Tanısal Egzersiz Elektrokardiyografi Testi Yapılan Hastalarda Serum Tiyol Disulfid Dengesi ve Endokan Düzeyleri

Abstract

Giriş: İnflamasyon ve oksidatif stres artmış kardiyovasküler risk ile ilişkilidir. Duke koşu bandı skoru ve kalp hızı toparlanması (KHT) gibi egzersiz elektrokardiyografi (EKG) testinden türetilen parametreler prognostik öneme sahiptir ve kardiyovasküler risk tahmini için kullanılabilir. Endokan ve tiyol/disülfid dengesi, inflamatuvar ve oksidatif durumu yansıtan yeni biyolojik belirteçlerdir. Bu çalışmanın amacı, bir egzersiz EKG testi yapılan hastalarda serum tiyol/disülfid dengesi ve endokan düzeylerini araştırmak ve bu belirteçlerin Duke treadmill skoru ve KHT ile ilişkisini değerlendirmektir.

Hastalar ve Yöntem: Tanısal egzersiz EKG testi yapılan hastalar Duke skoru ve KHT’ye göre iki gruba ayrıldı. Yüksek Duke skoru-orta/düşük Duke skoru grupları ile künt ve normal KHT grupları arasında serum endokan düzeyleri ve tiyol/disülfid dengesi karşılaştırıldı.

Bulgular: Serum endokan düzeyleri, Duke treadmill skoru ve KHT’ye göre gruplar arasında benzerdi. Tiyol /disülfid oranı, azalmış KHT’li hastalarda normal KHT’li hastalara göre anlamlı derecede düşüktü. Yüksek/Duke skoru olan hastalarda, düşük/orta Duke skoru olan hastalara göre, serum nativ tiyol düzeyleri, total tiyol düzeyleri ve total tiyol/disülfid oranı anlamlı olarak yüksekti. Doğal tiyol düzeyleri ve total tiyol düzeyleri Duke skoru ile anlamlı korelasyon göstermekteydi. Çok değişkenli regresyon analizinde, azalmış KHT’inin bağımsız öngördürücüleri hipertansiyon ve diyabet varlığı; düşük/orta Duke skorunun bağımsız öngördürücüleri ise hipertansiyon varlığı ve düşük endokan düzeyleridir.

Sonuç: Serum tiyol düzeyleri Duke skoru ile ilişkilidir ve düşük endokan seviyeleri düşük/orta Duke skoru ile ilişkilidir.

Keywords

• İnflamasyon,oksidatif stres,Duke skoru,tiyol disülfid dengesi,endokan

Serum Thiol/Disulfide Homeostasis and Endocan Levels in Patients Who Underwent Diagnostic Exercise Electrocardiography Test

Abstract

Introduction: Inflammation and oxidative stress are associated with increased risk of cardiovascular diseases. Parameters derived from exercise electrocardiography (ECG) test, such as Duke treadmill score and heart rate recovery (HRR), have prognostic importance and can be used to predict cardiovascular risk. Endocan and thiol/disulfide homeostasis are emerging biomarkers that reflect the inflammatory and oxidative status. The aim of this study was to investigate serum thiol/disulfide homeostasis and endocan levels in an exercise ECG testing patient cohort and to evaluate the association of these markers with Duke treadmill score and HRR.

Patients and Methods: Patients who underwent diagnostic exercise ECG test were divided into two groups according to Duke treadmill score and HRR. Serum endocan levels and thiol/disulfide homeostasis were compared between high and low/intermediate Duke treadmill score groups and blunted and normal HRR groups.

Results: Serum endocan levels were similar between the groups according to Duke treadmill score and HRR. Thiol/disulfide ratio was significantly lower in patients with blunted HRR than in those with normal HRR. Serum native thiol levels, total thiol levels, and total thiol/disulfide ratio were significantly elevated in patients with a high Duke treadmill score than in those with low/intermediate Duke treadmill score. Native thiol levels and total thiol levels were significantly correlated with Duke treadmill score. Multivariate regression analysis revealed that hypertension and diabetes were independent predictors of blunted HRR, whereas hypertension and low endocan levels were those of low/intermediate Duke treadmill score.

Conclusion: Serum thiol levels are correlated with Duke treadmill score, and low endocan levels are associated with low/intermediate Duke treadmill score.

Keywords

• Inflammation,oxidative stress,Duke score,heart rate recovery,thiol/disulfide homeostasis,endocan

References

1. 1. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34:2949-3003.
2. 2. Comini MA. Measurement and meaning of cellular thiol: disulphide redox status. Free Radic Res 2016;50:246-71.
3. 3. Sen CK, Packer L. Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 2000;72(Suppl 2):653S-669S.
4. 4. Turell L, Radi R, Alvarez B. The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic Biol Med 2013;65:244-53.
5. 5. Kalinina EV, Chernov NN, Novichkova MD. Role of glutathione, glutathione transferase, and glutaredoxin in regulation of redox-dependent processes. Biochemistry (Mosc) 2014;79:1562-83.
6. 6. Kondo N, Nakamura H, Masutani H, Yodoi J. Redox regulation of human thioredoxin network. Antioxid Redox Signal 2006;8:1881-90.
7. 7. Abid MR, Yi X, Yano K, Shih SC, Aird WC. Vascular endocan is preferentially expressed in tumor endothelium. Microvasc Res 2006;72:136-45.
8. 8. Sarrazin S, Adam E, Lyon M, Depontieu F, Motte V, Landolfi C, et al. Endocan or endothelial cell specific molecule-1 (ESM-1): a potential novel endothelial cell marker and a new target for cancer therapy. Biochim Biophys Acta 2006;1765:25-37.

