|Year : 2022 | Volume
| Issue : 3 | Page : 127-132
The value of admission C-reactive protein in prediction of both SYNTAX score and thrombolysis in myocardial infarction flow in STEMI patients undergoing primary percutaneous coronary intervention
Kirollos Philops1, Tarek Ahmed Naguib2, Mohammad Mustafa Al-Daydamony2, Ahmed Said Eldamanhory2, Elshaimaa Aly M. Elsadek Seaoud2
1 Department of Cardiology, National Heart Institute, Cairo, Egypt
2 Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
|Date of Submission||28-Jun-2021|
|Date of Acceptance||26-Jul-2021|
|Date of Web Publication||14-Sep-2022|
Dr. Elshaimaa Aly M. Elsadek Seaoud
Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig 44159
Source of Support: None, Conflict of Interest: None
Introduction: C-reactive protein (CRP) has come to prominence in the cardiovascular field with the inflammatory hypothesis of atherosclerosis. Many studies evaluated the role of CRP as a prognostic marker in ST-segment elevation myocardial infarction (STEMI). The aim of our work was to study the relation between admission CRP level and the angiographic severity of coronary artery disease in patients presenting with acute ST elevation myocardial infarction. Patients and Methods: Admission CRP was measured for 100 STEMI patients before primary percutaneous coronary intervention (PCI). Complexity of coronary lesion was assessed using both Syntax score and thrombolysis in myocardial infarction (TIMI) flow. Results: Syntax score was significantly higher in the 3rd CRP tertile (20.24 ± 5.6 and P = 0.000), TIMI 0 flow was the highest in the 3rd tertile (24% and P = 0.001). We found a significant positive correlation between Syntax score and CRP and a significant negative correlation between CRP and TIMI flow (P = 0.001 and 0.005, respectively). Receiver operating characteristic curve constructed to determine the sensitivity of admission CRP to determine intermediate to high risk SYNTAX score showed a level ≥8.4 mg/dl as 71% sensitive (area under the curve [AUC] =0.65 and a P = 0.02) and an admission CRP of ≥4.8 mg/dl to be 81% sensitive in determining no or faint antegrade flow (TIMI 0 and 1) (AUC = 0.71. P =0.001). Conclusion: There is a strong positive correlation between admission CRP and the syntax score and TIMI flow in STEMI patients undergoing primary PCI, thus adding CRP to the risk scoring systems used to assess STEMI patients before PPCI can help better risk stratify patients before going into the cath laboratory.
Keywords: admission C-reactive protein, predictive value, primary percutaneous coronary intervention, SYNTAX score, thrombolysis in myocardial infarction flow
|How to cite this article:|
Philops K, Naguib TA, Al-Daydamony MM, Eldamanhory AS, Elsadek Seaoud EA. The value of admission C-reactive protein in prediction of both SYNTAX score and thrombolysis in myocardial infarction flow in STEMI patients undergoing primary percutaneous coronary intervention. J Indian coll cardiol 2022;12:127-32
|How to cite this URL:|
Philops K, Naguib TA, Al-Daydamony MM, Eldamanhory AS, Elsadek Seaoud EA. The value of admission C-reactive protein in prediction of both SYNTAX score and thrombolysis in myocardial infarction flow in STEMI patients undergoing primary percutaneous coronary intervention. J Indian coll cardiol [serial online] 2022 [cited 2023 Feb 8];12:127-32. Available from: https://www.joicc.org/text.asp?2022/12/3/127/356064
| Introduction|| |
C-reactive protein (CRP) is a plasma protein synthesized in the liver after acute inflammation. It has come to prominence in the cardiovascular field with the inflammatory hypothesis of atherosclerosis. Myocardial infarction is a cause of myocardial necrosis which is a cause of acute-phase response of inflammatory process. Many studies search for the role of CRP as a prognostic factor of STEMI patients., Historically, minor CRP elevation (<10 μg/ml) was clinically insignificant, but many years ago, studies have demonstrated an association between minor CRP elevation (3–10 μg/ml) and risk of developing cardiovascular disease. There is a relation between complexity of coronary lesion and elevated CRP in patients with non-ST segment elevation myocardial infarction (STEMI) and acute coronary syndrome. CRP acts as an independent marker for transmural involvement of myocardium in patients presented with acute STEMI. Recently, there is a relation between circulating CRP level and development of coronary endothelial dysfunction. The aim of our work was to study the relation between the admission of CRP level and the angiographic severity of coronary artery disease in patients presenting with acute STEMI.
| Patients and Methods|| |
The study cohort included a total of 100 consecutive patients who were retrospectively analyzed. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and has been approved by our Institutional Ethics Committee.
