Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Epicardial adipose tissue (EAT) is defined as a fat depot localized between the myocardial surface and the visceral layer of the pericardium and is a type of visceral fat. EAT is one of the most important risk factors for atherosclerosis and cardiovascular events and a promising new therapeutic target in CVDs. In health conditions, EAT has a protective function, including protection against hypothermia or mechanical stress, providing myocardial energy supply from free fatty acid and release of adiponectin. In patients with obesity, metabolic syndrome, or diabetes mellitus, EAT becomes a deleterious tissue promoting the development of CVDs. Previously, we showed an adverse modulation of gene expression in pericoronary adipose tissue in patients with coronary artery disease (CAD). Here, we summarize the currently available evidence regarding the role of EAT in the development of CVDs, including CAD, heart failure, and atrial fibrillation. Due to the rapid development of the COVID-19 pandemic, we also discuss data regarding the association between EAT and the course of COVID-19. Finally, we present the potential therapeutic possibilities aiming at modifying EAT’s function. The development of novel therapies specifically targeting EAT could revolutionize the prognosis in CVDs.

Trimethylamine-N-oxide (TMAO) has been suggested as a marker and mediator of cardiovascular diseases. However, data are contradictory, and the mechanisms are obscure. Strikingly, the role of the TMAO precursor trimethylamine (TMA) has not drawn attention in cardiovascular studies even though toxic effects of TMA were proposed several decades ago. We assessed plasma TMA and TMAO levels in healthy humans (HH) and cardiovascular patients qualified for aortic valve replacement (CP). The cytotoxicity of TMA and TMAO in rat cardiomyocytes was evaluated using an MTT test. The effects of TMA and TMAO on albumin and lactate dehydrogenase (LDH) were assessed using fluorescence correlation spectroscopy. In comparison to HH, CP had a two-fold higher plasma TMA (p < 0.001) and a trend towards higher plasma TMAO (p = 0.07). In CP plasma, TMA was inversely correlated with an estimated glomerular filtration rate (eGFR, p = 0.002). TMA but not TMAO reduced cardiomyocytes viability. Incubation with TMA but not TMAO resulted in the degradation of the protein structure of LDH and albumin. In conclusion, CP show increased plasma TMA, which is inversely correlated with eGFR. TMA but not TMAO exerts negative effects on cardiomyocytes, likely due to its disturbing effect on proteins. Therefore, TMA but not TMAO may be a toxin and a marker of cardiovascular risk.

Epicardial adipose tissue (EAT) volume is associated with cardiovascular disease (CVD). Data regarding the influence of extremely intensive training on CVD are scarce. We compared EAT volume among ultra-marathon runners and in the sedentary control group, and assessed the correlations between EAT and risk factors of coronary artery disease (CAD). EAT volume around three main coronary vessels and right ventricle (RV) was measured in 30 healthy amateur ultrarunners and 9 sex- and age-matched sedentary controls using cardiac magnetic resonance. In addition, body composition, lipid profile, interleukin-6 (IL-6) plasma concentration, and intima-media thickness (IMT) were measured as well. The EAT volume was lower in all measured locations in the ultrarunners’ group compared to control group (p < 0.001 for all). Ultrarunners had lower BMI and fat percentage (FAT%) and more favorable lipid profile compared to the control group (p < 0.05 for all). Ultrarunners had lower rate of pathologically high levels of plasma IL-6 (>1 pg/mL) compared to the control group (17% vs. 56%, p < 0.05). IMT was similar in both groups. In the ultrarunners’ group, there was a positive correlation between EAT surrounding left anterior descending artery, circumflex artery, and RV and FAT%, and between EAT around circumflex artery and LDL and non-HDL cholesterol (p < 0.05 for all). In summary, extremely intensive training may decrease the risk of cardiovascular events in adult population of amateur athletes by reducing the amount and pro-inflammatory activity of EAT. However, more research is needed to draw firm conclusions regarding the anti- and pro-inflammatory effects of intensive training.