Association between epicardial adipose tissue, high-sensitivity C-reactive protein and myocardial dysfunction in middle-aged men with suspected metabolic syndrome

Dong-Hyuk Cho, Hyung Joon Joo, Mi-Na Kim, Do-Sun Lim, Wan Joo Shim, Seong-Mi Park, Dong-Hyuk Cho, Hyung Joon Joo, Mi-Na Kim, Do-Sun Lim, Wan Joo Shim, Seong-Mi Park

Abstract

Background: As body fat composition and metabolism differ between men and women, we evaluated sex-related differences in the association among epicardial adipose tissue (EAT), secretome profile, and myocardial function of subjects with suspected metabolic syndrome.

Methods: We evaluated 277 participants (men, n = 140; 56.1 ± 4.7 years) who underwent conventional echocardiography and two-dimensional speckle tracking from the Seoul Metabolic Syndrome cohort. EAT was measured from the right ventricular free wall perpendicular to the aortic annulus at end systole. Global longitudinal strain (GLS) was obtained from 18 apical segments. Apolipoprotein A1, apolipoprotein B, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) levels were measured using immunoturbidimetry assay.

Results: Mean age, body mass index, and hs-CRP level did not differ by sex. Waist circumference, fasting blood glucose level, and triglyceride/high-density lipoprotein cholesterol ratio were higher, and apolipoprotein AI and adiponectin levels were lower in men. No significant difference in mean EAT thickness was found (7.02 ± 1.81 vs. 7.13 ± 1.70 mm, p = 0.613). Men had a higher left ventricular (LV) mass index and lower GLS. EAT thickness was associated with hs-CRP level in men alone (ß = 0.206, p = 0.015). LV mass index (ß = 2.311, p = 0.037) and function represented by e' (ß = - 0.279, p = 0.001) and GLS (ß = - 0.332, p < 0.001) were independently associated with EAT thickness in men alone.

Conclusions: In middle-aged subjects with suspected metabolic syndrome, EAT was associated with inflammation represented by hs-CRP level, LV mass, and subclinical myocardial dysfunction only in men, suggesting that the inflammatory activity of EAT induced myocardial remodeling and dysfunction in middle-aged subjects but was attenuated in women. Trial registration NCT02077530 (date of registration: November 1, 2013).

Keywords: Epicardial adipose tissue; Global longitudinal strain; High-sensitivity C-reactive protein; Metabolic syndrome; Sex.

Figures

Fig. 1
Fig. 1
Comparison of high-sensitivity C-reactive protein levels according to median e′ velocity (a), and GLS (b). * means p-value is less than 0.05 compared with the high-sensitivity C-reactive protein level of the subjects without myocardial dysfunction in each group
Fig. 2
Fig. 2
The association of epicardial adipose tissue thickness with myocardial function (ad) and high-sensitivity C-reactive protein level (e, f) in men and women

