Journal of Cardiology 65 (2015) 2–4
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Editorial
The role of pericardial fat: The good, the bad and the ugly
Keywords: Pericardial adipose tissue Epicardial adipose tissue Coronary artery disease
Pericardial adipose tissue has been increasingly attracting physicians’ attention in association with metabolic syndrome and cardiovascular disease. This fat tissue covers the surface of the heart and surrounds adventitia of coronary arteries, and the close relationship between the volume of the pericardial fat and coronary artery disease motivates physicians and researchers for further investigation. The recent advance in medical imaging technology enables us to quantify the pericardial adipose tissue using multi-detector computed tomography (MDCT), magnetic resonance imaging, and echocardiography; however, the method to measure the fat volume has not been standardized in any imaging modalities. In this issue of the journal, Okura et al. measured pericardial fat volume by MDCT and demonstrated that accumulation of the normalized pericardial fat volume was related to increased severity of coronary artery disease in patients with preserved ejection fraction [1]. There is some confusion in the literature regarding the definition of pericardial fat. The pericardial fat is somehow a loose terminology. The true visceral adipose tissue surrounding myocardium is epicardial adipose tissue (EAT) or subepicardial fat (Fig. 1). This fat is located below the parietal pericardium. On the other hand, the fat deposited outside the parietal pericardium is para-cardiac fat or paracardial fat [2]. It is also referred to as thoracic fat or intrathoracic fat [3], and some investigators call this fat ‘‘pericardial fat’’ because this fat adjusted to outer surface of the pericardium (pericardi-al fat). However, some use the terms pericardial fat and EAT interchangeably, and the others use this term as the fat deposit either inside the visceral pericardium or outside the parietal pericardium, i.e. the EAT plus paracardial fat, that is, all the fat close to the heart (peri-cardial fat). The EAT and myocardium share the same coronary blood flow and influence each other [4], while the paracardial fat originates from primitive thoracic mesenchyme, and it is supplied by noncoronary sources. Thus, it is important to distinguish these two different pericardial visceral fat depots in the view of pathophysiology and in evaluating relationships with coronary
DOI of original article: http://dx.doi.org/10.1016/j.jjcc.2014.03.015.
artery disease. However, previous reports from both the Framingham Heart Study and the Multi-Ethnic Study of Atherosclerosis do not seem to discriminate between these two [5], dealing with ‘‘pericardial fat’’ as any adipose tissue located near pericardial sac. Okura et al. were also not able to distinguish EAT from paracardiac fat by a 64 detector row CT system and measured ‘‘pericardial fat’’ as a complex of epicardial fat, pericardium, and paracardial fat. Consequently they omitted a discussion about specific EAT. The pericardial fat volume measured by 64-slice MDCT could be one of the important cardiovascular risk factors, because of the biochemical and biomolecular properties and anatomically close connection to coronary arteries, the EAT conceptually could have more direct relationship between coronary artery diseases. Hence, further studies will be necessary to clarify this issue. Echocardiography is the modality that can easily distinguish the EAT from paracardial fat. However only thickness can be measured by normal scanning, and the volume of the fat cannot be obtained even using 3-dimensional echocardiography [6]. The linear measurement of the fat thickness at a specific location may not reflect the total EAT volume. Thus, in terms of quantification, MDCT by which one can measure 3-dimensional fat volume may be more sensitive and specific than echocardiography. The interobserver reliability and intraobserver reproducibility of measuring EAT thickness are higher by MDCT than by echocardiography. While Okura et al. could not measure the EAT volume, the EAT can be distinguished from thoracic fat using the latest MDCT machine [3]. The EAT volume, rather than its thickness, may be the most consistent measure of risk [7]. However, echocardiographic EAT thickness is still useful because it is inexpensive, reproducible, repeatable, and still a direct measure of visceral fat without X-ray exposure. It has been reported that higher inflammatory markers were observed in the EAT than in the subcutaneous adipose tissue in patients with coronary artery disease [8]. Several researchers reported that dense macrophage, T-lymphocyte, and mast cell infiltration were observed in the EAT, but not in the subcutaneous fat in patients with coronary artery disease [9,10]. Although the role of the pericardial fat is not fully recognized, the volume has been associated with coronary artery disease. Recent metaanalysis in nine studies showed a statistically significant increase in the EAT thickness at the right ventricular free wall in the coronary artery disease group compared to the non-coronary artery disease group [11]. Furthermore, in the population-based Heinz Nixdorf Recall cohort study, a significant association of EAT volume with cardiovascular risk factors was found and the EAT
http://dx.doi.org/10.1016/j.jjcc.2014.07.004 0914-5087/ß 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
[(Fig._1)TD$IG]
Editorial / Journal of Cardiology 65 (2015) 2–4
3
Fig. 1. Identification of epicardial adipose tissue and paracardial fat by echocardiography (left) and contrast enhanced 320-slice multi-detector computed tomography (right). The asterisks (*) indicate left descending coronary artery. ‘‘Pericardial fat’’ includes both epicardial fat (located within or deep into the pericardium) and paracardial fat (located superficial to the pericardium). Sometimes, pericardial fat is referred to as paracardial fat.
