The Relationship Between Serum Apolipoprotein B Levels and Severity of Coronary Lesions Using The Syntax Score in Non-St Segment Elevation Acute Myocardial Infarction Patients at Haji Adam Malik General Hospital Medan

INTRODUCTION

Cardiovascular disease ranks first as the cause of death in the world.[1] Data from the Global Burden of Cardiovascular Disease and Risk Collaboration released in December 2022 revealed that Coronary Heart Disease (CHD) is the main cause of death from cardiovascular causes, namely 9.44 million people in 2021 and the number 185 million people with disabilities.[2] Indonesian data itself is quite consistent with the prevalence in the global population, namely the ratio of deaths due to CHD is almost close to 150 per 100,000 population.[2] Riskesdas data in 2018 shows the prevalence of CHD sufferers in North Sumatra is around 1.3% of the total population.[3]

Coronary heart disease is a pathological process characterized by accumulation of atherosclerotic plaque in epicardial arteries, both obstructive and non-obstructive. This process can occur over a long period of time, in stable periods but can suddenly change to become unstable, usually due to an acute atherothrombotic event due to plaque rupture or erosion. The dynamic course of this disease process can appear in a variety of clinical presentations, which are categorized into Acute Coronary Syndrome (CCS) and Chronic Coronary Syndrome (CCS). ST (IMANEST), and Acute Myocardial Infarction with ST Segment Elevation (IMAEST).[5] Partial thrombus occlusion occurs in IMANEST and APTS, while total thrombus occlusion occurs in IMAEST.[6]

Various risk factors affect the development of CHD, including Low-density Lipoprotein Cholesterol (LDL-C), Apolipoprotein (Apo) B, ApoA1, total cholesterol, triglycerides, high-density lipoprotein (HDL-C), and lipoprotein (a) (Lp[a]) so that it is used as a therapeutic target based on current clinical practice guidelines. 7 It is recommended that patients with high risk undergo a second layer of examination, including non-HDL cholesterol, apoprotein B (apoB), apoprotein A (apoA), lipoprotein (a), small- dense LDL, and oxidized-LDL.[8]

Apolipoprotein B is a structural protein that is the main component of very low density lipoprotein (VLDL), medium density lipoprotein (IDL), and low density lipoprotein (LDL). Each of these lipoprotein particles carries one apoB molecule.[9] Knowledge of apoB levels can describe the number of potentially atherogenic lipoprotein particles.[7] Apolipoproteins also play an important role in structural bonding, lipid transport and stable lipoproteins, but also play a role in regulating enzyme activity in metabolism. lipoprotein and recognition of lipoprotein receptors.[10] Apolipoprotein B also plays a role in stimulating smooth muscle proliferation in the arteries and into the subendothelium. Because of this role, it is suspected that apoB is the most likely component to cause atherosclerosis.

Currently, there are various scoring systems used to assess the severity of coronary artery stenosis. The SYNergy score between percutaneous coronary intervention (PCI) with TAXus and cardiac surgey (SYNTAX) (SS) is a scoring system that has been widely and routinely used in clinical practice to determine the complexity of coronary lesions based on anatomical characteristics such as lesion location, severity, bifurcation, and calcification. 12 In a study conducted by Boyraz B (2022) comparing the SYNTAX score and the Gensini score in the severity of coronary lesions and the selection of Coronary Artery Bypass Surgery (CABG) decisions in multivessel CHD patients at Diyarbakir Gazi Yaşargil Education and Research Hospital Turkey showed the SYNTAX score was superior to the score Gensini (AUC 0.759 vs 0.680; p<0.001).[13] In its development, the SYNTAX score began to be applied in risk stratification of coronary lesions, identification of individual risk profiles, which allows its application as a predictor of coronary lesion severity in general.[14]

In a study that tested the relationship between serum LDL-C and ApoB on the severity of coronary lesions as assessed by the SYNTAX score by Taiwu Lin, et al (2018) concluded that ApoB and LDL-C had a positive correlation with the SYNTAX score (r=0.632 and 0.599; p< 0.1), but this study excluded ACS patients, patients with a history of myocardial infarction and CABG.[7] Another study conducted by Nurulita, et al (2011) at Dr. Wahidin Sudirohusodo Makassar concluded that ApoB could be used as a predictor of ACS (r>0.4; p<0.01) but did not correlate it with the severity of the lesion.[15] Until now, no studies had been conducted linking apoB levels and severity of coronary lesions using the SYNTAX score specifically in the IMANEST population.

