Abstract
Background: Increased level of high-sensitivity C-reactive protein (hs-CRP) is associated with no-reflow phenomenon. Therefore, even when timely coronary revascularization is performed through the primary percutaneous coronary intervention (pPCI), the process can induce reperfusion injury.
Purpose: We evaluated the influence of hs-CRP level on the no-reflow phenomenon in patients with ST-segment elevation myocardial infarction (STEMI).
Methods: In this study, we included one hundred and eighty-two consecutive patients with STEMI of onset < 12 h, who underwent pPCI. The levels of creatine kinase (CK), the MB fraction of creatine kinase (CK-MB), troponin I, hs-CRP, and other routine laboratory parameters were measured. Measurement of hs-CRP was done on the day of admission by Cobas assay (particle-enhanced immunoturbidimetric assay) on Cobas c501 (Roche). Thereafter, patients were divided in two groups according to the thrombolysis in myocardial infarction (TIMI) flow grade.
Results: From a total of 182 STEMI patients who underwent pPCI, the median value of hs-CRP of the patients with TIMI grade flow 3 (successful reperfusion) was 8.5 (0.4–268) and of the patients with no-reflow phenomenon (unsuccessful reperfusion, TIMI flow grade ≤ 2) was 37.90 (1.8–271.20), p < 0.0001. Receiver operating characteristics (ROC) curve of hs-CRP plots the true positive rate against the false positive rate at different cutoff points, AUC = 0.73 (95% CI, 0.64–0.81), and the cutoff value for the hs-CRP was 18.0 mg/L, p=0.0001.
Conclusions: hs-CRP may be associated with no-reflow phenomenon in STEMI patients. The cutoff value for hs-CRP may be used to identify patients at risk for reperfusion injury.
Keywords: C-reactive protein, no-reflow phenomenon, STEMI
1. Introduction
Ischemic heart disease (IHD) is the most common cause of death and disability worldwide.
Myocardial infarction (MI) is associated with cardiac troponin (cTn) release detecting the presence of acute myocardial injury [1]. Based on the initial electrocardiogram (ECG), patients with acute coronary syndrome (ACS) can be differentiated into two working diagnoses: ST-segment elevation MI (STEMI) and non-ST-elevation (NSTE)-ACS [2].
In patients with STEMI, even prompt reperfusion by primary percutaneous coronary intervention (pPCI) in-hospital mortality rate ranges between 4% and 12%, 1-year mortality is 7%, and goes up to 12% in-high risk STEMI patients that are presented with cardiogenic shock [3–5].
The role of C-reactive protein (CRP) as predictor for inflammatory marker should be emphasized since it can clearly present the prediction on the no-reflow phenomenon. Thus, the CRP as a marker of acute inflammatory response may be comprised in myocardial ischemia/reperfusion injury in STEMI patients undergoing PCI (Figure 1) [6].
Figure 1.
C-reactive protein and ERK pathway. CRP: C-reactive protein, ERK: extracellular signal-regulated kinase, MEK: mitogen extracellular kinase, ROS: reactive oxygen species.
The CRP as marker of the elevated inflammatory state including albumin (the ratio of CRP to albumin-CAR) is used in predicting long-term mortality among heart failure with reduced ejection fraction (HFrEF) patients with implantable cardiac defibrillators as well as for the prediction of atrial fibrillation recurrence following cryoablation [7, 8]. Also, CRP can directly reflect the acute inflammatory responses to diseases [9].
The CRP gene is located on chromosome 1q23 while the CRP molecule itself consists of five nonglycosylated polypeptide subunits, where each contains 206 amino acid residues. The majority of CRP is synthesized in the liver but also in atherosclerotic lesions being regulated by interleukin-6 (IL-6), interleukin-1(IL-1), and tumor necrosis factor alpha (TNF-ɑ) [10, 11].
Reperfusion of an occluded coronary artery is required to prevent infarction of the ischemic myocardium, but reperfusion can trigger myocardial injury, a phenomenon called myocardial reperfusion injury (MRI). The pathogenesis of ischemia reperfusion injury consists of the mitochondrial permeability transition pore (mPTP) and the mitoKATP channel opening, generation of reactive oxygen species (ROS) and Ca2+ overload (Figure 1) [12].