From a group of 200 patients referred to the emergency department, at Zagazig University Hospitals between March 2019 and March 2020 with STEMI, 30 patients who presented after 24 h of chest pain, 20 patients who had an ongoing acute or chronic inflammatory condition, 15 patients who had a diagnosis of an active collagen disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, and scleroderma), ten patients who had chronic liver disease and 25 patients who had chronic renal impairment were excluded.
Patients were included if they met the following criteria: (a) Patients had a diagnosis of ST elevation acute myocardial infarction within the first 24 h of chest pain.
Coronary flow was assessed by thrombolysis in myocardial infarction (TIMI) grade to semi quantitatively assess coronary artery perfusion beyond point of occlusion on coronary angiography.
Thrombolysis in myocardial infarction flow
This TIMI classification was developed by the TIMI study group to semiquantitatively assess coronary artery perfusion beyond the point of occlusion on coronary angiography.
- TIMI 0: no antegrade flow beyond the point of occlusion
- TIMI 1: faint antegrade coronary flow beyond the occlusion with incomplete filling of the distal coronary bed
- TIMI 2: delayed or sluggish antegrade flow with complete filling of the distal territory
- TIMI 3: normal flow with complete filling of the distal territory (Chesebro et al., 1987).
SYNTAX score was used to evaluate the complexity of the coronary arteries lesions, this score is derived from the summation of the individual scores for each separate lesion defined as ≥50% luminal obstruction in vessels ≥1.5 mm. The SYNTAX scores were calculated for all patients using the dedicated software (available at http://www.syntaxscore.com/calc/start.htm).
All angiographic parameters were calculated by two experienced cardiologists who were blinded to the procedural data and clinical outcome on the angiograms obtained before the procedure.
A blood sample to measure CRP was drawn immediately at hospital arrival, targeting the least possible time delay from symptoms onset high-sensitivity CRP was measured using a commercially available immuno-enzymatic nephelometric method (Dade-Behring, Newark, Delaware, USA) with a precision limit of 0.3 mg/l and variation coefficient of 7.6%.
All the analyses were performed using the SPSS for Windows 20.0 Software Package (Armonk, NY, USA:IBM Corp). The continuous variables were presented as mean and standard deviation. The categorical variables were presented as percentages. All the data were tested for the normal distribution with the Kolmogorov–Smirnov test. Differences between frequencies (qualitative variables) and percentages in groups were compared using the Chi-square test. Differences between parametric quantitative independent groups were assessed by the t-test and ANOVA test and P < 0.05 for significant results and < 0.001 for highly significant results. We tried to avoid information bias through prospectively collecting data, using standardized method for measurement of CRP. Wald test was used to assess the significant of each independent variable in a binary logistic regression model.
| Results|| |
The study included a total of 100 consecutive patients (mean age 56 ± 8.2 years, 87% were males). CRP levels were measured at a median of 6.1 h after symptom onset (25th–75th percentile 5–11 h). The mean CRP value was 8.1 ± 5.9 mg/L (25th–75th percentile 4.69–24.2 mg/L). Baseline characteristics of the study population are summarized in [Table 1], mean age of our population was 56.43 (±8.2), 85% were males 57% were smokers, 71% were diabetic and 56% were hypertensive. The mean CRP of the population was 8.16 (±5.9), mean syntax score was 17.305 (±7.4) and 60% of our study population had a TIMI 0 flow on admission and 73% had an LAD lesion on angiogram, 36% presented within the first 6 h of chest pain, 34% presented more than 6 h up to 12 h while 30% presented after 12 h.
