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Il tessuto adiposo epicardico (EAT) è un fattore di rischio cardiovascolare in quanto promuove la progressione della fibrillazione atriale, della malattia coronarica e dell’insufficienza cardiaca. EAT si caratterizza per rapido metabolismo, misurabilità clinica e facile modificabilità e rappresenta un bersaglio terapeutico peculiare per farmaci innovativi, quali gli agonisti del recettore del peptide glucagone-simile 1 e gli inibitori del co-trasportatore sodio-glucosio 2, che appaiono salutari dal punto di vista cardiometabolico ben oltre i loro effetti sul glucosio e sul peso corporeo (Materiale Supplementare).

Graphical Abstract

Human epicardial adipose tissue (EAT) is a unique and multifunctional fat compartment of the heart. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Due to its distinctive transcriptome and functional proximity to the heart, EAT can play a key role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Clinically, EAT, given its rapid metabolism and simple measurability, can be considered a novel therapeutic target, owing to its responsiveness to drugs with pleiotropic and clear beneficial cardiovascular effects such as the glucagon-like peptide-1 receptor (GLP-1R) agonists.Human EAT is found to express the genes encoding the receptors of glucose-dependent insulinotropic polypeptide receptor (GIPR), glucagon receptor (GCGR), and GLP-1. The immunohistochemistry indicates that GIP and GCG receptor proteins are present in EAT samples. Epicardial adipose tissue GIPR is inversely associated with genes involved in free fatty acid (FFA) oxidation and transport and with genes promoting FFA biosynthesis and adipogenesis. Epicardial adipose tissue GCGR is correlated with genes promoting FFA transport and activation for mitochondrial beta-oxidation and white-to-brown adipocyte differentiation and with genes reducing FFA biosynthesis and adipogenesis.As the myocardium relies mostly on FFAs as fuel and is in direct contiguity with EAT, these findings may have a great importance for the modulation of the myocardial activity and performance. Given the emerging use and cardiovascular effects of GLP-1R agonists, dual GIPR/GLP-1R agonists, and GLP-1R/GIPR/GCGR triagonists, we believe that pharmacologically targeting and potentially modulating organ-specific fat depots through G-protein–coupled receptors may produce beneficial cardiovascular and metabolic effects.

Purpose: The visceral fat of patients affected by abdominal obesity is inflamed, and the main histopathologic feature is the high density of crown-like structures (CLS). Epicardial adipose tissue (EAT) is a visceral fat of paramount importance for its relationships with coronary vessels and myocardium. Its inflammation in patients with abdominal obesity could be of clinical relevance, but histopathological studies on CLS density in EAT are lacking. This study aimed to assess the histopathology of EAT biopsies obtained from patients undergoing open-heart surgery. Methods: We collected EAT biopsies from 10 patients undergoing open-heart surgery for elective coronary artery bypass grafting (CABG) (n= 5) or valvular replacement (VR) (n= 5). Biopsies were treated for light microscopy and immunohistochemistry. We quantify the CLS density in each EAT sample. Results: Despite all patients having abdominal obesity, in EAT samples, no CLS were detected in the VR group; in contrast, CLS were detected in the CABG group (about 17 CLS/104adipocytes vs. 0.0 CLS/104adipocytes, CABG vs. VR group, respectively). An impressive density of CLS (100 times that of other patients) was found in one patient (LS) in the CABG group that had a relevant anamnestic aspect: relatively rapid increase of weight gain, especially in abdominal adipose tissue, coincident with myocardial infarction. Conclusions: CLS density could be an important predictive tool for cardiovascular diseases. Furthermore, the LS case implies a role for timing in weight gain. Level of evidence: No level of evidence; this is a basic science study.

Purpose: Chest X-ray (CXR) severity score and BMI-based obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored. Methods: This retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19. Results: Patients with abdominal obesity showed significantly higher CXR severity scores and had higher rates of CXR severity scores ≥ 8 compared to those without abdominal obesity (P< 0.001; P= 0.001, respectively). By contrast, patients with normal weight, with overweight and those with BMI-based obesity showed no significant differences in either CXR severity scores or in the rates of CXR severity scores ≥ 8 (P= 0.104; P= 0.271, respectively). Waist circumference and waist-to-height ratio (WHtR) correlated more closely with CXR severity scores than BMI (r= 0.43, P< 0.001; r= 0.41, P< 0.001; r= 0.17, P= 0.012, respectively). The area under the curves (AUCs) for waist circumference and WHtR were significantly higher than that for BMI in identifying a high CXR severity score (≥ 8) (0.68 [0.60–0.75] and 0.67 [0.60–0.74] vs 0.58 [0.51–0.66], P= 0.001). A multivariate analysis indicated abdominal obesity (risk ratio: 1.75, 95% CI: 1.25–2.45, P< 0.001), bronchial asthma (risk ratio: 1.73, 95% CI: 1.07–2.81, P= 0.026) and oxygen saturation at admission (risk ratio: 0.96, 95% CI: 0.94–0.97, P< 0.001) as the only independent factors associated with high CXR severity scores. Conclusion: Abdominal obesity phenotype is associated with a high CXR severity score better than BMI-based obesity in hospitalized patients with COVID-19. Therefore, when visiting the patient in a hospital setting, waist circumference should be measured, and patients with abdominal obesity should be monitored closely.