Increased volume of epicardial fat is an independent risk factor for accelerated progression of sub-clinical coronary atherosclerosis

doi:10.1016/j.atherosclerosis.2011.09.041

Atherosclerosis

Volume 220, Issue 1, January 2012, Pages 223-230

https://doi.org/10.1016/j.atherosclerosis.2011.09.041 Get rights and content

Abstract

Background

Epicardial adipose tissue (EAT), a metabolically active visceral fat depot surrounding the heart, has been implicated in the pathogenesis of coronary artery disease (CAD) through possible paracrine interaction with the coronary arteries. We examined the association of EAT with metabolic syndrome and the prevalence and progression of coronary artery calcium (CAC) burden.

Methods

CAC scan was performed in 333 asymptomatic diabetic patients without prior history of CAD (median age 54 years, 62% males), followed by a repeat scan after 2.7 ± 0.3 years. CAC progression was defined as >2.5 mm³ increase in square root transformed volumetric CAC scores. EAT and intra-thoracic fat volumes were quantified using a dedicated software (QFAT), and were examined in relation to the metabolic syndrome, baseline CAC scores and CAC progression.

Results

Both epicardial and intra-thoracic fat were associated with metabolic syndrome after adjustment for conventional cardiovascular risk factors, but the association was attenuated after additional adjustment for body mass index. EAT, but not intra-thoracic fat, showed significant association with baseline CAC scores (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.04–1.22, p = 0.04) and CAC progression (OR 1.12, 95% CI 1.05–1.19, p < 0.001) after adjustment for conventional measures of obesity and risk factors.

Conclusion

EAT volume measured on non-contrast CT is an independent marker for the presence and severity of coronary calcium burden and also identifies individuals at increased risk of CAC progression. EAT quantification may thus add to the prognostic value of CAC imaging.

Introduction

Central obesity is an established risk factor for cardiovascular disease [1]. Expansion and inflammation of visceral adipose tissue (VAT) is pathologically linked to insulin resistance [2], which is in turn associated with hypertension and atherogenic dyslipidaemia; this cluster of risk factors is referred to as metabolic syndrome. VAT is therefore regarded as a metabolically active endocrine and paracrine organ which secretes an array of pro-inflammatory and pro-atherogenic cytokines. Epicardial adipose tissue (EAT) is an ectopic VAT depot that envelopes the heart, within the confines of the pericardium. It shares the same embryological origin as intra-abdominal VAT [3]. Several lines of evidence suggest that EAT may be a contributing factor in the pathogenesis of coronary artery disease (CAD). First, coronary artery segments that have an intra-myocardial course and therefore not in direct contact with EAT rarely contain atherosclerotic plaques [4]. Secondly, EAT thickness measured during autopsy correlates with the presence and severity of underlying CAD [5]. Finally, EAT secretes a number of inflammatory cytokines [6] which may exert a paracrine effect on the coronary arteries, given the anatomical contiguity between the two structures without any intervening fascial barriers. Furthermore, in patients with CAD, EAT expresses higher levels of pro-atherogenic IL-6 mRNA and lower levels of anti-atherogenic adiponectin mRNA compared to patients without CAD [7].

Coronary artery calcium (CAC) is pathognomonic of coronary atherosclerosis and CAC score reflects the total atherosclerotic plaque burden. Over the last two decades, CAC scoring has evolved as a useful tool for CAD screening and risk-stratification. Recent studies have shown that the non-contrast computed tomography (CT) scan obtained for CAC scoring allows reproducible quantification of EAT volume [8]. In cross-sectional studies, EAT volume was shown to be associated with multiple metabolic risk factors and CAD [8], [9], [10]. In this study, we sought to evaluate, for the first time, the effect of EAT on the progression of subclinical coronary atherosclerosis as determined by serial CAC scans performed 2.7 years apart.

