Effect of Revascularization on Exercise-Induced Changes in Cardiac and Prothrombotic Biomarkers in Patients with Coronary Artery Disease

C H Hansen, J Cwikiel, V Bratseth, H Arnesen, A Flaa, I Seljeflot, C H Hansen, J Cwikiel, V Bratseth, H Arnesen, A Flaa, I Seljeflot

Abstract

We examined whether resting levels and exercise-induced changes during exercise ECG stress test (EST) of cardiac Troponin T (cTnT), NT-proBNP and prothrombotic markers were affected by revascularization in patients with coronary artery disease (CAD).EST1 was performed before coronary angiography and revascularization, and patients (n = 20) with confirmed CAD, performed another EST (EST2) 9 weeks later. Blood samples were drawn at rest and within five min after termination of ESTs.cTnT and NT-proBNP increased during exercise at both ESTs (p < 0.001, all). Resting cTnT levels at EST2 versus EST1 were significantly higher (p = 0.02) whereas NT-proBNP did not differ. At both visits, increased D-dimer (p = 0.008 and <0.001), pro-thrombin fragment 1 + 2 (p = 0.009 and 0.001) and tissue factor pathway inhibitor (TFPI) (p < 0.001 and 0.001) during exercise were demonstrated. Resting levels of endogenous thrombin potential (ETP) and TFPI were reduced at EST2 versus EST1 (p < 0.01).Revascularization did not affect exercise-induced release of cardiac and prothrombotic biomarkers and did not reduce resting levels of cTnT or NT-proBNP, suggesting revascularization per se not to prevent secretion of biomarkers. The lower resting levels of ETP and TFPI after revascularization may however, be indicative of reduced thrombin generation and endothelial activation.Clinicaltrials.gov, CADENCE, NCT01495091 https://ichgcp.net/clinical-trials-registry/NCT01495091?term = 01495091&draw = 2&rank = 1.

Keywords: D-dimer; ETP; TFPI; cardiac troponin T; coronary artery disease; exercise stress test; prothrombin fragment 1  +  2.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Resting (dark grey) and exercise induced (light grey) Troponin T (upper panel) and NT-proBNP (lower panel) levels at both examinations.