The extracellular signal-regulated kinase 1/2 (ERK1/2) belongs to the mitogen-activated protein kinase (MAPK) family playing an essential role in signal transduction from surface receptors to the nucleus. CRP induces ERK 1/2 phosphorylation and is accompanied by ROS overproduction (Figure 1) [13].
The types of myocardial ischemia reperfusion injury include myocardial stunning, no-reflow phenomenon (microvascular damage), reperfusion arrhythmia, and lethal myocardial reperfusion injury. Based on the thrombolysis in myocardial infarction (TIMI) flow grade, no-reflow phenomenon is characterized by a TIMI flow ≤ 2 [14]Therefore, even when timely coronary revascularization is performed through the administration of thrombolytic therapy or a pPCI, the process can induce reperfusion injury. During this process, cardiomyocyte death occurs through several pathophysiological mechanisms and contributes up to 50% of the final myocardial infarct size [14].
Therefore, the prediction of no-reflow is very important in patients with STEMI. These laboratory markers such as CRP and ECG markers can be used in order to predict these endpoints [15]. Furthermore, artificial intelligence (AI) and machine learning (ML) systems can be used in order to precisely predict no-reflow [16].
To the best of our knowledge, no study has investigated the predictive value of high-sensitivity CRP level on the no-reflow phenomenon in STEMI patients.
The purpose of this study was to assess relationship between hs-CRP and TIMI flow grade as well as to determine the cutoff value for hs-CRP that may be used to identify patients at risk for no-reflow phenomenon.
2. Methods
2.1. Study Design
In this prospective observational study, we included one hundred and eighty-two consecutive patients with STEMI. These patients were enrolled in our center from March 2023 to February 2024.
Inclusion criteria for STEMI patients were (a) persistent chest pain, (b) an ECG with new ST elevation at the J-point in at least two contiguous leads (≥ 2.5 mm in men < 40 years, ≥ 2 mm in men ≥ 40 years, or ≥ 1.5 mm in women regardless of age in leads V2-V3 and/or ≥ 1 mm in the other leads (in the absence of left ventricular [LV] hypertrophy or left bundle branch block [LBBB])), (c) increased hs-cardiac troponin (hs-cTn) (ESC 0/1 h and 0/2 h algorithms), and (d) patients who underwent pPCI (persistent ST-segment elevation and symptoms of ischemia of ≤ 12 h duration) [2].
Clinical history data were obtained during hospitalization and included coronary risk factors (diabetes mellitus, dyslipidemia, arterial hypertension, and smoking), previous medications, and time from onset to admission.
Before PCI procedure, all patients received acetylsalicylic acid 150–300 mg, clopidogrel 600 mg, and unfractionated heparin (UFH) 70–100UI/kg. Additional treatment with glycoprotein IIb/IIIa inhibitors or intracoronary treatments such as vasodilators were left at the discretion of the treating cardiologist. Based on coronary angiography, no-reflow phenomenon was defined as TIMI flow grade ≤ 2 (unsuccessful reperfusion) [17, 18].
An echocardiographic examination was performed in all patients for assessment of left ventricular ejection fraction (EF).
Laboratory parameters were measured, including the creatine kinase (CK), the MB fraction of creatine kinase (CK-MB), hs-cTnI, hs-CRP, and other routine laboratory parameters were measured. Measurement of hs-CRP was done on the day of admission by Cobas assay (particle-enhanced immunoturbidimetric assay) on Cobas c501 (Roche).
The institutional ethic committee on human research approved this study.
2.2. Statistical Analysis
The main objective of the study was the influence of the hs-CRP on the no-reflow phenomenon in STEMI patients. The data follow a non-normal distribution, and nonparametric tests were taken into account in group comparisons. Mean ± standard deviation and median were used to present continuous variables while by count and percentage were expressed for categorical variables. Comparison of laboratory variables between patients with different TIMI flows (TIMI flow ≤ 2 or 3) was performed using Kruskal–Wallis and Mann–Whitney tests.
