Weight of Pericardial Fat on Coronaropathy

Abstract

HomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 29, No. 5Weight of Pericardial Fat on Coronaropathy Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBWeight of Pericardial Fat on Coronaropathy Karine Clément, Arnaud Basdevant and Anne Dutour Karine ClémentKarine Clément From INSERM, U872 Nutriomic team 7 (K.C., A.B.), Centre de Recherche des Cordeliers; Université Pierre et Marie Curie-Paris 6 (K.C., A.B.); Assistance Publique Hôpitaux de Paris, APHP (K.C., A.B.), Department of Nutrition and Endocrinology, Pitié-Salpêtrière Hospital; INSERM U626 (A.D.), Marseille; Université de la Méditerranée (A.D.), Marseille; Assistance Publique - Hôpitaux de Marseille (A.D.), Endocrinologie and metabolic disease department, Marseille, France. Search for more papers by this author , Arnaud BasdevantArnaud Basdevant From INSERM, U872 Nutriomic team 7 (K.C., A.B.), Centre de Recherche des Cordeliers; Université Pierre et Marie Curie-Paris 6 (K.C., A.B.); Assistance Publique Hôpitaux de Paris, APHP (K.C., A.B.), Department of Nutrition and Endocrinology, Pitié-Salpêtrière Hospital; INSERM U626 (A.D.), Marseille; Université de la Méditerranée (A.D.), Marseille; Assistance Publique - Hôpitaux de Marseille (A.D.), Endocrinologie and metabolic disease department, Marseille, France. Search for more papers by this author and Anne DutourAnne Dutour From INSERM, U872 Nutriomic team 7 (K.C., A.B.), Centre de Recherche des Cordeliers; Université Pierre et Marie Curie-Paris 6 (K.C., A.B.); Assistance Publique Hôpitaux de Paris, APHP (K.C., A.B.), Department of Nutrition and Endocrinology, Pitié-Salpêtrière Hospital; INSERM U626 (A.D.), Marseille; Université de la Méditerranée (A.D.), Marseille; Assistance Publique - Hôpitaux de Marseille (A.D.), Endocrinologie and metabolic disease department, Marseille, France. Search for more papers by this author Originally published1 May 2009https://doi.org/10.1161/ATVBAHA.108.182907Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:615–616The regional distribution of adipose tissue (AT) is a major determinant of metabolic and cardiovascular diseases. The mass of fat in the visceral area associates independently of obesity with the development and progression of cardiovascular diseases in a series of clinical and epidemiological studies.1 This led to the concept of a pathophysiological link between abdominal obesity and metabolic syndrome. More recently, fat depots localized around the heart, highly variable among individuals, were proposed to contribute to the pathogenesis of coronaropathy independently of other visceral depots (ie, in the omental and mesenteric area).2,3 The study by Greif et al3a in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology highlights the association between pericardial adipose tissue (PAT) and the number of atherosclerotic plaques evaluated concomitantly by Dual source CT scan. This measurement was qualitatively interpretable in 264 consecutive patients with a large range of age, a normal or moderately increased body mass index (BMI), and no a priori coronary disease. An estimated volume of pericardial fat more than 300 cm3 provided an incremental value for the presence of coronary atherosclerosis (odds ratio 4.1) independently of well known risk factors (hyperglycemia or diabetes, hypercholesterolemia, hypertension, and smoking). Ninety-five percent of patients with PAT volume >300 cm3 had one or more atherosclerotic plaques by ROC estimation. In univariate statistical analysis, PAT volume was correlated with adipose tissue–derived inflammatory biomarkers like TNFα and adiponectin. Intriguingly the amount of PAT was not related to the severity of vascular alteration; ie, the mass of PAT was similar in subjects with noncalcified and in those with advanced calcified plaques. Based on the finding that young subjects with early stage plaques revealed a significant increase in PAT volume, it is suggested that PAT augmentation could precede the formation of plaque calcification and mature atherosclerotic plaque. The authors propose that PAT volume could be used for risk stratification in the absence of coronary calcium. Though practical constraints (cost and radiation exposure) limit the routine use of CT scan to estimate individual cardiovascular risk at the population level, this study contributes to the fascinating discussion regarding the potentially causal role of fat abundance around the heart in coronary atherosclerosis. It also provides new insight