Blood Adipokins in Young People with Early Ischemic Heart Disease on the Background of Abdominal Obesity

Aim      To study blood adipokines spectrum in people aged 25–44 years with early ischemic heart disease (IHD), including that associated with abdominal obesity (AO).

Material and methods  A cross-sectional study was performed on a random sample of the population aged 25–44 years in Novosibirsk. 1457 subjects (653 men, 804 women) were evaluated. This study included 123 people divided into four study subgroups: subgroup 1, with IHD associated with AO (n=24); subgroup 2, with IHD and without AO (n=25); subgroup 3, without IHD and with AO (n=44); and subgroup 4, without either IHD or AO (n=30). Concentrations of serum adipokines were measured simultaneously by multiplex assay with a Luminex MAGPIX flow fluorometer and by immune enzyme assay with a MULTISCAN analyzer.

Results Subjects with early IHD had lower blood concentrations of adipsin and visfatin than subjects without IHD. Subjects with early IHD associated with AO had higher blood concentrations of adipsin, plasminogen activator inhibitor-1, and leptin and lower concentrations of monocyte chemoattractant protein-1 (MCP-1) and visfatin compared to subjects with early IHD and without AO. The multivariate logistic regression analysis showed that lower blood concentrations of MCP-1 were associated with a likelihood of early IHD.

Conclusion      In young people aged 25–44 years, lower blood concentrations of MCP-1 were associated with a likelihood of early IHD, including that associated with AO.

1. Roth GA, Huffman MD, Moran AE, Feigin V, Mensah GA, Naghavi M et al. Global and Regional Patterns in Cardiovascular Mortality From 1990 to 2013. Circulation. 2015;132(17):1667–78. DOI: 10.1161/CIRCULATIONAHA.114.008720

2. Andreenko E.Yu., Yavelov I.S., Loukianov M.M., Vernohaeva A.N., Drapkina O.M., Boytsov S.A. Ischemic Heart Disease in Subjects of Young Age: Current State of the Problem: Prevalence and Cardio-Vascular Risk Factors. Kardiologiia. 2018;58(10):53–8. DOI: 10.18087/cardio.2018.10.10184

3. Krzysztoszek J, Laudańska-Krzemińska I, Bronikowski M. Assessment of epidemiological obesity among adults in EU countries. Annals of Agricultural and Environmental Medicine. 2019;26(2):341–9. DOI: 10.26444/aaem/97226

4. Neeland IJ, Ross R, Després J-P, Matsuzawa Y, Yamashita S, Shai I et al. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. The Lancet Diabetes & Endocrinology. 2019;7(9):715–25. DOI: 10.1016/S2213-8587(19)30084-1

5. Chait A, den Hartigh LJ. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Frontiers in Cardiovascular Medicine. 2020;7:22. DOI: 10.3389/fcvm.2020.00022

6. Kwaifa IK, Bahari H, Yong YK, Noor SM. Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications. Biomolecules. 2020;10(2):291. DOI: 10.3390/biom10020291

7. Francisco V, Pino J, Gonzalez-Gay MA, Mera A, Lago F, Gómez R et al. Adipokines and inflammation: is it a question of weight? Obesity and inflammatory diseases. British Journal of Pharmacology. 2018;175(10):1569–79. DOI: 10.1111/bph.14181

8. Ragino YI, Stakhneva EM, Polonskaya YV, Kashtanova EV. The Role of Secretory Activity Molecules of Visceral Adipocytes in Abdominal Obesity in the Development of Cardiovascular Disease: A Review. Biomolecules. 2020;10(3):374. DOI: 10.3390/biom10030374

9. Ha EE, Bauer RC. Emerging Roles for Adipose Tissue in Cardiovascular Disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 2018;38(8):e137–44. DOI: 10.1161/ATVBAHA.118.311421

10. Carbone S, Canada JM, Billingsley HE, Siddiqui MS, Elagizi A, Lavie CJ. Obesity paradox in cardiovascular disease: where do we stand? Vascular Health and Risk Management. 2019;15:89–100. DOI: 10.2147/VHRM.S168946

11. Dutheil F, Gordon BA, Naughton G, Crendal E, Courteix D, Chaplais E et al. Cardiovascular risk of adipokines: a review. Journal of International Medical Research. 2018;46(6):2082–95. DOI: 10.1177/0300060517706578

12. Otelea MR, Streinu-Cercel A, Băicus C, Maria Nitescu M. The Adipokine Profile and the Cardiometabolic Risk in Non-Obese Young Adults. Balkan Medical Journal. 2019;36(3):155–61. DOI: 10.4274/balkanmedj.galenos.2018.2018.0789

13. Pello AM, Cristóbal C, Tarín N, Huelmos A, Aceña Á, Carda R et al. Differential profile in inflammatory and mineral metabolism biomarkers in patients with ischemic heart disease without classical coronary risk factors. Journal of Cardiology. 2015;66(1):22–7. DOI: 10.1016/j.jjcc.2014.11.006

14. Yu F, Li J, Huang Q, Cai H. Increased Peripheral Blood Visfatin Concentrations May Be a Risk Marker of Coronary Artery Disease: A Meta-Analysis of Observational Studies. Angiology. 2018;69(9):825–34. DOI: 10.1177/0003319718771125

