Correlation between neutrophil to lymphocyte ratio (NLR) and red cell distribution width to platelet ratio with ST segment resolution and 2 month complications in patients with acute myocardial infarction undergoing primary coronary intervention

Hamidreza Varastehravan, Aryan Naghedi, Azam Yalameh Alia-badi, Seyedeh Mahdieh Namayandeh, Pardis Rezaei Shirinabadi. Correlation between neutrophil to lymphocyte ratio (NLR) and red cell distribution width to platelet ratio (RPR) with ST segment resolution (STR) and 2 month complications in patients with acute myocardial infarction undergoing primary coronary intervention. Cardiometry; Issue 15; November 2019; p.49-55; DOI: 10.12710/cardiometry.2019.15.4955; Available from:

Coronary artery occlusion leads to acute myocardial infarction which causes a great number of mortality and morbidity each year (1). Although coronary interventions can enhance blood perfusion in infarct area, but this method is not always successful. Finding a reason for the fact that despite angioplasty we still face no reflow zones has been a big challenge for cardiologists (2).

Risk assessment is one of the initial steps in approaching a patient with acute myocardial infarction. Risk assessment includes predicting size of ischemic and infarct area, evaluating success rate of angioplasty and predicting complications followed by coronary intervention. These days, researchers are focusing on finding a routine bedside technique for risk assessment and prognosis of these patients. Among these tests biochemical tests and electrocardiogram (ECG) can be mentioned (3, 4).

Complete blood count (CBC) test which is often done routine in the moment of admission includes important prognostic data. Neutrophil to lymphocyte ratio (NLR) as a composition of 2 important and independent inflammatory markers, is considered as a

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simple and non-specific index for inflammation (5, 6). Based on this, NLR can be used for risk assessment in patients suspected to myocardial infarction (7, 8).

Other CBC items such as platelets and red blood cell (RBC)s were also studied by previous researchers. Platelet indexes such as platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) are recognized as important risk predictors (9-11). In previous studies it was reported that red cell distribution width (RDW) is significantly elevated in patients with acute myocardial infarction (12). Based on this, RDW to platelet ratio which is abbreviated as RPR can be mentioned as an important risk assessment marker too.

ST segment resolution (STR) indicates adequate reperfusion in small vessel level and normal perfusion state in infarct area and can be used as an accurate and simple marker to evaluate myocardial reperfusion in infarct area (13, 14).

In this study we aimed to investigate the relationship between NLR and RPR with STR in patients undergoing coronary intervention and check them for complications after 2 months. At the end we want to check the value of these indexes for risk assessment and prognosis of patients with myocardial infarction undergoing coronary intervention.

Materials and methods

This is a cohort study with 2 months of follow up. All patients with typical chest pain diagnosed as myocardial infarction who were admitted in Afshar heart center for primary coronary intervention were included in this study. All patients with evidences of infection, systemic inflammatory diseases, liver dysfunction, known malignancy, isolated posterior infarction, bundle branch blocks, external pace makers, all types of anemia, steroids consumption, trauma and panic disorders were excluded. At the end a total number of 211 patients were enrolled in our study.

After excluding mentioned patients all patients were asked to sign an informed consent form. All included patients had the right to quite the study for any reason at any time they wish. ECG and venous blood sampling was done for all patients. ST segment elevation, NLR and RPR was measured and recorded in a questionnaire for all patients. Then all patients underwent primary coronary intervention and 90 minutes after coronary intervention another ECG was recorded for all patients and STR was measured for all of them.

Myocardial infarction was diagnosed based on published guidelines by America association of cardiology and European society of cardiology which is defined as classical, clinical signs and symptoms, elevation of cardiac biomarkers and ST segment elevation in at least 2 adjacent led.

Recorded ECG was a standard 12 led ECG. ST segment elevation was defined as elevated J point for at least 0.1 mV in at least 2 adjacent led except V2 and V3, 0.15 mV in females, 0.2 mV in males older than 40 years and 0.25 mV in males younger than 40 years.

STR was defined as: 1) complete resolution (more than 70%), 2) partial resolution (between 50%-70%) and 3) no resolution (less than 50%).

