Association of Plasminogen Activator Inhibitor-1 and Cardiovascular Events Development in Patients with Prediabetes
DOI:
https://doi.org/10.3889/oamjms.2021.6825Keywords:
Plasminogen activator inhibitor-1, Cardiovascular event, Prediabetes, Endothelial dysfunctionAbstract
Background. Plasminogen activator inhibitor-1(PAI-1) is a marker of endothelial dysfunction(ED) and a predictor of both the development of type 2 diabetes mellitus, and a cardiovascular event(CVE). Its role in the CVE development was sufficiently studied in patients without carbohydrate metabolism disorders, and understudied in patients with prediabetes.
Aim: the research interest is the study of PAI-1 in patients with prediabetes and its effect on the CVE development.
Materials and methods. The case-control study of 168 patients aged from 18 to 65 was carried out among the local population from January to December 2019.
After clinical examination, patients were divided into 3 groups: group 1 (n=55)– patients with prediabetes and with CVE; group 2 (n=93) - patients with prediabetes and without CVE; the control group n=20.
Results. Differences in PAI-1 level were found in groups 1 (Me=30718.6 pg/ml) and 2 (Me=24692.0 pg/ml; p≤0.001), even greater differences were found in both groups compared to the control one (p≤0.001).
The correlation analysis has found in both group influence such IR indicators as fasting glucose, IR-HOMA index, glucagon, C-peptide to elevation of PAI-1. These findings indicate that with an elevation of the PAI-1 level, the concentration of fasting glucose, glucagon, C-peptide and scores of IR-HOMA index increase in both group.
The Binary regression analysis has demonstrated, that an elevation of the PAI-1 biomarker increases the likelihood of CVE by 3.3 fold in patients with prediabetes (p≤0.01). In addition to, a model has been derived for assessing the risk of cardiovascular events in patients with prediabetes.
Conclusions. Elevation of PAI-1 concentration is associated with insulin resistance which leads to ED, and further development risk of CVE in patients with prediabetes.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Cardiovascular Deseases. World Health Organization. Key Facts; 2017. Available from: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds). [Last accessed on 2021 Feb 01].
World Health Organization. Health of the Population of the Republic of Kazakhstan and the Activities of Health Organizations in 2017/Stat. Astana, Kazakhstan: World Health Organization; 2018. p. 354.
Adeva-Andany MM, Martínez-Rodríguez J, González-Lucán M. Insulin resistance is a cardiovascular risk factor in humans. Diabetes Metab Syndr. 2019;13(2):1449-55. https://doi.org/10.1016/j.dsx.2019.02.023 PMid:31336505
Kannel WB, McGee DL. Diabetes and cardiovascular risk factors: The Framingham study. Circulation. 1979;59(1):8-13. https://doi.org/10.1161/01.cir.59.1.8 PMid:758126
Selvin E, Steffes MW, Brancati FL. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med. 2010;362(9):800-11. https://doi.org/10.1056/nejmoa0908359 PMid:20200384
Janus A, Szahidewicz-Krupska E, Mazur G, Doroszko A. Insulin resistance and endothelial dysfunction constitute a common therapeutic target in cardiometabolic disorders. Mediators Inflamm. 2016;2016:3634948. https://doi.org/10.1155/2016/3634948 PMid:27413253
Somodi S, Seres I, Lőrincz H, Harangi M, Fülöp P, Paragh G. Plasminogen activator inhibitor-1 level correlates with lipoprotein subfractions in obese nondiabetic subjects. Int J Endocrinol. 2018;2018:9596054. https://doi.org/10.1155/2018/9596054 PMid:30002679
Lalić K, Nedeljković M, Jotić A, Babić R, Rajković N, Popović L, et al. Endothelial dysfunction of coronary arteries in subjects without diabetes: An association with both insulin resistance and impaired insulin secretion response. Diabetes Res Clin Pract. 2018;139:179-87. https://doi.org/10.1016/j.diabres.2018.03.005 PMid:29526680
Natali A, Toschi E, Baldeweg S, Ciociaro D, Favilla S, Sacca L, et al. Clustering of insulin resistance with vascular dysfunction and low-grade inflammation in Type 2 diabetes. Diabetes. 2006;55(4):1133-40. https://doi.org/10.2337/diabetes.55.04.06.db05-1076 PMid:16567539
Ford MA, McConnell JP, Lavi S, Rihal CS, Prasad A, Sandhu GS, et al. Coronary artery endothelial dysfunction is positively correlated with low density lipoprotein and inversely correlated with high density lipoprotein subclass particles measured by nuclear magnetic resonance spectroscopy. Atherosclerosis. 2009;207(1):111-5. https://doi.org/10.1016/j.atherosclerosis.2009.04.039 PMid:19515370
Adly AA, Elbarbary NS, Ismail EA, Hassan SR. Plasminogen activator inhibitor-1 (PAI-1) in children and adolescents with Type 1 diabetes mellitus: relation to diabetic micro-vascular complications and carotid intima media thickness. J Diabetes Complications. 2014;28(3):340-7. https://doi.org/10.1016/j.jdiacomp.2014.01.011 PMid:24581943
