Online first
Original Article
Published online: 2023-09-26

open access

Page views 455
Article views/downloads 242
Get Citation

Connect on Social Media

Connect on Social Media

Diagnostic value of soluble urokinase‐type plasminogen activator receptor in patients with acute coronary syndrome: A systematic review and meta-analysis

Michal Pruc12, Iwona Jannasz3, Damian Swieczkowski4, Grzegorz Procyk5, Aleksandra Gasecka5, Zubaid Rafique6, Francesco Chirico7, Nicola Luigi Bragazzi8, Milosz J. Jaguszewski9, Jaroslaw Wysocki10, Lukasz Szarpak61112
Pubmed: 37772350


Background: In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS. Methods: A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used if I2 < 50%; otherwise, the random-effects model was performed. Results: Five studies with 3417 participants were included in the meta-analysis. Pooled analysis showed that mean suPAR levels in the ACS group were statistically significantly higher than in the control group (3.56 ± 1.38 vs. 2.78 ± 0.54 ng/mL, respectively; mean difference: 1.04; 95% confidence interval: 0.64–1.44; I2 = 99%; p < 0.001). Conclusions: In the context of acute coronary syndrome, suPAR is a potential biomarker for the early identification of medical conditions in individuals who are being treated in emergency rooms.

Article available in PDF format

View PDF Download PDF file


  1. Bhatt DL, Lopes RD, Harrington RA. Diagnosis and treatment of acute coronary syndromes: a review. JAMA. 2022; 327(7): 662–675.
  2. Sarkees ML, Bavry AA. Acute coronary syndrome (unstable angina and non-ST elevation MI). BMJ Clin Evid. 2009; 2009.
  3. Montalescot G, Dallongeville J, Van Belle E, et al. STEMI and NSTEMI: are they so different? 1 year outcomes in acute myocardial infarction as defined by the ESC/ACC definition (the OPERA registry). Eur Heart J. 2007; 28(12): 1409–1417.
  4. Hamm CW, Bassand JP, Agewall S. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011; 32: 2999–3054.
  5. Ibanez B, James S, Agewall S, et al. 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(2): 119–177.
  6. Reichlin T, Hochholzer W, Bassetti S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med. 2009; 361(9): 858–867.
  7. Thygesen K, Alpert J, Jaffe A, et al. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018; 138(20): e618–e651.
  8. D'Souza M, Sarkisian L, Saaby L, et al. Diagnosis of unstable angina pectoris has declined markedly with the advent of more sensitive troponin assays. Am J Med. 2015; 128(8): 852–860.
  9. Brush JE, Kaul S, Krumholz HM. Troponin testing for clinicians. J Am Coll Cardiol. 2016; 68(21): 2365–2375.
  10. Daubert MA, Jeremias A. The utility of troponin measurement to detect myocardial infarction: review of the current findings. Vasc Health Risk Manag. 2010; 6: 691–699.
  11. Zimodro JM, Gasecka A, Jaguszewski M, et al. Role of copeptin in diagnosis and outcome prediction in patients with heart failure: a systematic review and meta-analysis. Biomarkers. 2022; 27(8): 720–726.
  12. Bruins Slot MHE, Reitsma JB, Rutten FH, et al. Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction: a systematic review and meta-analysis. Heart. 2010; 96(24): 1957–1963.
  13. Keller T, Tzikas S, Zeller T, et al. Copeptin improves early diagnosis of acute myocardial infarction. J Am Coll Cardiol. 2010; 55(19): 2096–2106.
  14. Szarpak L, Lapinski M, Gasecka A, et al. Performance of copeptin for early diagnosis of acute coronary syndromes: a systematic review and meta-analysis of 14,139 patients. J Cardiovasc Dev Dis. 2021; 9(1): 6.
  15. Qiao XR, Zheng T, Xie Y, et al. MiR-146a rs2910164 (G/C) polymorphism is associated with the development and prognosis of acute coronary syndromes: an observational study including case control and validation cohort. J Transl Med. 2023; 21(1): 325.
  16. Masoodi Khabar P, Ghydari ME, Vazifeh Shiran N, et al. Platelet microRNA-484 as a novel diagnostic biomarker for acute coronary syndrome. Lab Med. 2023; 54(3): 256–261.
  17. Gager GM, Eyileten C, Postuła M, et al. Expression patterns of MiR-125a and MiR-223 and their association with diabetes mellitus and survival in patients with non-st-segment elevation acute coronary syndrome. Biomedicines. 2023; 11(4).
  18. Ling H, Guo Z, Shi Y, et al. Serum exosomal microRNA-21, microRNA-126, and PTEN are novel biomarkers for diagnosis of acute coronary syndrome. Front Physiol. 2020; 11: 654.
  19. Grodzka O, Procyk G, Gąsecka A. The role of microRNAs in myocarditis-what can we learn from clinical trials? Int J Mol Sci. 2022; 23(24).
  20. Procyk G, Klimczak-Tomaniak D, Sygitowicz G, et al. Circulating and platelet micrornas in cardiovascular risk assessment and antiplatelet therapy monitoring. J Clin Med. 2022; 11(7).
  21. Martinez-Arroyo O, Ortega A, Flores-Chova A, et al. High miR-126-3p levels associated with cardiovascular events in a general population. Eur J Intern Med. 2023; 113: 49–56.
  22. Choi YY, Kim A, Lee Y, et al. The miR-126-5p and miR-212-3p in the extracellular vesicles activate monocytes in the early stage of radiation-induced vascular inflammation implicated in atherosclerosis. J Extracell Vesicles. 2023; 12(5): e12325.
