males in age group 20 to 40, 41 to 60, above 60 year respectively. Intra-luminal should parallel echocardiography and invasive angiography. Traditional cross sectional imaging (with computed tomography and magnetic resonance imaging) includes the vessel wall. The mean total AAOD was 33.5mm and 36.0 mm in females and males respectively. The upper normal limits (mean + 2 standard deviations) of Intra-luminal AAOD, mean+ standard deviation, was 38.0, 40.7 and 42.4 mm for females and 40.2, 42.9 and 45.0 mm for males in age group 20 to 40, 41 to 60, above 60 year respectively. The inter and intra observer, scanner and repeated measurement variability was low (R value >0.91, P<0.001, coefficient variation <3.2%). AAOD was 1.7 mm less in end-diastole than end systole(P<0.001).
The ascending aortic diameter increases with age and male gender. Gender specific and age adjusted normals for aortic diameters are necessary to differentiate pathologic atherosclerotic changes in the ascending aorta. Use of intra-luminal or total aortic diameter values depends on the comparison study that may be employed.
PMCID: PMC2577848  PMID: 18572117
Ascending aortic diameter; Electron beam CT; MDCT; Aging aorta
20.  Impact of Body Mass Index on the relationship of epicardial adipose tissue to metabolic syndrome and coronary artery disease in an Asian population 
In a previous study, we demonstrated that the thickness of epicardial adipose tissue (EAT), measured by echocardiography, was increased in patients with metabolic syndrome (MS) and coronary artery disease (CAD). Several studies on obese patients, however, failed to demonstrate any relationship between EAT and CAD. We hypothesized that body mass index (BMI) affected the link between EAT and MS and CAD.
We consecutively enrolled 643 patients (302 males, 341 females; 59 ± 11 years), who underwent echocardiography and coronary angiography. The EAT thickness was measured on the free wall of the right ventricle at the end of diastole. All patients were divided into two groups: high BMI group, ≥27 kg/m2 (n = 165), and non-high BMI group, < 27 kg/m2 (n = 478).
The median and mean EAT thickness of 643 patients were 3.0 mm and 3.1 ± 2.4 mm, respectively. In the non-high BMI group, the median EAT thickness was significantly increased in patients with MS compared to those without MS (3.5 vs. 1.9 mm, p < 0.001). In the high BMI group, however, there was no significant difference in the median EAT thickness between patients with and without MS (3.0 vs. 2.5 mm, p = 0.813). A receiver operating characteristic (ROC) curve analysis predicting MS revealed that the area under the curve (AUC) of the non-high BMI group was significantly larger than that of the high BMI group (0.659 vs. 0.506, p = 0.007). When compared to patients without CAD, patients with CAD in both the non-high and high BMI groups had a significantly higher median EAT thickness (3.5 vs. 1.5 mm, p < 0.001 and 4.0 vs. 2.5 mm, p = 0.001, respectively). However, an ROC curve analysis predicting CAD revealed that the AUC of the non-high BMI group tended to be larger than that of the high BMI group (0.735 vs. 0.657, p = 0.055).
While EAT thickness was significantly increased in patients with MS and CAD, the power of EAT thickness to predict MS and CAD was stronger in patients with BMI < 27 kg/m2. These findings showed that the measurement of EAT thickness by echocardiography might be especially useful in an Asian population with a non-high BMI, less than 27 kg/m2.
PMCID: PMC2913996  PMID: 20604967
21.  The Relationship between the Severity of Coronary Artery Disease and Epicardial Adipose Tissue Depends on The Left Ventricular Function 
PLoS ONE  2012;7(11):e48330.
Epicardial adipose tissue (EAT) is an active metabolic and endocrine organ. Previous studies focusing mainly on patients with preserved left ventricular function (LVF) could show a correlation between increased amounts of EAT and the extent and activity of coronary artery disease (CAD). However, to date, there are no data available about the relationship between EAT and the severity of CAD with respect to the whole spectrum of LVF impairment. Therefore, we evaluated this relationship in patients with CAD.
250 patients with CAD and 50 healthy controls underwent CMR examination to assess EAT. The severity of CAD was defined using the angiographic Gensini score (GSS).
