Acute reperfusion treatment in cases with ST-elevation myocardial infarction and peripheral neutrophilia

Musa İlker Durak; Ahmet Ünalır

doi:10.5606/e-cvsi.2024.1671

Abstract

Objectives

The study aimed to assess the correlation between neutrophil count at admission and during the short-term follow-up period with clinical outcomes in individuals presenting with ST-elevation myocardial infarction (STEMI).

Patients and methods

This prospective study was conducted between March 2010 and September 2010. Seventy-two patients (58 males, 14 females; mean age: 67Â±12 years; range, 50 to 89 years) diagnosed with acute coronary syndrome presenting with STEMI were included in the study. Complete blood count, serum glucose, urea, creatinine levels, and glomerular filtration rate were assessed in patients at 0, 4, 24, and 48 h. Patients were stratified according to the Killip-Kimball classification. Adverse clinical outcomes were defined as death, reinfarction, and cerebrovascular disease.

Results

Adverse clinical outcomes were significantly higher in patients with higher age and Killip-Kimball scores (p=0.04, p<0.01). A correlation was identified between the white blood cell (WBC) count at 48 h (p=0.04) and the neutrophil count at all time points with adverse clinical outcomes (p<0.05).

Conclusion

In our study, a correlation was determined between WBC and neutrophil counts and the rates of in-hospital mortality and adverse clinical outcomes in individuals presenting with acute STEMI. Elevated neutrophil count assessed upon admission to the hospital and during short-term follow-up may be utilized to identify high-risk patients.

Keywords:

Acute coronary syndrome, Killip-Kimball Classification, neutrophil count, ST elevation myocardial infarction

Introduction

Acute coronary syndrome (ACS) is a group of clinical syndromes caused by acute myocardial ischemia. It can lead to heart failure, arrhythmias, and even sudden death. It is recognized as a prominent factor contributing to disability and mortality on a global scale.[1] Neutrophils, which are innate immune cells within the body, play a crucial role as the initial barrier of protection against pathogens. Stimulation of neutrophils can trigger various pathological processes, including inflammation.[2] It has been demonstrated that systemic inflammatory mediators play a significant role in atherosclerosis and coronary artery disease.[3] The elevation of circulating white blood cells (WBCs), nonspecific markers of inflammation, can lead to adverse clinical outcomes in coronary artery disease, including ST-elevation myocardial infarction (STEMI).[4] It has been reported that particularly neutrophils are associated with extensive infarct areas, worse angiographic outcomes, and adverse short-term prognosis in STEMI.[5] Neutrophils are known to trigger coagulation, increase microvascular permeability, and mediate ischemia reperfusion injury in ACS.[6]

According to current guidelines, the gold standard treatment following STEMI is percutaneous coronary intervention.[7] Acute reperfusion therapy is preferred in situations where percutaneous coronary intervention cannot be performed. It has been shown that early reperfusion therapy improves outcomes in patients with STEMI.[8]

The relationship between neutrophil counts and angiographic indexes during reperfusion is not clear.

The objective of this study was to assess the correlation between neutrophil count at admission and during the short-term follow-up period with clinical outcomes in patients diagnosed with STEMI.

Methods

This prospective study was conducted at the Eskişehir Osmangazi University Faculty of Medicine between March 2010 and September 2010. Seventy-two patients (58 males, 14 females; mean age: 67±12 years; range, 50 to 89 years) diagnosed with ACS and presenting with STEMI upon admission to the emergency department were included in the study.

A STEMI was defined according to the criteria outlined in the consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction.[9] Patients under 18 years of age, pregnant individuals, those with active malignancy or active infection within the last three months, and patients with multiple organ failure were excluded from the study. Adverse clinical outcomes during follow-up included death, reinfarction, and cerebrovascular disease (CVD).

The Killip-Kimball classification (KC) was developed by Killip and Kimball[10] to stratify patients into four groups according to clinical criteria. In the present study, patients were divided into two groups according to the KC: Group 1 consisted of 60 (83.3%) patients with KC-I (no signs of congestion) or KC-II (S3 heart sound and basal rales on auscultation, and Group 2 consisted of 12 (26.7%) patients with KC-III (acute pulmonary edema) or KC-IV (cardiogenic shock).

Complete blood count was performed for all patients at 0, 4, 24, and 48 h after admission.

