The Association of Epicardial Adipose Tissue and High Risk Plaque Characteristics: A Systematic Review and Meta-Analysis

Abstract

Background--Epicardial adipose tissue (EAT) is hypothesized to alter atherosclerotic plaque composition, with potential development of high-risk plaque (HRP). EAT can be measured by volumetric assessment (EAT-v) or linear thickness (EAT-t). We performed a systematic review and random-effects meta-analysis to assess the association of EAT with HRP and whether this association is dependent on the measurement method used.Methods and Results--Electronic databases were systematically searched up to October 2016. Studies reporting HRP by computed tomography or intracoronary imaging and studies measuring EAT-v or EAT-t were included. Odds ratios were extracted from multivariable models reporting the association of EAT with HRP and described as pooled estimates with 95% confidence intervals (CIs). Analysis was stratified by EAT measurement method. Nine studies (n=3772 patients) were included with 7 measuring EAT-v and 2 measuring EAT-t. Increasing EAT was significantly associated with the presence of HRP (odds ratio: 1.26 [95% CI, 1.11-1.43]; P<0.001). Patients with HRP had higher EAT-v than those without (weighted mean difference: 28.3 mL [95% CI, 18.8-37.8 mL]; P<0.001). EAT-v was associated with HRP (odds ratio: 1.19 [95% CI, 1.06-1.33]; P<0.001); however, EAT-t was not (odds ratio: 3.09 [95% CI, 0.56-17]; P=0.2). Estimates remained significant when adjusted for small-study effect bias (odds ratio: 1.13 [95% CI, 1.03-1.28]; P=0.04).Conclusions--Increasing EAT is associated with the presence of HRP, and patients with HRP have higher quantified EAT-v. The association of EAT-v with HRP is significant compared with EAT-t; however, a larger scale study is still required, and further evaluation is needed to assess whether EAT may be a potential therapeutic target for novel pharmaceutical agents.

Relation of cardiac adipose tissue to coronary calcification and myocardial microvascular function in type 1 and type 2 diabetes

“…Furthermore, we evaluated the associations between cardiac adipose tissue and myocardial flow reserve, left ventricular ejection fraction, CAC score and 123 I-MIBG uptake, separately in the three groups ( Table 2 and (14) 37 (13) 37 (14) 0.99 14 (10) 15 (8) 13 (12) 0.68 24 h systolic blood pressure (mmHg) 126 (14) 123 (11) 132 (14) 0.06 136 (10) 136 (10) 138 (10) 0.47…”

“…Results from studies in type 2 diabetes and mixed populations (diabetes and non-diabetes) are conflicting. In the studies reporting an association between epicardial adipose tissue and coronary artery disease, including high risk plaque characteristics and CAC [13][14][15], it remains uncertain if the associations demonstrated are truly independent from traditional risk factors. We report a lack of association between cardiac adipose tissue and CAC score in persons with type 2 diabetes free of cardiovascular disease in line with results from a study in a mixed population (34% had diabetes) with suspected or known coronary artery disease (referred for clinically indicated invasive coronary angiography) [16].…”

“…Due to the proximity of the structures, cardiac adipose tissue could through paracrine signalling promote calcification or impair the myocardial microcirculatory function [7,10]. Knowledge of these associations in persons with diabetes, who are known to have higher amounts of cardiac adipose tissue and higher risk of cardiovascular disease compared to persons without diabetes, is sparse [6,[11][12][13][14][15][16]. A study in patients with systolic heart failure demonstrated an association between epicardial adipose tissue thickness and cardiac sympathetic denervation, implying that cardiac adipose tissue could affect autonomic nerve function [17].…”

The Effect of Periplaque Fat on Coronary Plaque Vulnerability in Patients with Stable Coronary Artery Disease – a 128-multislice CT-based Study

“…23 Recent studies connected the epicardial adipose tissue with the presence of high-risk coronary plaques, defined as presenting one of the following features: low attenuation, positive remodeling, napkin ring sign, spotty calcifications; studies have also shown that patients with high-risk plaques present a larger volume of epicardial fat, compared to those with no high-risk plaques. 24,25 Pericoronary and periplaque fat Pericoronary adipose tissue, as a fragment of the total epicardial fat, is located in direct contact to the coronary artery wall and has pro-inflammatory properties through its paracrine effect and local release of inflammatory cytokines, which can trigger plaque formation, progression, vulnerabilization, and even rupture. 26 Pericoronary fat (PF) has also been associated with the presence of vulnerable coronary plaques, even after adjustment for obesity and smoking.…”

Epicardial Fat and Coronary Vulnerability

“…Based on the anatomic proximity of EAT to the arterial adventitia of coronary arteries, the "outside in" hypothesis of atherosclerosis has been recently launched, according to which EAT components may trigger vascular inflammation and plaque destabilization through paracrine and vasocrine mechanisms. [9][10][11][12][13] It has been demonstrated that the amount of EAT is directly correlated with both the length and the severity of coronary lesions, at the same time being associated with the transformation of atherosclerotic plaques into a vulnerable phenotype, considered to be "high risk" for major cardiovascular events. 11 In a large study conducted by Nerlekar et al, a strong correlation was found between several CT features of vulnerable atherosclerotic plaques, such as low-attenuation lesions and positive remodeling at the lesion site.…”