[(Fig._2)TD$IG]
Fig. 2. Echocardiograms from a 48-year-old man suffering from acute myocardial infarction. One day after the onset echocardiographic thickness of epicardial adipose tissue (EAT) was 12 mm (A). The thickness reduced to 8 mm after 6 months of cardiac rehabilitation (B). PCF, paracardial fat.
volume was significantly associated with coronary events, independent of traditional cardiovascular risk factors [3]. Since gender and ethnic-specific differences in the EAT volume have been reported [12], one should take care of these differences in evaluating cardiovascular risk by EAT parameters. Whether the volume of EAT can be reduced with interventions and whether this will reduce risk of events remains to be demonstrated. We experienced a case of a 48-year-old man suffering from acute myocardial infarction whose echocardiographic EAT thickness reduced in 6 months with cardiac rehabilitation (Fig. 2). Regression of EAT has been observed in subjects who underwent weight loss [13], exercise [14], atorvastatin administration [15], ezetimibe therapy [16], and so on. The physiological functions of EAT include protection of coronary artery from tension or torsion and heat, an energy source of myocardium, and neurological role for the cardiac nervous system. It is likely the EAT plays an important role in modulating cardiac function; however, excess EAT becomes harmful as discussed above. Whether quantification of the EAT
may really have the diagnostic properties to serve as an indicator of cardiovascular risk should be analyzed in large, randomized, and multiethnic populations. References [1] Okura K, Maeno K, Okura S, Takemori H, Toya D, Tanaka N, Miyayama S. Pericardial fat volume is an independent risk factor for the severity of coronary artery disease in patients with preserved ejection fraction. J Cardiol 2015; 65:37–41. [2] Nelson AJ, Worthley MI, Psaltis PJ, Carbone A, Dundon BK, Duncan RF, Piantadosi C, Lau DH, Sanders P, Wittert GA, Worthley SG. Validation of cardiovascular magnetic resonance assessment of pericardial adipose tissue volume. J Cardiovasc Magn Reson 2009;11:15–23. [3] Mahabadi AA, Berg MH, Lehmann N, Kalsch H, Bauer M, Kara K, Dragano N, Moebus S, Jo¨ckel KH, Erbel R, Mo¨hlenkamp S. Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study. J Am Coll Cardiol 2013;61:1388–95. [4] Corradi D, Maestri R, Callegari S, Pastori P, Goldoni M, Luong TV, Bordi C. The ventricular epicardial fat is related to the myocardial mass in normal, ischemic and hypertrophic hearts. Cardiovasc Pathol 2004;13:313–6. [5] Rosito GA, Massaro JM, Hoffmann U, Ruberg FL, Mahabadi AA, Vasan RS, O’Donnell CJ, Fox CS. Pericardial fat, visceral abdominal fat, cardiovascular
4
[6]
[7]
[8]
[9]
[10]
[11]
[12]
Editorial / Journal of Cardiology 65 (2015) 2–4 disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation 2008;117:605–13. Chaowalit N, Somers VK, Pellikka PA, Rihal CS, Lopez-Jimenez F. Subepicardial adipose tissue and the presence and severity of coronary artery disease. Atherosclerosis 2006;186:354–9. Greif M, Becker A, von Ziegler F, Lebherz C, Lehrke M, Broedl UC, Tittus J, Parhofer K, Becker C, Reiser M, Knez A, Leber AW. Pericardial adipose tissue determined by dual source CT is a risk factor for coronary atherosclerosis. Arterioscler Thromb Vasc Biol 2009;29:781–6. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Sarov-Blat L, O’Brien S, Keiper EA, Johnson AG, Martin J, Goldstein BJ, Shi Y. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 2003;108:2460–6. Hirata Y, Tabata M, Kurobe H, Motoki T, Akaike M, Nishio C, Higashida M, Mikasa H, Nakaya Y, Takanashi S, Igarashi T, Kitagawa T, Sata M. Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue. J Am Coll Cardiol 2011;58:248–55. Shimabukuro M, Hirata Y, Tabata M, Dagvasumberel M, Sato H, Kurobe H, Fukuda D, Soeki T, Kitagawa T, Takanashi S, Sata M. Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 2013;33:1077–84. Wu FZ, Chou KJ, Huang YL, Wu MT. The relation of location-specific epicardial adipose tissue thickness and obstructive coronary artery disease: systemic review and meta-analysis of observational studies. BMC Cardiovasc Disord 2014;14:62. Dagvasumberel M, Shimabukuro M, Nishiuchi T, Ueno J, Takao S, Fukuda D, Hirata Y, Kurobe H, Soeki T, Iwase T, Kusunose K, Niki T, Yamaguchi K, Taketani Y, Yagi S, et al. Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: a 3-dimensional cardiac computed tomography imaging study in Japanese subjects. Cardiovasc Diabetol 2012;11:106.
