SOME FIBRINOLYTIC PARAMETERS IN CORONARY ARTERY DISEASE PATIENTS: FOCUS ON UNSTABLE ANGINA SUBGROUPS
Abstract
Background and aim. Unstable angina is classified into new-onset, progressive, and angina at rest. Though hemostasis plays a crucial role in the pathogenesis of coronary artery disease, including unstable angina, limited data exist regarding peculiarities of fibrinolytic parameters in the above-mentioned types of unstable angina. Our study aims to investigate if there is a difference in the fibrinolytic state between the groups of patients with new-onset, progressive unstable angina in comparison with stable angina patients depending on medical history data, electrocardiographic and hemodynamic features.
Materials and methods. In our cross-sectional study, we recruited 93 coronary artery disease patients (mean age 62.32 (6.94) years, 41 males (44.1%)). They were divided into 3 groups: stable angina patients (n=22) (control), new-onset unstable angina patients (n=21), and progressive unstable angina patients (n=50). The groups were comparable by baseline characteristics. Blood samples were obtained before treatment onset. The concentrations of tissue plasminogen activator and inhibitor of plasminogen activator (type 1) were measured by the ELISA method. We registered 14 points at the admission department, particularly age, sex, body mass index, smoking, presence of the family history of cardiovascular disorders, ST-segment depression, T-wave variability, arrhythmias, left bundle branch blockage, heart rate, systolic and diastolic blood pressure, Sokolov-Lyon voltage criteria, and unstable angina type (new-onset or progressive). After comparison of fibrinolytic parameters’ concentrations among groups under investigation, we defined the main independent predictors among observed 14 parameters to create optimal regression models for assessment of fibrinolytic parameters concentrations.
Results and conclusion. The groups under investigation differ significantly in concentration of tissue plasminogen activator (P<0.001) and inhibitor of plasminogen activator (type 1) (P<0.001). The tissue plasminogen activator concentration correlated significantly with ST depression (r=0.344, P=0.001), T wave variability (r=-0.233, P=0.02), systolic blood pressure (r=-0.675, P<0.001), diastolic blood pressure (r=-0.655, P<0.001), heart rate (r=-0.568, P<0.001) and clinical unstable angina subgroups (r=-0.706, P<0.001) as well as plasminogen activator inhibitor (type 1) concentration associated with age (r=-0.560, P<0.001), body mass index (r=-0.249, P=0.049), ST-segment depression (r=0.542, P<0.001), arrhythmia (r=0.210, P=0.03), systolic blood pressure (r=0.310, P=0.04), and clinical unstable angina subgroups (r=-0.406, P<0.001). An optimal regression models for tissue plasminogen activator and its inhibitor assessment included systolic blood pressure, heart rate, unstable angina subgroup (R2adj. = 65.0%, P<0.001) and systolic blood pressure, unstable angina subgroup (R2adj. = 42.7%, P<0.001), respectively. Thus, fibrinolytic state among unstable angina clinical types differs significantly independently on observed baseline clinical, electrocardiographic and hemodynamic parameters. This finding confirms the utility of Braunwald unstable angina classification.
Downloads
References
Hajar R. Coronary Heart Disease: From Mummies to 21st Century. Heart Views. 2017;18(2):68‐74. doi: 10.4103/HEARTVIEWS.HEARTVIEWS_57_17
Brown RA, Shantsila E, Varma C, Lip GY. Current Understanding of Atherogenesis. Am J Med. 2017;130(3):268‐282. doi: 10.1016/j.amjmed.2016.10.022
Nowbar AN, Gitto M, Howard GP, Francis DP, Al-Lamee R. Mortality from ischemic heart disease. Circulation: Cardiovascular Quality and Outcomes. 2019;12(6). Retrieved from: https://www.ahajournals.org/doi/10.1161/CIRCOUTCOMES.118.005375 doi: 10.1161/CIRCOUTCOMES.118.005375
Khan MA, Hashim MJ, Mustafa H, Baniyas MY, Al Suwaidi SKBM, AlKatheeri R, et al. Global Epidemiology of Ischemic Heart Disease: Results from the Global Burden of Disease Study. Cureus. 2020;12(7):e9349. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/32742886/ doi: 10.7759/cureus.9349
Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C. ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407-477. doi: 10.1093/eurheartj/ehz425
Collet JP, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL, et al. ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2020:ehaa575. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/32860058/ doi: 10.1093/eurheartj/ehaa575
Manning P, Awtry EH. Unstable Angina: Presentation, Diagnosis, and Management. Encyclopedia of Cardiovascular Research and Medicine. 2018:606-615. Retrieved from: https://www.sciencedirect.com/science/article/pii/B9780128096574997503?via%3Dihub doi: 10.1016/B978-0-12-809657-4.99750-3
Andrews JPM, Fayad ZA, Dweck MR. New methods to image unstable atherosclerotic plaques. Atherosclerosis. 2018;272(5):118-128. doi: 10.1016/j.atherosclerosis.2018.03.021
Acara AC, Bolatkale M. Endothelial Nitric Oxide Level as a Predictor of Coronary Complexity in Patients With Unstabe Angina Pectoris. Am J Med Sci. 2019;357(6):453-460. doi: 10.1016/j.amjms.2019.02.011