  23. Hodges GW, Bang CN, Wachtell K, et al. suPAR: a new biomarker for cardiovascular disease? Can J Cardiol. 2015; 31(10): 1293–1302.
  24. Yudkin JS, Kumari M, Humphries SE, et al. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2000; 148(2): 209–214.
  25. Backes Y, van der Sluijs KF, Mackie DP, et al. Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review. Intensive Care Med. 2012; 38(9): 1418–1428.
  26. Sidenius N, Andolfo A, Fesce R, et al. Urokinase regulates vitronectin binding by controlling urokinase receptor oligomerization. J Biol Chem. 2002; 277(31): 27982–27990.
  27. Thunø M, Macho B, Eugen-Olsen J. suPAR: the molecular crystal ball. Dis Markers. 2009; 27(3): 157–172.
  28. Matuszewski M, Ładny J, Rafique Z, et al. Prediction value of soluble urokinase plasminogen activator receptor (suPAR) in COVID-19 patients - a systematic review and meta-analysis. Ann Agric Environ Med. 2023; 30(1): 142–147.
  29. Lyngbæk S, Marott JL, Sehestedt T, et al. Cardiovascular risk prediction in the general population with use of suPAR, CRP, and Framingham Risk Score. Int J Cardiol. 2013; 167(6): 2904–2911.
  30. Chenevier-Gobeaux C, Lemarechal H, Doumenc B, et al. Prognostic value of soluble urokinase plasminogen activator receptor in patients presenting to the emergency department with chest pain suggestive of acute coronary syndrome. Clin Biochem. 2021; 92: 19–24.
  31. Canto JG, Shlipak MG, Rogers WJ, et al. Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain. JAMA. 2000; 283(24): 3223–3229.
  32. Rouan GW, Lee TH, Cook EF, et al. Clinical characteristics and outcome of acute myocardial infarction in patients with initially normal or nonspecific electrocardiograms (a report from the Multicenter Chest Pain Study). Am J Cardiol. 1989; 64(18): 1087–1092.
  33. Page M, McKenzie J, Bossuyt P, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71.
  34. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010; 25(9): 603–605.
  35. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005; 5: 13.
  36. Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011; 343: d5928.
  37. Can Ü, Yerlikaya F, Toker A, et al. Serum level of suPAR and YKL-40, a new biomarker in patients with acute myocardial infarction? Acta Med Anatol. 2015; 3(4): 137.
  38. Nikorowitsch J, Borchardt T, Appelbaum S, et al. Cardio-Renal biomarker soluble urokinase-type plasminogen activator receptor is associated with cardiovascular death and myocardial infarction in patients with coronary artery disease independent of troponin, C-reactive protein, and renal function. J Am Heart Assoc. 2020; 9(8): e015452.
  39. Schernthaner C, Lichtenauer M, Wernly B, et al. Multibiomarker analysis in patients with acute myocardial infarction. Eur J Clin Invest. 2017; 47(9): 638–648.
  40. Sörensen NA, Nikorowitsch J, Neumann JT, et al. Predictive value of soluble urokinase-type plasminogen activator receptor for mortality in patients with suspected myocardial infarction. Clin Res Cardiol. 2019; 108(12): 1386–1393.
  41. Topf A, Mirna M, Paar V, et al. The differential diagnostic value of selected cardiovascular biomarkers in Takotsubo syndrome. Clin Res Cardiol. 2022; 111(2): 197–206.
  42. Velissaris D, Zareifopoulos N, Koniari I, et al. Soluble urokinase plasminogen activator receptor as a diagnostic and prognostic biomarker in cardiac disease. J Clin Med Res. 2021; 13(3): 133–142.
  43. Hindy G, Tyrrell DJ, Vasbinder A, et al. Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis. J Clin Invest. 2022; 132(24): e158788.
  44. Wlazeł RN, Migała M, Zielińska M, et al. Soluble urokinase plasminogen activator receptor in one-year prediction of major adverse cardiac events in patients after first myocardial infarction treated with primary percutaneous coronary intervention. Arch Med Sci. 2019; 15(1): 72–77.
  45. Eapen DJ, Manocha P, Ghasemzadeh N, 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. J Am Heart Assoc. 2014; 3(5): e001118.
  46. Theilade S, Rossing P, Eugen-Olsen J, et al. SuPAR level is associated with myocardial impairment assessed with advanced echocardiography in patients with type 1 diabetes with normal ejection fraction and without known heart disease or end-stage renal disease. Eur J Endocrinol. 2016; 174(6): 745–753.
  47. Shuai T, Yan P, Xiong H, et al. Association between soluble urokinase-type plasminogen activator receptor levels and chronic kidney disease: a systematic review and meta-analysis. Biomed Res Int. 2019; 2019: 6927456.
  48. Borné Y, Persson M, Melander O, et al. Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation. Eur J Heart Fail. 2014; 16(4): 377–383.
  49. Mirna M, Wernly B, Paar V, et al. Multi-biomarker analysis in patients after transcatheter aortic valve implantation (TAVI). Biomarkers. 2018; 23(8): 773–780.
  50. Li Y, Ding Y, Zhao Y, et al. Prognostic value of soluble urokinase-type plasminogen activator receptor in coronary artery disease: a meta-analysis. Eur J Clin Invest. 2022; 52(12): e13867.