A receiver operating characteristic (ROC) curve as a graphical method plots the true positive rate against the false positive rate at different cutoff points, allowing the most appropriate cutoff to be chosen for the particular context. We used ROC curve analyses to determine a cutoff value for hs-CRP and its association with TIMI flow grade. The area under the curve is used as a summary measure of how well a variable predict a binary outcome. All statistical analyses were performed using SPSS statistics Version 22.
3. Results
We studied 182 STEMI patients admitted to the coronary care unit in the cardiology clinic. Baseline characteristics of the study population are presented in Table 1. The mean age was 63.17 ± 10.48 years old and 112 (61.53%) were male. Medical history included hypertension (57.69%), diabetes mellitus (24.17%), smoking (44.5%), and dyslipidemia (42.85%). The median value of the hs-CRP was 31.2 (0.40–271.20), while the median value of the CK-MB and troponin I were 90.00 (32.40–929.0) and 75.0 (25.0–6030.0). In terms of coronary angiographic findings, the culprit lesion was as follows: the left anterior descending artery (LAD) 41.2%, right coronary artery (RCA) 39.56% and left circumflex artery (LCx) 19.23%.
Table 1.
Baseline characteristics of patients.
| Characteristics | Value |
|---|---|
| Age (yr) | 63.17 (±10.48) |
| Gender (male), n (%) | 112 (61.53) |
| BMI (kg/m2) | 28.07 (±4.65) |
| Medical history | |
| Hypertension, n (%) | 105 (57.69) |
| Diabetes mellitus, n (%) | 44 (24.17) |
| Smoking, n (%) | 81 (44.5) |
| Dyslipidemia, n (%) | 78 (42.85) |
| Ejection fraction (%) | 49.75 (±9.06) |
| Laboratory values | |
| Hemoglobin (mg/dL) | 132.57 (±17.25) |
| Creatinine (μmol/L) | 96.0 (43.0–479.9) |
| Creatine kinase (U/I) | 907.0 (175.20–6809.0) |
| Creatine kinase-MB (U/I) | 90.0 (32.40–929.0) |
| Troponin I (pg/mL) | 75.0 (25.0–6030.0) |
| hs-CRP (mg/L) | 31.2 (0.4–271.2) |
| Glucose (mmol/L) | 10.82 (6.06) |
| Cholesterol (mmol/L) | 5.08 (1.17) |
| Triglyceride (mmol/L) | 2.07 (1.45) |
| Coronary angiographic findings | |
| Culprit lesion, n (%) | |
| LAD | 75 (41.20) |
| LCx | 35 (19.23) |
| RCA | 72 (39.56) |
| Final TIMI grade flow, n (%) | |
| 3 | 132 (72.52) |
| 2 | 50 (27.47) |
Note: Data are presented as a median (range), number of subjects (percentage), or mean ± SD.
Abbreviations: BMI, body mass index; TIMI, thrombolysis in myocardial infarction.
Of the 182 patients, 132 (72.52%) had TIMI flow grade 3 and 50 (27.47%) had TIMI flow grade ≤ 2. The mean age was 63.09 (±10.97) in patients with TIMI = 3 and 63.38 (±9.13) in those with TIMI ≤ 2. As for the laboratory parameters, the median value of hs-CRP of the patients with TIMI grade flow 3 was 8.5 (0.4–268) and 37.90 of those with no-reflow phenomenon (TIMI flow grade ≤ 2) (1.8–271.20) (p < 0.0001) (Table 2). ROC curve of hs-CRP plots the true positive rate against the false positive rate at different cutoff points, AUC = 0.73 (95% CI: 0.64–0.81), the cut off value for the hs-CRP was 18.0 mg/L, p=0.0001 (Figure 2). Also, Figure 2 presents the ROC curve analysis for others biomarkers (troponin I, CK, CK-MB, and hemoglobin).
Table 2.
