Gianluca Iacobellis

Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart.

A growing amount of evidence suggests that regional fat distribution plays an important part in the development of an unfavorable metabolic and cardiovascular risk profile. Epicardial fat is a metabolically active organ that generates various bioactive molecules, which might significantly affect cardiac function. This small, visceral fat depot is now recognized as a rich source of free fatty acids and a number of bioactive molecules, such as adiponectin, resistin and inflammatory cytokines, which could affect the coronary artery response. The observed increases in concentrations of inflammatory factors in patients who have undergone coronary artery bypass grafting remain to be confirmed in healthy individuals. Furthermore, epicardial adipose mass might reflect intra-abdominal visceral fat. Therefore, we propose that echocardiographic assessment of this tissue could serve as a reliable marker of visceral adiposity. Epicardial adipose tissue is also clinically related to left ventricular mass and other features of the metabolic syndrome, such as concentrations of LDL cholesterol, fasting insulin and adiponectin, and arterial blood pressure. Echocardiographic assessment of epicardial fat could be a simple and practical tool for cardiovascular risk stratification in clinical practice and research. In this paper, we briefly review the rapidly emerging evidence pointing to a specific role of epicardial adipose tissue both as a cardiac risk marker and as a potentially active player in the development of cardiac pathology.

Echocardiographic epicardial fat: a review of research and clinical applications.

Epicardial fat plays a role in cardiovascular diseases. Because of its anatomic and functional proximity to the myocardium and its intense metabolic activity, some interactions between the heart and its visceral fat depot have been suggested. Epicardial fat can be visualized and measured using standard two-dimensional echocardiography. Standard parasternal long-axis and short-axis views permit the most accurate measurement of epicardial fat thickness overlying the right ventricle. Epicardial fat thickness is generally identified as the echo-free space between the outer wall of the myocardium and the visceral layer of pericardium and is measured perpendicularly on the free wall of the right ventricle at end-systole. Echocardiographic epicardial fat thickness ranges from a minimum of 1 mm to a maximum of almost 23 mm. Echocardiographic epicardial fat thickness clearly reflects visceral adiposity rather than general obesity. It correlates with metabolic syndrome, insulin resistance, coronary artery disease, and subclinical atherosclerosis, and therefore it might serve as a simple tool for cardiometabolic risk prediction. Substantial changes in echocardiographic epicardial fat thickness during weight-loss strategies may also suggest its use as a marker of therapeutic effect. Echocardiographic epicardial fat measurement in both clinical and research scenarios has several advantages, including its low cost, easy accessibility, rapid applicability, and good reproducibility. However, more evidence is necessary to evaluate whether echocardiographic epicardial fat thickness may become a routine way of assessing cardiovascular risk in a clinical setting.

Epicardial adipose tissue: emerging physiological, pathophysiological and clinical features

Epicardial adipose tissue is an unusual visceral fat depot with anatomical and functional contiguity to the myocardium and coronary arteries. Under physiological conditions, epicardial adipose tissue displays biochemical, mechanical and thermogenic cardioprotective properties. Under pathological circumstances, epicardial fat can locally affect the heart and coronary arteries through vasocrine or paracrine secretion of proinflammatory cytokines. What influences this equilibrium remains unclear. Improved local vascularization, weight loss, and targeted pharmaceutical interventions could help to return epicardial fat to its physiological role. This review focuses on the emerging physiological and pathophysiological aspects of the epicardial fat and its numerous and innovative clinical applications. Particular emphasis is placed on the paracrine/endocrine properties of epicardial fat and its role in the development and progression of atherosclerosis.

Threshold Values of High-risk Echocardiographic Epicardial Fat Thickness

Objective: Echocardiographic epicardial adipose tissue is a new index of cardiac and visceral adiposity with great potential as a diagnostic tool and therapeutic target. In this study, we sought to provide threshold values of echocardiographic epicardial fat thickness associated with metabolic and anthropometric risk factors.

Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women

Background   A possible relationship between thyroid hormones and adipose tissue metabolism in humans has been suggested.

