EXAMINING THE ROLE OF SUPAR AND HS-CRP LEVELS IN PREDICTING CORONARY ARTERY DISEASE SEVERITY IN ACUTE MYOCARDIAL INFARCTION: AN AGE-STRATIFIED ANALYSIS INCORPORATING SYNTAX SCORE

Year 2024, Volume: 25 Issue: 4, 365 - 378, 22.12.2024

Muhammet Salih Ateş , Abdullah Tunçez , Muhammed Ulvi Yalcin , Kenan Demir , Nazif Aygül , Behlül Bülent Altunkeser , Hüseyin Tezcan , Onur Can Polat , Aslıhan Merve Toprak , Bahadir Ozturk

https://doi.org/10.69601/meandrosmdj.1531084

Abstract

ABSTRACT
Objective: This study examines the association between traditional inflammatory biomarkers, suPAR levels in elderly and young myocardial infarction patients, and coronary artery disease severity.
Materials and Methods: In this study, 332 participants, including 227 acute myocardial infarction (AMI) patients and 107 controls, underwent evaluation through Syntax Score analysis, suPAR, and hs-CRP level assessments. AMI patients were divided into young and elderly groups based on age. Syntax Score was utilized to ascertain the severity of coronary artery disease.
Results: suPAR plasma concentrations were significantly higher in AMI patients compared to controls, with values of 2.76 (2.32-3.56) in the young MI group and 3.33 (2.43-4.41) in the elderly MI group, versus 2.33 (1.94-3.11) in the control group (p<0.001). Additionally, hs-CRP levels were notably elevated in the elderly MI groups (p<0.001). The ROC analysis identified threshold values for suPAR at 3.10 pg/mL and hs-CRP at 6.5 mg/dL to predict a Syntax Score of 23 or higher, with suPAR showing 74.7% sensitivity, 69.9% specificity, and an AUC of 0.811 (p<0.001). The sensitivity of Hs-CRP was 65.8%, the specificity was 60.2%, and the AUC was 0.700 (p<0.001).
Conclusion: Our study reveals a pivotal relationship between inflammatory markers, particularly suPAR, and Syntax Score in MI patients, suggesting its potential in refining cardiovascular risk assessment and informing future diagnostic and therapeutic approaches for coronary artery disease management.

Keywords

suPAR, Hs-CRP, Young Myocardial Infarction, Elderly Myocardial Infarction

Ethical Statement

Ethical clearance was granted by Selcuk University's Ethics Committee (Decision No: 2019/92, Date: 08.05.2019).

Supporting Institution

The study received funding support from the Selcuk University Scientific Research Projects Coordinatorship, under the project identifier 19102049.

SuPAR ve Hs-CRP Düzeylerinin Akut Miyokard Enfarktüsünde Koroner Arter Hastalığı Şiddetini Öngörmedeki Rolünün Değerlendirilmesi: Syntax Skoru ile Yaşa Göre Ayrıştırılmış Bir Analiz

