A biomarker for estimating no-reflow phenomenon in PCI-treated non-ST-segment elevation myocardial infarction patients: serum Cystatin C
Abstract
Aims: Cystatin C (Cys-C) is a biochemical marker associated not only with renal function but also with inflammatory processes. We aimed to investigate the relationship between the post-percutaneous coronary intervention (PCI) no-reflow phenomenon (NRP) and Cys-C in patients with non-ST-segment elevation acute coronary syndrome (NST-ACS).
Methods: This retrospective, single-center observational study consecutively enrolled patients who were hospitalized with a diagnosis of NST-ACS and underwent PCI between October 2021 and February 2022. Baseline characteristics, medications, admission laboratory parameters, and angiographic features were recorded. Logistic regression and sensitivity analyses were performed to identify parameters associated with NRP.
Results: Out of 199 patients (mean age: 62.0±10.3, 59.8% male), 36 (18.1%) developed NRP. Patients who developed NRP had a lower ejection fraction (49.7±10.3% vs. 53.5±7.1%, p=0.046) and were less likely to be male (36.1% vs. 65.0%, p=0.001). Additionally, individuals with NRP exhibited higher blood urea and C-reactive protein levels than those without NRP (p<0.05 for both). Similarly, serum Cys-C levels were elevated in the former group (1.44±0.57 vs. 1.07±0.40 mg/L, p=0.001). Multivariable logistic regression analysis demonstrated that Cys-C [odds ratio (OR)=4.793, p=0.014] and culprit lesion [OR=8.112, p=0.043 for LCx, OR=27.025, p=0.001 for RCA] were independently associated with NRP. Receiver operating characteristic curve analysis showed a cut-off point >1.1 mg/L for Cys-C determined NRP with 72.2% sensitivity and 66.9% specificity (area under the curve=0.711, p<0.001).
Conclusion: We have demonstrated a potential association between the serum Cys-C level at admission and the occurrence of NRP among NST-ACS patients undergoing PCI.
Keywords
Cystatin C no-reflow phenomenon non-ST-segment elevation acute coronary syndrome percutaneous coronary intervention
Ethical Statement
Ethics Committee Approval: The study was initiated with the approval of the University of Health Sciences, Adana City Training & Research Hospital Clinical Researches Ethics Committee (Date: 21.12.2023, Decision No: 3051). Informed Consent: Because the study was designed retrospectively, no written informed consent form was obtained from patients. Referee Evaluation Process: Externally peer-reviewed. Conflict of Interest Statement: The authors have no conflicts of interest to declare. Financial Disclosure: The authors declared that this study has received no financial support. Author Contributions: All of the authors declare that they have all participated in the design, execution, and analysis of the paper, and that they have approved the final version.
References
- Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095-2128.
- Jernberg T, Lindahl B, James S, Larsson A, Hansson L-O, Wallentin L. Cystatin C: a novel predictor of outcome in suspected or confirmed non-ST-elevation acute coronary syndrome. Circ. 2004;110(16):2342-2348.
- James SK, Lindahl B, Siegbahn A, et al. N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV substudy. Circ. 2003;108(3):275-281.
- Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835-842.
- Fox KA, Dabbous OH, Goldberg RJ, et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ. 2006;333(7578):1091.
- Stouffer GA, Lenihan D, Lerakis S, et al. Incidence and management of “no-reflow” following percutaneous coronary interventions. Am J Med Sci. 2005;329(2):78-85.
- Harbalıoğlu H, Genç Ö, Alıcı G, Quisi A, Yıldırım A. Impact of HAT2CH2 Score on the development of no-reflow phenomenon in patients with ST-segment elevation myocardial infarction. Angiol. 2024;75(1):44-53.
- Fajar JK, Heriansyah T, Rohman MS. The predictors of no reflow phenomenon after percutaneous coronary intervention in patients with ST elevation myocardial infarction: a meta-analysis. Indian Heart J. 2018;70(Suppl 3):S406-S418.
- Dong‐bao L, Qi H, Zhi L, Shan W, Wei‐ying J. Predictors and long‐term prognosis of angiographic slow/no‐reflow phenomenon during emergency percutaneous coronary intervention for ST‐elevated acute myocardial infarction. Clin Cardiol. 2010;33(12):E7-E12.
- Wong DT, Puri R, Richardson JD, Worthley MI, Worthley SG. Myocardial ‘no-reflow’—diagnosis, pathophysiology and treatment. Int J Cardiol. 2013;167(5):1798-1806.