Substantial Changes in Epicardial Fat Thickness After Weight Loss in Severely Obese Subjects

We sought to evaluate the effect of weight loss on echocardiographic epicardial fat thickness, as index of visceral adiposity, and whether epicardial fat change after the weight loss can be proportionally different from overall body weight changes and related to cardiac parameters changes in severely obese subjects. This was an interventional study in 20 severely obese subjects (12 women, 8 men, BMI 45 ± 5 kg/m2, 35 ± 10 years) who underwent 6‐month very low calorie diet weight loss program. Baseline and after 6‐month weight loss anthropometrics, echocardiographic epicardial fat thickness, left ventricular mass (LVM), and diastolic function parameters were assessed. Subjects lost 20% of original body weight, BMI reduced by 19% of original BMI, waist circumference decreased by 23% of initial waist circumference. Epicardial fat thickness decreased from 12.3 ± 1.8 to 8.3 ± 1 mm P < 0.001 after the 6‐month very low calorie diet, as −32% of baseline epicardial fat thickness. LVM and diastolic function changes were better correlated with epicardial fat changes. We showed that significant weight loss can be associated with significant reduction in the epicardial fat thickness, marker of visceral adiposity in severely obese subjects. Epicardial fat decrease, therefore visceral fat decrease, can be proportionally higher than overall adiposity decrease. Epicardial fat changes are significantly associated with obesity‐related cardiac morphological and functional changes during weight loss. Measurement of echocardiographic epicardial fat thickness may provide an additional tool in understanding the metabolic risk associated with variation in fat distribution.

The double role of epicardial adipose tissue as pro- and anti-inflammatory organ.

Obesity is associated with low grade inflammation. Whether this is just an adaptive response to excess adiposity to maintain a normal oxygen supply or a chronic activation of the innate immune system is still unknown. Recent research has focused on the origin of the inflammatory markers in obesity and the extent to which adipose tissue has a direct effect. The production of adipokines by visceral adipose tissue is of particular interest since their local secretion by visceral fat depots may provide a novel mechanistic link between obesity and the associated vascular complications. Growing evidences suggest that the epicardial adipose tissue, the visceral fat depot located around the heart, may locally interact with myocardium and coronary arteries. Epicardial fat is a source of adiponectin and adrenomedullin, adipokines with anti-inflammatory properties, and several proinflammatory cytokines as well as Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin 1 (IL1), IL-1 h, Interleukin (IL6), Monocyte Chemoattractive Protein-1 (MCP-1), Nerve Growth Factor (NGF), resistin, Plasminogen Activator Inhibitor-1 (PAI-1), and free fatty acids. Epicardial adipose tissue could locally modulate the heart and vasculature, through paracrine secretion of pro- and anti-inflammatory cytokines, thereby playing a possible role in the adiposity-related inflammation and atherosclerosis. On the other hand, epicardial fat could exert a protective effect through adiponectin and adrenomedullin secretion as response to local or systemic metabolic or mechanical insults. Future studies will continue to provide new and fascinating insights into the double role of epicardial adipose tissue in the development of cardiovascular pathology and/or in protecting the heart and arteries.

Epicardial Adipose Tissue As New Cardio-Metabolic Risk Marker and Potential Therapeutic Target in the Metabolic Syndrome

Increased visceral adiposity, is an emerging cardiovascular risk factor. There is now a compelling need to quantify visceral adipose tissue not only for diagnostic purposes, but also for therapeutic interventions with weight reduction drugs or pharmaceuticals targeted to adipose tissue, as well as anti-obesity medications, thiazolidinediones, fibrates, angiotensin receptor blockers, highly active antiretroviral therapy and hormone replacement therapy. Among visceral adipose tissues, growing evidences suggest that cardiac adiposity may play an important role in the development of an unfavorable cardiovascular risk profile. Recent papers suggest that epicardial fat, index of cardiac and visceral adiposity, could locally modulate the morphology and function of the heart. The close anatomical relationship between epicardial adipose tissue and the adjacent myocardium should readily allow local paracrine interactions between these tissues. Echocardiography has been recently proposed for the direct assessment of epicardial adipose tissue. Echocardiographic assessment of epicardial fat may be a helpful tool not only for diagnostic purposes, as marker of visceral adiposity and inflammation, but also for therapeutic interventions with drugs that can modulate the adipose tissue. In this article, epicardial adipose tissues structure, function, method of assessment and reliability as a diagnostic tool and potential therapeutic target is reviewed.