References

    1. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, et al. Heart disease and stroke statistics—2017 update: a report from the american heart association. Circulation. 2017;135(10):e146–e603. doi: 10.1161/CIR.0000000000000485.
    1. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, et al. Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209. doi: 10.1161/CIR.0b013e3182009701.
    1. Bairey Merz CN, Shaw LJ, Reis SE, Bittner V, Kelsey SF, Olson M, Johnson BD, Pepine CJ, Mankad S, Sharaf BL, et al. Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study: part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol. 2006;47(3 Suppl):S21–S29. doi: 10.1016/j.jacc.2004.12.084.
    1. Waters DD, Gordon D, Rossouw JE, Cannon RO 3rd, Collins P, Herrington DM, Hsia J, Langer R, Mosca L, Ouyang P et al: Women’s ischemic syndrome evaluation: current status and future research directions: report of the National Heart, Lung and Blood Institute workshop: October 2–4, 2002 : Section 4: lessons from hormone replacement trials. Circulation 2004, 109(6):e53–5.
    1. Blaak E. Gender differences in fat metabolism. Curr Opin Clin Nutr Metab Care. 2001;4(6):499–502. doi: 10.1097/00075197-200111000-00006.
    1. Makovey J, Naganathan V, Sambrook P. Gender differences in relationships between body composition components, their distribution and bone mineral density: a cross-sectional opposite sex twin study. Osteoporos Int. 2005;16(12):1495–1505. doi: 10.1007/s00198-005-1841-4.
    1. Power ML, Schulkin J. Sex differences in fat storage, fat metabolism, and the health risks from obesity: possible evolutionary origins. Br J Nutr. 2008;99(5):931–940. doi: 10.1017/S0007114507853347.
    1. Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev. 2010;11(1):11–18. doi: 10.1111/j.1467-789X.2009.00623.x.
    1. Camhi SM, Bray GA, Bouchard C, Greenway FL, Johnson WD, Newton RL, Ravussin E, Ryan DH, Smith SR, Katzmarzyk PT. The relationship of waist circumference and BMI to visceral, subcutaneous, and total body fat: sex and race differences. Obesity (Silver Spring) 2011;19(2):402–408. doi: 10.1038/oby.2010.248.
    1. Iacobellis G, Willens HJ. Echocardiographic epicardial fat: a review of research and clinical applications. J Am Soc Echocardiogr. 2009;22(12):1311–1319. doi: 10.1016/j.echo.2009.10.013.
    1. Gruzdeva O, Uchasova E, Dyleva Y, Borodkina D, Akbasheva O, Belik E, Karetnikova V, Brel N, Kokov A, Kashtalap V. Relationships between epicardial adipose tissue thickness and adipo-fibrokine indicator profiles post-myocardial infarction. Cardiovasc Diabetol. 2018;17(1):40. doi: 10.1186/s12933-018-0679-y.
    1. Iacobellis G, Pistilli D, Gucciardo M, Leonetti F, Miraldi F, Brancaccio G, Gallo P, di Gioia CR. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine. 2005;29(6):251–255.
    1. Lai YH, Yun CH, Yang FS, Liu CC, Wu YJ, Kuo JY, Yeh HI, Lin TY, Bezerra HG, Shih SC, et al. Epicardial adipose tissue relating to anthropometrics, metabolic derangements and fatty liver disease independently contributes to serum high-sensitivity C-reactive protein beyond body fat composition: a study validated with computed tomography. J Am Soc Echocardiogr. 2012;25(2):234–241. doi: 10.1016/j.echo.2011.09.018.
    1. Hirata Y, Kurobe H, Akaike M, Chikugo F, Hori T, Bando Y, Nishio C, Higashida M, Nakaya Y, Kitagawa T. Enhanced inflammation in epicardial fat in patients with coronary artery disease. Int Heart J. 2011;52(3):139–142. doi: 10.1536/ihj.52.139.