- Zhou H, He X-y, Zhuang S-w, et al. Clinical and procedural predictors of no-reflow in patients with acute myocardial infarction after primary percutaneous coronary intervention. World J Emerg Med. 2014;5(2):96.
- Ndrepepa G, Tiroch K, Fusaro M, et al. 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J Am Coll Cardiol. 2010;55(21):2383-2389.
- Mehta RH, Harjai KJ, Boura J, et al. Prognostic significance of transient no-reflow during primary percutaneous coronary intervention for ST-elevation acute myocardial infarction. Am J Cardiol. 2003;92(12):1445-1447.
- Mussap M, Plebani M. Biochemistry and clinical role of human cystatin C. Crit Rev Clin Lab Sci. 2004;41(5-6):467-550.
- Laterza OF, Price CP, Scott MG. Cystatin C: an improved estimator of glomerular filtration rate? Clin Chem. 2002;48(5):699-707.
- Correa S, Morrow DA, Braunwald E, et al. Cystatin C for risk stratification in patients after an acute coronary syndrome. J Am Heart Assoc. 2018;7(20):e009077.
- Åkerblom A, Wallentin L, Siegbahn A, et al. Cystatin C and estimated glomerular filtration rate as predictors for adverse outcome in patients with ST-elevation and non-ST-elevation acute coronary syndromes: results from the platelet inhibition and patient outcomes study. Clin Chem. 2012;58(1):190-199.
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- Baumgartner H, Hung J, Bermejo J, et al. Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging. 2017;18(3):254-275.
- Gibson CM, Schömig A. Coronary and myocardial angiography: angiographic assessment of both epicardial and myocardial perfusion. Circ. 2004;109(25):3096-3105.
- Kirma C, Izgi A, Dundar C, et al. Clinical and procedural predictors of no-reflow phenomenon after primary percutaneous coronary interventions experience at a single center. Circ J. 2008;72(5):716-721.
- Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes: developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2023;44(38):3720-3826.
- Rezkalla SH, Stankowski RV, Hanna J, Kloner RA. Management of no-reflow phenomenon in the catheterization laboratory. JACC: Cardiovasc Intervent. 2017;10(3):215-223.
- Bouleti C, Mewton N, Germain S. The no-reflow phenomenon: state of the art. Arch Cardiovasc Dis. 2015;108(12):661-674.
- Durante A, Camici PG. Novel insights into an “old” phenomenon: the no reflow. Int J Cardiol. 2015;187:273-280.
- Kurtul A, Murat SN, Yarlioglues M, Duran M, Celik IE, Kilic A. Mild to moderate renal impairment is associated with no-reflow phenomenon after primary percutaneous coronary intervention in acute myocardial infarction. Angiol. 2015;66(7):644-651.
- Pantsios C, Kapelios C, Vakrou S, et al. Effect of elevated reperfusion pressure on “no reflow” area and infarct size in a porcine model of ischemia-reperfusion. J Cardiovasc Pharmacol Ther. 2016;21(4):405-411.
- Ipek G, Onuk T, Karatas MB, et al. CHA2DS2-VASc score is a predictor of no-reflow in patients with st-segment elevation myocardial infarction who underwent primary percutaneous intervention. Angiol. 2016;67(9):840-845.
- Harding SA. The role of vasodilators in the prevention and treatment of no-reflow following percutaneous coronary intervention. Heart. 2006;92(9):1191-1193.
- Cheng C, Liu XB, Bi SJ, Lu QH, Zhang J. Serum cystatin C levels relate to no-reflow phenomenon in percutaneous coronary interventions in ST-segment elevation myocardial infarction. PLoS One. 2019;14(8):e0220654.
- Rofyda OF, Hussein SE, Rasha AT, et al. The relationship between the levels of serum cystatin C and the occurrence of the no-reflow phenomenon during primary percutaneous coronary interventions. Med J Cairo Univ. 2023;91(06):897-908.
- Cerne D, Kaplan-Pavlovcic S, Kranjec I, Jurgens G. Mildly elevated serum creatinine concentration correlates with the extent of coronary atherosclerosis. Ren Fail. 2000;22(6):799-808.
- Baigent C, Burbury K, Wheeler D. Premature cardiovascular disease in chronic renal failure. Lancet. 2000;356(9224):147-152.