Main characteristics and TIMI flow grade.
| Characteristics | TIMI flow grade = 3 (n = 132) | TIMI flow grade ≤ 2 (n = 50) | p value |
|---|---|---|---|
| Age (yr) | 63.09 (±10.97) | 63.38 (±9.13) | 0.85 |
| BMI (kg/m2) | 29.32 (4.46) | 28.07 (4.65) | 0.09 |
| Hypertension, n (%) | 75 (56.81) | 30 (60.0) | 0.23 |
| Diabetes mellitus, n (%) | 23 (17.42) | 21 (42.0) | 0.004 |
| Smokers, n (%) | 65 (49.24 | 16 (32.0) | 0.12 |
| Dyslipidemia, n (%) | 52 (39.39) | 26 (52.0) | 0.65 |
| Ejection fraction (%) | 49.75 (±9.06) | 45.79 (±9.46) | < 0.0001 |
| Hemoglobin (mg/dL) | 133.07 (±16.25) | 131.2 (±19.61) | 0.32 |
| Creatinine (μmol/L) | 96.2 (43.0–314.6) | 93.20 (51.8–479.9) | 0.34 |
| Creatine kinase (U/I) | 891.5 (175.20–7550.0) | 1129.0 (180.0–6809.0) | 0.9 |
| Creatine kinase-MB (U/I) | 93.0 (32.40–910.0) | 140.51 (40.1–929.0) | 0.65 |
| hs-cTnI (pg/mL) | 63.8 (25.0–5405.0) | 86.07 (32.0–6030.0) | 0.01 |
| hs-CRP (mg/L) | 8.5 (0.4–268) | 37.90 (1.8–271.20) | < 0.0001 |
| Glucose (mmol/L) | 10.38 (6.03) | 11.99 (6.05) | 0.09 |
| Cholesterol (mmoL/L) | 5.11 (1.18) | 5.0 (1.15) | 0.58 |
| Triglyceride (mmol/L) | 2.13 (1.55) | 1.91 (1.13) | 0.82 |
Figure 2.
ROC curve analysis of biomarkers for the prediction of TIMI flow grade.
4. Discussion
In this study, we investigated the impact (the predictive value) of hs-CRP level on the no-reflow phenomenon in STEMI patients.
Treatment of STEMI with percutaneous coronary intervention (PCI) as a preferable reperfusion therapy, despite opening of the occluded coronary artery, may be complicated with no-reflow phenomenon as strong evidence for myocardial reperfusion injury [19, 20].
CRP is an indicator of acute-phase inflammation and a mediator of atherosclerosis stimulating expression of adhesion molecules and inflammatory cells. It enhances uptake of oxidized low-density lipoprotein into macrophage through expression of tissue factor leading to plaque formation and thrombosis. CRP is also thought to contribute to vasoconstriction at the microvascular level and endothelial damage in which no-reflow is involved. Leukocytes play a key role in the pathophysiology of no-reflow as it accumulates in small vessel beds in the infarct zone. Aggregation of activated leukocytes in the capillary region may directly disrupt blood flow.
In addition to CRP, serum albumin (SA) levels can be used as biomarkers of systemic inflammation knowing its protective effects against endothelial damage and thrombotic state. Albumin is a negative acute-phase reactant and its serum concentrations are expected to decline in proinflammatory conditions such as atherosclerotic heart disease. C-reactive protein to serum albumin ratio (CRA) is used as a marker of cardiovascular disease. It has shown to be associated with no-reflow phenomenon and it is significant factor for coronary thrombus burden in STEMI patients undergoing PCI [21–24].
No-reflow is a dynamic and complex phenomenon as a result of alteration of coronary microcirculation where one of the main mechanisms is reperfusion injury [25].
Upon reperfusion injury, ROS were significantly induced following with endothelial dysfunction, deoxyribonucleic acid (DNA) damage and local inflammation causing cell death (Figure 1) [26, 27].
The influence of CRP on myocardial ischemia-reperfusion injury (MIRI) is mediated through extracellular regulated protein kinases 1/2 (ERK1/2) increasing production of ROS and Ca2+ [13, 28]. ERK1/2 is a serine/threonine protein kinase belonging to the mitogen-activated protein kinase (MAPK) family, which is abnormally expressed in MIRI (Figure 1) [29, 30]. In our study, ROC curve analysis of hs-CRP for the prediction of the no-reflow phenomenon (unsuccessful reperfusion, TIMI flow grade ≤ 2) was statistically significant, AUC = 0.73 (95% CI: 0.64–0.81), p=0.0001, confirming its influence as well as on MIRI (Figure 2).
