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Predictive Value of Serum Myeloperoxidase level in occurrence of In- Hospital Complications in Patients with acute ST Elevation Myocardial Infarction -: Author(s): Rehab Ibrahim Yassen, MD, Neveen Ibrahim Samy, MD, Ahlam Rabea Hussein Mohammed, MBBCh . Corresponding author: Neveen Ibrahim Samy, MD, Department of cardiology, Menoufia University Hospitals, Menoufia, Egypt. Reviewers: Mahmoud kamel, MD, Department of cardiology, Menoufia University Hospitals, Menoufia, Egypt,email [email protected] . Waleed Abdou, MD, Department of cardiology, Menoufia University Hospitals, Menoufia, Egypt,email [email protected] . Hend ELdeeb, MD, Department of cardiology, Menoufia University Hospitals, Menoufia, Egypt,email [email protected] . Morad Mena , MD, Department of cardiology, Menoufia University Hospitals, Menoufia, Egypt,email [email protected] . Email: [email protected] Abstract Background : Worldwide ,ishaemic heart disease is the single most common cause of death and its frequency is increasing .

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Predictive Value of Serum Myeloperoxidase level in occurrence of In- Hospital Complications in Patients with acute ST Elevation Myocardial Infarction:-

Author(s):

Rehab Ibrahim Yassen, MD, Neveen Ibrahim Samy, MD, Ahlam Rabea Hussein Mohammed, MBBCh .

Corresponding author:

Neveen Ibrahim Samy, MD, Department of cardiology, Menoufia University Hospitals, Menoufia, Egypt.

Reviewers:

Mahmoud kamel, MD, Department of cardiology, Menoufia University Hospitals, Menoufia, Egypt,email [email protected] .

Waleed Abdou, MD, Department of cardiology, Menoufia University Hospitals, Menoufia, Egypt,email [email protected] .

Hend ELdeeb, MD, Department of cardiology, Menoufia University Hospitals, Menoufia, Egypt,email [email protected] .

Morad Mena , MD, Department of cardiology, Menoufia University Hospitals, Menoufia, Egypt,email [email protected] .

Email: [email protected]

Abstract

Background:

Worldwide ,ishaemic heart disease is the single most common cause of death and its frequency is increasing .

Polymorphonuclear neutrophils (PMNs) have gained attention as critical mediators of acute coronary syndromes (ACS).

Myeloperoxidase, a hemoprotein abundantly expressed by PMNs and secreted during activation, possesses potent pro-inflammatory properties and may contribute directly to tissue injury. However, whether myeloperoxidase also provides prognostic information in patients with ACS remains unknown.(1)

Objective:

The main aim of the study was to assess the predictive value of serum myeloperoxidase level in occurrence of in hospital complications in patients with acute ST elevation myocardial infarction.

Methods:

A total of 105 subjects were included in the study: 80 patients diagnosed with acute STEMI and 25 age and sex matched apparently health control subjects. They were compared regarding serum MPO level and occurrence of in-hospital complications. MPO was measured in the serum of the patients by ELISA technique 24 hours after CCU admission after obtaining an informed written consent from the study subjects .

Results:

Serum MPO levels were significantly different between the study groups in which higher results were reported in patients with acute ST segment elevation myocardial infarction (12.2 ± 4.9 ng/mL) compared to the apparently healthy control subjects (2.3 ± 0.7 ng/mL) (p value<0.001).

Also Serum MPO levels were significantly different between the study groups in which higher results were reported in patients with in hospital complications of acute ST segment elevation myocardial infarction (14.1 ± 4.1 ng/mL) compared to the patients without complications of ST segment elevation myocardial infarction (10.2 ± 4.9 ng/ml) (p value<0.001).

Conclusion:

It can be concluded that there is MPO level predicting complicated MI

The cut off value of MPO is ≥ 12.8 (ng/mL) with sensitivity 72.5% ,spesitivity 95% and accuracy 95% .

Keywords:

ST elevation myocardial infarction complication, MPO serum levels .

