Relationship Between Syntax Score and Cystatin C in Patients with Acute Coronary Syndrome

Abstract

Introduction: The SYNTAX (SYNergy between PCI with TAXUS and Cardiac Surgery) score (SS) is an angiographic scoring system to determine the severity of coronary artery disease (CAD). As far as we know, studies examining the relationship between SYNTAX Score and Cystatin C (Cys-C) are limited in the literature. In this study, we aimed to investigate the relationship between Cys-C level and SS in patients presenting with ST-elevation myocardial infarction (STEMI). Patients and Methods: One hundred ninety-two patients who underwent coronary angiography for STEMI between June 2021 and December 2021 in our center were included in the study. The patients were divided into two groups according to their SS values: Group 1 included patients with SS< 22, and Group 2 included patients with SS≥ 22. The two groups were compared in terms of baseline characteristics and serum Cys-C levels. Results: Patients in Group 2 had significantly higher Cys-C levels than those in Group 1 (1.7 ± 0.53 vs 1.3 ± 0.29; p= 0.006). In the correlation analysis, SS showed a positive correlation with the Cys-C level (r= 0.189, p= 0.015). Multivariate logistic regression analysis showed that Cys-C level was an independent predictor of high SS (β= 0.306, p= 0.006). When receiver operating characteristic (ROC) curve analysis was performed, the optimal cut-off value of Cys-C to predict severe coronary artery disease (indicating high SS) was Cys-C≥1.56, which was predictive for severe coronary artery disease with 74% sensitivity and 72% specificity [area under the curve (AUC)= 0.745, 95% confidence interval (CI)= 0.624-0.835, p< 0.001). Conclusion: Cystatin C levels are independently associated with high SS in STEMI patients. In summary, our findings show that Cys-C is a promising clinical biomarker that can be used to assess the severity of coronary artery lesions, potentially providing additional information to established risk markers.

Keywords

• Syntax score
• cystatin C
• ST-elevation myocardial infarction

References

1. 1. Malakar AK, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S. A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol 2019;234:16812-23. [Crossref]
2. 2. Ferguson TW, Komenda P, Tangri N. Cystatin C as a biomarker for estimating glomerular filtration rate. Curr Opin Nephrol Hypertens 2015;24:295-300. [Crossref]
3. 3. van der Laan SW, Fall T, Soumaré A, Teumer A, Sedaghat S, Baumert J, et all. Cystatin C and cardiovascular disease: A Mendelian randomization study. J Am Coll Cardiol 2016;68:934-45. [Crossref]
4. 4. Levin A, Lan JH. Cystatin C and cardiovascular disease: Causality, association, and clinical implications of knowing the difference. J Am Coll Cardiol 2016;68:946-8. [Crossref]
5. 5. Shlofmitz E, Kuku KO, Waksman R, Garcia-Garcia HM. Intravascular ultrasound-guided drug-eluting stent implantation. Minerva Cardioangiol 2019;67(4):306-17. [Crossref]
6. 6. Medical Advisory Secretariat. Intravascular ultrasound to guide percutaneous coronary interventions: An evidence-based analysis. Ont Health Technol Assess Ser 2006;6:1-97.
7. 7. Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, et al. The SYNTAX score: An angiographic tool grading the complexity of coronary artery disease. EuroIntervention 2005;1:219-27.
8. 8. Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020;41:255-323. [Crossref]