Thus, in our study, the group of patients with no-reflow (unsuccessful reperfusion, TIMI flow grade ≤ 2) was characterized with higher value of hs-CRP compared with the group of patients with successful reperfusion (TIMI flow grade = 3), p < 0.0001 (Table 2). This study demonstrates that in patients with higher value of hs-CRP may be aggravated MIRI, as also investigated in preclinical studies [31].
Moreover, another result of this study shows that the level of cardiac troponin I (cTnI) can help to predict no-reflow phenomenon (p=0.01) as well as diabetes mellitus is associated with no-reflow (p=0.004) (Table 2) [32].
5. Conclusion
hs-CRP may be associated with no-reflow phenomenon in STEMI patients. The cut-off value for hs-CRP (18 mg/L) may be used to identify patients at risk for no-reflow phenomenon/reperfusion injury; therefore, additional treatment options should be kept in mind.
Data Availability Statement
The data used to support the findings of this study are available on request from the corresponding author.
Ethics Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by Ethical Committee of Hospital and University Clinical Service of Kosovo-University Clinical Center of Kosova (protocol number 1266, date 17.05.2021).
Consent
Informed consent was obtained from all subjects involved in the study.
Conflicts of Interest
The authors declare no conflicts of interest.
Author Contributions
X.K. and J.V.: conceptualization; X.K. and D.K.: methodology; D.K. and B.B.: software; A.B. and J.V.: validation; X.K., B.B., and A.B.: investigation; X.K. and A.B.: original draft preparation; A.B.: reviewing and editing; J.V. and A.B.: supervision. All authors have read and agreed to the published version of the manuscript.
The authorship is based on the latest guidelines of the International Committee of Medical Journal Editors. All authors listed are in agreement regarding the manuscript.
Funding
No funding was received for this manuscript.
References
- 1.Thygesen K., Alpert J. S., Jaffe A. S., et al. Executive Group on Behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Circulation . 2018;138:e618–e651. doi: 10.1161/CIR.0000000000000617. [DOI] [PubMed] [Google Scholar]
- 2.Byrne R. A., Rossello X., Coughlan J., et al. 2023 ESC Guidelines for the Management of Acute Coronary Syndromes. European Heart Journal . 2023;44(38) doi: 10.1093/ehjacc/zuad107. [DOI] [PubMed] [Google Scholar]
- 3.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) European Heart Journal . 2018;39(2):119–177. doi: 10.1093/eurheartj/ehx393. [DOI] [PubMed] [Google Scholar]
- 4.Townsend N., Wilson L., Bhatnagar P., Wickramasinghe K., Rayner M., Nichols M. Cardiovascular Disease in Europe: Epidemiological Update 2016. European Heart Journal . 2016;37(42):3232–3245. doi: 10.1093/eurheartj/ehw334. [DOI] [PubMed] [Google Scholar]
- 5.Hausenloy D. J., Botker H. E., Engstrom T., et al. Targeting Reperfusion Injury in Patients With ST-Segment Elevation Myocardial Infarction: Trials and Tribulations. European Heart Journal . 2017;38(13):935–941. doi: 10.1093/eurheartj/ehw145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Wang Q. Q., Qiu Y. G., Zhu Y. J., et al. Cyclophosphamide Protects Against Myocardial Ischemia/Reperfusion Injury in Rats: One of the Therapeutic Targets Is High Sensitivity C-Reactive Protein. The Journal of Thoracic and Cardiovascular Surgery . 2009;137(4):991–996. doi: 10.1016/j.jtcvs.2008.04.033. [DOI] [PubMed] [Google Scholar]
- 7.Çinier G., Hayıroğlu M. İ., Kolak Z., et al. The Value of C‐Reactive Protein‐to‐Albumin Ratio in Predicting Long‐Term Mortality Among HFrEF Patients With Implantable Cardiac Defibrillators. European Journal of Clinical Investigation . 2021;51(8):p. e13550. doi: 10.1111/eci.13550. [DOI] [PubMed] [Google Scholar]