[Table 2] presents the clinical and angiographic data of patients according to CRP tertiles. The cutoff points for the CRP tertiles were <4.69 mg/L, 4.7–11.4 mg/L, and ≥11.5 mg/L. Syntax score was significantly higher in the 3rd tertile (20.24 ± 5.6 and P = 0.000), and similarly, the prevalence of TIMI 0 flow was the highest in the 3rd tertile (24% and P = 0.001).
|Table 2: Comparison of baseline characteristics and coronary angiographic outcomes according to C-reactive protein tertiles|
Click here to view
Correlation done between CRP and both Syntax score and TIMI flow is presented in [Table 3] and reveals a significant positive correlation between Syntax and CRP while a significant negative correlation was seen between CRP and TIMI flow (P = 0.001 and 0.005, respectively). [Figure 1] shows the receiver operating characteristic curve constructed to determine the sensitivity of admission CRP to determine intermediate to high risk SYNTAX score. At a value of ≥8.4 mg/dl was 71% sensitive and 66% specific with an area under the curve (AUC) of 0.65 and a P= 0.02. [Figure 2] shows sensitivity of admission CRP to determine no or faint antegrade flow (TIMI 0 and 1) in those patients, an admission value ≥ 4.8 mg/dl showed81% sensitivity and 58% specificity with an AUC of 0.71 and a P = 0.001).
|Figure 1: Receiver operating characteristic to determine cut-off value hs-C-reactive protein to determine cut-off for intermediate to high Syntax score|
Click here to view
|Figure 2: Receiver operating characteristic to determine cut-off value of hs-C-reactive protein value to determine low thrombolysis in myocardial infarction flow|
Click here to view
|Table 3: Correlation between C-reactive protein and both syntax score and thrombolysis in myocardial infarction flow|
Click here to view
Multilogistic regression analysis to define the independent predictors of high Syntax score is shown in [Table 4]. Dyslipidemia was the most powerful predictor (odds ratio [OR] =14.4, P = 0.02) followed by diabetes mellitus (OR = 3.5, P = 0.028) and TIMI flow which showed an OR = ‒3.36, P = 0.000). Age and admission systolic blood pressure showed an OR = 0.217 and 0.145, respectively, and P = 0.019 and 0.000, respectively).
|Table 4: Multivariate logistic regression to determine independent predictors of high syntax score|
Click here to view
| Discussion|| |
The primary finding of this retrospective study is that a higher CRP is related a higher Syntax and lower TIMI flow in patients admitted with STEMI within the first 24 h and undergoing primary peripheral component interconnect (PCI). We found a direct positive correlation between syntax score and CRP level and a negative correlation with TIMI flow in these patients. A multilogistic regression model designed to determine the predictors of high syntax score revealed that dyslipidemia was the most powerful predictor followed by diabetes mellitus and TIMI flow both older age and higher systolic blood pressure had a weak predictive power. An admission CRP of ≥8.4 mg/l was 71% sensitive and 66% specific to determine intermediate to high risk syntax. While an admission CRP of ≥4.8 mg/l showed a sensitivity of 81% to determine no or faint antegrade flow (TIMI 0 and 1). A multilogistic regression model to determine the predictors of a high Syntax score dyslipidemia was the most powerful predictor, followed by diabetes mellitus and TIMI flow. Age and admission systolic blood pressure were the less powerful predictors.
In 2006, Huffman et al. measured the level of CRP in 191 consecutive patients with acute myocardial infarction undergoing primary PCI and found a significant relation between increased CRP levels at time of admission and impaired reperfusion in myocardium related to the infarct-related artery. This was similar to the work done by Celik and colleagues in 2005 who measured the levels of high sensitivity CRP and white blood cell count in 75 patients presenting with acute myocardial infarction who underwent primary PCI they concluded that admission high sensitivity CRP had statistically significant independent association with poor myocardial perfusion.
In 2017, Groot et al. measured hs-CRP levels at baseline, 2 weeks, and 7 weeks and 4 months post-PCI in 376 consecutive STEMI patients. They evaluated relation between high-sensitivity CRP and long-term reperfusion success of primary percutaneous intervention in STEMI. The determination of success of myocardial reperfusion was by evaluating myocardial blush grade. They found that impaired microvascular reperfusion after PCI in STEMI patients strongly related to increased hs-CRP levels at presentation and remain higher until 2 months follow-up.