Introduction:

Cardiovascular disease, and specifically acute myocardial infarction (AMI), is the main cause of morbidity and mortality worldwide, despite current preventive and therapeutic strategies(2)

Acute coronary syndromes (ACS) are characterized by increased platelet activation

and aggregation within the coronary circulation.(3)

Thrombus formation at a ruptured or eroded plaque and distal embolization of

platelet aggregates eventually lead to myocyte necrosis.(4)

In particular, the occurrence of minor myocardial injury as observed in ACS is

reliably assessed by measuring the release of troponins, which have emerged as

powerful tools for risk assessment and therapeutic management of patients with

ACS. (5)

There is growing evidence that myocardial cell injury not only is related to platelet activation but also is preceded by recruitment and activation of polymorphonuclear neutrophils (PMNs).(6)

PMNs, despite their apparent insignificance in coronary atherogenesis, have been shown to increasingly undergo degranulation within the coronary circulation in ACS.(7)

One of the principal mediators secreted on PMN activation is myeloperoxidase (MPO), a haemoprotein traditionally viewed as a microbicidal enzyme.(8) However, there is accumulating evidence that MPO also displays potent proatherogenic properties.

For example, MPO can oxidize LDL cholesterol, thereby propagating uptake by macrophages and perpetuating foam cell formation.(9)

Furthermore, MPO has been shown to activate metalloproteinases and promote destabilization and rupture of the atherosclerotic plaque surface.(10)

Also, MPO catalytically consumes endothelium- derived nitric oxide, thereby reducing nitric oxide bioavailability and impairing its vasodilatory and antiinflammatory functions.(11)

PMNs have been demonstrated to release MPO into the coronary circulation, yielding elevated MPO plasma levels in patients with unstable angina and acute myocardial infarc tion.( 12)

Therefore, the main objective of the current research is to study the correlation between serum vitamin D level and systemic hypertension.

Methods:

Study Design:

This is a cross- sectional observational study that included 80 subjects with acute STEMI who came to National Heart Institute during the period from june 2018 to june 2019.

and 25 subject age,sex matched as control group.

The subjects were divided into 3 groups :-

Group I : included 40 patients without complication of ST segment elevation myocardial infarction .

Group II : included 40 patients with complications of ST segment myocardial infarction.

Group III: included 25 subjects as control group.

The patients with acute ST elevation myocardial infarction were diagnosed by the full criteria of ST elevation myocardial infarction: Persistent typical chest pain, ECG findings as ST-segment elevation (measured at the J-point) is considered suggestive of ongoing coronary artery acute occlusion in the following cases at least two contiguous leads with ST-segment elevation 2.5 mm in men < 40 years,2 mm in men 40 years, or 1.5 mm in women 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)].(13)

In patients with inferior MI, it is recommended to record right precordial leads (V3R and V4R) seeking ST-segment elevation, to identify concomitant right ventricular (RV) infarction.(14) Likewise, ST-segment depression in leads V1–V3 suggests myocardial ischaemia, especially when the terminal T-wave is positive (ST-segment elevation equivalent), and confirmation by concomitant ST-segment elevation 0.5 mm recorded in leads V7–V9 should be considered as a means to identify posterior MI. In the presence of LBBB, the ECG diagnosis of AMI is difficult but often possible if marked ST-segment abnormalities are present.

Patients with a clinical suspicion of ongoing myocardial ischaemia and LBBB should be managed in a way similar to STEMI patients, regardless of whether the LBBB is previously known.

Criteria that can be used to improve the diagnostic accuracy of STEMI in LBBB:Concordant ST-Segment elevation >1mm in leads with apositive QRS complex ,concordant ST-Segment depression >1 mm in V1-V3 and disconcordant ST-Segment elevation >5mm in leads with anegative QRS complex.

Patients with diseases known to cause elevation of serum level myeloperoxidase as multiple sclerosis , rheumatoid arthritis, end stage renal Disease, leukemia and end stage liver disease were excluded from the study.

This study was approved by the local ethics committee and written informed consent was obtained from all participant .