[13] Iacobellis G, Singh N, Wharton S, Sharma AM. Substantial changes in epicardial fat thickness after weight loss in severely obese subjects. Obesity (Silver Spring) 2008;16:1693–7. [14] Kim MK, Tomita T, Kim MJ, Sasai H, Maeda S, Tanaka K. Aerobic exercise training reduces epicardial fat in obese men. J Appl Physiol 2009;106:5–11. [15] Park JH, Park YS, Kim YJ, Lee IS, Kim JH, Lee JH, Choi SW, Jeong JO, Seong IW. Effects of statins on the epicardial fat thickness in patients with coronary artery stenosis underwent percutaneous coronary intervention: comparison of atorvastatin with simvastatin/ezetimibe. J Cardiovasc Ultrasound 2010;18:121–6. [16] Takase H, Dohi Y, Okado T, Hashimoto T, Goto Y, Kimura G. Effects of ezetimibe on visceral fat in the metabolic syndrome: a randomised controlled study. Eur J Clin Invest 2012;42:1287–94.
Hirotsugu Yamada (MD, PhD, FJCC)* Masataka Sata (MD, PhD, FJCC) Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan *Corresponding author at: Department of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima 770-8503, Japan. Tel.: +81 886339311; fax: +81 886337798 E-mail address: [email protected] (H. Yamada). 7 July 2014 Available online 19 August 2014
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Editorial
The role of pericardial fat: The good, the bad and the ugly
Keywords: Pericardial adipose tissue Epicardial adipose tissue Coronary artery disease
Pericardial adipose tissue has been increasingly attracting physicians’ attention in association with metabolic syndrome and cardiovascular disease. This fat tissue covers the surface of the heart and surrounds adventitia of coronary arteries, and the close relationship between the volume of the pericardial fat and coronary artery disease motivates physicians and researchers for further investigation. The recent advance in medical imaging technology enables us to quantify the pericardial adipose tissue using multi-detector computed tomography (MDCT), magnetic resonance imaging, and echocardiography; however, the method to measure the fat volume has not been standardized in any imaging modalities. In this issue of the journal, Okura et al. measured pericardial fat volume by MDCT and demonstrated that accumulation of the normalized pericardial fat volume was related to increased severity of coronary artery disease in patients with preserved ejection fraction [1]. There is some confusion in the literature regarding the definition of pericardial fat. The pericardial fat is somehow a loose terminology. The true visceral adipose tissue surrounding myocardium is epicardial adipose tissue (EAT) or subepicardial fat (Fig. 1). This fat is located below the parietal pericardium. On the other hand, the fat deposited outside the parietal pericardium is para-cardiac fat or paracardial fat [2]. It is also referred to as thoracic fat or intrathoracic fat [3], and some investigators call this fat ‘‘pericardial fat’’ because this fat adjusted to outer surface of the pericardium (pericardi-al fat). However, some use the terms pericardial fat and EAT interchangeably, and the others use this term as the fat deposit either inside the visceral pericardium or outside the parietal pericardium, i.e. the EAT plus paracardial fat, that is, all the fat close to the heart (peri-cardial fat). The EAT and myocardium share the same coronary blood flow and influence each other [4], while the paracardial fat originates from primitive thoracic mesenchyme, and it is supplied by noncoronary sources. Thus, it is important to distinguish these two different pericardial visceral fat depots in the view of pathophysiology and in evaluating relationships with coronary
DOI of original article: http://dx.doi.org/10.1016/j.jjcc.2014.03.015.
