Morphofunctional Analysis of the Role of Epicardial Adipose Tissue in the Formation of the Obesity Paradox in Chronic Heart Failure
https://doi.org/10.18087/cardio.2024.3.n2469
Abstract
Based on the available modern medical literature, the article summarizes data on the morpho-functional significance of epicardial adipose tissue (EAT) in health and heart failure, analyzes the likelihood and reliability of the formation of the obesity paradox, and also discusses its possible morpho-functional mechanisms. The authors reviewed and analyzed the consequences of the obesity paradox in the aspect of the normal EAT phenotype protectivity. The review proposed ways of further research in this direction aimed at a deep anatomical and physiological analysis and at determining the morpho-functional role of EAT in the adaptive mechanisms of myocardial trophic provision, which may be an important part of the pathogenetic connection between obesity and CHF and, therefore, can improve outcomes in such patients.
Supporting agencies: No conflict of interest is reported.
About the Authors
V. E. Milyukov
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Doctor of Medical Sciences, Professor, Head of the Department of Topographic Anatomy and Operativ Surgery, Pirogov Russian National Research Medical University (RNRMU),
Moscow, Russia
V. A. Bryukhanov
Sechenov First Moscow State Medical University
Russian Federation
Russian Federation
student of Institute of Clinical Medicine named after N.V. Sklifosovsky, Federal State Autonomous Educational Institution of Higher Education First Moscow State Medical University named after I.M. Sechenov of the Ministry of Health of the Russian Federation (Sechenov University)
Moscow, Russia
C. C. Nguyen
Yersin University
Viet Nam
Viet Nam
Cand. of Med. Sci., Dean of the Faculty of Pharmacy and Nursing, Yersin university of Da Lat of Viet Nam. 27, Ton That Tung str.,
Da Lat city, Viet Nam
References
1. Shalnova S.A., Drapkina O.M. Contribution of the ESSE-RF study to preventive healthcare in Russia. Cardiovascular Therapy and Prevention. 2020;19(3):209–15. DOI: 10.15829/1728-8800-2020-2602
2. Savina A.A., Feyginova S.I. Obesity prevalence in population of Russian Federation: before COVID-19 pandemic. Social Aspects of Population Health. 2022;68(5):4. DOI: 10.21045/2071-5021-2022-68-5-4
3. Powell-Wiley TM, Poirier P, Burke LE, Després J-P, Gordon-Larsen P, Lavie CJ et al. Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2021;143(21):e984–1010. DOI: 10.1161/CIR.0000000000000973
4. Polyakov D.S., Fomin I.V., Belenkov Yu.N., Mareev V.Yu., Ageev F.T., Artemjeva E.G. et al. Chronic heart failure in the Russian Federation: what has changed over 20 years of follow-up? Results of the EPOCH-CHF study. Kardiologiia. 2021;61(4):4–14. DOI: 10.18087/cardio.2021.4.n1628
5. Zhai AB, Haddad H. The impact of obesity on heart failure. Current Opinion in Cardiology. 2017;32(2):196–202. DOI: 10.1097/HCO.0000000000000370
6. Lawson CA, Zaccardi F, Squire I, Okhai H, Davies M, Huang W et al. Risk Factors for Heart Failure: 20-Year Population-Based Trends by Sex, Socioeconomic Status, and Ethnicity. Circulation: Heart Failure. 2020;13(2):e006472. DOI: 10.1161/CIRCHEARTFAILURE.119.006472