METHOD

This research is a retrospective cohort study. Researchers will examine all research subjects with a diagnosis of heart failure with reduced ejection fraction (HFrEF) at Haji Adam Malik General Hospital Medan and see if the patient has been rehospitalized within 30 days and 6 months since the last hospitalization. The inclusion criteria for this study were subjects with heart failure with EF <40% who were treated at the Integrated Heart Center at H. Adam Malik Hospital. Meanwhile, poor echocardiographic features cannot assess diastolic function. Patients with organic valvular heart defects, patients with congenital heart disease, and patients with arrhythmias and pacemaker use are included as exclusion criteria.

Before the research started, the researchers asked for information on passing the ethical review (ethical clearance) to the Standing Committee for Research Ethics Assessment, Faculty of Medicine, University of North Sumatra.

All samples of this study were patients with a diagnosis of heart failure with reduced ejection fraction (HFrEF) who were treated at the Integrated Heart Center of Haji Adam Malik General Hospital Medan in January 2021-December 2021 who met the inclusion and exclusion criteria. The diagnosis of heart failure was made based on the heart failure guidelines from ESC and PERKI. Collecting samples using the total sampling method.

The researcher examined the patient's medical record to see the history, physical examination, electrocardiography (ECG), blood laboratory and echocardiography results and then recorded the complete data. Patients with a diagnosis of heart failure underwent pre-discharge echocardiography to assess diastolic function. Diastolic function is assessed using the ratio E/A, average ratio E/E', TR velocity, LA volume index, and deceleration time. Then the degree of diastolic dysfunction was assessed using the 2016 American Society of Echocardiography (ASE) guidelines concerning Evaluation of Left Ventricular Diastolic Function. Based on the ASE guidelines regarding the evaluation of diastolic function, the degree of diastolic dysfunction is divided into 3, namely, grade I dysfunction, grade II dysfunction, and grade III dysfunction. The degree of dysfunction is then grouped according to LA filling pressure, where grade I dysfunction has normal LA filling pressure, and grade II and III dysfunction has increased filling pressure. Based on this, the population with diastolic dysfunction will be divided into 3 groups, namely the group with Grade I diastolic dysfunction, the group with Grade II diastolic dysfunction, and the group with Grade III diastolic dysfunction. Echocardiographic examination will be carried out with GE Healthcare VIVID S60N and GE Healthcare VIVID e9 BT13 machines and carried out by residents participating in the education specialist program for heart and blood vessels who are currently at the Non-Invasive Cardiology Imaging stage and the results of the examination have been validated by two cardiologists and specialists in heart and vessels echocardiography consultant blood.

The patient will be followed up by means of telecommunications and asked whether the patient experienced rehospitalization due to heart failure within 30 days and 6 months after being hospitalized. The data collected was then carried out the chi square test. Statistical data analysis using computer statistical tools, p value <0.05 is said to be statistically significant.

RESULT

Description Characteristics Sample

This study was studies cohort retrospective with patient undergoing heart failure with reduced ejection fraction (HFrEF) at the Heart Center Integrated RSUP Haji Adam Malik Medan started January 2021 to December 2021 as subject research . Of the total 110 subjects entered in this study, only 93 subjects fulfilled criteria inclusion and exclusion as well as have complete echocardiographic data and can contacted through telecommunication. Whole subject study experience dysfunction diastolic. Characteristics observed samples was age, type sex, comorbid (CAD, HHD, DM, cardiomyopathy), fraction ejection ventricle left (LV EF), mitral inflow, tissue doppler imaging (TDI), degrees dysfunction diastolic ventricle left, left atrial volume index (LAVI), contractility ventricle ( TAPSE) and 30 days rehospitalization as well as 6 months .