After blood sampling the blood analysis was done to measure CBC, cardiac biomarkers, kidney function tests, electrolytes and lipid profile. Because of the importance of NLR and RPR in this study all blood samples were analyzed using Siemens Diagnostic Clinitek device in Afshar heart center medical laboratory.

For primary coronary intervention all patients underwent angiography using Judkins technique, then primary angioplasty was performed after 70 U/Kg heparin bolus injection. All coronary interventions were done by the same interventional cardiologist to reduce inter-person skill variability.

All data were analyzed using SPSS V.16 software. Kolmogorov-Smirnov test was used to check normal distribution of data. Continuous data were reported as mean±standard deviation and discrete data were reported as percent. Independent T test was used to analyze quantitative data. Chi-square test was used for discrete data. P value below 0.05 was considered to be statistically significant.

Results and discussion

This study was designed to investigate the relationship between NLR and RPR with STR along with 2 month complications in patients with acute myocardial infarction undergoing primary coronary intervention in 211 patients.

Among 211 patients in our study, 181 (85.8%) were male and 30 (14.2%) were female. We checked age, blood pressure, pulse rate, left ventricular ejection fraction, weight, hemoglobin, cholesterol, triglycerides, low density lipoprotein (LDL), high density lipoprotein (HDL), urea, creatinine, creatinine phosphokinase (CPK), CPK-MB, white blood cell (WBC) count, NLR, PDW, RDW, RPR, platelet count

Table 1. Average of neutrophil, lymphocyte, NLR, RDW, PDW and RPR variables based on STR

Variables	ST segment Resolution			P value
	50%>	50-70%	70%<
Neutrophil	67.01±16.62	69.25±14.76	64.92±14.10	0.248
Lymphocyte	24.41±13.40	23.11±13.36	30.75±38.16	0.152
NLR	4.43±3.91	4.54±3.41	3.29±2.36	0.043
RDW	13.18±1.26	13.43±1.58	12.95±0.95	0.090
PDW	13.80±2.39	13.19±2.59	13.58±2.78	0.359
RPR	0.98±0.20	1.05±0.24	1.00±0.21	0.160

and hospitalization days for all patients and recorded all the data in our questionnaire. The average age of patients was 61.15±12.68 years and ranged between 31 and 95 years.

The most common site of myocardial infarction was recorded to be in anteroseptal area of myocardium (42.2%) and the most common vessel involved in our patient was recorded to be left anterior descending (LAD) artery (55%).

All patients were divided into 3 groups based on STR in our study. Complete resolution was defined as more than 70% resolution, partial resolution was defined as 50% to 70% resolution and no resolution was defined as less than 50% of resolution. Results of our study for neutrophil count, lymphocyte count, NLR, RDW, PDW and RPR variables based on STR are reported as mean±SD and summed up in table No.1.

As it is seen in table No.1, there is a statistically significant correlation between NLR and STR (P val-ue<0.05) which means that NLR is significantly lower in patients with STR>70%.

In this study we also observed all patients for 2 months for possible complications. Patients were divided in 4 groups based on recorded complications: 1) no complication 2) acute coronary events 3) decompensated heart failure 4) cardiovascular death. During 2 months we recorded 7 patients with cardiovascular death, 2 patients with new admission because of acute ischemia and 1 patient with hospitalization because of decompensated heart failure. In the performed analysis there was a significant correlation reported between STR and 2 month complications (P value=0.04). More details are presented in table No.2.

Results of our study based on the correlation between neutrophil count, lymphocyte count, NLR, RDW, PDW and RPR variables with 2 month complications are summed up in table No.3.

Table 2. Distribution of 2 months complications in patients

Two months complications	Number of patients	Percentage
No complication	201	95.3%
Acute coronary events	2	0.9%
Decompensated heart failure	1	0.5%
Cardiovascular death	7	3.3%
Total	211	100%

Table 3. Correlation between neutrophil, lymphocyte, NLR, RDW, PDW, RPR and two month complications in patients

Variables	P value
neutrophil	0.049
lymphocyte	0.045
NLR	0.012
RDW	0.184
PDW	0.094
RPR	0.030

As it is seen in table No.3, there is a statistically significant correlation between neutrophil count, lymphocyte count, NLR and RPR variables and 2 month complications (P value<0.05) which means that mentioned variables are significantly higher in patients with major adverse cardiac events within 2 months after primary coronary intervention.