Abstract

ÖZET
Amaç: Bu çalışma, yaşlı ve genç miyokard enfarktüsü hastalarında geleneksel inflamatuar biyobelirteçler ve suPAR düzeyleri ile koroner arter hastalığı şiddeti arasındaki ilişkiyi incelemektedir.
Materyal ve Metot: Çalışmada, 227 miyokard infarktüsü (MI) hastası ve 107 kontrol grubu olmak üzere toplam 332 katılımcı Syntax Skor analizi, suPAR ve hs-CRP düzeylerinin değerlendirilmesine tabi tutulmuştur. MI hastaları, yaşa göre genç ve yaşlı gruplara ayrılmıştır. Koroner arter hastalığı şiddetinin belirlenmesinde Syntax Skoru kullanılmıştır.
Bulgular: SuPAR plazma konsantrasyonları, MI hastalarında kontrol grubuna göre anlamlı derecede daha yüksek bulunmuştur; genç MI grubunda 2.76 (2.32-3.56) ve yaşlı MI grubunda 3.33 (2.43-4.41) iken, kontrol grubunda 2.33 (1.94-3.11) (p<0.001). Ayrıca, hs-CRP düzeyleri yaşlı MI grubunda belirgin şekilde yüksek bulunmuştur (p<0.001). ROC analizi, Syntax Skoru 23 veya daha yüksek olan hastaları öngörmek için suPAR için 3.10 pg/mL ve hs-CRP için 6.5 mg/dL eşik değerlerini belirlemiştir; suPAR, %74.7 duyarlılık, %69.9 özgüllük ve 0.811 AUC ile (p<0.001) anlamlı bulunmuştur. Hs-CRP'nin duyarlılığı %65.8, özgüllüğü %60.2 ve AUC'si 0.700 (p<0.001) olarak saptanmıştır.
Sonuç: Çalışmamız, özellikle suPAR olmak üzere inflamatuar belirteçler ile Syntax Skoru arasındaki önemli ilişkiyi ortaya koymakta ve bu biyomarkerlerin kardiyovasküler risk değerlendirmesini iyileştirme potansiyelini ve koroner arter hastalığı yönetiminde gelecekteki tanısal ve terapötik yaklaşımları bilgilendirme olasılığını önermektedir.

