Epicardial and Pericoronary Adipose Tissue, Coronary Inflammation, and Acute Coronary Syndromes

Abstract

Vascular inflammation is recognized as the primary trigger of acute coronary syndrome (ACS). However, current noninvasive methods are not capable of accurately detecting coronary inflammation. Epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), in addition to their role as an energy reserve system, have been found to contribute to the development and progression of coronary artery calcification, inflammation, and plaque vulnerability. They also participate in the vascular response during ischemia, sympathetic stimuli, and arrhythmia. As a result, the evaluation of EAT and PCAT using imaging techniques such as computed tomography (CT), cardiac magnetic resonance (CMR), and nuclear imaging has gained significant attention. PCAT-CT attenuation, which measures the average CT attenuation in Hounsfield units (HU) of the adipose tissue, reflects adipocyte differentiation/size and leukocyte infiltration. It is emerging as a marker of tissue inflammation and has shown prognostic value in coronary artery disease (CAD), being associated with plaque development, vulnerability, and rupture. In patients with acute myocardial infarction (AMI), an inflammatory pericoronary microenvironment promoted by dysfunctional EAT/PCAT has been demonstrated, and more recently, it has been associated with plaque rupture in non-ST-segment elevation myocardial infarction (NSTEMI). Endothelial dysfunction, known for its detrimental effects on coronary vessels and its association with plaque progression, is bidirectionally linked to PCAT. PCAT modulates the secretory profile of endothelial cells in response to inflammation and also plays a crucial role in regulating vascular tone in the coronary district. Consequently, dysregulated PCAT has been hypothesized to contribute to type 2 myocardial infarction with non-obstructive coronary arteries (MINOCA) and coronary vasculitis. Recently, quantitative measures of EAT derived from coronary CT angiography (CCTA) have been included in artificial intelligence (AI) models for cardiovascular risk stratification. These models have shown incremental utility in predicting major adverse cardiovascular events (MACEs) compared to plaque characteristics alone. Therefore, the analysis of PCAT and EAT, particularly through PCAT-CT attenuation, appears to be a safe, valuable, and sufficiently specific noninvasive method for accurately identifying coronary inflammation and subsequent high-risk plaque. These findings are supported by biopsy and in vivo evidence. Although speculative, these pieces of evidence open the door for a fascinating new strategy in cardiovascular risk stratification. The incorporation of PCAT and EAT analysis, mainly through PCAT-CT attenuation, could potentially lead to improved risk stratification and guide early targeted primary prevention and intensive secondary prevention in patients at higher risk of cardiac events.

Keywords: acute coronary syndromes; coronary inflammation; epicardial adipose tissue; pericoronary adipose tissue.

Figure 1

CT scan of a 49-year-old male patient depicting the epicardial adipose tissue (red) immediately internal to the pericardium.

Figure 2

CT scan of a 39-year-old female patient. (a) 3D reconstruction of the heart, focusing on the middle segment of RCA. (b,c) PCAT distribution around RCA in longitudinal and ortogonal view, respectively (yellow spots). CT, computed tomography; PCAT, pericoronary adipose tissue; RCA, right coronary artery.

Figure 3

Interaction between EAT, PCAT, and atherogenesis. EAT, epicardial adipose tissue; FFA, free fatty acid; HRP, high-risk plaque; IL, interleukin; LPA, lysophosphatidic acid; MCP, monocyte chemoattractant protein; PAI, plasminogen activator inhibitor; TNF, tumor necrosis factor. EAT, located around the coronary arteries, secretes various bioactive molecules such as adipokines, cytokines, and FFAs. In the presence of cardiovascular risk factors, EAT undergoes inflammation, which is characterized by increased infiltration of immune cells. Dysfunction of PCAT and its effects on the coronary arteries can contribute to the initiation and progression of atherosclerosis, leading to the development of HRP.