To determine the best cut off for NLR, we used Roc curve which NLR=5 was the best cut off. We also analyzed our data with NLR=5 cut off using Chi-square test which there was a significant correlation recorded between 2 month complications and NLR=5. Details are reported in table No.4.

Table 4. Number of two month complications based on NLR=5 cut off

2 month complications	NLR cut off		Total
	NLR≥5	NLR<5
No complication	144 (71.6%)	67(28.4%)	201
Acute coronary events	2 (100%)	0 (0%)	2
Decompensated heart failure	1 (100%)	0 (0%)	1
Cardiovascular death	2 (28.6%)	5 (71.4%)	7
P value	0.035

Table 5. Correlation between STR and two-month mortality

Variable	Correlation coefficient (r)	P value
STR	-0.114	0.049

Table 6. Number of two month complications based on STR

Complications	ST segment Resolution			Total
	50%>	50-70%	70%<
No complication	68 (33.8%)	60 (29.9%)	73 (36.3%)	201
Acute coronary event	0 (0%)	1 (50%)	1 (50%)	2
Decompensated heart failure	0 (0%)	1 (100%)	0 (0%)	1
Cardiovascular death	4 (57.1%)	3 (42.9%)	0 (0%)	7

The correlation between STR and 2-month mortality was also investigated using Pearson correlation test. As seen in table No.5, the results revealed that with a correlation coefficient of r=-0.114 and P val-ue=0.049 there is a significant negative correlation between STR and 2-months mortality.

The results of present study showed that in STR<50% group there were 4 patients recorded with cardiovascular death. in STR between 50-70% group, there were 3 patients with cardiovascular death and 1 patient with acute coronary event and 1 patient hospitalized with decompensated heart failure. In STR>70% there was only 1 patient with acute coronary event recorded. The results are summed up as seen in table No.6.

Coronary artery occlusion leads to acute myocardial infarction which causes a great number of annual mortality and morbidity. Based on the most recent guidelines, primary coronary intervention in patients with ST segment elevation is suggested (1). After discovering the important role of WBC elevation in patients with acute myocardial infarction, researchers focused on finding a reliable and accurate risk assessment and prognostic value for CBC indexes (7, 8). Neutrophil to lymphocyte ratio is used as a risk assessment marker in patients with possibility of myo- cardial infarction. As different subtypes of WBC were under evaluation, other CBC indexes such as platelets and RBCs were also hot subjects for valuable studies. Considering the role of platelet in clot formation and coronary artery occlusion in infarct area, platelet markers such as MPV and PDW were introduced as risk assessment makers in numerous studies (9, 10). On the other side RDW changes were also significant in patients with acute myocardial infarction (12). Based on this RDW to platelet ratio (RPR), was also introduced as a very important risk assessment marker in different studies because RPR has a high value in estimating fibrosis complexity (15).

Our study was conducted to determine the correlation between NLR and RPR with ST segment resolution in patients undergoing primary coronary intervention with acute myocardial infarction.

Our study showed that age average in patients was 61.15±12.68 ranged between 31 and 95. In Yaylak et al study performed in turkey the age average was also 56±10 (16). In another study by Celik et al in Ankara it was again reported that the age average was 59±11 (17). In Gul et al study the age average was 56±13 (18). In another study conducted in Japan the age average was reported to be 66±1 (19). in most performed studies, acute myocardial infarction happened in 60s in majority of patients (20-22). Based on reported data it seems that acute myocardial infarction happens mostly in 60s and early 70s of age.

Our study revealed that among 211 patients, 181 of them (85.8%) were male and 30 of them (14.2%) were female which is accordance with the results of other studies which report that acute myocardial infarction happens more in men compared to women (16-22).

The results of our study showed that average RPR, NLR and STR in studied patients were respectively as 1.01±0.21, 4.07±3.31 and 0.418±0.32. in our study there was a statistically significant correlation recorded between mean NLR value based on STR value but there was no statistically significant correlation recorded between neutrophil count, lymphocyte count, RDW, PDW and RPR based on STR value in present study. It means that average NLR value was significantly lower in patients with STR>70%. In our study there was also a significant correlation reported between neutrophil count, lymphocyte count, NLR, and RPR based on 2 month complications but there was no significant relationship found between RDW and PDW indexes and 2 month complications in studied patients.

