The relationship of epicardial obesity and levels of cardiac fibrosis markers

Lipotoxic myocardial damage with its fibrosis and subsequent formation of heart failure may develop due to epicardial obesity (EO). The possibility of early diagnosis of lipotoxic cardiac fibrosis is not well understood.

Aim. To study the relationship of EO with the level of myocardial fibrosis markers.

Material and methods. The study included 80 men aged 54,3±8,2 with grades I-III obesity. The level of metabolic factors, pro-inflammatory cytokines, adipokines (adiponectin, leptin), soluble leptin receptor and free fatty acids was determined for all patients; the presence of EO was determined by echocardiography with epicardial fat thickness (EFT) ≥7 mm. Coronary artery disease, arterial hypertension, type 2 diabetes mellitus, the presence of left ventricular diastolic dysfunction were the exclusion criteria of the study.

Results. The patients were divided into 2 groups: group I with EO (n=49) and group II without EO (n=31). Group I showed a statistically significant increase in the levels of interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-α (TNF-α), leptin, a decrease in adiponectin, as well as an increase in all studied myocardial fibrosis markers. In addition, in the group with EO, a positive relationship between the EFT and TNF-α (r=0,29; p=0,041), IL-6 (r=0,28; p=0,049), leptin (r=0,41; p=0,004) and a negative relationship with the level of adiponectin (r=-0,29; p=0,042). We determine a significant effect of the degree of EO on the increase in the level of cardiac fibrosis markers (r=0,28, p=0,049), collagen (r=0,33, p=0,019), transforming growth factor-β (r=0,29, p=0,045).

Conclusion. The results suggest that elevated levels of profibrotic factors in patients with EO may be signs of the presence of preclinical, and therefore, earlier lipotoxic myocardial fibrosis, which was not detected during echocardiographic research in the form of diastolic dysfunction.

1. Izaola O, de Luis D, Sajoux I, et al. Inflammation and obesity (lipoinflammation). Nutr Hosp. 2015;31(6):2352-8. doi:10.3305/nh.2015.31.6.8829.

2. Murtazalieva PM, Karelkina EV, Shishkova AA, et al. Pilot project “Improvement of medical care for patients with chronic heart failure”: results of the first stage. Russ J Cardiol. 2018;23(12):44-50 (In Russ.) doi:10.15829/1560-4071-2018-12-44-51.

3. Packer M. Epicardial Adipose Tissue May Mediate Deleterious Effects of Obesity and Inflammation on the Myocardium. J Am Coll Cardiol. 2018;71(20):2360-72. doi:10.1016/j.jacc.2018.03.509.

4. Ouchi N, Parker JL, et al. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85-97. doi:10.1038/nri2921.

5. Wu D, Li L, Wu LL. Research Progress of Adipokines in Cardiac FibrosisSheng Li Ke Xue Jin Zhan. 2015;46(6):401-7.

6. Donoso MA, Muñoz-Calvo MT, Barrios V, et al. Increased leptin/adiponectin ratio and free leptin index are markers of insulin resistance in obese girls during pubertal development. Horm Res Paediatr. 2013;80(5):363-70. doi:10.1159/000356046.

7. Iacobellis G, Willens HJ. Echocardiographic Epicardial Fat: A Review of Research and Clinical Applications. JASE 2009;22(12):1311-9. doi:10.1016/j.echo.2009.10.013.

8. Chumakova GA, Veselovskaya NG, Ott AV, et al. Epicardial obesity and a range of metabolic risk factors relation with the prevalence index of coronary atherosclerosis. Cardiovascular Therapy and Prevention. 2015;14(2):35-40. (In Russ.) doi:10.15829/1728-8800-2015-2-35-40.

9. Xu Y, Cheng X, Hong K, et al. How to interpret epicardial adipose tissue as a cause of coronary artery disease: a metaanalysis. Coron Artery Dis. 2012;23:227-33. doi:10.1097/MCA.0b013e328351ab2c.

10. Drapkina OM, Emelyanov IM. Fibrosis and atrial fibrillation — mechanisms and Arterial’naya Gipertenziya (Arterial Hypertension). 2013;19(6):487-94. (In Russ.) doi:10.18705/1607-419X-2013-19-6-487-494.

11. Muñoz-Durango N, Fuentes CA, Castillo AE, et al. Role of the Renin-AngiotensinAldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension. Int J Mol Sci. 2016;17(7):797. doi:10.3390/ijms17070797.

12. Neilan TG, Coelho-Filho OR, Danik SB, et al. Cmr quantification of myocardial scar provides additive prognostic information in nonischemic cardiomyopathy. JACC. Cardiovascular imaging. 2013; 6:944-54. doi:10.1016/j.jcmg.2013.05.013.

13. Chumakova GA, Veselovskaya NG. Clinical significance of visceral obesity. Moscow: GEOTAR-Media 2016. р 155 (In Russ.) ISBN 978-5-9704-3988-3.

14. Gritsenko OV, Chumakova GA, Shevlyakov IV, Trubina EV. The mechanisms of heart failure development in obesity. Russian Journal of Cardiology. 2018;(5):81-6. (In Russ.) doi:10.15829/1560-4071-2018-5-81-86.