15. Ohtsuki T, Satoh K, Shimizu T, Ikeda S, Kikuchi N, Satoh T et al. Identification of Adipsin as a Novel Prognostic Biomarker in Patients With Coronary Artery Disease. Journal of the American Heart Association. 2019;8(23):e013716. DOI: 10.1161/JAHA.119.013716

16. Tafere GG, Wondafrash DZ, Zewdie KA, Assefa BT, Ayza MA. Plasma Adipsin as a Biomarker and Its Implication in Type 2 Diabetes Mellitus. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2020;13:1855–61. DOI: 10.2147/DMSO.S253967

17. Lo JC, Ljubicic S, Leibiger B, Kern M, Leibiger IB, Moede T et al. Adipsin Is an Adipokine that Improves β Cell Function in Diabetes. Cell. 2014;158(1):41–53. DOI: 10.1016/j.cell.2014.06.005

18. Yarmolinsky J, Bordin Barbieri N, Weinmann T, Ziegelmann PK, Duncan BB, Schmidt MI. Plasminogen activator inhibitor-1 and type 2 diabetes: a systematic review and meta-analysis of observational studies. Scientific Reports. 2016;6(1):17714. DOI: 10.1038/srep17714

19. Smits MM, Woudstra P, Utzschneider KM, Tong J, Gerchman F, Faulenbach M et al. Adipocytokines as features of the metabolic syndrome determined using confirmatory factor analysis. Annals of Epidemiology. 2013;23(7):415–21. DOI: 10.1016/j.annepidem.2013.03.001

20. Tofler GH, Massaro J, O’Donnell CJ, Wilson PWF, Vasan RS, Sutherland PA et al. Plasminogen activator inhibitor and the risk of cardiovascular disease: The Framingham Heart Study. Thrombosis Research. 2016;140:30–5. DOI: 10.1016/j.thromres.2016.02.002

21. Meltzer ME, Doggen CJM, de Groot PG, Rosendaal FR, Lisman T. Plasma levels of fibrinolytic proteins and the risk of myocardial infarction in men. Blood. 2010;116(4):529–36. DOI: 10.1182/blood-2010-01-263103

22. Singh M, Bedi US, Singh PP, Arora R, Khosla S. Leptin and the clinical cardiovascular risk. International Journal of Cardiology. 2010;140(3):266–71. DOI: 10.1016/j.ijcard.2009.07.019

23. Sierra-Johnson J, Romero-Corral A, Lopez-Jimenez F, Gami AS, Sert Kuniyoshi FH, Wolk R et al. Relation of Increased Leptin Concentrations to History of Myocardial Infarction and Stroke in the United States Population. The American Journal of Cardiology. 2007;100(2):234–9. DOI: 10.1016/j.amjcard.2007.02.088

24. Kappelle PJWH, Dullaart RPF, van Beek AP, Hillege HL, Wolffenbuttel BHR. The plasma leptin/adiponectin ratio predicts first cardiovascular event in men: A prospective nested case–control study. European Journal of Internal Medicine. 2012;23(8):755–9. DOI: 10.1016/j.ejim.2012.06.013

25. Auguet T, Aragonès G, Guiu-Jurado E, Berlanga A, Curriu M, Martinez S et al. Adipo/cytokines in atherosclerotic secretomes: increased visfatin levels in unstable carotid plaque. BMC cardiovascular disorders. 2016;16(1):149. DOI: 10.1186/s12872-016-0320-5

26. Zheng L-Y, Xu X, Wan R-H, Xia S, Lu J, Huang Q. Association between serum visfatin levels and atherosclerotic plaque in patients with type 2 diabetes. Diabetology & Metabolic Syndrome. 2019;11(1):60. DOI: 10.1186/s13098-019-0455-5

27. Bremer AA, Devaraj S, Afify A, Jialal I. Adipose Tissue Dysregulation in Patients with Metabolic Syndrome. The Journal of Clinical Endocrinology & Metabolism. 2011;96(11):E1782–8. DOI: 10.1210/jc.2011-1577

28. Arner E, Mejhert N, Kulyte A, Balwierz PJ, Pachkov M, Cormont M et al. Adipose Tissue MicroRNAs as Regulators of CCL2 Production in Human Obesity. Diabetes. 2012;61(8):1986–93. DOI: 10.2337/db11-1508

29. Amano SU, Cohen JL, Vangala P, Tencerova M, Nicoloro SM, Yawe JC et al. Local Proliferation of Macrophages Contributes to Obesity-Associated Adipose Tissue Inflammation. Cell Metabolism. 2014;19(1):162–71. DOI: 10.1016/j.cmet.2013.11.017

30. Inouye KE, Shi H, Howard JK, Daly CH, Lord GM, Rollins BJ et al. Absence of CC Chemokine Ligand 2 Does Not Limit Obesity-Associated Infiltration of Macrophages Into Adipose Tissue. Diabetes. 2007;56(9):2242–50. DOI: 10.2337/db07-0425

31. Cranford TL, Enos RT, Velázquez KT, McClellan JL, Davis JM, Singh UP et al. Role of MCP-1 on inflammatory processes and metabolic dysfunction following high-fat feedings in the FVB/N strain. International Journal of Obesity. 2016;40(5):844–51. DOI: 10.1038/ijo.2015.244