    1. Malavazos AE, Ermetici F, Cereda E, Coman C, Locati M, Morricone L, Corsi MM, Ambrosi B. Epicardial fat thickness: relationship with plasma visfatin and plasminogen activator inhibitor-1 levels in visceral obesity. Nutr Metab Cardiovasc Dis. 2008;18(8):523–530. doi: 10.1016/j.numecd.2007.09.001.
    1. Pierdomenico SD, Pierdomenico AM, Cuccurullo F, Iacobellis G. Meta-analysis of the relation of echocardiographic epicardial adipose tissue thickness and the metabolic syndrome. Am J Cardiol. 2013;111(1):73–78. doi: 10.1016/j.amjcard.2012.08.044.
    1. Ueno K, Anzai T, Jinzaki M, Yamada M, Jo Y, Maekawa Y, Kawamura A, Yoshikawa T, Tanami Y, Sato K. Increased epicardial fat volume quantified by 64-multidetector computed tomography is associated with coronary atherosclerosis and totally occlusive lesions. Circ J. 2009;73(10):1927–1933. doi: 10.1253/circj.CJ-09-0266.
    1. Mahabadi AA, Berg MH, Lehmann N, Kalsch H, Bauer M, Kara K, Dragano N, Moebus S, Jockel KH, Erbel R, et al. 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(13):1388–1395. doi: 10.1016/j.jacc.2012.11.062.
    1. Iacobellis G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat Rev Endocrinol. 2015;11(6):363–371. doi: 10.1038/nrendo.2015.58.
    1. Cavalcante JL, Tamarappoo BK, Hachamovitch R, Kwon DH, Alraies MC, Halliburton S, Schoenhagen P, Dey D, Berman DS, Marwick TH. Association of epicardial fat, hypertension, subclinical coronary artery disease, and metabolic syndrome with left ventricular diastolic dysfunction. Am J Cardiol. 2012;110(12):1793–1798. doi: 10.1016/j.amjcard.2012.07.045.
    1. Kim SA, Kim MN, Shim WJ, Park SM. Epicardial adipose tissue is related to cardiac function in elderly women, but not in men. Nutr Metab Cardiovasc Dis. 2017;27(1):41–47. doi: 10.1016/j.numecd.2016.11.001.
    1. Watanabe K, Kishino T, Sano J, Ariga T, Okuyama S, Mori H, Matsushima S, Ohtsuka K, Ohnishi H, Watanabe T. Relationship between epicardial adipose tissue thickness and early impairment of left ventricular systolic function in patients with preserved ejection fraction. Heart Vessels. 2016;31(6):1010–1015. doi: 10.1007/s00380-015-0650-8.
    1. El Khoudary SR, Shields KJ, Janssen I, Hanley C, Budoff MJ, Barinas-Mitchell E, Everson-Rose SA, Powell LH, Matthews KA. Cardiovascular Fat, menopause, and sex hormones in women: the SWAN cardiovascular fat ancillary study. J Clin Endocrinol Metab. 2015;100(9):3304–3312. doi: 10.1210/JC.2015-2110.
    1. Cho SA, Joo HJ, Cho JY, Lee SH, Park JH, Hong SJ, Yu CW, Lim DS. Visceral fat area and serum adiponectin level predict the development of metabolic syndrome in a community-based asymptomatic population. PLoS ONE. 2017;12(1):e0169289. doi: 10.1371/journal.pone.0169289.
    1. Joo HJ, Cho SA, Cho JY, Lee S, Park JH, Yu CW, Hong SJ, Lim DS. Different relationship between physical activity, arterial stiffness and metabolic status in obese subjects. J Phys Act Health. 2017;14(9):716–725. doi: 10.1123/jpah.2016-0595.
    1. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1 e14–39 e14. doi: 10.1016/j.echo.2014.10.003.
    1. Lin HH, Lee JK, Yang CY, Lien YC, Huang JW, Wu CK. Accumulation of epicardial fat rather than visceral fat is an independent risk factor for left ventricular diastolic dysfunction in patients undergoing peritoneal dialysis. Cardiovasc Diabetol. 2013;12(1):127. doi: 10.1186/1475-2840-12-127.