Keywords

suPAR, Hs-CRP, Genç Miyokard Enfarktüsü, Yaşlı Miyokard Enfarktüsü

References

• 1. Ong S-B, Hernández-Reséndiz S, Crespo-Avilan GE, Mukhametshina RT, Kwek X-Y, Cabrera-Fuentes HA, et al. Inflammation following acute myocardial infarction: multiple players, dynamic roles, and novel therapeutic opportunities. Pharmacol Ther 2018; 186: 73-87.
• 2. Arbel Y, Strauss BH. suPAR: A cardiac biomarker with a future? Can J Cardiol 2015; 31: 1223-4.
• 3. Baghai TC, Varallo-Bedarida G, Born C, Häfner S, Schüle C, Eser D, et al. Classical risk factors and inflammatory biomarkers: one of the missing biological links between cardiovascular disease and major depressive disorder. Int J Mol Sci 2018; 19: 1740.
• 4. Li Y, Ding Y, Zhao Y, Gui Y, Shen Y, Xiang Q. Prognostic value of soluble urokinase‐type plasminogen activator receptor in coronary artery disease: A meta‐analysis. Eur J Clin Invest 2022; 52: e13867.
• 5. Torino C, Pizzini P, Cutrupi S, Postorino M, Tripepi G, Mallamaci F, et al. Soluble urokinase plasminogen activator receptor (suPAR) and all-cause and cardiovascular mortality in diverse hemodialysis patients. Kidney international reports 2018; 3: 1100-9.
• 6. Rasmussen LJH, Petersen JEV, Eugen-Olsen J. Soluble urokinase plasminogen activator receptor (suPAR) as a biomarker of systemic chronic inflammation. Front Immunol 2021; 12: 780641.
• 7. Estreicher A, Mühlhauser J, Carpentier J-L, Orci L, Vassalli J-D. The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes. The Journal of cell biology 1990; 111: 783-92.
• 8. Thunø M, Macho B, Eugen-Olsen J. suPAR: the molecular crystal ball. Dis Markers 2009; 27: 157-72.
• 9. Wang X-Y, Zhang F, Zhang C, Zheng L-R, Yang J. The biomarkers for acute myocardial infarction and heart failure. BioMed research international 2020; 2020.
• 10. Sörensen NA, Nikorowitsch J, Neumann JT, Rübsamen N, Goßling A, Hartikainen TS, et al. Predictive value of soluble urokinase-type plasminogen activator receptor for mortality in patients with suspected myocardial infarction. Clin Res Cardiol 2019; 108: 1386-93.
• 11. Pan Y, Wang L, Xie Y, Tan Y, Chang C, Qiu X, et al. Characterization of differentially expressed plasma proteins in patients with acute myocardial infarction. J Proteomics 2020; 227: 103923.
• 12. Wlazel RN, Szwabe K, Guligowska A, Kostka T. Soluble urokinase plasminogen activator receptor level in individuals of advanced age. Sci Rep 2020; 10: 15462.
• 13. Serruys PW, Onuma Y, Garg S, Sarno G, van den Brand M, Kappetein A-P, et al. Assessment of the SYNTAX score in the Syntax study. EuroIntervention 2009; 5: 50-6.
• 14. Kul S, Akgul O, Uyarel H, Ergelen M, Kucukdagli OT, Tasal A, et al. High SYNTAX score predicts worse in-hospital clinical outcomes in patients undergoing primary angioplasty for acute myocardial infarction. Coron Artery Dis 2012; 23: 542-8.
• 15. Girasis C, Garg S, Räber L, Sarno G, Morel M-A, Garcia-Garcia HM, et al. SYNTAX score and Clinical SYNTAX score as predictors of very long-term clinical outcomes in patients undergoing percutaneous coronary interventions: a substudy of SIRolimus-eluting stent compared with pacliTAXel-eluting stent for coronary revascularization (SIRTAX) trial. Eur Heart J 2011; 32: 3115-27.
• 16. Altunova M, Karakayalı M, Kahraman S, Avcı Y, Demirci G, Sevinç S, et al. Systemic Immune-inflammatory index is associated with residual SYNTAX score in patients with st-segment elevation myocardial infarction. Anatolian Journal of Cardiology 2023; 27: 472.
• 17. Castellon X, Bogdanova V. Chronic inflammatory diseases and endothelial dysfunction. Aging Dis 2016; 7: 81.
• 18. Corban MT, Prasad A, Nesbitt L, Loeffler D, Herrmann J, Lerman LO, et al. Local production of soluble urokinase plasminogen activator receptor and plasminogen activator inhibitor‐1 in the coronary circulation is associated with coronary endothelial dysfunction in humans. Journal of the American Heart Association 2018; 7: e009881.
• 19. Hindy G, Tyrrell DJ, Vasbinder A, Wei C, Presswalla F, Wang H, et al. Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis. The Journal of clinical investigation 2022; 132.
• 20. Goodchild TT, Li Z, Lefer DJ. Soluble urokinase plasminogen activator receptor: From biomarker to active participant in atherosclerosis and cardiovascular disease. The Journal of Clinical Investigation 2022; 132.