The GSS ranged from 2–364. Linear regression analysis revealed a significant correlation between EAT and GSS (r = 0.177, p = 0.01). Patients with mild (GSS≤10) and moderate CAD (GSS>10−≤40) showed comparable EAT to healthy controls. However, in patients with severe CAD (GSS>40) EAT was significantly reduced (p<0.0001) compared to healthy controls. Interestingly, patients with the same GSS revealed different EAT depending on the left ventricular function (LVF). Patients with preserved LVF (LVF≥50%) showed more EAT mass compared to those with reduced LVF (LVF<50%) regardless of the GSS. In patients with preserved LVF and mild CAD, EAT was comparable to healthy controls (61.8±19.4 g vs. 62.9±14.4 g, p = 0.8). In patients with moderate CAD, EAT rose significantly to 83.1±24.9 g (p = 0.01) and started to decline to 66.4±23.6 g in patients with severe CAD (p = 0.03). Contrary, in CAD patients with reduced LVF, EAT was already significantly reduced in patients with mild CAD as compared to healthy controls (p = 0.001) and showed a stepwise decline with increasing CAD severity.
The relationship between EAT and the severity of CAD depends on LVF. These findings emphasize the multifactorial interaction between EAT and the severity of CAD.
PMCID: PMC3487764  PMID: 23133630
22.  Usefulness of metabolic syndrome score in the prediction of angiographic coronary artery disease severity according to the presence of diabetes mellitus: relation with inflammatory markers and adipokines 
It is a matter of debate whether metabolic syndrome (MS) improves cardiovascular risk prediction beyond the risk associated with its individual components. The present study examined the association of MS score with high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), resistin, adiponectin, and angiographic coronary artery disease (CAD) severity according to the presence of DM. In addition, the predictive value of various clinical and biochemical parameters were analyzed, including the MS score for angiographic CAD.
The study enrolled 363 consecutive patients (196 men, 62 ± 11 years of age) who underwent coronary angiography for evaluation of chest pain. Blood samples were taken prior to elective coronary angiography. MS was defined by the National Cholesterol Education Program criteria, with MS score defined as the numbers of MS components. CAD was defined as > 50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD severity was assessed using the Gensini score.
Of the 363 patients studied, 174 (48%) had CAD and 178 (49%) were diagnosed with MS. When the patients were divided into 4 subgroups according to MS score (0–1, 2, 3, 4–5), IL-6 levels and the CAD severity as assessed by the Gensini score increased as MS scores increased. In contrast, adiponectin levels decreased significantly as MS scores increased. When subjects were divided into two groups according to the presence of DM, the relationships between MS score and IL-6, adiponectin, and Gensini score were maintained only in patients without DM. Age, smoking, DM, MS score, and adiponectin independently predicted angiographic CAD in the whole population. However, age is the only predictor for angiographic CAD in patients with DM.
In the presence of DM, neither adipokines nor MS score predicted angiographic CAD. However, in non-diabetic patients, IL-6 and adiponectin showed progressive changes according to MS score, and MS score was an independent predictor of CAD in patients without DM.
PMCID: PMC3850730  PMID: 24088407
Metabolic syndrome; Adipokines; Coronary artery disease; Diabetes mellitus
23.  The role of mediastinal adipose tissue 11β-hydroxysteroid d ehydrogenase type 1 and glucocorticoid expression in the development of coronary atherosclerosis in obese patients with ischemic heart disease 
Visceral fat deposition and its associated atherogenic complications are mediated by glucocorticoids. Cardiac visceral fat comprises mediastinal adipose tissue (MAT) and epicardial adipose tissue (EAT), and MAT is a potential biomarker of risk for obese patients.
Our objective was to evaluate the role of EAT and MAT 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and glucocorticoid receptor (GCR) expression in comparison with subcutaneous adipose tissue (SAT) in the development of coronary atherosclerosis in obese patients with coronary artery disease (CAD), and to assess their correlations with CD68 and fatty acids from these tissues.
Methods and results
Expression of 11β-HSD-1 and GCR was measured by qRT-PCR in EAT, MAT and SAT of thirty-one obese patients undergoing coronary artery bypass grafting due to CAD (obese CAD group) and sixteen obese patients without CAD undergoing heart valve surgery (controls). 11β-HSD-1 and GCR expression in MAT were found to be significantly increased in the obese CAD group compared with controls (p < 0.05). In the obese CAD group, 11β-HSD-1 and GCR mRNA levels were strongly correlated in MAT. Stearidonic acid was significantly increased in EAT and MAT of the obese CAD group and arachidonic acid was significantly expressed in MAT of the obese male CAD group (p < 0.05).
We report for the first time the increased expression of 11β-HSD-1 and GCR in MAT compared with EAT and SAT, and also describe the interrelated effects of stearidonic acid, HOMA-IR, plasma cortisol and GCR mRNA levels, explaining 40.2% of the variance in 11β-HSD-1 mRNA levels in MAT of obese CAD patients. These findings support the hypothesis that MAT contributes locally to the development of coronary atherosclerosis via glucocorticoid action.