References

    1. Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med. 1999;340(2):115-126.
    1. Lusis AJ. Atherosclerosis. Nature. 2000;407(6801):233-241.
    1. de Lemos JA, Drazner MH, Omland T, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010;304(22):2503-2512.
    1. Roos A, Bandstein N, Lundbäck M, Hammarsten O, Ljung R, Holzmann MJ. Stable high-sensitivity cardiac troponin T levels and outcomes in patients with chest pain. J Am Coll Cardiol. 2017;70(18):2226-2236.
    1. Omland T, de Lemos JA, Sabatine MS, et al. A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med. 2009;361(26):2538-2547.
    1. Beatty AL, Ku IA, Christenson RH, DeFilippi CR, Schiller NB, Whooley MA. High-sensitivity cardiac troponin T levels and secondary events in outpatients with coronary heart disease from the Heart and Soul Study. JAMA Intern Med. 2013;173(9):763-769.
    1. Hammadah M, Al Mheid I, Wilmot K, et al. Association between high-sensitivity cardiac troponin levels and myocardial ischemia during mental stress and conventional stress. JACC Cardiovasc Imaging. 2018;11(4):603-611.
    1. Daniels LB, Maisel AS. Natriuretic peptides. J Am Coll Cardiol. 2007;50(25):2357-2368.
    1. Lindholm D, Lindbäck J, Armstrong PW, et al. Biomarker-Based risk model to predict cardiovascular mortality in patients with stable coronary disease. J Am Coll Cardiol. 2017;70(7):813-826.
    1. Mishra RK, Beatty AL, Jaganath R, Regan M, Wu AH, Whooley MA. B-type natriuretic peptides for the prediction of cardiovascular events in patients with stable coronary heart disease: the Heart and Soul Study. J Am Heart Assoc. 2014;3(4).
    1. Ndrepepa G, Braun S, Schulz S, et al. Sensitive troponin and N-terminal probrain natriuretic peptide in stable angina. Eur J Clin Invest. 2011;41(10):1054-1062.
    1. Middleton N, Shave R, George K, et al. Impact of repeated prolonged exercise bouts on cardiac function and biomarkers. Med Sci Sports Exerc. 2007;39(1):83-90.
    1. Skadberg Ø, Kleiven Ø, Bjørkavoll-Bergseth M, et al. Highly increased troponin I levels following high-intensity endurance cycling may detect subclinical coronary artery disease in presumably healthy leisure sport cyclists: The North Sea Race Endurance Exercise Study (NEEDED) 2013. Eur J Prev Cardiol. 2017;24(8):885-894.
    1. Womack CJ, Nagelkirk PR, Coughlin AM. Exercise-induced changes in coagulation and fibrinolysis in healthy populations and patients with cardiovascular disease. Sports Med. 2003;33(11):795-807.
    1. Posthuma JJ, van der Meijden PE, Ten Cate H, Spronk HM. Short- and long-term exercise induced alterations in haemostasis: a review of the literature. Blood Rev. 2015;29(3):171-178.
    1. Acil T, Atalar E, Sahiner L, et al. Effects of acute exercise on fibrinolysis and coagulation in patients with coronary artery disease. Int Heart J. 2007;48(3):277-285.
    1. Cwikiel J, Seljeflot I, Fagerland MW, et al. High-sensitive cardiac Troponin T and exercise stress test for evaluation of angiographically significant coronary disease. Int J Cardiol. 2019;287:1-6.
    1. Tveit SH, Cwikiel J, Myhre PL, et al. Differential associations of cardiac troponin T and cardiac troponin I with coronary artery pathology and dynamics in response to short-duration exercise. Clin Biochem. 2021;88:23-29.
    1. Cwikiel J, Seljeflot I, Arnesen H, Berge E, Flaa A. Increase in Cardiac Biomarkers During Exercise Stress Test in Patients with Angiographically Verified Coronary Artery Disease. ESC; 2018.
    1. Cwikiel J, Seljeflot I, Berge E, et al. Pro-coagulant activity during exercise testing in patients with coronary artery disease. Thromb J. 2017;15(3).
    1. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377-381.
    1. Laufer EM, Mingels AM, Winkens MH, et al. The extent of coronary atherosclerosis is associated with increasing circulating levels of high sensitive cardiac troponin T. Arterioscler Thromb Vasc Biol. 2010;30(6):1269-1275.
    1. Ahmed W, Schlett CL, Uthamalingam S, et al. Single resting hsTnT level predicts abnormal myocardial stress test in acute chest pain patients with normal initial standard troponin. JACC Cardiovasc Imaging. 2013;6(1):72-82.
    1. Magnoni M, Masson S, Andreini D, et al. Usefulness of high-sensitivity cardiac troponin T for the identification of outlier patients with diffuse coronary atherosclerosis and low-risk factors. Am J Cardiol. 2016;117(9):1397-1404.
    1. Williams SG, Stables RH, Wright DJ, Taylor S, Thompson D, Tan LB. Relationship of serum cardiac markers following successful percutaneous coronary intervention and subsequent exercise capacity in patients with chronic stable angina: a pilot study. Cardiology. 2005;103(2):63-67.
    1. Kurz K, Giannitsis E, Zehelein J, Katus HA. Highly sensitive cardiac troponin T values remain constant after brief exercise- or pharmacologic-induced reversible myocardial ischemia. Clin Chem. 2008;54(7):1234-1238.
    1. Sabatine MS, Morrow DA, de Lemos JA, Jarolim P, Braunwald E. Detection of acute changes in circulating troponin in the setting of transient stress test-induced myocardial ischaemia using an ultrasensitive assay: results from TIMI 35. Eur Heart J. 2009;30(2):162-169.
    1. Røsjø H, Kravdal G, Høiseth AD, et al. Troponin I measured by a high-sensitivity assay in patients with suspected reversible myocardial ischemia: data from the akershus cardiac examination (ACE) 1 study. Clin Chem. 2012;58(11):1565-1573.
    1. Axelsson A, Ruwald MH, Dalsgaard M, Rossing K, Steffensen R, Iversen K. Serial measurements of high-sensitivity cardiac troponin T after exercise stress test in stable coronary artery disease. Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals. 2013;18(4):304-309.
    1. Kawabe M, Sato A, Hoshi T, Endo M, Yoshida I, Aonuma K. Incremental value of B-type natriuretic peptide for detection and risk reclassification of obstructive coronary artery disease on computed tomography angiography. J Cardiol. 2017;69(4):671-677.
    1. Singh HS, Bibbins-Domingo K, Ali S, Wu AH, Schiller NB, Whooley MA. N-terminal pro-B-type natriuretic peptide and inducible ischemia in the heart and soul study. Clin Cardiol. 2009;32(8):447-453.
    1. Asada J, Tsuji H, Iwasaka T, Thomas JD, Lauer MS. Usefulness of plasma brain natriuretic peptide levels in predicting dobutamine-induced myocardial ischemia. Am J Cardiol. 2004;93(6):702-704.
    1. Hall C. Essential biochemistry and physiology of (NT-pro)BNP. Eur J Heart Fail. 2004;6(3):257-260.
    1. Van Hylckama Vlieg A, Callas PW, Cushman M, Bertina RM, Rosendaal FR. Inter-relation of coagulation factors and d-dimer levels in healthy individuals. J Thromb Haemost. 2003;1(3):516-522.
    1. Sang Y, Roest M, de Laat B, de Groot PG, Huskens D. Interplay between platelets and coagulation. Blood Rev. 2021;46:100733.
    1. van Paridon PCS, Panova-Noeva M, van Oerle R, et al. Relation between tissue factor pathway inhibitor activity and cardiovascular risk factors and diseases in a large population sample. Thromb Haemost. 2021;121(2):174-181.
    1. Bratseth V, Pettersen A, Opstad TB, Arnesen H, Seljeflot I. Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment. Thromb J. 2012;10(1):12.

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