Tretjakovs P, Jurka A, Bormane I, Mikelsone I, Elksne K, Krievina G, et al. Circulating adhesion molecules, matrix metalloproteinase-9, plasminogen activator inhibitor-1, and myeloperoxidase in coronary artery disease patients with stable and unstable angina. Clin Chim Acta. 2012;413(1-2):25-9. https://doi.org/10.1016/j.cca.2011.10.009 PMid:22024218
Festa A, D’Agostino R Jr., Tracy RP, Haffner SM. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of Type 2 diabetes: The insulin resistance atherosclerosis study. Diabetes. 2002;51(4):1131-7. https://doi.org/10.2337/diabetes.51.4.1131 PMid:11916936
Festa A, Williams K, Tracy RP, Wagenknecht LE, Haffner SM. Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident Type 2 diabetes. Circulation. 2006;113(14):1753-9. https://doi.org/10.1161/circulationaha.106.616177 PMid:16585388
American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care. 2017;40(1):S11-24. https://doi.org/10.2337/dc17-s005 PMid:27979889
Summary of the 2007 European society of hypertension (ESH) and European society of cardiology (ESC) guidelines for the management of arterial hypertension. Vasc Health Risk Manag. 2007;3(6):783-95. https://doi.org/10.1080/08037050701461084 PMid:18200799
Firdaus M, Asbury JM, Reynolds DW. A new paradigm of cardiovascular risk factor modification. Vasc Health Risk Manage. 2005;1(2):101-9. https://doi.org/10.2147/vhrm.1.2.101.64078 PMid:17315396
Jung RG, Motazedian P, Ramirez FD, Simard T, Santo PD, Visintini S, et al. Association between plasminogen activator inhibitor-1 and cardiovascular events: A systematic review and meta-analysis. Thromb J. 2018;16:12. https://doi.org/10.1186/s12959-018-0166-4 PMid:29991926
Bastelica D, Morange P, Berthet B, Bordhi H, Lacroix O, Grino M, et al. Stromal cells are the main plasminogen activator inhibitor- 1-producing cells in human fat: Evidence of differences between visceral and subcutaneous deposits. Arterioscler Thromb Vasc Biol. 2002;22(1):173-8. https://doi.org/10.1161/hq0102.101552 PMid:11788479
Pandolfi A, Cetrullo D, Polishuck R, Alberta MM, Calafiore A, Pellegrini G, et al. Plasminogen activator inhibitor Type 1 is increased in the arterial wall of Type II diabetic subjects. Arterioscler Thromb Vasc Biol. 2001;21(8):1378-82. https://doi.org/10.1161/hq0801.093667 PMid:11498469
Maiello M, Boeri D, Podesta F, Cagliero E, Vichi M, Odetti P, et al. Increased expression of tissue plasminogen activator and its inhibitor and reduced fibrinolytic potential of human endothelial cells cultured in elevated glucose. Diabetes. 1992;41:1009-15. https://doi.org/10.2337/diab.41.8.1009 PMid:1628760
Chen YQ, Su M, Walia RR, Hao Q, Cowington JW, Vaughan DE. Sp1 sites mediate activation of the plasminogen activator inhibitor-1 promoter by glucose in vascular smooth muscle cells. J Biol Chem. 1998;273:8225-31. https://doi.org/10.1074/ jbc.273.14.8225 PMid:9525928
Wersh JW, Westerkuts LW, Venekamp WJ. Glycometabolic control and fibrinolysis in diabetic patients. Haemostasis. 1990;20:241-50. https://doi.org/10.1159/000216134 PMid:2242825
Davì G, Belvedere M, Vigneri S, Catalano I, Giammarresi C, Roccaforte S, et al. Influence of metabolic control on thromboxane biosynthesis and plasma plasminogen activator inhibitor Type-I in non-insulin-dependent-diabetes. Thromb Haemost. 1996;76:34-7. https://doi.org/10.1055/s-0038-1650518 PMid:8819248
Sobel BE. Increased plasminogen activator inhibitor-1 and vasculopathy: A reconcilable paradox. Circulation. 1999;99:2496-8. https://doi.org/10.1161/01.cir.99.19.2496
Erzen B, Sabovic M. In young post-myocardial infarction male patients elevated plasminogen activator inhibitor-1 correlates with insulin resistance and endothelial dysfunction. Heart Vessels. 2013;28:570-7. https://doi.org/10.1007/s00380-012-0287-9 PMid:23001714
D’Agostino RB Sr., Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care. The Framingham heart study. Circulation. 2008;117(6):743-53. https://doi.org/10.1161/circulationaha.107.699579 PMid:18212285
European Guidelines on CVD Prevention in Clinical Practice 2016 Eur J Prev Cardiol. 2016;23(11):1-96. https://doi.org/10.1177/2047487316653709 PMid: 27353126
Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA guideline on the prevention of cardiovascular disease: A report of the American college of cardiology and American heart association task force on clinical practice guidelines. Circulation. 2019;140(11):e563-95. https://doi.org/10.1161/cir.0000000000000725 PMid:30879355
Zhang L, Qiao Q, Tuomilehto J, Hammar N, Alberti KG, Eliasson M, et al, DECODE Study Group. Blood lipid levels in relation to glucose status in European men and women without a prior history of diabetes: The DECODE Study. Diabetes Res Clin Pract. 2008;82(3):364-77. https://doi.org/10.1016/j.diabres.2008.08.022 PMid:18922596
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2020 Yelena Laryushina, Viktoriya Parakhina, Lyudmila Turgunova, Dinara Sheryazdanova, Raushan Dosmagambetova, Anar Turmukhambetova, Olga Ponamareva, Maria Orbetzova (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)