    1. Fernandes-Cardoso A, Santos-Furtado M, Grindler J, Ferreira LA, Andrade JL, Santo MA. Epicardial fat thickness correlates with P-wave duration, left atrial size and decreased left ventricular systolic function in morbid obesity. Nutr Metab Cardiovasc Dis. 2017;27(8):731–738. doi: 10.1016/j.numecd.2017.05.009.
    1. Maimaituxun G, Shimabukuro M, Fukuda D, Yagi S, Hirata Y, Iwase T, Takao S, Matsuura T, Ise T, Kusunose K, et al. Local thickness of epicardial adipose tissue surrounding the left anterior descending artery is a simple predictor of coronary artery disease- new prediction model in combination with framingham risk score. Circ J. 2018;82(5):1369–1378. doi: 10.1253/circj.CJ-17-1289.
    1. Hedgire S, Baliyan V, Zucker EJ, Bittner DO, Staziaki PV, Takx RA, Scholtz JE, Meyersohn N, Hoffmann U, Ghoshhajra B. Perivascular epicardial fat stranding at coronary CT angiography: a marker of acute plaque rupture and spontaneous coronary artery dissection. Radiology. 2018;287(3):808–815. doi: 10.1148/radiol.2017171568.
    1. Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nat Rev Cardiol. 2005;2(10):536. doi: 10.1038/ncpcardio0319.
    1. Evin M, Broadhouse KM, Callaghan FM, McGrath RT, Glastras S, Kozor R, Hocking SL, Lamy J, Redheuil A, Kachenoura N, et al. Impact of obesity and epicardial fat on early left atrial dysfunction assessed by cardiac MRI strain analysis. Cardiovasc Diabetol. 2016;15(1):164. doi: 10.1186/s12933-016-0481-7.
    1. Ji Q, Zhang J, Du Y, Zhu E, Wang Z, Que B, Miao H, Shi S, Qin X, Zhao Y, et al. Human epicardial adipose tissue-derived and circulating secreted frizzled-related protein 4 (SFRP4) levels are increased in patients with coronary artery disease. Cardiovasc Diabetol. 2017;16(1):133. doi: 10.1186/s12933-017-0612-9.
    1. Du Y, Ji Q, Cai L, Huang F, Lai Y, Liu Y, Yu J, Han B, Zhu E, Zhang J, et al. Association between omentin-1 expression in human epicardial adipose tissue and coronary atherosclerosis. Cardiovasc Diabetol. 2016;15:90. doi: 10.1186/s12933-016-0406-5.
    1. Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, Okamoto Y, Ohashi K, Nagaretani H, Kishida K. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation. 2003;107(5):671–674. doi: 10.1161/01.CIR.0000055188.83694.B3.
    1. Graner M, Seppala-Lindroos A, Rissanen A, Hakkarainen A, Lundbom N, Kaprio J, Nieminen MS, Pietilainen KH. Epicardial fat, cardiac dimensions, and low-grade inflammation in young adult monozygotic twins discordant for obesity. Am J Cardiol. 2012;109(9):1295–1302. doi: 10.1016/j.amjcard.2011.12.023.
    1. Turak O, Ozcan F, Canpolat U, Isleyen A, Cebeci M, Oksuz F, Mendi MA, Cagli K, Golbasi Z, Aydogdu S. Increased echocardiographic epicardial fat thickness and high-sensitivity CRP level indicate diastolic dysfunction in patients with newly diagnosed essential hypertension. Blood Press Monit. 2013;18(5):259–264. doi: 10.1097/MBP.0b013e3283651d19.
    1. Kankaanpaa M, Lehto HR, Parkka JP, Komu M, Viljanen A, Ferrannini E, Knuuti J, Nuutila P, Parkkola R, Iozzo P. Myocardial triglyceride content and epicardial fat mass in human obesity: relationship to left ventricular function and serum free fatty acid levels. J Clin Endocrinol Metab. 2006;91(11):4689–4695. doi: 10.1210/jc.2006-0584.
    1. Gaborit B, Kober F, Jacquier A, Moro PJ, Cuisset T, Boullu S, Dadoun F, Alessi MC, Morange P, Clement K, et al. Assessment of epicardial fat volume and myocardial triglyceride content in severely obese subjects: relationship to metabolic profile, cardiac function and visceral fat. Int J Obes (Lond) 2012;36(3):422–430. doi: 10.1038/ijo.2011.117.