into the appropriate quantification and phenotyping of this depot as a new estimate of visceral fat. It is worthwhile mentioning that the measured “pericardial fat” is composed of epicardial fat (the epicardial adipose tissue (EAT) depot immediately adjacent to the heart wall, see Figure) and of the paracardial fat located on the external surface of the pericardium (ie, Mediastinal fat). The authors estimated in a subset of 120 subjects that both epicardial and pericardial fat volume were strongly correlated and related equally to the number of atherosclerotic plaques. This observation is interesting as far as EAT and paracardial fat do not share the same embryological origin (and vascularization) and as the pathophysiological role of paracardial fat is unknown. Furthermore, EAT lacks fascia and shares the same vascularization as the myocardium (ie, coronary arteries). EAT-derived bioactive molecules such as inflammatory, immune, and oxidative stress mediators and local fatty acids are pathophysiological candidates for the development of atherogenesis via diffusion in interstitial fluid across the adventitia and the arterial media, or transport via the vasa vasorum to cells of the atherosclerotic plaque2 (Figure). In vitro studies have shown that paracrine dialogs between human adipocytes and inflammatory cells present in adipose tissue (ie, macrophage, lymphocytes, and others) promote an increased synthesis of numerous biomolecules,4 leading to a low-grade inflammatory microenvironment.5 These conditions most likely promote plaque formation. The precise characterization of EAT-produced molecules, their cell origin, and their impact on epicardial adipocytes and myocardial biology remain to be identified. Gene expression studies have shown that EAT in obese patients who are candidates for coronary artery bypass graft appears more inflammatory than subcutaneous fat located in the legs. It was suggested that the inflammation state of EAT could lead to aggravation of vascular inflammation, plaque instability, and neovascularization.6 EAT could also exert a protective effect through the well-known buffering property of adipose tissue for toxic fatty acids, through the local secretion of adiponectin and adrenomedullin,7 or by providing additional energy to increased ventricular mass. This study also raises new questions concerning the contribution of paracardial fat to these metabolic and inflammatory alterations and of their consequences for coronary atherosclerosis. Although no clear link between PAT and the severity of coronaropathy (ie, presence of calcified and uncalcified plaques) was established in this imaging study, the need for understanding both the physiological and physiopathological links between this tissue and myocardial homeostatic function in subjects without and with coronaropathy is essential. Because this putative link might be modified in the complex stages of evolution of coronaropathy in individuals with various risk factors (incl. insulin resistance state), pathologies, and treatments, both the exploration of pericardial fat in different human conditions and the use of animal models prone to EAT expansion (ie, guinea pigs, rabbits, primates)8 are needed. Finally, the increased volume of EAT and its association with the low-grade inflammatory process could reflect a contribution to a more global phenomenon of visceral fat expansion as suggested by positive associations found between EAT measured by ultrasonography, surrogate markers of intraabdominal fat,9 or anthropometric measurement performed in autopsy studies10 (reviewed in2,3). Visceral fat, now well recognized as a risk depot for cardiovascular disease, is usually estimated in clinical studies by the measure of waist circumference, a parameter not evaluated in this study. The report of Greif et al illustrates the need to investigate the additional benefit of precisely quantifying pericardial fat per se (rather than detecting it as a morphological sign of coronary alteration) as a valuable and independent coronaropathy risk factor or as a marker of visceral abdominal fat,3 which is known to be inflamed in metabolic disease.Download figureDownload PowerPointFigure. Schematic role of EAT in the alteration of myocardial homeostasis. EAT volume can augment and pericardial fat composed of both EAT and paracardial fat with a volume >300 cm3 strongly increased the risk of atherosclerotic plaques. Here only EAT is shown. Multiple adipose-derived molecules can contribute to the alteration of myocardial