Table 1. Characteristics demographic subject study

Variable			N=93
Age	54.26 ± 13.23 years
Sex
Man			80 (86%)
Woman			24 (14%)
Comorbid
CAD			83 (89.2%)
HHD			32 (34.4%)
DM			19 (20.4%)
CKD			14 (15.1)
Cardiomyopathy			8 (8.6%)
LV EF		28.72 ± 7.6 %
Mitral inflow (E/A)		1.81 ± 1.26
TDI (E/e')		15.85 ± 6.83
TRV max		2.71 ± 0.9m/s
LAVI		39.82 ± 21.88 ml/m 2
TAPSE		16.94 ± 3.64 mm
dysfunction pre discharge diastolic
Grade I			40 (43%)
Grade II			22 (23.7%)
Grade III			31 (33.3%)
Rehospitalization
30 days			34 (36.6%)
6 months			21(26.6%)

Based on type gender, majority subject study is male (86%) with average age 54.26 ± 13.23 years. Majority subject study had comorbid disease heart coronary (CAD) about 83 people (89.2%) from 93 subjects research. This obtained average function parameter values diastolic in a echocardiography examanination was mitral inflow (E/A) 1.81 ± 1.26; TDI (E/e') 15.85 ± 6.83; TR Vmax 2.71 ± 0.9 m/s, LAVI 39.82 ± 21.88 ml/m² (table 1).

Based on degrees dysfunction diastolic ventricle left pre-discharge, about 40 people (43%) subjects with diastolic dysfunction grade I, 22 people (23.7%) with diastolic dysfunction grade II, and 31 people (33.3%) with diastolic dysfunction grade III. Based on range time patient experience rehospitalization, 34 people (36.6%) experience rehospitalization in 30 days since treatment last and 21 people (26.6%) experience rehospitalization in 6 months since treatment last (table 2).

Table 2. Characteristics subject based on Degrees dysfunction Diastolic

	dysfunction Grade I diastolic (N= 40)	dysfunction Grade II diastolic (N= 22)	dysfunction Grade III diastolic (N=31)
Age	57.6 ± 10.3	59.2 ± 9.1	46.4 ± 15.7
Sex
Man	35 (87.5%)	18 (81.8%)	27 (87%)
Woman	5 (1.25%)	4 (18.2%)	4 (13%)
Comorbid
CAD	39 (97.5%)	17 (77.2%)	27 (87%)
HHD	15 (37.5%)	8 (36.3%)	9 (29%)
DM	10 (25%)	4 (18.1%)	5 (16.1%)
CKD	7 (17.5%)	3 (13.6%)	4 (12.9%)
Cardiomyopathy	2 (5%)	2 (9%)	4 (12.9%)
LV EF	30.8 ± 8.24	29.1 ± 7.56	25.7 ± 5.7
Mitral inflow (E/A)	1.1 ± 1.19	1.4 ± 0.5	2.9 ± 0.9
TDI (E/e')	11.3 ± 5.4	18.9 ± 4.9	19.5 ± 6.4
LAVI	30.3 ±10.9	49.2 ± 36.6	45.3 ± 12.6
TAPSE	18 ± 2.9	17.1 ± 3.3	15.3 ± 4.2

Association between degrees dysfunction diastolic ventricle left moment pre-discharge with rehospitalization 30 days and 6 months in patients heart failure with reduced ejection fraction ( HFrEF )

This research has found significant relationship between degrees dysfunction diastolic ventricle left moment pre-discharge with 30 day rehospitalization of the patient heart failure with reduced ejection fraction ( HFrEF) (p-value < 0.001) (table 3).

Table 3. Association between degrees dysfunction diastolic ventricle left moment pre-discharge with 30 day rehospitalization of the patient heart failure with reduced ejection fraction ( HFrEF )

		Rehospitalization 30 days		p-values
		Yes	No	< 0.001
dysfunction diastolic ventricle left pre-discharge	Grade I	8	32
	Grade II	6	16
	Grade III	20	11

The chi square test

This research has found no significant relationship between degrees dysfunction diastolic ventricle left moment pre-discharge with 6 month rehospitalization of the patient heart failure with reduced ejection fraction ( HFrEF ) with p-value 1.000 (table 4).

Table 4. Association between degrees dysfunction diastolic ventricle left moment pre-discharge with 6 month rehospitalization of the patient heart failure with reduced ejection fraction ( HFrEF )

		Rehospitalization 6 months		p-values
		Yes	No	1,000
dysfunction diastolic ventricle left pre-discharge	Grade I	9	31
	Grade II	5	17
	Grade III	7	24

Fisher Exact Test

DISCUSSION

Heart failure is a complex clinical syndrome caused by a decrease in the structural and functional ability of the ventricles to fill or eject blood. The causes of heart failure can be caused by several factors including, ventricular pump disorders, increased afterload and impaired ventricular filling and relaxation. Heart failure was caused by abnormalities of ventricular emptying, due to impaired contractility and increased afterload and a systolic dysfunction. Meanwhile, heart failure caused by impaired diastolic relaxation or ventricular filling is called diastolic dysfunction.