- 8.Kalenderoglu K., Hayiroglu M. I., Cinar T., et al. Comparison of Inflammatory Markers for the Prediction of Atrial Fibrillation Recurrence Following Cryoablation. Biomarkers in Medicine . 2024;18(17-18):717–725. doi: 10.1080/17520363.2024.2395236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Güney B. Ç., Taştan Y. Ö., Doğantekin B., et al. Predictive Value of CAR for In-Hospital Mortality in Patients With COVID-19 Pneumonia: A Retrospective Cohort Study. Archives of Medical Research . 2021;52(5):554–560. doi: 10.1016/j.arcmed.2021.02.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Shrivastava A. K., Singh H. V., Raizada A., Singh S. K. C-Reactive Protein, Inflammation and Coronary Heart Disease. The Egyptian Heart Journal . 2015;67(2):89–97. doi: 10.1016/j.ehj.2014.11.005. [DOI] [Google Scholar]
- 11.Paffen E., DeMaat M. P. C-Reactive Protein in Atherosclerosis: A Causal Factor? Cardiovascular Research . 2006;71(1):30–39. doi: 10.1016/j.cardiores.2006.03.004. [DOI] [PubMed] [Google Scholar]
- 12.Liu N. B., Wu M., Chen C., et al. Novel Molecular Targets Participating in Myocardial Ischemia-Reperfusion Injury and Cardioprotection. Cardiology Research and Practice . 2019;2019(1):p. 6935147. doi: 10.1155/2019/6935147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Zhong Y., Cheng C. F., Luo Y. Z., et al. C-Reactive Protein Stimulates RAGE Expression in Human Coronary Artery Endothelial Cells In Vitro via ROS Generation and ERK/NF-κB Activation. Acta Pharmacologica Sinica . 2015;36(4):440–447. doi: 10.1038/aps.2014.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Fröhlich G. M., Meier P., White S. K., Yellon D. M., Hausenloy D. J. Myocardial Reperfusion Injury: Looking Beyond Primary PCI. European Heart Journal . 2013;34(23):1714–1722. doi: 10.1093/eurheartj/eht090. [DOI] [PubMed] [Google Scholar]
- 15.Hayıroğlu M. İ., Çınar T., Keskin M. How Can We Find Out the Perfect Admission Electrocardiographic Parameter to Predict No-Reflow? Journal of Electrocardiology . 2017;51(2):p. 354. doi: 10.1016/j.jelectrocard.2017.11.005. [DOI] [PubMed] [Google Scholar]
- 16.Hayıroğlu M. İ., Altay S. The Role of Artificial Intelligence in Coronary Artery Disease and Atrial Fibrillation. Balkan Medical Journal . 2023;40(3):p. 151. doi: 10.4274/balkanmedj.galenos.2023.06042023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Rossington J. A., Sol E E., Masoura K., et al. No-Reflow Phenomenon and Comparison to the Normal-Flow Population Postprimary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction: Case–Control Study (NORM PPCI) Open Heart . 2020;7(2):p. e001215. doi: 10.1136/openhrt-2019-001215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Bouleti C., Mewton N., Germain S. The No-Reflow Phenomenon: State of the Art. Archives of Cardiovascular diseases . 2015;108(12):661–674. doi: 10.1016/j.acvd.2015.09.006. [DOI] [PubMed] [Google Scholar]
- 19.Harrison R. W., Aggarwal A., Ou F. S., et al. American College of Cardiology National Cardiovascular Data Registry, Incidence and Outcomes of No-Reflow Phenomenon during Percutaneous Coronary Intervention Among Patients With Acute Myocardial Infarction. The American Journal of Cardiology . 2013;111(2):178–184. doi: 10.1016/j.amjcard.2012.09.015. [DOI] [PubMed] [Google Scholar]