homeostasis. Noteworthy, the altered capacity of fat storage in subcutaneous adipose tissues is a factor favoring visceral fat depots such as EAT (visc) as well as ectopic fat accumulation. sc indicates subcutaneous.See accompanying article on page 774The authors thank the ADAPT European Community’s 7th Framework Programme (FP7-HEALTH-2007-A), promoting the research on the adverse role of adipose tissues on inflammation related diseases (http://www.adapt-eu.net/) as well as Prof Juergen Eckel and Dr Henrike Sell for helpful suggestions.DisclosuresNone.FootnotesCorrespondence to Karine Clément, INSERM, U872 Nutriomic team 7, Centre de Recherche des Cordeliers, UMR S 872, Paris, F-75006 France. E-mail [email protected] References 1 Despres JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodes-Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008; 28: 1039–1049.LinkGoogle Scholar2 Sacks HS, Fain JN. Human epicardial adipose tissue: a review. Am Heart J. 2007; 153: 907–917.CrossrefMedlineGoogle Scholar3 Iacobellis G, Gao YJ, Sharma AM. Do cardiac and perivascular adipose tissue play a role in atherosclerosis? Curr Diab Rep. 2008; 8: 20–24.CrossrefMedlineGoogle Scholar3A Coronary Artery Disease Consortium. Large scale association analysis of novel genetic loci for coronary artery disease. Arterioscler Thromb Vasc Biol. 2009; 29: 774–780.LinkGoogle Scholar4 Keophiphath M, Achard V, Henegar C, Rouault C, Clement K, Lacasa D. Macrophage-secreted factors promote a profibrotic phenotype in human preadipocytes. Mol Endocrinol. 2009; 23: 11–24.CrossrefMedlineGoogle Scholar5 Lacasa D, Taleb S, Keophiphath M, Miranville A, Clement K. Macrophage-secreted factors impair human adipogenesis: involvement of proinflammatory state in preadipocytes. Endocrinology. 2007; 148: 868–877.CrossrefMedlineGoogle Scholar6 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: 2460–2466.LinkGoogle Scholar7 Silaghi A, Achard V, Paulmyer-Lacroix O, Scridon T, Tassistro V, Duncea I, Clement K, Dutour A, Grino M. Expression of adrenomedullin in human epicardial adipose tissue: role of coronary status. Am J Physiol Endocrinol Metab. 2007; 293: E1443–E1450.CrossrefMedlineGoogle Scholar8 Swifka J, Weiss J, Addicks K, Eckel J, Rosen P. Epicardial fat from guinea pig: a model to study the paracrine network of interactions between epicardial fat and myocardium? Cardiovasc Drugs Ther. 2008; 22: 107–114.CrossrefMedlineGoogle Scholar9 Iacobellis G, Ribaudo MC, Assael F, Vecci E, Tiberti C, Zappaterreno A, Di Mario U, Leonetti F. Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk. J Clin Endocrinol Metab. 2003; 88: 5163–5168.CrossrefMedlineGoogle Scholar10 Silaghi A, Piercecchi-Marti MD, Grino M, Leonetti G, Alessi MC, Clement K, Dadoun F, Dutour A. Epicardial adipose tissue extent: relationship with age, body fat distribution, and coronaropathy. Obesity (Silver Spring). 2008; 16: 2424–2430.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Le Jemtel T, Samson R, Ayinapudi K, Singh T and Oparil S (2019) Epicardial Adipose Tissue and Cardiovascular Disease, Current Hypertension Reports, 10.1007/s11906-019-0939-6, 21:5, Online publication date: 1-May-2019. Sato T, Aizawa Y, Yuasa S, Kishi S, Fuse K, Fujita S, Ikeda Y, Kitazawa H, Takahashi M, Sato M and Okabe M (2018) The effect of dapagliflozin treatment on epicardial adipose tissue volume, Cardiovascular Diabetology, 10.1186/s12933-017-0658-8, 17:1, Online publication date: 1-Dec-2018. Piché M and Poirier P (2018) Obesity, ectopic fat and cardiac metabolism, Expert Review of Endocrinology & Metabolism, 10.1080/17446651.2018.1500894, 13:4, (213-221), Online publication date: 4-Jul-2018. Basdevant A, Clément K and Oppert J (2014) Vers de nouveaux phénotypes et de nouvelles nosographies : de l’obésité aux maladies du tissu adipeux, Cahiers de Nutrition et de Diététique, 10.1016/j.cnd.2014.03.002, 49:3, (104-112), Online publication date: 1-Jun-2014. Sato T, Kameyama T, Ohori T, Matsuki A and Inoue H (2014) Effects of Eicosapentaenoic Acid Treatment on Epicardial and Abdominal Visceral Adipose Tissue Volumes in Patients with Coronary Artery Disease, Journal of Atherosclerosis and Thrombosis, 10.5551/jat.23390, 21:10, (1031-1043), . Basdevant A, Clément K and Oppert J (2013) Vers de nouveaux phénotypes et de nouvelles nosographies : de l’obésité aux maladies du tissu adipeuxTowards new phenotypes and nosography: from obesity to adipose tissue disorders, Obésité, 10.1007/s11690-013-0392-7, 8:4, (234-243), Online publication date: 1-Dec-2013. Basdevant A