Hemoglobin, hematocrit, WBC count, and neutrophil count data were compared. Analysis was conducted using the Siemens Advia 2120i device (Siemens Healthcare Diagnostics Inc., Tarrytown, USA).

Venous blood samples were obtained between 8:00 and 9:00 in the morning following an overnight fasting of 8 to 10 h. Serum glucose, urea, and creatinine levels were analyzed using the Cobas Integra 400 plus device (Roche Diagnostics, Basel, Switzerland). The glomerular filtration rate (GFR) value was determined using the Modification of Diet in Renal Disease criteria.

Statistical analysis

The data were analyzed using IBM SPSS version 19 software (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were expressed as frequency. For the comparison of continuous variables showing normal distribution, Student's t-test was used, while for those not showing normal distribution, the Mann-Whitney U test was employed. For the comparison of categorical variables, the chi-square test was used. A p-value <0.05 was considered statistically significant.

Results

Primary percutaneous coronary intervention was performed in 52 (72.2%) of the patients included in the study. Among the patients, 35 (48.6%) had hypertension, 15 (20.83%) had a family history of coronary artery disease, 28 (38.9%) had diabetes mellitus, 31 (43.1%) were smokers, and 14 (19.4%) had hyperlipidemia. Adverse outcomes were identified in 12 (16.7%) patients. Among these, reinfarction occurred in three (4.2%) patients, CVD in two (2.8%) patients, and death in seven (9.7%) patients. In the two patients who developed CVD, the etiology was ischemic in both cases, and no deaths were observed during follow-up (Table 1).

In the evaluation according to the presence of adverse outcomes, A positive relationship was found within the context of age between the two groups (p=0.01), while a negative relationship was observed within the context of smoking status (p=0.04). In patients with KC III-IV upon admission to the coronary intensive care unit, adverse clinical outcomes were significantly higher (p<0.01, Table 1).

White blood cell and neutrophil counts were assessed at 0, 4, 24, and 48 h. A relationship was observed between WBC count at 48 h (p=0.04) and neutrophil count at all time points with adverse clinical outcomes (p<0.05, Table 2).

The relationship between clinical characteristics, hematological parameters, KC scores, and mortality within adverse clinical outcomes was evaluated.

A significant relationship was found between advanced age, elevated WBC count at 48 h, elevated neutrophil count at all time points, and mortality (p<0.05). Out of the seven deceased patients, six were in Group 2, while only one patient was in Group 1 (p<0.01, Table 3).

When those with and without adverse clinical outcomes were compared, a positive relationship was observed between elevated blood sugar and creatinine levels, and a negative relationship was observed with GFR (p<0.01, Table 3).

When the patients were compared based on normal and elevated neutrophil levels, neutrophil levels were significantly higher in patients with higher age, creatinine, and KC scores (Table 4).

Discussion

Acute coronary syndrome is one of the most significant contributors to cardiovascular morbidity and mortality.[11] Inflammation plays a significant role in the development of ACS, according to a study.[12]

In this study, a direct correlation was observed between an increase in the WBC, particularly neutrophil count, at the time of diagnosis and during follow-up and adverse clinical outcomes in patients presenting to our emergency department due to STEMI. Adverse clinical outcomes were characterized as mortality, recurrent infarction, and CVD. In our study, the neutrophil count was significantly higher in those who were older and had high KC scores and creatinine levels. Patients with adverse clinical outcomes were older and had higher KC scores. In this group of patients, the neutrophil count was significantly elevated at the time of diagnosis and throughout the short follow-up period. Similarly, when it comes to their relationship with mortality, mortality was higher in those with high neutrophil counts, KC scores, and creatinine.

Acute myocardial infarction (AMI) is a systemic inflammatory disease triggered by acute inflammation.

The severity of inflammation correlates with the extent of myocardial infarction. In patients with elevated WBC and neutrophil counts during the course of AMI, a larger infarct size was observed.[13] In the study conducted by Tavares et al.,[14] individuals with higher neutrophil ratios were found to be older, had higher KC scores, had a higher rate of smoking, exhibited more impaired renal function, and experienced a higher rate of hospitalization for all causes. On the other hand, according to a study comparing neutrophil counts and infarct size in patients with AMI, individuals with high neutrophil counts at admission statistically had a significantly larger infarct area.[15] In another study involving 363 patients with AMI, it was observed that individuals with high neutrophil and WBC counts had significantly more extensive infarct areas along with a higher incidence of adverse cardiac endpoints.[16] In our study, adverse clinical outcomes were more prevalent in elderly patients and those with KC scores of III-IV.