• 21. Zaghloul A, Al-Bukhari TA, Al-Pakistani HA, Shalaby M, Halawani SH, Bajuaifer N, et al. Soluble endothelial protein C receptor and high sensitivity C reactive protein levels as markers of endothelial dysfunction in patients with type 1 and type 2 diabetes mellitus: their role in the prediction of vascular complications. Diabetes Res Clin Pract 2014; 106: 597-604.
• 22. Maio R, Perticone M, Suraci E, Sciacqua A, Sesti G, Perticone F. Endothelial dysfunction and C‐reactive protein predict the incidence of heart failure in hypertensive patients. ESC Heart Failure 2021; 8: 399-407.
• 23. Niknezhad N, Haghighatkhah HR, Zargari O, Ghalamkarpour F, Younespour S, Niknejad N, et al. High‐sensitivity C‐reactive protein as a biomarker in detecting subclinical atherosclerosis in psoriasis. Dermatol Ther 2020; 33: e13628.
• 24. Swastini DA, Wiryanthini IAD, Ariastuti NLP, Muliantara A. Atherosclerosis prediction with high sensitivity C-reactive protein (hs-CRP) and related risk factor in patient with dyslipidemia. Open access Macedonian journal of medical sciences 2019; 7: 3887.
• 25. Yu H, Rifai N. High-sensitivity C-reactive protein and atherosclerosis: from theory to therapy. Clin Biochem 2000; 33: 601-10.
• 26. Rezk A, Sarhan M, Elmoghl A. Highly-Sensitive C-reactive Protein Level and its Association with Intermediate and High Syntax Score in cases of Acute Coronary Syndrome. The Egyptian Journal of Hospital Medicine 2019; 75: 2064-70.
• 27. Karadeniz M, Duran M, Akyel A, Yarlıoğlueş M, Öcek AH, Çelik İE, et al. High sensitive CRP level is associated with intermediate and high syntax score in patients with acute coronary syndrome. Int Heart J 2015; 56: 377-80.
• 28. Lyngbæk S, Marott JL, Møller DV, Christiansen M, Iversen KK, Clemmensen PM, et al. Usefulness of soluble urokinase plasminogen activator receptor to predict repeat myocardial infarction and mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention. The American journal of cardiology 2012; 110: 1756-63.
• 29. Suberviola B, Castellanos-Ortega A, Ruiz Ruiz A, Lopez-Hoyos M, Santibañez M. Hospital mortality prognostication in sepsis using the new biomarkers suPAR and proADM in a single determination on ICU admission. Intensive Care Med 2013; 39: 1945-52.
• 30. Persson M, Engström G, Björkbacka H, Hedblad B. Soluble urokinase plasminogen activator receptor in plasma is associated with incidence of CVD. Results from the Malmö Diet and Cancer Study. Atherosclerosis 2012; 220: 502-5.
• 31. Eapen DJ, Manocha P, Ghasemzadeh N, Patel RS, Al Kassem H, Hammadah M, et al. Soluble urokinase plasminogen activator receptor level is an independent predictor of the presence and severity of coronary artery disease and of future adverse events. Journal of the American heart association 2014; 3: e001118.
• 32. Botha S, Fourie CM, Schutte R, Eugen-Olsen J, Schutte AE. Soluble urokinase plasminogen activator receptor and hypertension among black South Africans after 5 years. Hypertens Res 2015; 38: 439-44.
• 33. Tahhan AS, Hayek SS, Sandesara P, Hajjari J, Hammadah M, O'Neal WT, et al. Circulating soluble urokinase plasminogen activator receptor levels and peripheral arterial disease outcomes. Atherosclerosis 2017; 264: 108-14.
• 34. Persson M, Östling G, Smith G, Hamrefors V, Melander O, Hedblad B, et al. Soluble urokinase plasminogen activator receptor: a risk factor for carotid plaque, stroke, and coronary artery disease. Stroke 2014; 45: 18-23.
• 35. Yusuf S, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. The lancet 2004; 364: 937-52.
• 36. Pilote L, Karp I. GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary SYndrome). Am Heart J 2012; 163: 741-6. e2.
• 37. Spatz ES, Curry LA, Masoudi FA, Zhou S, Strait KM, Gross CP, et al. The variation in recovery: role of gender on outcomes of young AMI patients (VIRGO) classification system: a taxonomy for young women with acute myocardial infarction. Circulation 2015; 132: 1710-8.
• 38. Lichtman JH, Lorenze NP, D'Onofrio G, Spertus JA, Lindau ST, Morgan TM, et al. Variation in recovery: role of gender on outcomes of young AMI patients (VIRGO) study design. Circ Cardiovasc Qual Outcomes 2010; 3: 684-93.
• 39. Gao H, Wang Y, Shen A, Chen H, Li H. Acute myocardial infarction in young men under 50 years of age: clinical characteristics, treatment, and long-term prognosis. Int J Gen Med 2021: 9321-31.
• 40. Peters SA, Muntner P, Woodward M. Sex differences in the prevalence of, and trends in, cardiovascular risk factors, treatment, and control in the United States, 2001 to 2016. Circulation 2019; 139: 1025-35.