7. Sharma A, Lavie CJ, Borer JS, Vallakati A, Goel S, Lopez-Jimenez F et al. Meta-Analysis of the Relation of Body Mass Index to All-Cause and Cardiovascular Mortality and Hospitalization in Patients With Chronic Heart Failure. The American Journal of Cardiology. 2015;115(10):1428–34. DOI: 10.1016/j.amjcard.2015.02.024
8. Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Woo MA, Tillisch JH. The relationship between obesity and mortality in patients with heart failure. Journal of the American College of Cardiology. 2001;38(3):789–95. DOI: 10.1016/S0735-1097(01)01448-6
9. Fonarow GC, Srikanthan P, Costanzo MR, Cintron GB, Lopatin M. An obesity paradox in acute heart failure: Analysis of body mass index and inhospital mortality for 108927 patients in the Acute Decompensated Heart Failure National Registry. American Heart Journal. 2007;153(1):74–81. DOI: 10.1016/j.ahj.2006.09.007
10. Horwich TB, Fonarow GC, Clark AL. Obesity and the Obesity Paradox in Heart Failure. Progress in Cardiovascular Diseases. 2018;61(2):151–6. DOI: 10.1016/j.pcad.2018.05.005
11. Doesch C, Suselbeck T, Leweling H, Fluechter S, Haghi D, Schoenberg SO et al. Bioimpedance Analysis Parameters and Epicardial Adipose Tissue Assessed by Cardiac Magnetic Resonance Imaging in Patients With Heart Failure. Obesity. 2010;18(12):2326–32. DOI: 10.1038/oby.2010.65
12. Iacobellis G. Epicardial adipose tissue in contemporary cardiology. Nature Reviews Cardiology. 2022;19(9):593–606. DOI: 10.1038/s41569-022-00679-9
13. Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nature Clinical Practice Cardiovascular Medicine. 2005;2(10):536–43. DOI: 10.1038/ncpcardio0319
14. Marchington JM, Mattacks CA, Pond CM. Adipose tissue in the mammalian heart and pericardium: Structure, foetal development and biochemical properties. Comparative Biochemistry and Physiology Part B. 1989;94(2):225–32. DOI: 10.1016/0305-0491(89)90337-4
15. Perez-Miguelsanz J, Jiménez-Ortega V, Cano-Barquilla P, Garaulet M, Esquifino AI, Varela-Moreiras G et al. Early Appearance of Epicardial Adipose Tissue through Human Development. Nutrients. 2021;13(9):2906. DOI: 10.3390/nu13092906
16. Sacks HS, Fain JN, Bahouth SW, Ojha S, Frontini A, Budge H et al. Adult Epicardial Fat Exhibits Beige Features. The Journal of Clinical Endocrinology & Metabolism. 2013;98(9):E1448–55. DOI: 10.1210/jc.2013-1265
17. Chen P-S, Turker I. Epicardial Adipose Tissue and Neural Mechanisms of Atrial Fibrillation. Circulation: Arrhythmia and Electrophysiology. 2012;5(4):618–20. DOI: 10.1161/CIRCEP.112.974956
18. Saely CH, Geiger K, Drexel H. Brown versus White Adipose Tissue: A Mini-Review. Gerontology. 2012;58(1):15–23. DOI: 10.1159/000321319
19. Patel KHK, Hwang T, Se Liebers C, Ng FS. Epicardial adipose tissue as a mediator of cardiac arrhythmias. American Journal of Physiology-Heart and Circulatory Physiology. 2022;322(2):H129–44. DOI: 10.1152/ajpheart.00565.2021
20. Martínez-Sánchez N. There and Back Again: Leptin Actions in White Adipose Tissue. International Journal of Molecular Sciences. 2020;21(17):6039. DOI: 10.3390/ijms21176039
21. Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Archives of Medical Science. 2013;9(2):191–200. DOI: 10.5114/aoms.2013.33181
22. Golozoubova V, Cannon B, Nedergaard J. UCP1 is essential for adaptive adrenergic nonshivering thermogenesis. American Journal of Physiology-Endocrinology and Metabolism. 2006;291(2):E350–7. DOI: 10.1152/ajpendo.00387.2005
23. Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang A-H et al. Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human. Cell. 2012;150(2):366–76. DOI: 10.1016/j.cell.2012.05.016
24. Ojha S, Fainberg HP, Wilson V, Pelella G, Castellanos M, May ST et al. Gene pathway development in human epicardial adipose tissue during early life. JCI Insight. 2016;1(13):e87460. DOI: 10.1172/jci.insight.87460
25. Thoonen R, Ernande L, Cheng J, Nagasaka Y, Yao V, Miranda-Bezerra A et al. Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy. Journal of Molecular and Cellular Cardiology. 2015;84:202–11. DOI: 10.1016/j.yjmcc.2015.05.002
26. Iacobellis G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nature Reviews Endocrinology. 2015;11(6):363–71. DOI: 10.1038/nrendo.2015.58
27. Nerlekar N, Muthalaly RG, Wong N, Thakur U, Wong DTL, Brown AJ et al. Association of Volumetric Epicardial Adipose Tissue Quantification and Cardiac Structure and Function. Journal of the Ameri can Heart Association. 2018;7(23):e009975. DOI: 10.1161/JAHA.118.009975
28. Sörensen J, Harms HJ, Aalen JM, Baron T, Smiseth OA, Flachskampf FA. Myocardial Efficiency. JACC: Cardiovascular Imaging. 2020;13(7):1564–76. DOI: 10.1016/j.jcmg.2019.08.030
29. Birkenfeld AL, Jordan J, Dworak M, Merkel T, Burnstock G. Myocardial metabolism in heart failure: Purinergic signalling and other metabolic concepts. Pharmacology & Therapeutics. 2019;194:132–44. DOI: 10.1016/j.pharmthera.2018.08.015
30. Pezeshkian M, Noori M, Najjarpour-Jabbari H, Abolfathi A, Darabi M, Darabi M et al. Fatty Acid Composition of Epicardial and Subcutaneous Human Adipose Tissue. Metabolic Syndrome and Related Disorders. 2009;7(2):125–32. DOI: 10.1089/met.2008.0056
31. Marchington JM, Pond CM. Site-specific properties of pericardial and epicardial adipose tissue: the effects of insulin and high-fat feeding on lipogenesis and the incorporation of fatty acids in vitro. International Journal of Obesity. 1990;14(12):1013–22. PMID: 2086494
32. Ernault AC, Meijborg VMF, Coronel R. Modulation of Cardiac Arrhythmogenesis by Epicardial Adipose Tissue. Journal of the American College of Cardiology. 2021;78(17):1730–45. DOI: 10.1016/j.jacc.2021.08.037
33. Patel VB, Shah S, Verma S, Oudit GY. Epicardial adipose tissue as a metabolic transducer: role in heart failure and coronary artery disease. Heart Failure Reviews. 2017;22(6):889–902. DOI: 10.1007/s10741-017-9644-1
34. Antonopoulos AS, Antoniades C. The role of epicardial adipose tissue in cardiac biology: classic concepts and emerging roles. The Journal of Physiology. 2017;595(12):3907–17. DOI: 10.1113/JP273049
35. Salazar J, Luzardo E, Mejías JC, Rojas J, Ferreira A, Rivas-Ríos JR et al. Epicardial Fat: Physiological, Pathological, and Therapeutic Implications. Cardiology Research and Practice. 2016;2016:1291537. DOI: 10.1155/2016/1291537
36. Antonopoulos AS, Margaritis M, Verheule S, Recalde A, Sanna F, Herdman L et al. Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling. Circulation Research. 2016;118(5):842–55. DOI: 10.1161/CIRCRESAHA.115.307856
37. Antonopoulos AS, Margaritis M, Coutinho P, Shirodaria C, Psarros C, Herdman L et al. Adiponectin as a Link Between Type 2 Diabetes and Vascular NADPH Oxidase Activity in the Human Arterial Wall: The Regulatory Role of Perivascular Adipose Tissue. Diabetes. 2015;64(6):2207–19. DOI: 10.2337/db14-1011