artery disease. However, previous reports from both the Framingham Heart Study and the Multi-Ethnic Study of Atherosclerosis do not seem to discriminate between these two [5], dealing with ‘‘pericardial fat’’ as any adipose tissue located near pericardial sac. Okura et al. were also not able to distinguish EAT from paracardiac fat by a 64 detector row CT system and measured ‘‘pericardial fat’’ as a complex of epicardial fat, pericardium, and paracardial fat. Consequently they omitted a discussion about specific EAT. The pericardial fat volume measured by 64-slice MDCT could be one of the important cardiovascular risk factors, because of the biochemical and biomolecular properties and anatomically close connection to coronary arteries, the EAT conceptually could have more direct relationship between coronary artery diseases. Hence, further studies will be necessary to clarify this issue. Echocardiography is the modality that can easily distinguish the EAT from paracardial fat. However only thickness can be measured by normal scanning, and the volume of the fat cannot be obtained even using 3-dimensional echocardiography [6]. The linear measurement of the fat thickness at a specific location may not reflect the total EAT volume. Thus, in terms of quantification, MDCT by which one can measure 3-dimensional fat volume may be more sensitive and specific than echocardiography. The interobserver reliability and intraobserver reproducibility of measuring EAT thickness are higher by MDCT than by echocardiography. While Okura et al. could not measure the EAT volume, the EAT can be distinguished from thoracic fat using the latest MDCT machine [3]. The EAT volume, rather than its thickness, may be the most consistent measure of risk [7]. However, echocardiographic EAT thickness is still useful because it is inexpensive, reproducible, repeatable, and still a direct measure of visceral fat without X-ray exposure. It has been reported that higher inflammatory markers were observed in the EAT than in the subcutaneous adipose tissue in patients with coronary artery disease [8]. Several researchers reported that dense macrophage, T-lymphocyte, and mast cell infiltration were observed in the EAT, but not in the subcutaneous fat in patients with coronary artery disease [9,10]. Although the role of the pericardial fat is not fully recognized, the volume has been associated with coronary artery disease. Recent metaanalysis in nine studies showed a statistically significant increase in the EAT thickness at the right ventricular free wall in the coronary artery disease group compared to the non-coronary artery disease group [11]. Furthermore, in the population-based Heinz Nixdorf Recall cohort study, a significant association of EAT volume with cardiovascular risk factors was found and the EAT
http://dx.doi.org/10.1016/j.jjcc.2014.07.004 0914-5087/ß 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
[(Fig._1)TD$IG]
Editorial / Journal of Cardiology 65 (2015) 2–4
3
Fig. 1. Identification of epicardial adipose tissue and paracardial fat by echocardiography (left) and contrast enhanced 320-slice multi-detector computed tomography (right). The asterisks (*) indicate left descending coronary artery. ‘‘Pericardial fat’’ includes both epicardial fat (located within or deep into the pericardium) and paracardial fat (located superficial to the pericardium). Sometimes, pericardial fat is referred to as paracardial fat.
[(Fig._2)TD$IG]
Fig. 2. Echocardiograms from a 48-year-old man suffering from acute myocardial infarction. One day after the onset echocardiographic thickness of epicardial adipose tissue (EAT) was 12 mm (A). The thickness reduced to 8 mm after 6 months of cardiac rehabilitation (B). PCF, paracardial fat.