All participants were subjected to detailed history: including age and gender, history of smoking, hypertension, diabetes mellitus and dyslipidemia ,clinical examination as blood Pressure measurement, pulse,neck veins and auscultation of heart to detect Additional sounds,murmurs , 12 lead ECG : ST-segment changes of myocardial infarction to diagnose ST segment elevation myocardial infarction , and to detect LVH and arrhythmias as AF, Trans-thoracic echocardiography to assess wall motion abnormality, evaluate the LV systolic function, assess valve abnormality as MR and mechanical complication as VSR and evaluate LV diastolic function and Laboratory investigation to assess the blood level of following blood cardiac markers CKMB,Troponin, and Myeloperoxidase and serum creatinine. MPO was measured in the serum of the patients by ELISA technique 24 hours after CCU admission .

Statistical Analysis:

Data were collected ,revised and edited into a master table using Microsoft Excel 2010.

Data were then revised, coded and analyzed using Statistical Program for Social Science (SPSS) version 25.0 for windows (SPSS Inc., Chicago, IL, USA) and NCSS 12.0 for windows (NCSS LCC., Kaysville, UT, USA).

Quantitative data of normal distribution were expressed as mean ± standard deviation (SD).

Qualitative data were expressed as frequency and percentage.

P-value <0.05 was considered significant, p-value <0.001 was considered as highly significant and p-value >0.05 was considered insignificant .

Results:

Our study included 80 patients with acute STEMI who came to National Heart Institute (patients group), while the control group included 25 apparently healthy control subjects with no significant difference between both groups as regarding age and sex.

Our study was conducted during the period from june 2018 to june 2019.

The mean age of non- complicated group was (55.0±11.6),complicated group mean age was (54.5±9.7) and of control group (52.3±9.2) .Table (1).

Table (1): Demographic data of studied subjects :-

Group I

N=40

Group II

N=40

Group III:

N=25

P-Value

(sig)

Age (years)

55.0±11.6

54.5±9.7

52.3±9.2

0.621 (NS)

Sex

Female

13(32.5%)

7(17.5%)

10(40%)

0.116 (NS)

Male

27(67.5%)

33(82.5%)

15(60%)

P= probability , NS = non Significant , P-Value = statistically significant at P< 0.05 .

Concerning the risk factors diabetes mellitus was more prevalent in complicated patients than non- complicated patients. . Table (2)&figure (1)

Table (2): Comparison between the studied groups regarding the risk factors :-

Group I

N=40

Group II

N=40

Group III

N=25

P-value

(Sig.)

P-value

(I, II)

P-value

(I, III)

P-value

(II, III)

Risk factors

DM

21 (52.5%)

32 (80%)

11 (44%)

0.006 (S)

0.041

0.158

0.002

HTN

23 (57.5%)

25 (62.5%)

11 (44%)

0.336 (NS)

0.588

0.177

0.089

Smoking

20 (50%)

18 (45%)

7 (28%)

0.206 (NS)

0.619

0.115

0.310

Dyslipidemia

18 (45%)

19 (47.5%)

8 (32%)

0.443 (NS)

0.899

0.367

0.324

Family history

4 (10%)

6 (15%)

3 (12%)

0.792 (NS)

0.794

0.911

0.831

DM=diabetes mellitus , P= probability , HTN=hypertension ,

P-Value=statistically significant at P< 0.05 .

Figure 1: Comparison between the studied groups regarding demographic data and the risk factors :-

DM=diabetes mellitus , HTN=hypertension .

Concerning the complications of STEMI 17 patients was complicated with heart failure ,11 patients was complicated with arrhythmia "AF,ventricular tachycardia",8 patients was complicated with conduction disturbance " complete heart block" and 4 patients was complicated with mechanical complications"ventricular septal rupture, severe mitral regurge .Table(4)

Table (4):In hospital complications of the studied patients :-

Complications

Arrhythmia

11 (27.5%)

Conduction disturbance

8 (20%)

Heart failure

17 (42.5%)

Mechanical

4 (10%)

systolic blood pressure and diastolic blood pressure were significantly lower in complicated patients than non- complicated patients(p value<0.001 ). On the contrary heart rate was significantly higher in complicated patients than non-complicated patients (p value<0.05 ) .Table(5) & figure (2) .