Section snippets

Study population

The study includes 333 asymptomatic diabetic patients, who were part of a prospective trial that evaluated the role of non-invasive cardiac imaging and biomarkers in CAD risk stratification. Study methods were described in detail in previous reports [11]. Briefly, participants were recruited from four diabetes clinics in secondary care (Northwick Park and Central Middlesex Hospitals, London, UK), if they met the following criteria: (1) history of type II diabetes mellitus >1 year duration, (2)

Results

A total of 333 asymptomatic subjects with type II diabetes mellitus underwent the baseline CAC scan. Median age was 54 years, 62% were males. Over half of the participants were of Asian origin (n = 169, 51%), 21% were Caucasians and 28% were of Afro-Caribbean descent. Table 1 summarizes the patient characteristics and compares the distribution of different variables across tertiles of EAT volume.

Discussion

Epicardial adipose tissue is a unique fat depot in the body in terms of the size of its adipocytes, biochemical composition and metabolic activity. Per gram of tissue, EAT contains the greatest number of adipocytes [16], which are significantly smaller than those in sub-cutaneous and other visceral fat depots. EAT shows significantly higher rates of lipolysis [3] and lipogenesis [17] compared to other visceral fat depots. Physicians in the 19th century made the pertinent observation that in

Conclusion

Non-contrast CT obtained for CAC scoring offers an opportunity to non-invasively quantify the volume of epicardial and intra-thoracic fat depots. Expansion of EAT and intra-thoracic fat is related to metabolic syndrome, but such association is not independent of other measures of visceral adiposity. EAT but not intra-thoracic fat is related to the prevalence and progression of coronary calcium burden, suggesting a paracrine effect of this fat depot on the coronary arteries. EAT quantification

Conflict of interest

None.

References (30)

J.S. Yudkin et al.
“Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease
Lancet
(2005)
J.M. Marchington et al.
Adipose tissue in the mammalian heart and pericardium: structure, foetal development and biochemical properties
Comp Biochem Physiol B Comp Biochem
(1989)
S. Eiras et al.
Extension of coronary artery disease is associated with increased IL-6 and decreased adiponectin gene expression in epicardial adipose tissue
Cytokine
(2008)
D. Dey et al.
Computer-aided non-contrast CT-based quantification of pericardial and thoracic fat and their associations with coronary calcium and Metabolic Syndrome
Atherosclerosis
(2010)
D.V. Anand et al.
The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects
J Am Coll Cardiol
(2006)
E. Catmull et al.
A class of local interpolating splines
G. Bastarrika et al.
Relationship between coronary artery disease and epicardial adipose tissue quantification at cardiac CT: comparison between automatic volumetric measurement and manual bidimensional estimation
Acad Radiol
(2010)
N. Alexopoulos et al.
Epicardial adipose tissue and coronary artery plaque characteristics
Atherosclerosis
(2010)
G. Iacobellis et al.
Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease
Cytokine
(2005)
M. Konishi et al.
Pericardial fat inflammation correlates with coronary artery disease
Atherosclerosis
(2010)

J. Ding et al.

The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA)

Am J Clin Nutr

(2009)

H.B. Hubert et al.

Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study

Circulation

(1983)

F. Robicsek et al.

The freedom from atherosclerosis of intramyocardial coronary arteries: reduction of mural stress – a key factor

Eur J Cardiothorac Surg

(1994)

A. Silaghi et al.

Epicardial adipose tissue extent: relationship with age, body fat distribution, and coronaropathy

Obesity

(2008)

T. Mazurek et al.

Human epicardial adipose tissue is a source of inflammatory mediators

Circulation

(2003)

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Increased volume of epicardial fat is an independent risk factor for accelerated progression of sub-clinical coronary atherosclerosis

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Results

Discussion

Conclusion

Conflict of interest

Lancet

Comp Biochem Physiol B Comp Biochem

Cytokine

Atherosclerosis

J Am Coll Cardiol

Acad Radiol

Atherosclerosis

Cytokine

Atherosclerosis

Am J Clin Nutr

Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study

Circulation

The freedom from atherosclerosis of intramyocardial coronary arteries: reduction of mural stress – a key factor

Eur J Cardiothorac Surg

Epicardial adipose tissue extent: relationship with age, body fat distribution, and coronaropathy

Obesity

Human epicardial adipose tissue is a source of inflammatory mediators

Circulation