9. 9. Jones NR, McCormack T, Constanti M, McManus RJ. Diagnosis and management of hypertension in adults: NICE guideline update 2019. Br J Gen Pract 2020;70:90-1. [Crossref]
10. 10. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119-77. [Crossref]
11. 11. Kern M. What is the SYNTAX score and how should we use it? Cath Lab Digest 2009;17:(8).
12. 12. Nakamura M. Angiography is the gold standard and objective evidence of myocardial ischemia is mandatory if lesion severity is questionable. - Indication of PCI for angiographically significant coronary artery stenosis without objective evidence of myocardial ischemia (Pro)-. Circ J 2011;75:204-10. [Crossref]
13. 13. Bundhun PK, Sookharee Y, Bholee A, Huang F. Application of the SYNTAX score in interventional cardiology: A systematic review and meta-analysis. Medicine (Baltimore) 2017;96:7410 [Crossref]
14. 14. Safarian H, Alidoosti M, Shafiee A, Salarifar M, Poorhosseini H, Ne matipour E. The SYNTAX score can predict major adverse cardiac events following percutaneous coronary intervention. Heart views 2014;15:99-105. [Crossref]
15. 15. Singh RB, Mengi SA, Xu YJ, Arneja AS, Dhalla NS. Pathogenesis of atherosclerosis: A multifactorial process. Exp Clin Cardiol 2002;7:40-53
16. 16. Kleber ME, Goliasch G, Grammer TB, Pilz S, Tomaschitz A, Silbernagel G, et al. Evolving biomarkers improve prediction of long-term mortality in patients with stable coronary artery disease: the BIO-VILCAD score. J Intern Med 2014;276:184-94. [Crossref]
17. 17. Jernberg T, Lindahl B, James S, Larsson A, Hansson LO, Wallentin L. Cystatin C: A novel predictor of outcome in suspected or confirmed non-ST-elevation acute coronary syndrome. Circulation 2004;110:2342-8. [Crossref]
18. 18. Negrusz-Kawecka M, Poręba R, Hulok A, Sciborski K, Marczak J, Bańkowski T. Evaluation of the significance of cystatin C levels in patients suffering from coronary artery disease. Adv Clin Exp Med 2014;23:551-8. [Crossref]
19. 19. Koc M, Batur MK, Karaarslan O, Abali G. Clinical utility of serum cystatin C in predicting coronary artery disease. Cardiol J 2010;17:374-80.
20. 20. Ichimoto E, Jo K, Kobayashi Y, Inoue T, Nakamura Y, Kuroda N, et al. Prognostic significance of cystatin C in patients with ST-elevation myocardial infarction. Circ J 2009;73:1669-73. [Crossref]
21. 21. Yang H, Zhang L, Xu CH. Use of the SYNTAX Score II to predict mortality in interventional cardiology: A systematic review and meta-analysis. Medicine (Baltimore) 2019;98:e14043. [Crossref]
22. 22. Chichareon P, Onuma Y, van Klaveren D, Modolo R, Kogame N, Takahashi K, et al. Validation of the updated logistic clinical SYNTAX score for all-cause mortality in the GLOBAL LEADERS trial. EuroIntervention 2019;15:e539-e546. [Crossref]
23. 23. Woitas RP, Kleber ME, Meinitzer A, Grammer TB, Silbernagel G, Pilz S, et al. Cystatin C is independently associated with total and cardiovascular mortality in individuals undergoing coronary angiography. The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Atherosclerosis 2013;229:541-8. [Crossref]
24. 24. Pan J, Sun X, Zhang P, Chen H, Lin J. Relationship between serum cystatin-C and coronary lesion severity in coronary artery disease patients with a normal glomerular filtration rate. J Int Med Res 2021;49:300060520985639. [Crossref]
25. 25. Lee M, Saver JL, Huang WH, Chow J, Chang KH, Ovbiagele B. Impact of elevated cystatin C level on cardiovascular disease risk in predominantly high cardiovascular risk populations: A meta-analysis. Circ Cardiovasc Qual Outcomes 2010;3:675-83. [Crossref]
26. 26. Yang S, Song L, Zhao L, Dong P, Lai L, Wang H. Predictive value of cystatin C in people with suspected or established coronary artery disease: A meta-analysis. Atherosclerosis 2017;263:60-7. [Crossref]
27. 27. Ristiniemi N, Lund J, Tertti R, Christensson A, Ilva T, Porela P, et al. Cystatin C as a predictor of all-cause mortality and myocardial infarction in patients with non-ST-elevation acute coronary syndrome. Clin Biochem 2012;45:535-40. [Crossref]
28. 28. Niccoli G, Conte M, Della Bona R, Altamura L, Siviglia M, Dato I, et al. Cystatin C is associated with an increased coronary atherosclerotic burden and a stable plaque phenotype in patients with ischemic heart disease and normal glomerular filtration rate. Atherosclerosis 2008;198:373-80. [Crossref]
29. 29. Zi M, Xu Y. Involvement of cystatin C in immunity and apoptosis. Immunol Lett 2018;196:80-90. [Crossref]
30. 30. Popović P, Dincić D, Popović-Milatović A, Banović T, Drasković-Pavlović B. Imunski i inflamatorni aspekti ateroskleroze [Immunologic and inflammatory aspects of atherosclerosis]. Vojnosanit Pregl 2000;57:89-98.
31. 31. Nasonov EL, Paniukova EV, Aleksandrova EN. S-reaktivnyĭ belok--marker vospaleniia pri ateroskleroze (novye dannye) [C-reactive protein--marker of inflammation in atherosclerosis (new data)]. Kardiologiia 2002;42:53-62.
32. 32. Bengtsson E, To F, Grubb A, Håkansson K, Wittgren L, Nilsson J, et al. Absence of the protease inhibitor cystatin C in inflammatory cells results in larger plaque area in plaque regression of apoE-deficient mice. Atherosclerosis 2005;180:45-53. [Crossref]
33. 33. Liu J, Sukhova GK, Sun JS, Xu WH, Libby P, Shi GP. Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol 2004;24:1359-66. [Crossref]
34. 34. Ge C, Ren F, Lu S, Ji F, Chen X, Wu X. Clinical prognostic significance of plasma cystatin C levels among patients with acute coronary syndrome.Clin Cardiol 2009;32:644-8. [Crossref]
35. 35. Windhausen F, Hirsch A, Fischer J, van der Zee PM, Sanders GT, van Straalen JP, et al. Cystatin C for enhancement of risk stratification in non-ST elevation acute coronary syndrome patients with an increased troponin T. Clin Chem 2009;55:1118-25. [Crossref]
36. 36. Yang H, Wang C, Guo M, Zhou Y, Feng Z, Yin Z. Correlations between peroxisome proliferator activator receptor γ, cystatin C, or advanced oxidation protein product, and atherosclerosis in diabetes patients. Pathol Res Pract 2015;211:235-9. [Crossref]
37. 37. Bengtsson E, To F, Grubb A, Håkansson K, Wittgren L, Nilsson J, et al. Absence of the protease inhibitor cystatin C in inflammatory cells results in larger plaque area in plaque regression of apoE-deficient mice. Atherosclerosis 2005;180:45-53. [Crossref]
38. 38. Qi L, Liu H, Cheng L, Cui C, Chen X, Yang S, et al. Impact of renal insufficiency on prognosis of patients with acute coronary syndrome. Int J Gen Med 2021;14:8919-8927. [Crossref]
39. 39. Arboix A, Miguel M, Císcar E, García-Eroles L, Massons J, Balcells M. Cardiovascular risk factors in patients aged 85 or older with ischemic stroke. Clin Neurol Neurosurg 2006;108:638- 43. [Crossref]
40. 40. Kaneko R, Sawada S, Tokita A, Honkura R, Tamura N, Kodama S, et al. Serum cystatin C level is associated with carotid arterial wall elasticity in subjects with type 2 diabetes mellitus: A potential marker of early-stage atherosclerosis. Diabetes Res Clin Pract 2018;139:43-51. [Crossref]