- Lou B, Luo Y, Zhang H, et al. Association between cystatin C and Cardiac function in acute myocardial infarction patients: a real-world analysis. Dis Markers. 2022;2022:7267937.
- Suthahar N, Lau ES, Blaha MJ, et al. Sex-specific associations of cardiovascular risk factors and biomarkers with incident heart failure. J Am Coll Cardiol. 2020;76(12):1455-1465.
- Pantea-Roșan LR, Pantea VA, Bungau S, et al. No-reflow after PPCI—a predictor of short-term outcomes in STEMI patients. J Clin Med. 2020;9(9):2956.
- Grubb A, Björk J, Nyman U, et al. Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation. Scand J Clin Lab Invest. 2011;71(2):145-149.
- Urbonaviciene G, Shi GP, Urbonavicius S, Henneberg EW, Lindholt JS. Higher cystatin C level predicts long-term mortality in patients with peripheral arterial disease. Atheroscler. 2011;216(2):440-445.
- Lassus J, Harjola VP. Cystatin C: a step forward in assessing kidney function and cardiovascular risk. Heart Fail Rev. 2012;17(2):251-261.
- Niccoli G, Conte M, Della Bona R, 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. Atheroscler. 2008;198(2):373-380.
Abstract
References
- Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095-2128.
- Jernberg T, Lindahl B, James S, Larsson A, Hansson L-O, Wallentin L. Cystatin C: a novel predictor of outcome in suspected or confirmed non-ST-elevation acute coronary syndrome. Circ. 2004;110(16):2342-2348.
- James SK, Lindahl B, Siegbahn A, et al. N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV substudy. Circ. 2003;108(3):275-281.
- Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835-842.
- Fox KA, Dabbous OH, Goldberg RJ, et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ. 2006;333(7578):1091.
- Stouffer GA, Lenihan D, Lerakis S, et al. Incidence and management of “no-reflow” following percutaneous coronary interventions. Am J Med Sci. 2005;329(2):78-85.
- Harbalıoğlu H, Genç Ö, Alıcı G, Quisi A, Yıldırım A. Impact of HAT2CH2 Score on the development of no-reflow phenomenon in patients with ST-segment elevation myocardial infarction. Angiol. 2024;75(1):44-53.
- Fajar JK, Heriansyah T, Rohman MS. The predictors of no reflow phenomenon after percutaneous coronary intervention in patients with ST elevation myocardial infarction: a meta-analysis. Indian Heart J. 2018;70(Suppl 3):S406-S418.
- Dong‐bao L, Qi H, Zhi L, Shan W, Wei‐ying J. Predictors and long‐term prognosis of angiographic slow/no‐reflow phenomenon during emergency percutaneous coronary intervention for ST‐elevated acute myocardial infarction. Clin Cardiol. 2010;33(12):E7-E12.
- Wong DT, Puri R, Richardson JD, Worthley MI, Worthley SG. Myocardial ‘no-reflow’—diagnosis, pathophysiology and treatment. Int J Cardiol. 2013;167(5):1798-1806.
- Zhou H, He X-y, Zhuang S-w, et al. Clinical and procedural predictors of no-reflow in patients with acute myocardial infarction after primary percutaneous coronary intervention. World J Emerg Med. 2014;5(2):96.
- Ndrepepa G, Tiroch K, Fusaro M, et al. 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J Am Coll Cardiol. 2010;55(21):2383-2389.
- Mehta RH, Harjai KJ, Boura J, et al. Prognostic significance of transient no-reflow during primary percutaneous coronary intervention for ST-elevation acute myocardial infarction. Am J Cardiol. 2003;92(12):1445-1447.
- Mussap M, Plebani M. Biochemistry and clinical role of human cystatin C. Crit Rev Clin Lab Sci. 2004;41(5-6):467-550.
- Laterza OF, Price CP, Scott MG. Cystatin C: an improved estimator of glomerular filtration rate? Clin Chem. 2002;48(5):699-707.
- Correa S, Morrow DA, Braunwald E, et al. Cystatin C for risk stratification in patients after an acute coronary syndrome. J Am Heart Assoc. 2018;7(20):e009077.
- Åkerblom A, Wallentin L, Siegbahn A, et al. Cystatin C and estimated glomerular filtration rate as predictors for adverse outcome in patients with ST-elevation and non-ST-elevation acute coronary syndromes: results from the platelet inhibition and patient outcomes study. Clin Chem. 2012;58(1):190-199.
- Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2018; 40(2):87-165.
- Baumgartner H, Hung J, Bermejo J, et al. Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging. 2017;18(3):254-275.
- Gibson CM, Schömig A. Coronary and myocardial angiography: angiographic assessment of both epicardial and myocardial perfusion. Circ. 2004;109(25):3096-3105.
- Kirma C, Izgi A, Dundar C, et al. Clinical and procedural predictors of no-reflow phenomenon after primary percutaneous coronary interventions experience at a single center. Circ J. 2008;72(5):716-721.
- Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes: developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2023;44(38):3720-3826.
- Rezkalla SH, Stankowski RV, Hanna J, Kloner RA. Management of no-reflow phenomenon in the catheterization laboratory. JACC: Cardiovasc Intervent. 2017;10(3):215-223.
- Bouleti C, Mewton N, Germain S. The no-reflow phenomenon: state of the art. Arch Cardiovasc Dis. 2015;108(12):661-674.
- Durante A, Camici PG. Novel insights into an “old” phenomenon: the no reflow. Int J Cardiol. 2015;187:273-280.
- Kurtul A, Murat SN, Yarlioglues M, Duran M, Celik IE, Kilic A. Mild to moderate renal impairment is associated with no-reflow phenomenon after primary percutaneous coronary intervention in acute myocardial infarction. Angiol. 2015;66(7):644-651.
- Pantsios C, Kapelios C, Vakrou S, et al. Effect of elevated reperfusion pressure on “no reflow” area and infarct size in a porcine model of ischemia-reperfusion. J Cardiovasc Pharmacol Ther. 2016;21(4):405-411.
- Ipek G, Onuk T, Karatas MB, et al. CHA2DS2-VASc score is a predictor of no-reflow in patients with st-segment elevation myocardial infarction who underwent primary percutaneous intervention. Angiol. 2016;67(9):840-845.
- Harding SA. The role of vasodilators in the prevention and treatment of no-reflow following percutaneous coronary intervention. Heart. 2006;92(9):1191-1193.
- Cheng C, Liu XB, Bi SJ, Lu QH, Zhang J. Serum cystatin C levels relate to no-reflow phenomenon in percutaneous coronary interventions in ST-segment elevation myocardial infarction. PLoS One. 2019;14(8):e0220654.
- Rofyda OF, Hussein SE, Rasha AT, et al. The relationship between the levels of serum cystatin C and the occurrence of the no-reflow phenomenon during primary percutaneous coronary interventions. Med J Cairo Univ. 2023;91(06):897-908.
- Cerne D, Kaplan-Pavlovcic S, Kranjec I, Jurgens G. Mildly elevated serum creatinine concentration correlates with the extent of coronary atherosclerosis. Ren Fail. 2000;22(6):799-808.
- Baigent C, Burbury K, Wheeler D. Premature cardiovascular disease in chronic renal failure. Lancet. 2000;356(9224):147-152.
- Lou B, Luo Y, Zhang H, et al. Association between cystatin C and Cardiac function in acute myocardial infarction patients: a real-world analysis. Dis Markers. 2022;2022:7267937.
- Suthahar N, Lau ES, Blaha MJ, et al. Sex-specific associations of cardiovascular risk factors and biomarkers with incident heart failure. J Am Coll Cardiol. 2020;76(12):1455-1465.
- Pantea-Roșan LR, Pantea VA, Bungau S, et al. No-reflow after PPCI—a predictor of short-term outcomes in STEMI patients. J Clin Med. 2020;9(9):2956.
- Grubb A, Björk J, Nyman U, et al. Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation. Scand J Clin Lab Invest. 2011;71(2):145-149.
- Urbonaviciene G, Shi GP, Urbonavicius S, Henneberg EW, Lindholt JS. Higher cystatin C level predicts long-term mortality in patients with peripheral arterial disease. Atheroscler. 2011;216(2):440-445.
- Lassus J, Harjola VP. Cystatin C: a step forward in assessing kidney function and cardiovascular risk. Heart Fail Rev. 2012;17(2):251-261.
- Niccoli G, Conte M, Della Bona R, 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. Atheroscler. 2008;198(2):373-380.
Details
| Primary Language | English |
|---|---|
| Subjects | Cardiology |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | March 8, 2024 |
| Submission Date | December 29, 2023 |
| Acceptance Date | January 18, 2024 |
| Published in Issue | Year 2024 Volume: 6 Issue: 2 |
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