    1. Fei J, Cook C, Blough E, Santanam N. Age and sex mediated changes in epicardial fat adipokines. Atherosclerosis. 2010;212(2):488–494. doi: 10.1016/j.atherosclerosis.2010.06.044.
    1. Kocher C, Christiansen M, Martin S, Adams C, Wehner P, Gress T, Santanam N. Sexual dimorphism in obesity-related genes in the epicardial fat during aging. J Physiol Biochem. 2017;73(2):215–224. doi: 10.1007/s13105-016-0542-0.
    1. Bolego C, Cignarella A, Staels B, Chinetti-Gbaguidi G. Macrophage function and polarization in cardiovascular disease: a role of estrogen signaling? Arterioscler Thromb Vasc Biol. 2013;33(6):1127–1134. doi: 10.1161/ATVBAHA.113.301328.
    1. Khan D, Ansar Ahmed S. The immune system is a natural target for estrogen action: opposing effects of estrogen in two prototypical autoimmune diseases. Front Immunol. 2016;6:635. doi: 10.3389/fimmu.2015.00635.
    1. Stubbins RE, Holcomb VB, Hong J, Nunez NP. Estrogen modulates abdominal adiposity and protects female mice from obesity and impaired glucose tolerance. Eur J Nutr. 2012;51(7):861–870. doi: 10.1007/s00394-011-0266-4.
    1. Wang D, Wang C, Wu X, Zheng W, Sandberg K, Ji H, Welch WJ, Wilcox CS. Endothelial dysfunction and enhanced contractility in microvessels from ovariectomized rats: roles of oxidative stress and perivascular adipose tissue. Hypertension. 2014;63(5):1063–1069. doi: 10.1161/HYPERTENSIONAHA.113.02284.
    1. Arnold AP, Cassis LA, Eghbali M, Reue K, Sandberg K. Sex hormones and sex chromosomes cause sex differences in the development of cardiovascular diseases. Arterioscler Thromb Vasc Biol. 2017;37(5):746–756. doi: 10.1161/ATVBAHA.116.307301.
    1. Sacks HS, Fain JN, Bahouth SW, Ojha S, Frontini A, Budge H, Cinti S, Symonds ME. Adult epicardial fat exhibits beige features. J Clin Endocrinol Metab. 2013;98(9):E1448–E1455. doi: 10.1210/jc.2013-1265.
    1. Pedersen SB, Bruun JM, Kristensen K, Richelsen B. Regulation of UCP1, UCP2, and UCP3 mRNA expression in brown adipose tissue, white adipose tissue, and skeletal muscle in rats by estrogen. Biochem Biophys Res Commun. 2001;288(1):191–197. doi: 10.1006/bbrc.2001.5763.
    1. Velickovic K, Cvoro A, Srdic B, Stokic E, Markelic M, Golic I, Otasevic V, Stancic A, Jankovic A, Vucetic M, et al. Expression and subcellular localization of estrogen receptors alpha and beta in human fetal brown adipose tissue. J Clin Endocrinol Metab. 2014;99(1):151–159. doi: 10.1210/jc.2013-2017.
    1. Franssens BT, Hoogduin H, Leiner T, van der Graaf Y, Visseren FLJ. Relation between brown adipose tissue and measures of obesity and metabolic dysfunction in patients with cardiovascular disease. J Magn Reson Imaging. 2017;46(2):497–504. doi: 10.1002/jmri.25594.
    1. Nam H-Y, Jun S. Association between active brown adipose tissue and coronary artery calcification in healthy men. Nuklearmedizin. 2017;56(05):184–190. doi: 10.3413/Nukmed-0887-17-03.
    1. Basurto Acevedo L, Barrera Hernández S, Fernández Muñoz MdJ, Saucedo García RP, Rodríguez Luna AK, Martínez Murillo C. An increase in epicardial fat in women is associated with thrombotic risk. Clínica e Investigación en Arteriosclerosis (English Edition); 2018.
    1. Ridker PM, Luscher TF. Anti-inflammatory therapies for cardiovascular disease. Eur Heart J. 2014;35(27):1782–1791. doi: 10.1093/eurheartj/ehu203.

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