- 20.Krasniqi X., Vincelj J., Gashi M., Berisha B., Kocinaj D. Association Between Apelin-12 and Creatine Kinase-MB, Depending on Success of Reperfusion in STEMI Patients. Cardiovascular Journal of Africa . 2024;35(1):35–39. doi: 10.5830/CVJA-2023-002. https://hdl.handle.net/10520/ejc-cardio1_v35_n1_a7 . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Kaplangoray M., Toprak K., Aslan R., Deveci E., Gunes A., Ardahanli İ. High CRP-Albumin Ratio Is Associated High Thrombus Burden in Patients With Newly Diagnosed STEMI. Medicine . 2023;102(41):p. e35363. doi: 10.1097/MD.0000000000035363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Kaplangoray M., Toprak K., Cicek O. F., Deveci E. Relationship Between the Fibrinogen/Albumin Ratio and Microvascular Perfusion in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction: A Prospective Study. Arquivos Brasileiros de Cardiologia . 2023;120:p. e20230002. doi: 10.36660/abc.20230002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Kaplangoray M., Toprak K., Aydın C., Aslan R. Investigation of the Relationship Between Modified Glasgow Prognostic Score and No-Reflow Phenomenon in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction. The European Research Journal . 2023;9(5):894–902. doi: 10.18621/eurj.1284893. [DOI] [Google Scholar]
- 24.Krasniqi X., Bakalli A., Kocinaj D., Vincelj J., Berisha B. Protective Value of Apelin-12 Level on the No-Reflow Phenomenon in STEMI Patients. European Heart Journal: Acute Cardiovascular Care . 2025;14(Supplement_1) [Google Scholar]
- 25.Annibali G., Scrocca I., Aranzulla T. C., Meliga E., Maiellaro F., Musumeci G. No-Reflow Phenomenon: A Contemporary Review. Journal of Clinical Medicine . 2022;11(8):p. 2233. doi: 10.3390/jcm11082233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Liem D. A., Honda H. M., Zhang J., Woo D., Ping P. Past and Present Course of Cardioprotection Against Ischemia-Reperfusion Injury. Journal of Applied Physiology . 2007;103(6):2129–2136. doi: 10.1152/japplphysiol.00383. [DOI] [PubMed] [Google Scholar]
- 27.Wu M. Y., Yiang G. T., Liao W. T., et al. Current Mechanistic Concepts in Ischemia and Reperfusion Injury. Cellular Physiology and Biochemistry . 2018;46(4):1650–1667. doi: 10.1159/000489241. [DOI] [PubMed] [Google Scholar]
- 28.Chen Y., Wang J., Yao Y., et al. CRP Regulates the Expression and Activity of Tissue Factor as Well as Tissue Factor Pathway Inhibitor via NF-Κb and ERK 1/2 MAPK Pathway. FEBS Letters . 2009;583(17):2811–2818. doi: 10.1016/j.febslet.2009.07.037. [DOI] [PubMed] [Google Scholar]
- 29.Kong T., Liu M., Ji B., Bai B., Cheng B., Wang C. Role of the Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway in Ischemia-Reperfusion Injury. Frontiers in Physiology . 2019;10:p. 1038. doi: 10.3389/fphys.2019.01038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Bhagatte Y., Lodwick D., Storey N. Mitochondrial ROS Production and Subsequent ERK Phosphorylation Are Necessary for Temperature Preconditioning of Isolated Ventricular Myocytes. Cell Death and Disease . 2012;3(7):p. e345. doi: 10.1038/cddis.2012.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Pei W. N., Hu H. J., Liu F., Xiao B., Zuo Y. B., Cui W. C-Reactive Protein Aggravates Myocardial Ischemia/reperfusion Injury Through Activation of Extracellular-Signal-Regulated Kinase 1/2. Journal Of Geriatric Cardiology: Jgc . 2018;15(7):p. 492. doi: 10.11909/j.issn.1671-5411.2018.07.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Maruszak N., Pilch W., Januszek R., Malinowski K. P., Surdacki A., Chyrchel M. Risk Factors of Suboptimal Coronary Blood Flow After a Percutaneous Coronary Intervention in Patients With Acute Anterior Wall Myocardial Infarction. Journal of Personalized Medicine . 2023;13(8):p. 1217. doi: 10.3390/jpm13081217. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data used to support the findings of this study are available on request from the corresponding author.