Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue

Abstract

Background: Epicardial adipose tissue (EAT) thickness and pro-inflammatory status has been shown to be associated with several cardiac diseases, including aortic stenosis (AS). Thus, cardiac visceral fat could represent a potential new target for drugs. In the present study we evaluate the effect of statin therapy on EAT accumulation and inflammation. Methods: Echocardiographic EAT thickness was assessed in 193 AS patients taking (n.87) and not taking (n.106) statins, undergoing cardiac surgery. To explore the association between statin therapy and EAT inflammation, EAT biopsies were obtained for cytokines immunoassay determination in EAT secretomes. An in vitro study was also conducted and the modulation of EAT and subcutaneous adipose tissue (SCAT) secretomes by atorvastatin was assessed in paired biopsies. Results: Statin therapy was significantly associated with lower EAT thickness (p b 0.0001) and with lower levels of EAT-secreted inflammatory mediators (p b 0.0001). Of note, there was a significant correlation between EAT thickness and its pro-inflammatory status. In vitro, atorvastatin showed a direct anti-inflammatory effect on EAT which was significantly higher compared to the SCAT response to statin incubation (p b 0.0001). Conclusions: The present study indicates a robust association between statin therapy and reduced EAT accumulation in patients with AS. The present data also suggest a direct relationship between EAT thickness and its inflammatory status, both modulated by statin therapy. The in vitro results support the hypothesis of a direct action of statins on EAT secretory profile. Overall our data suggest EAT as a potential new therapeutic target for statin therapy.

Validation of the echocardiographic assessment of epicardial adipose tissue thickness at the Rindfleisch fold for the prediction of coronary artery disease

“…Since the increasing evidence on the role of cardiac visceral adiposity in the pathophysiology of cardiovascular diseases, the measurement of EAT thickness should be strongly encouraged. In this regard, we have recently observed that EAT measurement proposed in this study is directly correlated with the levels of inflammatory mediators secreted by EAT [14]. Given its proximity to the myocardium and absence of fascial boundaries, EAT directly influences myocardial homeostasis through vasocrine and paracrine mechanisms.…”

“…At this level, it is possible to directly visualize and measure the fat deposit between the visceral layer of the pericardium and the myocardium. In patients with aortic stenosis, we have recently reported [14] that this measure is accurate and reproducible. In the same population, we have also demonstrated that the increase of EAT thickness directly correlates with the levels of EAT-derived inflammatory mediators, thus being expression of an EAT proinflammatory phenotype.…”

Epicardial Adipose Tissue, Adiponectin and Leptin: A Potential Source of Cardiovascular Risk in Chronic Kidney Disease

“…Nakazato et al [72] showed a 2% regression in EAT volume in 54 patients who lost 5% of their initial body weight in 4 y, compared to a 23% increase in 71 subjects who gained weight. Two groups of investigations reported that EAT volume decreased after intensive lipid-lowering therapy with statins [73,74]. The latter may have occurred because of the known anti-inflammatory activity and inhibition of vasa-vasorum proliferation by statins, which are believed to directly contribute to the development of atherosclerosis [75].…”

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

“…Statins are commonly used in patients with obesity and type 2 diabetes to prevent atherosclerotic events, but they have striking effects in lessening epicardial adipocyte mass and inflammation, [98][99][100][101] and thereby preventing fibrosis in the underlying myocardium. 102,103 This anti-inflammatory action may explain why statins ameliorate the development of an atrial myopathy in experimentally induced cardiac stress and in patients with AF.…”