38. D’Marco L, Puchades MJ, Gorriz JL, Romero-Parra M, Lima-Martínez M, Soto C et al. Epicardial Adipose Tissue, Adiponectin and Leptin: A Potential Source of Cardiovascular Risk in Chronic Kidney Disease. International Journal of Molecular Sciences. 2020;21(3):978. DOI: 10.3390/ijms21030978
39. Song Y, Song F, Wu C, Hong Y-X, Li G. The roles of epicardial adipose tissue in heart failure. Heart Failure Reviews. 2022;27(1):369–77. DOI: 10.1007/s10741-020-09997-x
40. Peacock WF. Novel biomarkers in acute heart failure: MR-pro-adrenomedullin. Clinical Chemistry and Laboratory Medicine. 2014;52(10):1433–5. DOI: 10.1515/cclm-2014-0222
41. Yasu T, Nishikimi T, Kobayashi N, Ikeda N, Ueba H, Nakamura T et al. Up-regulated synthesis of mature-type adrenomedullin in coronary circulation immediately after reperfusion in patients with anterior acute myocardial infarction. Regulatory Peptides. 2005;129(1–3):161–6. DOI: 10.1016/j.regpep.2005.02.008
42. Wang W, McKinnie SMK, Patel VB, Haddad G, Wang Z, Zhabyeyev P et al. Loss of Apelin Exacerbates Myocardial Infarction Adverse Remodeling and Ischemia‐reperfusion Injury: Therapeutic Potential of Synthetic Apelin Analogues. Journal of the American Heart Association. 2013;2(4):e000249. DOI: 10.1161/JAHA.113.000249
43. Japp AG, Cruden NL, Barnes G, Van Gemeren N, Mathews J, Ada mson J et al. Acute Cardiovascular Effects of Apelin in Humans: Potential Role in Patients With Chronic Heart Failure. Circulation. 2010;121(16):1818–27. DOI: 10.1161/CIRCULATIONAHA.109.911339
44. Lage R, Moscoso I, Fernández-Trasancos Á, Cebro M, Couselo M, Fandiño-Vaquero R et al. Differential behaviour of epicardial adipose tissue-secretomes with high and low orosomucoid levels from patients with cardiovascular disease in H9C2 cells. Molecular and Cellular Endocrinology. 2015;416:77–87. DOI: 10.1016/j.mce.2015.08.025
45. Cherian S, Lopaschuk GD, Carvalho E. Cellular cross-talk between epicardial adipose tissue and myocardium in relation to the pathogenesis of cardiovascular disease. American Journal of Physiology-Endocrinology and Metabolism. 2012;303(8):E937–49. DOI: 10.1152/ajpendo.00061.2012
46. Iacobellis G. Aging Effects on Epicardial Adipose Tissue. Frontiers in Aging. 2021;2:666260. DOI: 10.3389/fragi.2021.666260
47. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H et al. Human Epicardial Adipose Tissue Is a Source of Inflammatory Mediators. Circulation. 2003;108(20):2460–6. DOI: 10.1161/01.CIR.0000099542.57313.C5
48. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H et al. Adiponectin, an Adipocyte-Derived Plasma Protein, Inhibits Endothelial NF-κB Signaling Through a cAMP-Dependent Pathway. Circulation. 2000;102(11):1296–301. DOI: 10.1161/01.CIR.102.11.1296
49. Zhang T, Yang P, Li T, Gao J, Zhang Y. Leptin Expression in Human Epicardial Adipose Tissue Is Associated with Local Coronary Athe rosclerosis. Medical Science Monitor. 2019;25:9913–22. DOI: 10.12659/MSM.918390
50. Ghantous CM, Azrak Z, Hanache S, Abou-Kheir W, Zeidan A. Differential Role of Leptin and Adiponectin in Cardiovascular System. International Journal of Endocrinology. 2015;2015:534320. DOI: 10.1155/2015/534320
51. Packer M. Epicardial Adipose Tissue May Mediate Deleterious Effects of Obesity and Inflammation on the Myocardium. Journal of the American College of Cardiology. 2018;71(20):2360–72. DOI: 10.1016/j.jacc.2018.03.509