Table (5): Comparison between the studied patients regarding the haemodynamics :-

Haemodynamics

Group I

N=40

Group II

N =40

P-value

(Sig.)

SBP (mmHg)

Mean ± SD

120 ± 22

89 ± 16

<0.001 (HS)

DBP (mmHg)

Mean ± SD

76 ± 13

57 ± 11

<0.001 (HS)

HR (beat/min)

Mean ± SD

89 ± 19

107 ± 32

0.003 (S)

SBP=systolic blood pressure , DBP=diastolic blood pressure , HR=heart rate .

HS=highly significant , P-Value = statistically significant at P< 0.05 , SD = standard deviation . Figure 2: Comparison between the studied patients regarding haemodynamics :-

SBP=systolic blood pressure , DBP=diastolic blood pressure , HR=heart rate .

By comparing conventional echocardiography data between the studied groups we found that LVESD was significantly larger in complicated patients than non- complicated patients(p value<0.001 ), moreover it was significantly larger in complicated patients than control group (p value<0.005).Moreover LVEDD was significantly larger in complicated patients than control group(p value <0.005). On the contrary EF was significantly lower in complicated patients than non complicated patients and control group (p value<0.001 ),moreover it was lower in non complicated patients than control group (p value<0.001). Morever late diastolic wave velocity( A wave )was higher in complicated patients than non complicated patients and control group (p value<0.005 ) while early diastolic wave velocity ( E wave) and E/A ratio were significantlly lower in complicated patients than non complicated patients and control group (p value<0.001 ) ,moreover it was significantly lower in non complicated patients than control group (p value<0.001) .(Table 7)

Table (7): Comparison between the studied groups regarding the echocardiographic data:-

Echocardiographic data

Group I

N=40

Group II

N =40

Group III:

N=25

P-value

(Sig.)

P-value

(I, II)

P-value

(I, III)

P-value

(II, III)

LA (cm)

Mean ± SD

3.7 ± 0.4

3.8 ± 0.3

3.6 ± 0.3

0.425 (NS)

0.432

0.477

0.163

LVEDD (cm)

Mean ± SD

5.0 ± 0.3

5.1 ± 0.4

4.9 ± 0.4

0.662 (NS)

0.686

0.055

0.024

LVESD (cm)

Mean ± SD

3.3 ± 0.3

3.8 ± 0.6

3.1 ± 0.4

<0.001 (HS)

<0.001

0.051

0.008

EF (%)

Mean ± SD

50.1 ± 5.6

38.0 ± 5.4

53.2 ± 6.4

<0.001 (HS)

<0.001

<0.001

<0.001

E wave velocity (m/s)

Mean ± SD

0.84 ± 0.11

0.56 ± 0.08

0.92 ± 0.14

<0.001 (HS)

<0.001

<0.001

<0.001

A wave velocity (m/s)

Mean ± SD

0.76 ± 0.13

0.83 ± 0.09

0.68 ± 0.11

0.008 (S)

0.003

<0.001

<0.001

E/A

Mean ± SD

1.11 ± 0.22

0.68 ± 0.08

1.19 ± 0.25

<0.001 (HS)

<0.001

<0.001

<0.001

P-Value = statistically significant at P< 0.05 , LA=left atrium , LVESD= left ventricular end systolic dimension , EF=ejection fraction , LVEDD=left ventricular end diastolic dimension , ( E wave)= early diastolic wave velocity ,

( A wave )= late diastolic wave velocity , E/A= early diastolic wave velocity/ late diastolic wave velocity .

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However, by looking at the serum level of MPO at MI patient in comparison with controls MPO level at MI patient was 12.2 ± 4.9 (ng/mL) and 2.3 ± 0.7 (ng/mL) at controls which mean MPO level is significant at MI patients. Table (9) &figure 3

Table (9): Comparison between the studied groups regarding the MPO serum level:-

Group I

N=40

Group II

N =40

Group III:

N=25

P-value

(Sig.)

