Epicardial fat volume (EFV), also referred to as epicardial adipose tissue (EAT), has been recently reported to be a novel cardiovascular risk marker [1,2,3]. Early detection of excess EFV (i.e., > 69 ± 20 in females and males) has been found to correlate with early cardiovascular structural and functional abnormalities among subjects with various comorbidities, such as type 2 diabetes and obesity, which mandates early treatment through lifestyle modifications and aggressive medical therapy . Epicardial fat belongs to the category of perivascular adipose tissue which also includes the fat surrounding the renal arteries. EFV is unlike abdominal visceral adipose tissue due to its differences in mRNA. Epicardial adipocytes are also smaller than that of abdominal visceral adipocytes .
It has been reported that many obese and/or diabetic individuals have increased EFV, which has been associated with many risk factors contributing to coronary artery disease (CAD) [1,2,3, 6]. Additionally, other studies have found an association between excess EFV and metabolic syndrome [7, 8]. EFV has also been correlated with other independent cardiac biomarkers, such as high levels of C-reactive protein, BNP, and microalbuminuria, along with cardiovascular risk factors (i.e., hypertension, dyslipidemia, and hyperglycemia). It has also been associated with cardiovascular structural and functional abnormalities, such as an abnormal rise in blood pressure post-mild protocol exercise, carotid intima-media thickness, and left ventricular hypertrophy .
Under normal physiological conditions, epicardial fat is known to produce anti-inflammatory and anti-atherosclerotic cytokines, such as adiponectin and adrenomedullin, for cardioprotective function including increased free fatty acid oxidation, nitric oxide synthesis, and vasodilation [10,11,12]. A decrease in nitric oxide availability and vasodilator imbalance has been linked to the development of microvascular disease-based angina . Accordingly, it is time to focus on epicardial fat pathophysiology as an important risk marker for cardiovascular disease (CVD), including atypical chest pain syndrome.
Epicardial fat is defined as the adipose tissue which directly overlies the heart. It can cover 80% of the heart muscle while making up 20% of the heart’s mass [1,2,3, 5, 13]. Epicardial fat is vascularized by branches of the coronary arteries, and it has no fascia layer separating it from the myocardium; hence, it shares the same microcirculation, suggesting a close and strong interaction with both tissue structures . The physiologic function of epicardial fat is complex and not yet completely understood [5, 13]. There is growing evidence that human epicardial fat produces bioactive cytokines. These cytokines are involved in the regulation of endothelial function, where epicardial fat has been shown to be the strongest predictor of endothelial dysfunction through abnormal local pulse wave velocity in carotid arterial stiffness in menopausal women .
Chest pain is the second most common chief complaint in the US emergency departments, accounting for 8 million visits annually. Women have been statistically shown to present with chest pain more often than men . More specifically, once obstructive CAD is ruled out as the cause for this chest pain, microvascular dysfunction makes up 40% of these atypical recurring chest pain diagnoses, particularly in women. This atypical chest pain is referred to as atypical chest pain syndrome and includes a group of syndromes that affect the smaller arterioles in the myocardium, as opposed to the macrovascular coronary arteries. The cause for chest pain in patients with microvascular dysfunction occurs due to reduced blood flow that could be from thickening of the arterioles, from underlying endothelial dysfunction, or from increased resistance in the heart’s microcirculation [15, 16]. The complete pathophysiology of this atypical chest syndrome is still unknown, but it is often attributed to a response from increased myocardial demand due to structural and functional abnormalities.
Excessive accumulation of epicardial fat is also associated with cardiovascular structural and functional abnormalities [1,2,3, 5] and further increases the workload of the heart through its endocrine/paracrine pathophysiology . Some studies have explored the relationship between epicardial fat and abnormal stress tests or atypical chest pain due to the ability of the epicardial fat to act as a vasoconstrictor in coronary microcirculation [18, 19]. Therefore, it can be further theorized that the pro-inflammatory response hormones induced by excess EFV may result in microvascular dysfunction causing the atypical chest pain often observed in female patients. This study aims to assess whether excess EFV in female subjects is associated with significant microvascular disease, which might ultimately contribute to the atypical chest pain syndrome in subjects without obstructive coronary artery disease.