52. Poggi AL, Gaborit B, Schindler TH, Liberale L, Montecucco F, Carbone F. Epicardial fat and atrial fibrillation: the perils of atrial failure. EP Europace. 2022;24(8):1201–12. DOI: 10.1093/europace/euac015
53. Vyas V, Blythe H, Wood EG, Sandhar B, Sarker S-J, Balmforth D et al. Obesity and diabetes are major risk factors for epicardial adipose tissue inflammation. JCI Insight. 2021;6(16):e145495. DOI: 10.1172/jci.insight.145495
54. Zhou M, Wang H, Chen J, Zhao L. Epicardial adipose tissue and atrial fibrillation: Possible mechanisms, potential therapies, and future directions. Pacing and Clinical Electrophysiology. 2020;43(1):133–45. DOI: 10.1111/pace.13825
55. Tereshchenko S.N., Galyavich A.S., Uskach T.M., Ageev F.T., Arutyunov G.P., Begrambekova Yu.L. et al. 2020 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2020;25(11):311–74. DOI: 10.15829/1560-4071-2020-4083
56. Kitzman DW, Shah SJ. The HFpEF Obesity Phenotype: The Elephant in the Room. Journal of the American College of Cardiology. 2016;68(2):200–3. DOI: 10.1016/j.jacc.2016.05.019
57. Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA. Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Circulation. 2017;136(1):6–19. DOI: 10.1161/CIRCULATIONAHA.116.026807
58. Pérez-Belmonte LM, Moreno-Santos I, Gómez-Doblas JJ, García-Pinilla JM, Morcillo-Hidalgo L, Garrido-Sánchez L et al. Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure. International Journal of Medical Sciences. 2017;14(9):891–5. DOI: 10.7150/ijms.19854
59. Choy M, Huang Y, Peng Y, Liang W, He X, Chen C et al. Association between epicardial adipose tissue and incident heart failure mediating by alteration of natriuretic peptide and myocardial strain. BMC Medicine. 2023;21(1):117. DOI: 10.1186/s12916-023-02836-4
60. Ateş K, Demir M. Importance of epicardial adipose tissue as a predictor of heart failure with preserved ejection fraction. Revista da Associação Médica Brasileira. 2022;68(9):1178–84. DOI: 10.1590/1806-9282.20220069
61. Chong B, Jayabaskaran J, Ruban J, Goh R, Chin YH, Kong G et al. Epicardial Adipose Tissue Assessed by Computed Tomography and Echocardiography Are Associated With Adverse Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. Circulation: Cardiovascular Imaging. 2023;16(5):e015159. DOI: 10.1161/CIRCIMAGING.122.015159
62. Pugliese NR, De Biase N, Mazzola M, Paneni F, Del Punta L, Gargani L et al. Prognostic significance of epicardial adipose tissue in heart failure with preserved and reduced ejection fraction. European Heart Journal. 2021;42(Suppl 1):ehab724.0820. DOI: 10.1093/eurheartj/ehab724.0820
63. Jin X, Hung C, Tay WT, Soon D, Sim D, Sung K et al. Epicardial adipose tissue related to left atrial and ventricular function in heart failure with preserved versus reduced and mildly reduced ejection fraction. European Journal of Heart Failure. 2022;24(8):1346–56. DOI: 10.1002/ejhf.2513
64. Van Woerden G, Van Veldhuisen DJ, Westenbrink BD, De Boer RA, Rienstra M, Gorter TM. Connecting epicardial adipose tissue and heart failure with preserved ejection fraction: mechanisms, management and modern perspectives. European Journal of Heart Failure. 2022;24(12):2238–50. DOI: 10.1002/ejhf.2741
65. Pugliese NR, Paneni F, Mazzola M, De Biase N, Del Punta L, Gargani L et al. Impact of epicardial adipose tissue on cardiovascular haemodynamics, metabolic profile, and prognosis in heart failure. European Journal of Heart Failure. 2021;23(11):1858–71. DOI: 10.1002/ejhf.2337