and Aron-Wisnewsky J (2013) Obésité : un processus évolutif Physiologie et physiopathologie du tissu adipeux, 10.1007/978-2-8178-0332-6_16, (235-247), . Basdevant A and Aron-Wisnewsky J (2013) Obesity: An Evolving Process Physiology and Physiopathology of Adipose Tissue, 10.1007/978-2-8178-0343-2_16, (231-242), . Gaborit B, Kober F, Jacquier A, Moro P, Flavian A, Quilici J, Cuisset T, Simeoni U, Cozzone P, Alessi M, Clément K, Bernard M and Dutour A (2012) Epicardial Fat Volume Is Associated With Coronary Microvascular Response in Healthy Subjects: A Pilot Study, Obesity, 10.1038/oby.2011.283, 20:6, (1200-1205), Online publication date: 1-Jun-2012. Gaborit B and Dutour A (2012) Le tissu adipeux épicardique : un nouveau tissu à prendre en compte, Médecine des Maladies Métaboliques, 10.1016/S1957-2557(12)70391-7, 6:3, (190-194), Online publication date: 1-Jun-2012. Cherian S, Lopaschuk G and Carvalho E (2012) Cellular cross-talk between epicardial adipose tissue and myocardium in relation to the pathogenesis of cardiovascular disease, American Journal of Physiology-Endocrinology and Metabolism, 10.1152/ajpendo.00061.2012, 303:8, (E937-E949), Online publication date: 15-Oct-2012. Gaborit B, Kober F, Jacquier A, Moro P, Cuisset T, Boullu S, Dadoun F, Alessi M, Morange P, Clément K, Bernard M and Dutour A (2011) Assessment of epicardial fat volume and myocardial triglyceride content in severely obese subjects: relationship to metabolic profile, cardiac function and visceral fat, International Journal of Obesity, 10.1038/ijo.2011.117, 36:3, (422-430), Online publication date: 1-Mar-2012. Payne G, Kohr M and Tune J (2012) Epicardial perivascular adipose tissue as a therapeutic target in obesity-related coronary artery disease, British Journal of Pharmacology, 10.1111/j.1476-5381.2011.01370.x, 165:3, (659-669), Online publication date: 1-Feb-2012. Ciangura C and Poitou-Bernert C (2011) Complications des obésités, EMC - Endocrinologie - Nutrition, 10.1016/S1155-1941(11)51424-6, 8:1, (1-12), Online publication date: 1-Jan-2011. Sacks H and Fain J (2011) Human epicardial fat: what is new and what is missing?, Clinical and Experimental Pharmacology and Physiology, 10.1111/j.1440-1681.2011.05601.x, 38:12, (879-887), Online publication date: 1-Dec-2011. Basdevant A and Ciangura C (2010) L’obésité, une maladie en soi, Bulletin de l'Académie Nationale de Médecine, 10.1016/S0001-4079(19)32345-3, 194:1, (13-24), Online publication date: 1-Jan-2010. Clément K (2010) Pathological Alteration of Human Adipose Tissue in Obesity Novel Insights into Adipose Cell Functions, 10.1007/978-3-642-13517-0_1, (1-13), . Dutour A, Achard V, Sell H, Naour N, Collart F, Gaborit B, Silaghi A, Eckel J, Alessi M, Henegar C and Clément K (2010) Secretory Type II Phospholipase A2 Is Produced and Secreted by Epicardial Adipose Tissue and Overexpressed in Patients with Coronary Artery Disease, The Journal of Clinical Endocrinology & Metabolism, 10.1210/jc.2009-1222, 95:2, (963-967), Online publication date: 1-Feb-2010. Basdevant A and Ciangura C (2009) Nouveaux regards sur les déterminants de l’obésité, Bulletin de l'Académie Nationale de Médecine, 10.1016/S0001-4079(19)32465-3, 193:6, (1259-1269), Online publication date: 1-Jun-2009. Iacobellis G and Willens H (2009) Echocardiographic Epicardial Fat: A Review of Research and Clinical Applications, Journal of the American Society of Echocardiography, 10.1016/j.echo.2009.10.013, 22:12, (1311-1319), Online publication date: 1-Dec-2009. Costa R, Neves K, Tostes R and Lobato N (2018) Perivascular Adipose Tissue as a Relevant Fat Depot for Cardiovascular Risk in Obesity, Frontiers in Physiology, 10.3389/fphys.2018.00253, 9 Gaborit B, Sengenes C, Ancel P, Jacquier A and Dutour A (2017) Role of Epicardial Adipose Tissue in Health and Disease: A Matter of Fat? Comprehensive Physiology, 10.1002/cphy.c160034, (1051-1082) Hong H, Hwang S, Park S, Ryu J, Choi H, Yoo H, Seo J, Kim S, Kim N, Baik S, Choi D, Kim S, Choi K and Mazzoccoli G (2015) Implications of Pericardial, Visceral and Subcutaneous Adipose Tissue on Vascular Inflammation Measured Using 18FDG-PET/CT, PLOS ONE, 10.1371/journal.pone.0135294, 10:8, (e0135294) Doukbi E, Soghomonian A, Sengenès C, Ahmed S, Ancel P, Dutour A and Gaborit B (2022) Browning Epicardial Adipose Tissue: Friend or Foe?, Cells, 10.3390/cells11060991, 11:6, (991) May 2009Vol 29, Issue 5 Advertisement Article InformationMetrics https://doi.org/10.1161/ATVBAHA.108.182907PMID: 19369652 Originally publishedMay 1, 2009 PDF download Advertisement