Sanchís et al. measured the level of CRP in 125 patients with non ST–elevation acute myocardial infarction. Troponin-I and CRP were measured, along with the complexity of the culprit lesion and (TIMI flow). He found that In NSTE-ACS, there is a close relation between elevated CRP, troponin elevation, and angiographic complexity of culprit coronary lesions. The highest CRP values associated with a higher troponin level, more complex lesion and TIMI flow <3.
In the early phase of AMI, CRP levels are probably a reaction to the inflammatory response following myocardial ischemia and not to chronic vascular inflammation. It allows CRP levels to be a simple marker of the magnitude of the inflammatory response to myocardial ischemia, potentially providing prognostic information regarding the risk of death. Therefore, measurement of CRP can offer a strategy for risk stratification and management of patients at the highest risk for adverse outcomes. Besides myocardial necrosis and ischemia, other kinds of tissue damage could cause CRP elevation in patients with AMI, such as atherosclerotic mass, underlying inflammatory process, and circulating pro-inflammatory cytokines.
The predictive power of the different risk factors of high syntax score was studied by El Kersh et al. in 2018. The study consisted of 52 patients with CAD who were admitted to Cardiology Department – Menoufia University Hospitals for elective coronary angiography. The overall SX score was calculated prospectively using the SYNTAX score algorithm. They found that aging, diabetes mellitus, and smoking were all the significant independent risk factors of the complexity of CAD and high SX score results. Hence, patients with these factors are expected to have a more complicated CAD than those in patients without these factors. Similarly, Shah et al. studied 200 patients divided into a diabetic and nondiabetic group. The found that diabetics had a higher prevalence of triple vessel disease, total occlusion of vessel, calcification and proximal vessel involvement, chronic total occlusion, and diffusely diseased vessels as compared to nondiabetics. They also total cholesterol high-density lipoprotein cholesterol was also correlated to the severity of CAD. Both studies show similar results to ours, aging reduces vascular endothelium function and arterial sclerosis progresses.
Discordant to our results was a study conducted by Ortolani et al. in 2008, they measured the level of CRP in 758 patients with acute STEMI which the median pain-to-balloon time of 3 h and they found a weak relationship between hs-CRP levels and CPKMB peak, LVEF, and post-PCI TIMI flow promoting the hypothesis that in this study hs-CRP levels were mainly related to a preexistent inflammatory (coronary) status. The fact that Ortolani et al. choose patients who presented only in the first 3 h of chest pain, might be the cause of this disagreement in results. Niccoli et al. in 2017 searched for the link between serum biomarkers of inflammation and characteristics of the thrombus in patients with STEMI, they compared optical coherence tomography and angiographic data closely relevant to thrombi, along with the histologic characteristics of aspirated thrombi in patients presenting with STEMI with or without inflammation as assessed by CRP and myeloperoxidase (MPO) and they stated that CRP and MPO were not correlated in STEMI patients, possibly reflecting different pathogenic mechanisms, it is worth mentioning that Nicolli et al., were mainly interested in assessment of thrombus age and burden rather than severity of coronary lesion, this might have caused this discordance.
Our findings have several clinical implications. Measuring serum CRP at time of presentation showed good correlation to both Syntax score and TIMI flow. Serum CRP in the second tertile (4.7–11.4 mg/l) showed >70% sensitivity to determine intermediate to high Syntax score and >80% to detection of no or faint antegrade flow (TIMI 0 and 1) in the cath lab. Thus, adding such a simple test to different risk assessment scores in STEMI patients can help refine risk assessment and better preparation of the patients before entering the cathlab.
This is a single-center study with a limited number of patients; large, multicenter studies are needed to validate these results.
| Conclusion|| |
There is a strong positive correlation between admission CRP and the syntax score and TIMI flow in STEMI patients undergoing primary PCI. There is a strong positive correlation between admission CRP and the syntax score and TIMI flow in STEMI patients undergoing primary PCI. Adding CRP to the risk scoring systems used to assess patients before PPCI can help better risk stratify patients before going into the cath lab.
Statement of ethics
The study was approved by Zagazig University ethical committee, Egypt. All patients provided written informed consent.
We gratefully acknowledge the invaluable assistance of the physicians of the Department of Cardiology, Zagazig University Hospital, Zagazig, and University School of Medicine. The study would not have been possible without their support.