MPO( ng/ml)

Mean ± SD

10.2 ± 4.9

14.1 ± 4.1

2.3 ± 0.7

<0.001 (HS)

P-Value = statistically significant at P< 0.05 , MPO=myeloperoxidase , P = probability . Figure (3): Comparison between the studied patients regarding the MPO serum level :-

According to the ROC curve analysis for MPO level predicting complicated MI

The cut off value of MPO is ≥ 12.8 (ng/mL) with sensitivity 72.5% ,spesitivity 95% and accuracy 95% .

ROC curve analysis for MPO levels predicting the occurrence of in hospital complications of ST elevation myocardial infarction patients :-

Discussion:

Ischemic Heart Disease (IHD) is the leading cause of death worldwide, accounting for 12.7% of global mortality.

Acute coronary syndrome (ACS) covers a wide spectrum of clinical conditions ranging from unstable angina to non-ST elevation myocardial infarction (N-STEMI) and ST elevation myocardial infarction (STEMI). (Govindarajan et al, 2016)(15)

An acute ST-elevation myocardial infarction is an event in which transmural myocardial ischemia results in myocardial injury or necrosis. STEMI is the most acute manifestation of coronary artery disease and is associated with great morbidity and mortality. (Kaya et al, 2015)(16)

Complications following ST-segment elevation myocardial infarction are myocardial dysfunction, arrhythmias, and mechanical complications as ventricular septal rupture and papillary muscle rupture and pericarditis. (Mariani et al, 2015)(17)

Oxidative stress and inflammation play vital roles in pathogenesis and progression of CAD leading to ACS. (Vitulli et al, 2014)(18)

Inflammation is implicated in all stages of atherosclerosis, from early lipid deposition to plaque rupture , Inflammation mediates the weakening of fibrous cap and makes the plaque more susceptible to rupture, thus precipitating ACS. (Libby et al, 2014)(19)

Reactive oxygen species and oxidative damage, which are induced by inflammatory cells, are important contributors to cardiovascular diseases, including ACS. (Panth et al, 2016)(20)

Myeloperoxidase (MPO) is secreted by leukocytes in response to oxidative stress , In cases of inflammation, MPO is profuse in leukocytes , It acts to produce reactive oxidative substances, and it causes catalytic activity in atherosclerotic lesions.

In patients who have angiographically documented CAD, MPO levels are found to be increased in lesions that are prone to rupture. (Kaya et al, 2015)(21)

Our study aimed to assess the predictive value of serum myeloperoxidase level in occurrence of in- hospital complications in patients with acute ST elevation myocardial infarction.

This is a cross-sectional observational study that included 80 patients with acute STEMI who admitted to National Heart Institute and 25 subjects age and sex matched as control group.

The subjects were divided into 3 groups, group I included 40 non complicated patients of ST segment elevation myocardial infarction, group II included 40 complicated patients of ST segment elevation myocardial infarction and group III included 25 subjects as control group.

Our study showed that diabetes mellitus was more prevalent in complicated patients than non-complicated patients (p value<0.05) and more prevalent in complicated patients than control subjects (p value<0.05).

On The Contrary there was no statistical difference between the studied groups regarding HTN, smoking, dyslipidemia and family history (p value<0.05).

Our study was concordant with a study conducted by Ammar et al, 2018 (22)on 100 patients presented with acute MI (divided into diabetic and nondiabetic groups) to assess the influence of DM on the clinical outcome in patients with acute myocardial infarction treated with primary coronary stenting within 24 h of the onset of symptoms and showed that diabetic patients were more likely to have major adverse cardiac events.

Diabetes mellitus is an important risk factor for the development of coronary disease, it influences outcomes following ACS. A subgroup analysis of patients with diabetes with STEMI in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial demonstrated significantly higher all-cause mortality at 30 days compared with patients without diabetes. (Ammar et al, 2018)(22).