In other studies, NLR index was proved to be an effective prognostic factor in patients with acute myocardial infarction.

A study was performed by Yaylak et al in turkey in 2016 to investigate the relationship between NLR and right ventricular dysfunction in patients with acute inferior myocardial infarction. In this study it was confirmed that NLR was significantly higher in patients with right ventricular dysfunction followed by acute inferior myocardial infarction which is in correspondence with results of our study (16).

In another study performed by Celik et al in turkey it was reported that RPR was higher in patients with no reflow areas after primary coronary intervention. In our study there was no statistically significant correlation found between RPR and STR, but there was a significant relationship between RPR and 2 month complications (17).

In a study performed in Pakistan it was revealed that cardiac complications and cardiac death were recorded to be more in patients with higher NLR which is in correspondence with the results of our study (18).

In a study performed in Japan it was concluded that RDW and PDW was significantly higher in patients with acute myocardial infarction (19). In this study they investigated the difference of these 2 indexes between patients with angina pectoralis and myocardial infarction. They proved the diagnostic value of these 2 indexes but they did nothing to evaluate the prognostic value of these indexes in their study.

In a study carried out in turkey it was shown that NLR was significantly higher in patients with grade 3 ischemia. The researchers in this article believe that it is possible to use NLR as a prognostic and risk assessment index in patients with acute myocardial infarction in near future (20), which is in correspondence with the results of our manuscript.

In another study done in 2013 it was summed up that NLR was elevated as an independent marker in patients with no reflow areas after primary coronary intervention. The researchers of this paper believe that NLR can be used as a simply accessible and cheap marker for risk assessment in patients with acute myocardial infarction (21). Results of this study confirms the results of Turkmen study of 2013.

To sum up, it is logical to conclude that NLR can be used for risk assessment and prognosis in patients with acute myocardial infarction but prognostic value of other indexes such as RPR, RDW and PDW needs further evaluation in prospective cohort studies.

There was a study performed in Konakli, Turley to investigate the relationship between NLR and coronary reflow in patients undergoing primary angioplasty. They included a total of 522 patients (417 males and 105 females) with age average of 61.9±11.9 with acute myocardial infarction undergoing primary coronary angioplasty. The researchers claimed that in hospital cardiac mortality in patients was higher in high NLR group (5.775.77 is an independent marker to predict in hospital cardiac mortality in patients with acute myocardial infarction which is in correspondence with the results of our study (23).

In a study in Hatay, Turkey the researchers aimed to evaluate the relationship between coronary artery no reflow and NLR in patients undergoing primary coronary angioplasty. In this study they included a number of 204 patients (176 males and 28 females) with age average of 55.1±9.2 with acute myocardial infarction. Coronary no reflow was confirmed using angiography and electrocardiography techniques. The results of this study showed that patients with coronary no reflow and no STR (STR<30%) had a higher NLR level compared to those with partial to complete

STR. They concluded that higher NLR at the time of admission in patients with acute myocardial infarction undergoing primary coronary intervention is correlated with coronary no reflow phenomenon and poor long term prognosis. The results of their study matches our results as well (10).

Conclusion

In our study we evaluated the relationship between neutrophil count, lymphocyte count, NLR, RDW, PDW and RPR with STR. There was only a significant correlation between NLR and STR. NLR was significantly lower in patients with STR>70%.

On the other hand, there was a significant relationship observed between all mentioned indexed except RDW and PDW with 2 month complications.

It can be concluded that it is possible to use NLR and RPR to predict STR and short term complications in patients with acute myocardial infarction undergoing primary coronary intervention.

Based on our results, it seems that applying mentioned cheap, fast and accessible markers along with other prognostic markers and clinical conditions in daily practice, can be helpful in prognosis prediction and choosing the best treatment strategy (using anti-inflammatory agents such as Canakinumab) in future to prevent recurrence of acute coronary infarction (56,63).

Statement on ethical issues

Research involving people and/or animals is in full compliance with current national and international ethical standards.

Conflict of interest

None declared.

Author contributions

The authors read the ICMJE criteria for authorship and approved the final manuscript.