Financial support and sponsorship
The authors are responsible for the study funding without the involvement of grants, scholarship, or any other sources of funding.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, et al.
The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994;331:417-24.
Ross R. Atherosclerosis – An inflammatory disease. N Engl J Med 1999;340:115-26.
Kushner I, Broder ML, Karp D. Control of the acute phase response. Serum C-reactive protein kinetics after acute myocardial infarction. J Clin Invest 1978;61:235-42.
Zebrack JS, Anderson JL, Maycock CA, Horne BD, Bair TL, Muhlestein JB, et al.
Usefulness of high-sensitivity C-reactive protein in predicting long-term risk of death or acute myocardial infarction in patients with unstable or stable angina pectoris or acute myocardial infarction. Am J Cardiol 2002;89:145-9.
Ohlmann P, Jaquemin L, Morel O, El Behlgiti R, Faure A, Michotey MO, et al.
Prognostic value of C-reactive protein and cardiac troponin I in primary percutaneous interventions for ST-elevation myocardial infarction. Am Heart J 2006;152:1161-7.
Verma S, Yeh ET. C-reactive protein and atherothrombosis – Beyond a biomarker: An actual partaker of lesion formation. Am J Physiol Regul Integr Comp Physiol 2003;285:R1253-6.
Sanchís J, Bodí V, Llácer A, Facila L, Martínez-Brotons A, Insa L, et al.
Relationship of C-reactive protein levels with angiographic findings and markers of necrosis in non-ST-segment elevation acute coronary syndrome. Rev Esp Cardiol 2004;57:382-7.
Su D, Li Z, Li X, Chen Y, Zhang Y, Ding D, et al.
Association between serum interleukin-6 concentration and mortality in patients with coronary artery disease. Mediators Inflamm 2013;2013:726178.
Sara JD, Prasad M, Zhang M, Lennon RJ, Herrmann J, Lerman LO, et al.
High-sensitivity C-reactive protein is an independent marker of abnormal coronary vasoreactivity in patients with non-obstructive coronary artery disease. Am Heart J 2017;190:1-11.
Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, et al.
Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 2008;358:1336-45.
Huffman KM, Samsa GP, Slentz CA, Duscha BD, Johnson JL, Bales CW, et al.
Response of high-sensitivity C-reactive protein to exercise training in an at-risk population. Am Heart J 2006;152:793-800.
Celik T, Iyisoy A, Kursaklioglu H, Turhan H, Kilic S, Kose S, et al.
The impact of admission C-reactive protein levels on the development of poor myocardial perfusion after primary percutaneous intervention in patients with acute myocardial infarction. Coron Artery Dis 2005;16:293-9.
Groot HE, Karper JC, Lipsic E, van Veldhuisen DJ, van der Horst IC, van der Harst P. High-sensitivity C-reactive protein and long term reperfusion success of primary percutaneous intervention in ST-elevation myocardial infarction. Int J Cardiol 2017;248:51-6.
Milano SS, Moura OV Jr., Bordin AA, Marques GL. C-reactive protein is a predictor of mortality in ST-segment elevation acute myocardial infarction. Int J Cardiovasc Sci 2019;32:118-24.
El Kersh AM, Reda AA, El Hadad MG, El-Sharnouby KH. Correlation between SYNTAX score and pattern of risk factors in patients referred for coronary angiography in cardiology department, Menoufia University. World J Cardiovasc Dis 2018;8:431-9.
Shah T. Clinical parameters and its association with coronary involvement in diabetic vs. non-diabetic cad patients with reference to syntax score. Interv Cardiol 2020;12:3-12.
Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Deanfield JE. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol 1994;24:471-6.
Ortolani P, Marzocchi A, Marrozzini C, Palmerini T, Saia F, Taglieri N, et al.
Predictive value of high sensitivity C-reactive protein in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention. Eur Heart J 2008;29:1241-9.
Niccoli G, Menozzi A, Capodanno D, Trani C, Sirbu V, Fineschi M, et al
. Relationship between serum inflammatory biomarkers and thrombus characteristics in patients with ST segment elevation myocardial infarction. Cardiology 2017;137:27-35.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]