Cioni G, Abouzaki NA, Jovin IS. Chapter 10 – Acute Coronary Syndrome: Thrombotic Lesions in Patients With Unstable Angina. Cardiovascular Thrombus. From Pathology and Clinical Presentations to Imaging, Pharmacotherapy and Interventions. Academic Press. 2018. pp. 147-161. Retrieved from: https://www.sciencedirect.com/science/article/pii/B9780128126158000107?via%3Dihub doi: 10.1016/B978-0-12-812615-8.00010-7
Basra SS, Virani SS, Paniagua D, Kar B, Jneid H. Acute Coronary Syndromes: Unstable Angina and Non-ST Elevation Myocardial Infarction. Heart Fail Clin. 2016;12(1):31-48. doi: 10.1016/j.hfc.2015.08.004
Braunwald E. Unstable angina: A Classification. Circulation. 1989;80(2):410-414. doi: 10.1161/01.CIR.80.2.410
Jia S, Yuan J. A re-evaluation of unstable angina braunwald classification in Chinese patients undergoing percutaneous coronary intervention. Heart. 2018;104:Article A26 Retrieved from: https://heart.bmj.com/content/104/Suppl_7/A26 doi: 10.1136/heartjnl-2018-ICS.35
Oikonomou E, Siasos G, Tsigkou V. Coronary Artery Disease and Endothelial Dysfunction: Novel Diagnostic and Therapeutic Approaches. Curr Med Chem. 2020;27(7):1052‐1080. doi: 10.2174/0929867326666190830103219
Brainin P, Frestad D, Prescott E. The prognostic value of coronary endothelial and microvascular dysfunction in subjects with normal or non-obstructive coronary artery disease: A systematic review and meta-analysis. Int J Cardiol. 2018;254:1‐9. doi: 10.1016/j.ijcard.2017.10.052
Gue YX, Gorog DA. Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation. Int J Mol Sci. 2017;18(9):1850. Retrieved from: https://www.mdpi.com/1422-0067/18/9/1850 doi: 10.3390/ijms18091850
Sillen M, Declerck PJ. Targeting PAI-1 in Cardiovascular Disease: Structural Insights Into PAI-1 Functionality and Inhibition. Front Cardiovasc Med. 2020;7:622473. Retrieved from: https://www.frontiersin.org/articles/10.3389/fcvm.2020.622473/full doi: 10.3389/fcvm.2020.622473
Tsujimoto T, Kajio H. Thrombotic/ Thrombolytic Balance as a Cardiac Treatment Determinant in Patients With Diabetes Mellitus and Coronary Artery Disease. J Am Heart Assoc. 2019;8(2):e011207. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497335/ doi: 10.1161/JAHA.118.011207
Lin H, Xu L, Yu S. Therapeutics targeting the fibrinolytic system. Exp Mol Med. 2020;52:367–379. doi: 10.1038/s12276-020-0397-x
Liu T, Han C, Sun L. Association between new circulating proinflammatory and anti-inflammatory adipocytokines with coronary artery disease. Coron Artery Dis. 2019;30(7):528‐535. doi:10.1097/MCA.0000000000000778
Asada Y, Sato Y, Hatakeyama K. Pathophysiology of atherothrombosis: Mechanisms of thrombus formation on disrupted atherosclerotic plaques. Pathol Int. 2020;70(6):309-322. doi: 10.1111/pin.12921
Juhan-Vague I, Pyke SD, Alessi MC, Jespersen J, Haverkate F, Thompson SG. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation. 1996;94(9):2057-2063. doi: 10.1161/01.cir.94.9.2057
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):1378-1382. doi: 10.1161/hq0801.093667
Heyman SN, Hanna Z, Nassar T, Shina A, Akkawi S, Goldfarb M, et al. The fibrinolytic system attenuates vascular tone: effects of tissue plasminogen activator (tPA) and aminocaproic acid on renal microcirculation. Br J Pharmacol. 2004;141(6):971-978. doi: 10.1038/sj.bjp.0705714
Dolan JM, Sim FJ, Meng H, Kolega J. Endothelial cells express a unique transcriptional profile under very high wall shear stress known to induce expansive arterial remodeling. Am J Physiol Cell Physiol. 2012;302(8):C1109-1118. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/22173868/ doi: 10.1152/ajpcell.00369.2011
Amelirad A, Shamsasenjan K, Akbarzadehlaleh P, Pashoutan Sarvar D. Signaling Pathways of Receptors Involved in Platelet Activation and Shedding of These Receptors in Stored Platelets. Adv Pharm Bull. 2019;9(1):38-47. doi: 10.15171/apb.2019.005
Liu W, Jiang L, Chen J, Gao C, Zhou J, Zhou J, et al. Association of adipokines with blood pressure, arterial elasticity and cardiac markers in dialysis patients: cross-sectional analysis of baseline data from a cohort study. Nutr Metab (Lond). 2017;14:34. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/22173868/ doi: 10.1186/s12986-017-0185-3
Braunwald E, Morrow DA. Unstable angina: is it time for a requiem? Circulation. 2013;127(24):2452-2457. doi: 10.1161/CIRCULATIONAHA.113.001258
Bilgic Gazioglu S, Akan G, Atalar F, Erten G. PAI-1 and TNF-α profiles of adipose tissue in obese cardiovascular disease patients. Int J Clin Exp Pathol. 2015;8(12):15919‐15925. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730077/
InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. Coronary artery disease: Overview. 2013 Feb 13 [Updated 2017 Jul 27]. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK355313/
Poggesi A, Pasi M, Pescini F, Pantoni L, Inzitari D. Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review. J Cereb Blood Flow Metab. 2016;36(1):72‐94. doi: 10.1038/jcbfm.2015.116
Liu T, Han C, Sun L. Association between new circulating pro-inflammatory and anti-inflammatory adipocytokines with coronary artery disease. Coron Artery Dis. 2019;30(7):528‐535. doi: 10.1097/MCA.0000000000000778
Copyright (c) 2021 Eastern Ukrainian Medical Journal
This work is licensed under a Creative Commons Attribution 4.0 International License.