PMCID: PMC3515420  PMID: 23009206
Mediastinal adipose tissue; Glucocorticoid; Inflammation; Coronary artery disease; Stearidonic acid; Cortisol
24.  What is the optimal cut-off point for low coronary artery calcium score assessed by computed tomography? Multi-Detector Computed Tomography ANIN Registry 
This prospective study was conducted to evaluate the incidence and predictors of coronary artery disease (CAD) in relation to the low coronary artery calcium (CAC) score among patients with intermediate probability of CAD.
Material and methods
A total of 1132 consecutive patients were included in the analysis (58.7 ±10.9 years, 46.7% males). Coronary computed tomography (CCT) angiography was performed in a multi-detector computed tomography scanner. Coronary artery calcium score was calculated by the Agatston method. Obstructive CAD was defined as the presence of coronary artery stenosis ≥ 50% on CCT angiography.
Coronary artery disease was diagnosed in nearly one-fourth of patients (n = 272, 24%). In the receiver operating characteristics (ROC) curve analysis a CAC score of 10 was used as an optimal cut-off point for discriminating obstructive CAD (sensitivity: 0.79, specificity: 0.75, p < 0.0001) whereas for a CAC score of 100 the sensitivity and specificity were 0.48 and 0.92, respectively. On multivariate analysis after adjustment for age, gender, hypertension, hyperlipidemia, creatinine levels, only in patients with CAC score ≤ 10 age (OR = 1.05, 95% CI: 1.02-1.08, p = 0.0005, OR = 1.05, 95% CI: 1.03-1.08, p < 0.0001) and male gender (OR = 3.45, 95% CI: 1.92-6.22, p < 0.0001), likewise in group with CAC score ≤ 100 age (OR = 1.05, 95% CI: 1.03-1.08, p < 0.0001) and male gender (OR = 3.31, 95% CI: 1.88-5.81, p < 0.0001) were independent predictors of obstructive CAD.
The cut-off point of 10 for CAC score determined patients with CAD with the best sensitivity and specificity. Therefore, a total CAC score < 10 should be classified as “low”. In patients with a low CAC score obstructive high risk plaques prone to rupture are presented and are associated with increasing age and male gender.
PMCID: PMC3915948  PMID: 24570687
coronary artery calcium score; coronary computed tomography; coronary artery disease
25.  Influence of Pericoronary Adipose Tissue on Local Coronary Atherosclerosis as Assessed by a Novel MDCT Volumetric Method 
Atherosclerosis  2011;219(1):151-157.
Pericoronary adipose tissue (PCAT) may create a pro-inflammatory state, contributing to the development of coronary artery disease (CAD). We sought to evaluate the feasibility of avolumetric PCAT quantification method using a novel threshold based computed tomography approach. In addition we determined the relation between PCAT volumes and CAD.
In 51 patients (49.5±5.1 years, 64.8% male) who underwent 64-slice MDCT, we measured threshold-based PCAT volumes using distance and anatomic-based methods. Using the most reproducible method, we performed the proximal 40-mm distance measurement in three groups as stratified by coronary plaque and high-sensitivity C-reactive protein (hs-CRP) levels: Group 1 (presence of coronary plaque, hs-CRP >2.0 mg/L); an intermediate group (Group 2, no plaque, hs-CRP >2.0 mg/L); and Group 3 (no plaque, hs-CRP<1.0 mg/L). We compared PCAT volumes to the presence of coronary plaque on a patient (n=51) and vessel (n=153) basis. On a subsegment basis (n=1224), we compared PCAT volume to the presence of plaque as well as plaque morphology.
Distance-based PCAT volume measurements yielded excellent reproducibility with intra-observer intraclass correlation (ICC) of 0.997 and inter-observer ICC of 0.951. On a both a per-patient and per-vessel analysis, adjusted PCAT volume was greater in patients with plaque (Group 1) than without plaque (Group 2 and 3, p<0.001). No difference in PCAT volume was seen between high and low hs-CRP groups without plaque (p=0.51). Adjusted PCAT volumes were higher in subsegments with plaque as compared without (p<0.001). Additionally, adjusted PCAT volume was greatest in subsegments with mixed plaque followed by non-calcified plaque, calcified plaque, and the lowest volume in segments with no plaque (p<0.001).
In this proof-of-concept study, threshold based PCAT volume assessment is feasible and highly reproducible. PCAT volume is increased in patients and vessels with coronary plaques. Surrounding vessel subsegments with coronary plaque, particularly mixed plaques, have greatest PCAT volume and highlight the effect of local PCAT in the development of coronary atherosclerosis.
PMCID: PMC3203345  PMID: 21782176
Coronary artery disease; pericoronary fat; epicardial fat; adipose tissue; inflammation; computed tomography

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