volume was significantly associated with coronary events, independent of traditional cardiovascular risk factors [3]. Since gender and ethnic-specific differences in the EAT volume have been reported [12], one should take care of these differences in evaluating cardiovascular risk by EAT parameters. Whether the volume of EAT can be reduced with interventions and whether this will reduce risk of events remains to be demonstrated. We experienced a case of a 48-year-old man suffering from acute myocardial infarction whose echocardiographic EAT thickness reduced in 6 months with cardiac rehabilitation (Fig. 2). Regression of EAT has been observed in subjects who underwent weight loss [13], exercise [14], atorvastatin administration [15], ezetimibe therapy [16], and so on. The physiological functions of EAT include protection of coronary artery from tension or torsion and heat, an energy source of myocardium, and neurological role for the cardiac nervous system. It is likely the EAT plays an important role in modulating cardiac function; however, excess EAT becomes harmful as discussed above. Whether quantification of the EAT
may really have the diagnostic properties to serve as an indicator of cardiovascular risk should be analyzed in large, randomized, and multiethnic populations. References [1] Okura K, Maeno K, Okura S, Takemori H, Toya D, Tanaka N, Miyayama S. Pericardial fat volume is an independent risk factor for the severity of coronary artery disease in patients with preserved ejection fraction. J Cardiol 2015; 65:37–41. [2] Nelson AJ, Worthley MI, Psaltis PJ, Carbone A, Dundon BK, Duncan RF, Piantadosi C, Lau DH, Sanders P, Wittert GA, Worthley SG. Validation of cardiovascular magnetic resonance assessment of pericardial adipose tissue volume. J Cardiovasc Magn Reson 2009;11:15–23. [3] Mahabadi AA, Berg MH, Lehmann N, Kalsch H, Bauer M, Kara K, Dragano N, Moebus S, Jo¨ckel KH, Erbel R, Mo¨hlenkamp S. Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study. J Am Coll Cardiol 2013;61:1388–95. [4] Corradi D, Maestri R, Callegari S, Pastori P, Goldoni M, Luong TV, Bordi C. The ventricular epicardial fat is related to the myocardial mass in normal, ischemic and hypertrophic hearts. Cardiovasc Pathol 2004;13:313–6. [5] Rosito GA, Massaro JM, Hoffmann U, Ruberg FL, Mahabadi AA, Vasan RS, O’Donnell CJ, Fox CS. Pericardial fat, visceral abdominal fat, cardiovascular
4
[6]
[7]
[8]
[9]
[10]
[11]
[12]
Editorial / Journal of Cardiology 65 (2015) 2–4 disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation 2008;117:605–13. Chaowalit N, Somers VK, Pellikka PA, Rihal CS, Lopez-Jimenez F. Subepicardial adipose tissue and the presence and severity of coronary artery disease. Atherosclerosis 2006;186:354–9. Greif M, Becker A, von Ziegler F, Lebherz C, Lehrke M, Broedl UC, Tittus J, Parhofer K, Becker C, Reiser M, Knez A, Leber AW. Pericardial adipose tissue determined by dual source CT is a risk factor for coronary atherosclerosis. Arterioscler Thromb Vasc Biol 2009;29:781–6. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Sarov-Blat L, O’Brien S, Keiper EA, Johnson AG, Martin J, Goldstein BJ, Shi Y. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 2003;108:2460–6. Hirata Y, Tabata M, Kurobe H, Motoki T, Akaike M, Nishio C, Higashida M, Mikasa H, Nakaya Y, Takanashi S, Igarashi T, Kitagawa T, Sata M. Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue. J Am Coll Cardiol 2011;58:248–55. Shimabukuro M, Hirata Y, Tabata M, Dagvasumberel M, Sato H, Kurobe H, Fukuda D, Soeki T, Kitagawa T, Takanashi S, Sata M. Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 2013;33:1077–84. Wu FZ, Chou KJ, Huang YL, Wu MT. The relation of location-specific epicardial adipose tissue thickness and obstructive coronary artery disease: systemic review and meta-analysis of observational studies. BMC Cardiovasc Disord 2014;14:62. Dagvasumberel M, Shimabukuro M, Nishiuchi T, Ueno J, Takao S, Fukuda D, Hirata Y, Kurobe H, Soeki T, Iwase T, Kusunose K, Niki T, Yamaguchi K, Taketani Y, Yagi S, et al. Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: a 3-dimensional cardiac computed tomography imaging study in Japanese subjects. Cardiovasc Diabetol 2012;11:106.
[13] Iacobellis G, Singh N, Wharton S, Sharma AM. Substantial changes in epicardial fat thickness after weight loss in severely obese subjects. Obesity (Silver Spring) 2008;16:1693–7. [14] Kim MK, Tomita T, Kim MJ, Sasai H, Maeda S, Tanaka K. Aerobic exercise training reduces epicardial fat in obese men. J Appl Physiol 2009;106:5–11. [15] Park JH, Park YS, Kim YJ, Lee IS, Kim JH, Lee JH, Choi SW, Jeong JO, Seong IW. Effects of statins on the epicardial fat thickness in patients with coronary artery stenosis underwent percutaneous coronary intervention: comparison of atorvastatin with simvastatin/ezetimibe. J Cardiovasc Ultrasound 2010;18:121–6. [16] Takase H, Dohi Y, Okado T, Hashimoto T, Goto Y, Kimura G. Effects of ezetimibe on visceral fat in the metabolic syndrome: a randomised controlled study. Eur J Clin Invest 2012;42:1287–94.
Hirotsugu Yamada (MD, PhD, FJCC)* Masataka Sata (MD, PhD, FJCC) Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan *Corresponding author at: Department of Cardiovascular Medicine, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima 770-8503, Japan. Tel.: +81 886339311; fax: +81 886337798 E-mail address: [email protected] (H. Yamada). 7 July 2014 Available online 19 August 2014