In this study, the average age of the research subjects was 54.26 ± 13.23 years with 86% male and 14% female. According to a study conducted by Framingham, the annual incidence of men with heart failure (per 1000 events) increased at the age of 50-59 years to 80-89 years, while women had a third lower incidence of heart failure than men. This is also in accordance with McDonagh et al who stated that the incidence of heart failure in developed countries, based on overall age, tends to increase with age: from about 1% for those aged <55 years, to >10% in those aged 70 years or more [3]. Januzzi and Mann also stated that although the incidence of heart failure in women is lower than men, women have a longer life expectancy than men so that the prevalence of heart failure in women is more in the age group >80 years [13].

In this study found comorbid CAD 89.2% and HHD 34%. This is in accordance with McDonagh et al which stated that in developing countries the majority of comorbidities in heart failure were found, namely CAD and hypertension [3]. The study by Saverese and Lind also stated that the majority of comorbid heart failure in Asia, Australia and the Middle East were CAD, but in Africa comorbid heart failure was found, namely HHD and cardiomyopathy [4].

In this study, the average value of the ratio E/e' was 15.85 ± 6.83 which indicates an increase in left ventricular diastolic pressure. Nagueh et al said that an E/e' ratio >15 indicates an increase in left ventricular filling pressure while an E/e' ratio <8 indicates normal left ventricular filling pressure [5]. An increase in the E/e' ratio is also a predictor of worsening prognosis in patients with heart failure [6,14].

Left ventricular diastolic dysfunction can be assessed using echocardiography. Diastolic dysfunction divided into 3 with grade 3 diastolic dysfunction is severe diastolic dysfunction characterized by mitral inflow E/A > 2 and indicates an increase in left ventricular filling pressure [5,6,14].

In this study, a significant association was found between the degree of left ventricular diastolic dysfunction during pre-discharge and 30-day rehospitalization in heart failure patients with reduced ejection fraction (HFrEF) (p-value <0.001). This is consistent with a study by Mann et al which stated that there was a relationship between worsening left ventricular diastolic dysfunction and 30-day rehospitalization [7]. This is because in patients with grade III diastolic dysfunction, an increase in LV filling pressure is still found which indicates that the patient suffer congested condition. Gheorghiade et al also stated that congestion hemodynamically which is characterized by a persistent increase in LV filling pressure is not immediately recognized and treated before the patient returns to the hospital which will result in rehospitalization events [15,16].

In this study, there was no significant association between the degree of left ventricular diastolic dysfunction during pre-discharge and 6 months of rehospitalization in heart failure patients with reduced ejection fraction (HFrEF) (p-value 1,000). This was also found in a study by Mann et al which stated that patients with worse diastolic dysfunction experienced rehospitalization within 30 days or had never been rehospitalized even at 6 months post-hospitalization. This is because patients who have better disease control in the initial phase of returning from the hospital will usually be able to maintain a lifestyle and also take heart failure medications regularly so that these patients will not experience rehospitalization and do not depend on previous the degree of diastolic dysfunction [7].

CONCLUSION

There is a very strong association between the severity of the disease and the quality of life of people with Parkinson's disease (p<0.001 r=0.872) and there is a difference in the quality of life of people with Parkinson's disease who receive monotherapy and polytherapy (p=0.041) so that there is an effect of the number of drugs on the quality of life of people with the Parkinson’s Disease.

DECLARATIONS

Ethics approval and consent to participate. Permission for this study was obtained from the Ethics Committee of Universitas Sumatera Utara and H. Adam Malik General Hospital.

CONSENT FOR PUBLICATION

The Authors agree to publication in Journal of Society Medicine.

FUNDING

This research has received no external funding.

COMPETING INTERESTS

None.

AUTHORS’ CONTRIBUTIONS

All authors significantly contribute to the work reported, whether in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas. Contribute to drafting, revising, or critically reviewing the article. Approved the final version to be published, agreed on the journal to be submitted, and agreed to be accountable for all aspects of the work.