Regarding to our results, SBP and DBP were significantly lower in complicated patients than non- complicated patients (p value<0.05).

On the contrary HR was significantly higher in complicated patients than non-complicated patients (p value<0.05)

Our results also was concordant with Gul et al 2018 (23)who assessed the importance of blood pressure on 261 patients after anterior STEMI and showed that SBP < 90 mmHg after AMI was generally considered to be a poor prognostic indicator and associated with higher incidence of cardiac complications.

Morever Mouhat et al, 2020 (24) aimed to identify optimal systolic blood pressure during the 48 first hours after admission for acute myocardial infarction and its prognostic value for cardiovascular mortality and stated that low SBP on admission is usually associated with a poor prognosis.

Regarding to our results, HR was significantly higher in complicated patients than non-complicated patients (p value<0.05)

This was concordant with Acharya, 2018(25) who studied the predictors of outcomes in myocardial infarction and cardiogenic shock and found that HR was a predictor of cardiac adverse effects and higher HR was associated with more complications.

In our study the complications were significantly lower in patients treated with primary PCI than who were received thrombolytic (p value <0.001)

In Lanz et al, 2019(26), who study the characteristics and outcomes of 2508 patients presented with STEMI showed that 50 % of complicated patients underwent PCI while all uncomplicated patients underwent PCI with statistical significant difference between both groups.

Our results showed that LVESD was significantly larger in complicated patients than non- complicated patients(p value<0.001), On the contrary EF was significantly lower in complicated patients than non-complicated patients (p value<0.001). Morever late diastolic wave velocity (A wave) was higher in complicated patients than non- complicated patients (p value<0.005) while early diastolic wave velocity (E wave) and E/A ratio were significantlly lower in complicated patients than non-complicated patients (p value<0.001).

A Study conducted by Ye et al, 2018(27) on 1600 patients to assess the reduced left ventricular ejection fraction as a risk factor for in-hospital mortality after PCI stated that the in-hospital mortality of patients with EF ≥50% was significantly lower than of patients with EF <50%.

Similary Brezinov et al, 2017(28) a study conducted on 8983 patients presented with ACS to identify factors associated with higher mortality stated that LVEF at admission is a strong predictor of mortality in ACS, and prognostic factors differ according to LVEF during admission.

Our results showed that serum CKMB was higher at complicated patients more than non-complicated patients.

This was concordant with a study conducted by Emukhvari et al, 2015 (29)on 105 patients with acute myocardial infarction and underwent PCI which stated that the elevated level of CKMB was associated with increased hospital complications rate, 30-day and 6 months hospitalization rate and 6 months mortality rate.

Our study showed that MPO level was significantly higher in complicated group than uncomplicated and control groups.

In concordant with our study, a study conducted by Kaya et al, 2012(30) on 73 patients with MI to assess the potential role of plasma myeloperoxidase level in predicting long-term outcome of acute myocardial infarction, stated that the evaluation of plasma myeloperoxidase levels might be useful in determining patients at high risk of death and MACE who can benefit from further aggressive treatment and closer follow-up and The STEMI patients who experienced MACE during the follow-up period also had significantly higher plasma MPO levels than did those who were MACE free.

In concordant with our results a study conducted by Govindarajan et al, 2016(31)

on 93 patients with chest pain to assess the prognostic value of plasma

myeloperoxidase level in patients with suspected ACS showed that patients with complication had higher level of mean MPO level with statistical significant difference between both complicated and uncomplicated groups so plasma MPO level on admission could predict the development of complications during their hospital stay.

Study Limitations:

· Small number of the study population

· Serum myeloperoxidase levels increased in obesity but we didn't exclude obese patients from our study as it is risk factor for CAD .

· We didn't follow up the changes in the serum myeloperoxidase level before discharge as it was done once .

· We didn't follow up the complicated patients with elevated serum myeloperoxidase level for long-term cardiovascular events.

Conclusion

In our study, we concluded that MPO level can predict occurrence of in- hospital Complications in Patients with acute ST Elevation Myocardial Infarction.

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