epicardial and Pericardial Fat: Close, but Very Different

TO THE EDITOR: I read the article by Ding et al. titled “The Association of Pericardial Fat With Calcified Coronary Plaque” recently published in Obesity with great interest (1). The authors showed that the volume of pericardial fat around the coronary arteries, newly measured by computed tomography (CT), is independently associated with calcified coronary plaque (1). Although this is undoubtedly a finding of remarkable note, it seems that Ding et al. indifferently discussed about pericardial and epicardial fat, as these should be the identical adipose tissue. In fact, when they cited our articles on echocardiographic measurement of epicardial fat thickness (2,3) and other reports on the biomolecular aspects of epicardial fat (4), they erroneously referred it as pericardial fat. This is not just a tedious matter of terminology, but it is an incorrect and misleading concept. Pericardial fat has to be distinguished from the epicardial fat. Anatomically, epicardial and pericardial adipose tissue are clearly different (5,6). Epicardial fat is located between the outer wall of the myocardium and the visceral layer of pericardium. Pericardial fat is anterior to the epicardial fat and therefore located between visceral and parietal pericardium. Much of the importance within the epicardial fat is its anatomical closeness to the myocardium and the fact that the two tissues share the same microcirculation. As we and others have shown that epicardial fat is metabolically active and source of several adipokines, potential interactions through paracrine or vasocrine mechanisms between epicardial fat and myocardium are strongly suggested (5,6). This is clearly not true for the pericardial fat. However, pericardial fat could really modulate coronary arteries, as Ding et al. suggested, but it should be more correctly considered as paracardiac or perivascular fat (7). Biochemically epicardial and pericardial fat are different. In humans the evidences that the epicardial adipose tissue is an active endocrine organ are robust (5,6), whereas the role pericardial fat as source of adipokines is still partially unknown. Echocardiographically epicardial and pericardial fat thickness are different (2). For the anatomical and biomolecular features that I briefly reported above, we first proposed to measure the epicardial fat rather than the pericardial fat thickness. Epicardial fat is identified as the echo-free space between the outer wall of the myocardium and the visceral layer of pericardium. Pericardial fat thickness can be identified as the hypoechoic space anterior to the epicardial fat and parietal pericardium and it does not significantly change size during the cardiac cycle (2). Clinically epicardial and pericardial fat are different. We largely demonstrated the role of echocardiographic epicardial fat in predicting metabolic syndrome (8), visceral adiposity (2,3), heart morphology (9,10), insulin resistance (11), fasting glucose (12), subclinical atherosclerosis (13), liver enzymes (14), and in serving as accurate therapeutic target (15). Pericardial fat has not yet shown all these features. The article by Ding et al. may definitively open new avenues on the role of pericardial fat (1). I agree that echocardiography can provide only a linear measurement of epicardial fat and may be not accurate as CT. However echocardiographic assessment of epicardial visceral fat would certainly be less expensive CT and as echocardiography is routinely performed in high-risk cardiac patients, this objective noninvasive measure may be readily available at no extra cost. For all these reasons, the need to distinguish between epicardial and pericardial fat was compelling. If a body of evidences is suggesting that epicardial fat could play an active role as cardiometabolic risk factor, diagnostic tool and therapeutic target, further studies will be necessary to strengthen the role of pericardial fat.

Epicardial fat: from the biomolecular aspects to the clinical practice.

Epicardial fat is the visceral fat depot of heart. It is a metabolically active organ with anatomical and functional contiguity to the myocardium. A dichotomous role has been attributed to the epicardial fat. Under physiological conditions, epicardial fat displays biochemical and thermogenic cardio-protective properties. Under pathological circumstances epicardial fat can locally affect the heart and coronary arteries through vasocrine or paracrine secretion of pro-inflammatory cytokines. Epicardial fat can be measured with imaging techniques. Epicardial fat thickness reflects intra-abdominal and myocardial fat and correlates with metabolic syndrome and coronary artery disease. Epicardial fat measurement may play a role in the stratification of the cardio-metabolic risk and serve as therapeutic target. Weight loss and anti-inflammatory drugs targeting the fat may modulate epicardial fat. Because epicardial and myocardial tissues share the same coronary arterial supply it is reasonable to hypothesize that improved local vascularisation may resume epicardial fat to its physiological role.