ACKNOWLEDGMENTS

None

REFERENCE

1. Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA. 2020; 323(6): 548–560.
2. Kelompok Studi Movement Disorder PERDOSSI. Buku Panduan Tatalaksana Penyakit Parkinson dan Gangguan Gerak Lainnya; 2015.
3. GBD 2016 Parkinson’s Disease Collaborators. Global, regional, and national burden of Parkinson’s disease, 1990–2016. A systematic analysis for the Global Burden of Disease Study 2016. The Lancet. Neurology. 2018; 17(11): 939–953
4. Susanti F. Hubungan ansietas dan depresi dengan tremor pada pasien penyakit Parkinson. Repository USU. Tesis. Universitas Sumatera Utara; 2021.
5. Opara J, Brola W, Leonardi M, Leonardi B. Quality of life in Parkinson’s disease. Journal of medicine and life. 2012; 5(4): 375–81.
6. Ellis JM, Fell MJ. Current approaches to the treatment of Parkinson’s Disease. Bioorganic & medicinal chemistry letters. 2017; 27(18): 4247–55.
7. Oktariza Y, Amalia L, Sobaryati S. Evaluasi Kualitas Hidup Pasien Parkinson Berdasarkan Terapi Berbasis Levodopa. Indonesian Journal of Clinical Pharmacy. 2019; 8: 4.
8. Dewati E, Tunjungsari, Ariarini N. Penyakit Parkinson. Dalam : Anindhita T, Winnugroho W, editors. Buku Ajar Neurologi. Edisi 1. Jakarta: Departemen Neurologi Fakultas Kedokteran Universitas Indonesia; 2017.p. 105-35.
9. Soh SE, McGinley J, Watts J, Iansek R, Murphy A, Menz H. Determinants of health-related quality of life in people with Parkinson’s disease: a path analysis. Quality of Life Research: an international journal of quality of life aspects of treatment, care and rehabilitation. 2013; 22 (7): 1543–53.
10. Amelia D, Syamsudin T, Ganiem AR. Penilaian kualitas hidup pasien Parkinson menggunakan PDQ-39 dan korelasinya dengan tingkat keparahan penyakit. Neurona. 2014; 31(3):1
11. Marinus J, Ramaker C, van Hilten JJ, Stiggelbout AM. Health related quality of life in Parkinson’s disease: a systematic review of disease specific instruments.  Journal of neurology, neurosurgery & psychiatry. 2002; 72 (2): 241-8. DOI: 10.1136/jnnp.72.2.241
12. Tambun O, Marisdina S, Bahar E. Faktor-faktor yang mempengaruhi kualitas hidup penderita penyakit parkinson dengan menggunakan Parkinson's Questionnaire-39. Jurnal neurona. 2021; 38 (4): 1
13. Collier TJ, Kanaan NM, Kordower JH. Ageing as a primary risk factor for Parkinson’s disease: evidence from studies of non-human primates. Nature Reviews Neuroscience. 2011; 12(6): 359–66.
14. Hirsch L, Jette N, Frolkis A, Steeves T, Pringsheim T. The Incidence of Parkinson’s Disease: A Systematic Review and Meta-Analysis. Neuroepidemiology. 2016; 46 (4): 292–300.
15. Lukas A, Subagya, Setyopranoto I. Korelasi antara ansietas, depresi, dan gangguan kognitif terhadap kualitas hidup penderita penyakit Parkinson. Berkala NeuroSains. 2018; 17 (3): 133-41.
16. Szasz JA, Simu M, Perju-Dumbrava L, Antonini A, Bergmann L, Popescu D. et al. Efficacy, safety and patient’s quality of life of long-term treatment with levodopa-carbidopa intestinal gel in advanced parkinson’s disease in romania: results from gloria observational study. Romanian Journal of Neurology. 2020; 19 (1): 27–35.
17. Valdes EG, Andel R, Sieurin J, Feldman AL, Edwards JD, Langstrom N. et al. Occupational Complexity and Risk of Parkinson’s Disease. Plos One. 2014; 9(9): 1-5.
18. Adinda F, Anwar Y, Hutagalung SH. Hubungan disfungsi otonom dengan kualitas hidup pada pasien penyakit parkinson. Tesis. Sumatera Utara: Fakultas Kedokteran Sumatera Utara, Program Pendidikan Dokter Spesialis; 2020.
19. Silitonga RS. Faktor-faktor yang berhubungan dengan kualitas hidup penderita parkinson di Poliklinik Saraf RS Dr. Kariadi. Tesis. E-Journal Undip. Universitas Diponegoro; 2017.