9. 9. Ates I, Kaplan M, Inan B, Alisik M, Erel O, Yilmaz N, et al. How does thiol/disulphide homeostasis change in prediabetic patients? Diabetes Res Clin Pract 2015;110:166-71.
10. 10. Ates I, Ozkayar N, Altay M, Yilmaz FM, Topcuoglu C, Alisik M, et al. Is disulphide/thiol ratio related to blood pressure in masked hypertension? Clin Exp Hypertens 2016;38:150-4.
11. 11. Kundi H, Ates I, Kiziltunc E, Cetin M, Cicekcioglu H, Neselioglu S, et al. A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med 2015;33:1567-71.
12. 12. Celik T, Balta S, Karaman M, Ahmet Ay S, Demirkol S, Ozturk C, et al. Endocan, a novel marker of endothelial dysfunction in patients with essential hypertension: comparative effects of amlodipine and valsartan. Blood Press 2015;24:55-60.
13. 13. Kose M, Emet S, Akpinar TS, Kocaaga M, Cakmak R, Akarsu M, et al. Serum endocan level and the severity of coronary artery disease: a pilot study. Angiology 2015;66:727-31.
14. 14. Kundi H, Gok M, Kiziltunc E, Topcuoglu C, Cetin M, Cicekcioglu H, et al. The Relationship between serum endocan levels with the presence of slow coronary flow: a cross-sectional study. Clin Appl Thromb Hemost 2017;23:472-7.
15. 15. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014;47:326-32.
16. 16. Jolly MA. Exercise electrocardiographic testing. In: Griffin BP (ed). Manual of Cardiovascular Medicine. 4th ed. Philadelphia LWW: 2013:768-90.
17. 17. Chaitman BR. Exercise stress testing. In: Libby P, Bonow RO, Mann DL, Zipes DP (eds). Braunwald’s heart disease a textbook of cardiovascular medicine 8ht ed. Philadelphia: Saunders Elsevier, 2008:195-226.
18. 18. Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetiere P. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med 2005;352:1951-8.
19. 19. Mark DB, Shaw L, Harrell FE Jr, Hlatky MA, Lee KL, Bengtson JR, et al. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Engl J Med 1991;325:849-53.
20. 20. Myers J, Tan SY, Abella J, Aleti V, Froelicher VF. Comparison of the chronotropic response to exercise and heart rate recovery in predicting cardiovascular mortality. Eur J Cardiovasc Prev Rehabil 2007;14:215-21.
21. 21. Gunaydin ZY, Bektas O, Gurel YE, Karagoz A, Kaya A, Kiris T, et al. The value of the Duke treadmill score in predicting the presence and severity of coronary artery disease. Kardiol Pol 2016;74:127-34.
22. 22. Schwartz PJ, La Rovere MT, Vanoli E. Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. Circulation 1992;85(Suppl 1):I77-91.
23. 23. Palatini P. Exercise testing in asymptomatic subjects: from diagnostic test to prognostic tool? Eur Heart J 2008;29:1803-6.
24. 24. Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol 2015;71:40-56.
25. 25. Luo C, Li Y, Liu D, Hu C, Du Z. The association of brachial flow-mediated dilation and high-sensitivity C-reactive protein levels with Duke treadmill score in patients with suspected microvascular angina. Exp Clin Cardiol 2012;17:197-201.
26. 26. Yurtdas M, Yaylali YT, Aladag N, Ozdemir M, Ceylan Y, Gencaslan M, et al. Heart rate recovery after exercise and its relation with neutrophil-to-lymphocyte ratio in patients with cardiac syndrome X. Coron Artery Dis 2014;25:485-92.
27. 27. Balta S, Mikhailidis DP, Demirkol S, Ozturk C, Celik T, Iyisoy A. Endocan: A novel inflammatory indicator in cardiovascular disease? Atherosclerosis 2015;243:339-43.
28. 28. Cox LA, van Eijk LT, Ramakers BP, Dorresteijn MJ, Gerretsen J, Kox M, et al. Inflammation-induced increases in plasma endocan levels are associated with endothelial dysfunction in humans in vivo. Shock 2015;43:322-6.
29. 29. Rodrigues KF, Pietrani NT, Bosco AA, Sousa LP, Ferreira CN, Sandrim VC, et al. Endocan: a new biomarker associated with inflammation in type 2 diabetes mellitus? Diabetes Metab Res Rev 2015;31:479-80.
30. 30. Kundi H, Balun A, Cicekcioglu H, Karayigit O, Topcuoglu C, Kilinckaya MF, et al. Admission endocan level may be a useful predictor for in-hospital mortality and coronary severity index in patients with ST-segment elevation myocardial infarction. Angiology 2017;68:46-51.
31. 31. Altintas N, Mutlu LC, Akkoyun DC, Aydin M, Bilir B, Yilmaz A, et al. Effect of CPAP on new endothelial dysfunction marker, endocan, in people with obstructive sleep apnea. Angiology 2016;67:364-74.
32. 32. Cremers CM, Jakob U. Oxidant sensing by reversible disulphide bond formation. J Biol Chem 2013;288:26489-96.
33. 33. Kundi H, Erel O, Balun A, Cicekcioglu H, Cetin M, Kiziltunc E, et al. Association of thiol/disulphide ratio with syntax score in patients with NSTEMI. Scand Cardiovasc J 2015;49:95-100.
34. 34. Altiparmak IH, Erkus ME, Sezen H, Demirbag R, Kaya Z, Sezen Y, et al. Evaluation of thiol levels, thiol/disulphide homeostasis and their relation with inflammation in cardiac syndrome X. Coron Artery Dis 2016;27:295-301.