Similar to the study conducted by Mello et al.,[17] it was observed that mortality rates increased with higher KC scores and age following ACS. The reason for the association between elevated neutrophil counts post STEMI and adverse clinical outcomes may be attributed, as demonstrated in previous studies, to the role of leukocytes, particularly neutrophils, in plaque rupture, reperfusion injury, and remodeling processes in ACS.[18] Furthermore, neutrophils may trigger the occurrence of reinfarction by facilitating platelet neutrophil interactions, thrombus formation, and the continuation of coagulation through the membrane attack complex-1 (CD11b-CD18) pathway.[19] The high neutrophil percentage may also be independently associated with damage occurring in microvascular perfusion. Interactions between neutrophils, platelets, and endothelium in ACS can also lead to cytokine release, which may contribute to microvascular dysfunction.[20] In a study involving 160 patients with non-ST-elevation ACS, it was found that cases with high neutrophil counts upon admission to the hospital had a statistically higher incidence of death, acute heart failure, and recurrent myocardial infarction.[21] In our study, patients in the group with high neutrophil counts had higher creatinine levels and lower GFR. Similar to our study, in a study conducted, impaired renal function resulted in increased mortality and prolonged intensive care unit stay in patients undergoing reperfusion therapy after STEMI.[22]

The most significant limitation of the study is the small number of participants. Additionally, two different reperfusion strategies were applied to the patients. Pharmacological reperfusion was attained through the administration of thrombolytic therapy, whereas mechanical reperfusion was achieved through primary percutaneous coronary intervention. These two methods have different effects on systemic inflammation. In our study, the majority of patients underwent primary percutaneous coronary intervention treatment.

In conclusion, a correlation was determined between WBC and neutrophil counts and the rates of in-hospital mortality and adverse clinical consequences in individuals presenting with acute STEMI. There are numerous studies conducted on the WBC count in patients diagnosed with ACS, including AMI.

However, the number of studies examining the relationship between neutrophil count and adverse clinical outcomes is limited. Elevated neutrophil count assessed upon admission to the hospital and during short-term follow-up may be utilized to identify highrisk patients.

Ethics Committee Approval: The study protocol was approved by the Eskişehir Osmangazi University Faculty of Medicine Ethics Committee (date: 21.05.2010, no: PR-10-03-19-09). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Patient Consent for Publication: A written informed consent was obtained from each patient.

Data Sharing Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author Contributions: Idea/concept, data collection and/ or processing, literature review, writing the article, critical review, references and fundings, materials: M.İ.D.; Design, control/supervision, analysis and/or interpretation: M.İ.D., A.Ü.

Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding: The authors received no financial support for the research and/or authorship of this article.

References

Collet JP, Thiele H. The 'Ten Commandments' for the 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2020;41:3495-7. doi:10.1093/eurheartj/ehaa624.

Wu Y, Wei S, Wu X, Li Y, Han X. Neutrophil extracellular traps in acute coronary syndrome. J Inflamm (Lond) 2023;20:17. doi: 10.1186/s12950-023-00344-z.

Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999;340:115-26. doi: 10.1056/NEJM199901143400207.

Seropian IM, Sonnino C, Van Tassell BW, Biasucci LM, Abbate A. Inflammatory markers in ST-elevation acute myocardial infarction. Eur Heart J Acute Cardiovasc Care 2016;5:382-95. doi: 10.1177/2048872615568965.

Kirtane AJ, Bui A, Murphy SA, Barron HV, Gibson CM. Association of peripheral neutrophilia with adverse angiographic outcomes in ST-elevation myocardial infarction. Am J Cardiol 2004;93:532-6. doi: 10.1016/j. amjcard.2003.11.013.

Biasucci LM, D'Onofrio G, Liuzzo G, Zini G, Monaco C, Caligiuri G, et al. Intracellular neutrophil myeloperoxidase is reduced in unstable angina and acute myocardial infarction, but its reduction is not related to ischemia. J Am Coll Cardiol 1996;27:611-6. doi: 10.1016/0735- 1097(95)00524-2.