66. Venkateshvaran A, Faxen UL, Hage C, Michaëlsson E, Svedlund S, Saraste A et al. Association of epicardial adipose tissue with proteomics, coronary flow reserve, cardiac structure and function, and quality of life in heart failure with preserved ejection fraction: insights from the PROMIS‐HFpEF study. European Journal of Heart Failure. 2022;24(12):2251–60. DOI: 10.1002/ejhf.2709
67. Drapkina O.M., Samorodskaya I.V., Starinskaya M.A., Kim O.T., Neymark A.E. Obesity: assessment and management tactics of patients. Collective monograph. -M.: NMIC TPM of the Ministry of Health of Russia, LLC ‘Silicea-Polygraph’;2021. - 176 p. ISBN 978-5-9907556-0-4
68. Marcks N, Aimo A, Januzzi JL, Vergaro G, Clerico A, Latini R et al. Reappraisal of the obesity paradox in heart failure: a meta-analysis of individual data. Clinical Research in Cardiology. 2021;110(8):1280–91. DOI: 10.1007/s00392-021-01822-1
69. Lavie CJ, Osman AF, Milani RV, Mehra MR. Body composition and prognosis in chronic systolic heart failure: the obesity paradox. The American Journal of Cardiology. 2003;91(7):891–4. DOI: 10.1016/S0002-9149(03)00031-6
70. Futter JE, Cleland JGF, Clark AL. Body mass indices and outcome in patients with chronic heart failure. European Journal of Heart Failure. 2011;13(2):207–13. DOI: 10.1093/eurjhf/hfq218
71. Brgdar A, Gharbin J, Elawad A, Khalafalla S, Bishaw A, Balogun AF et al. The Effects of Body Mass Index on In-Hospital Mortality and Outcomes in Patients With Heart Failure: A Nationwide Analysis. Cureus. 2022;14(2):e22691. DOI: 10.7759/cureus.22691
72. Adamson C, Jhund PS, Docherty KF, Bělohlávek J, Chiang C, Diez M et al. Efficacy of dapagliflozin in heart failure with reduced ejection fraction according to body mass index. European Journal of Heart Failure. 2021;23(10):1662–72. DOI: 10.1002/ejhf.2308
73. Zaikina M.P., Kapustina V.A., Savel’ev S.I. Obesity paradox in patients with cardiovascular diseases and diabetes mellitus type 2 (analytical review). Health Care of the Russian Federation. 2021;65(2):135–42. DOI: 10.47470/0044-197X-2021-65-2-135-142
74. Aldiss P, Davies G, Woods R, Budge H, Sacks HS, Symonds ME. ‘Browning’ the cardiac and peri-vascular adipose tissues to modu late cardiovascular risk. International Journal of Cardiology. 2017;228:265–74. DOI: 10.1016/j.ijcard.2016.11.074
75. Peczkowski KK, Mashali MA, Saad NS, Hare A, Campbell CM, Whitson BA et al. Quantification of Cardiac Adipose Tissue in Failing and Nonfailing Human Myocardium. Journal of the American Heart Association. 2022;11(13):e025405. DOI: 10.1161/JAHA.121.025405
76. Liu J, Yu Q, Li Z, Zhou Y, Liu Z, You L et al. Epicardial adipose tissue density is a better predictor of cardiometabolic risk in HFpEF patients: a prospective cohort study. Cardiovascular Diabetology. 2023;22(1):45. DOI: 10.1186/s12933-023-01778-8
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For citations:
Milyukov V.E., Bryukhanov V.A., Nguyen C.C. Morphofunctional Analysis of the Role of Epicardial Adipose Tissue in the Formation of the Obesity Paradox in Chronic Heart Failure. Kardiologiia. 2024;64(3):72-80. (In Russ.) https://doi.org/10.18087/cardio.2024.3.n2469
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