Ibánez B, James S, Agewall S, Antunes MJ, Bucciarelli- Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Rev Esp Cardiol (Engl Ed) 2017;70:1082. doi: 10.1016/j.rec.2017.11.010.

Ong ME, Wong AS, Seet CM, Teo SG, Lim BL, Ong PJ, et al. Nationwide improvement of door-to-balloon times in patients with acute ST-segment elevation myocardial infarction requiring primary percutaneous coronary intervention with out-of-hospital 12-lead ECG recording and transmission. Ann Emerg Med 2013;61:339-47. doi:10.1016/j.annemergmed.2012.08.020.

Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-69. doi: 10.1016/ s0735-1097(00)00804-4.

Killip T 3rd, Kimball JT. Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol 1967;20:457-64. doi: 10.1016/0002- 9149(67)90023-9.

Lewis EF, Moye LA, Rouleau JL, Sacks FM, Arnold JM, Warnica JW, et al. Predictors of late development of heart failure in stable survivors of myocardial infarction: The CARE study. J Am Coll Cardiol 2003;42:1446-53. doi:10.1016/s0735-1097(03)01057-x.

Chen B, Frangogiannis NG. Immune cells in repair of the infarcted myocardium. Microcirculation 2017;24. doi:10.1111/micc.12305.

Pek PP, Loy EY, Wah W, Ho AFW, Zheng H, Fook-Chong SMC, et al. Reperfusion treatment delays amongst patients with painless ST segment elevation myocardial infarction. CJEM 2017;19:355-63. doi: 10.1017/cem.2016.376.

Tavares F, Moraes PIM, Souza JM, Barbosa AH, Santos EM, Marcondes JA, et al. Prognostic role of neutrophil-tolymphocyte ratio in patients with ST-elevation myocardial infarction undergoing to pharmaco-invasive strategy. Cardiovasc Revasc Med 2022;34:99-103. doi: 10.1016/j. carrev.2021.01.027.

Dogan I, Karaman K, Sonmez B, Celik S, Turker O. Relationship between serum neutrophil count and infarct size in patients with acute myocardial infarction. Nucl Med Commun 2009;30:797-801. doi: 10.1097/ MNM.0b013e32832e3a16.

Chia S, Nagurney JT, Brown DF, Raffel OC, Bamberg F, Senatore F, et al. Association of leukocyte and neutrophil counts with infarct size, left ventricular function and outcomes after percutaneous coronary intervention for ST-elevation myocardial infarction. Am J Cardiol 2009;103:333-7. doi: 10.1016/j.amjcard.2008.09.085.

Mello BH, Oliveira GB, Ramos RF, Lopes BB, Barros CB, Carvalho Ede O, et al. Validation of the Killip-Kimball classification and late mortality after acute myocardial infarction. Arq Bras Cardiol 2014;103:107-17. doi: 10.5935/ abc.20140091.

Naruko T, Ueda M, Haze K, van der Wal AC, van der Loos CM, Itoh A, et al. Neutrophil infiltration of culprit lesions in acute coronary syndromes. Circulation 2002;106:2894- 900. doi: 10.1161/01.cir.0000042674.89762.20.

Bazzoni G, Dejana E, Del Maschio A. Platelet-neutrophil interactions. Possible relevance in the pathogenesis of thrombosis and inflammation. Haematologica 1991;76:491-9.

Frangogiannis NG, Youker KA, Rossen RD, Gwechenberger M, Lindsey MH, Mendoza LH, et al. Cytokines and the microcirculation in ischemia and reperfusion. J Mol Cell Cardiol 1998;30:2567-76. doi: 10.1006/jmcc.1998.0829.

Karabinos I, Koulouris S, Kranidis A, Pastromas S, Exadaktylos N, Kalofoutis A. Neutrophil count on admission predicts major in-hospital events in patients with a non-ST-segment elevation acute coronary syndrome. Clin Cardiol 2009;32:561-8. doi: 10.1002/clc.20624.

Choi JS, Kim MJ, Kang YU, Kim CS, Bae EH, Ma SK, et al. Does gender influence the impact of impaired renal function on prognosis after ST-segment elevated myocardial infarction? Cardiol J 2013;20:526-32. doi:10.5603/CJ.2013.0138.