Profile of Major Risk Factors in Acute Coronary Syndrome (ACS) at Pusat Pelayanan Jantung Terpadu (PPJT) Dr. Soetomo Public Hospital Surabaya Between the Period of January-December 2019

Background: Coronary heart disease (CHD) is a leading cause of death worldwide. One type of CHD that most often causes clinical manifestations and death is Acute Coronary Syndrome (ACS). In 2013 the prevalence of SKA in Indonesia reached 1.5% and it is estimated that it will continue to increase every year. Objective: This study aims to determine the profile of major risk factors for ACS sufferers in the Pusat Pelayanan Jantung Terpadu (PPJT) Dr. Soetomo Public Hospital Surabaya in the period January-December 2019. Methods: This study used a retrospective descriptive method to analyze the patient's electronic medical record (eMR). Results: Out of 623 patients diagnosed with ACS, 429 were excluded from the research. 194 patients who met the inclusion criteria were studied with the following details: 19 APTS patients, 43 N-STEMI patients, and 132 STEMI patients. It was found that 73% of ACS patients were male, with the 55-64 years’ age group dominating by 46%. Based on blood pressure and serum cholesterol examination data, it was found that 51% of patients had hypertension and 77% of patients had dyslipidemia (40% hypercholesterolemia, 42% hypertriglyceridemia, 40% low HDL-C levels, and 34% high LDL-C levels). 60% patients had type-2 diabetes mellitus and 52% of patients had a history of smoking. Conclusion: 73% of ACS patients in this study were men. Most common age groups were 55-64 years old (46%), had hypertension by 51%, had dyslipidemia by 77% (40% hypercholesterolemia, 42% hypertriglyceridemia, 40% low HDL-C levels, 34% high LDL-C), had type-2 diabetes mellitus by 60%, and had a smoking history by 52%. Original Research Profile of Major Risk Factors in Acute Coronary Syndrome (ACS) at Pusat Pelayanan Jantung Terpadu (PPJT) Dr. Soetomo Public Hospital Surabaya Between the Period of January-December 2019 Ikhsanuddin Qothi1, Muhamad Robi’ul Fuadi2, Agus Subagjo3 Medical Program, Faculty of Medicine, Faculty of Medicine, Universitas Airlangga, Indonesia. Clinical Pathology Departement, RSUD Dr. Soetomo, Surabaya, Indonesia. Cardiologist, Cardiology Department, RSUD Dr. Soetomo, Surabaya, Indonesia.


Profile of Major Risk Factors in Acute Coronary Syndrome (ACS) at Pusat Pelayanan Jantung Terpadu (PPJT) Dr. Soetomo Public Hospital Surabaya Between the Period of January-December 2019
Introduction Cardiovascular disease is the leading cause of death in the world. According to World Health Organization (WHO), in 2016 cardiovascular disease caused 17.9 million deaths, or equivalent to 31% of all deaths, worldwide and is predicted to keep increasing up to 23.6 million deaths by 2030 [1] . Coronary heart disease (CHD) can be classified into three groups: stable asymptomatic coronary heart disease, stable angina, and acute coronary syndrome [2] . Acute coronary syndrome (ACS) is the most common clinical manifestation of CHD and is the most likely to cause death, ACS is described as September 2021 | Vol 2 | Article 2 progressive CHD and often undergoes sudden change from stable to unstable or acute [3] .
Epidemiological data show that ACS caused 10 million deaths and 120 million disabilities between 1990-2010 in Asia-Pacific [4] . Recent studies showed an increase of 42% in ACS incidence rate compared to that in 1990. Meanwhile, back in 2013, ACS was responsible for 7.3-8.8 deaths worldwide [5] . In 2013 ACS prevalence in Indonesia is known to be at 1.5% or equivalent to 2,650,340 cases [6] .
Statistically, in the age group of <60 years, ACS occurs 7-10 years earlier in males than in females [9] . Hypertension has long been known as a significant risk factor for coronary heart disease [12] .
On the other hand, dyslipidemia is one of the major risk factors of coronary heart disease and plays a role before other risk factors arise [11] . Dyslipidemia is marked by an increase in total cholesterol level, LDL-C, and triglycerides, also a decrease in HDL-C [12] . According to a study regarding the risk factors of heart disease in the age group of ≥55 years old, hypertension is the most commonly found risk factor of CHD (33.1%), followed by increased lipid concentration (17.7%), smoking habit (10.7%), and diabetes mellitus (8.6%) [13] . Another study noted that one in three deaths in people >35 years old is caused by coronary heart disease, including ACS [14] . The easiest way to prevent coronary heart disease, especially ACS is by determining its etiology and try to reduce or avoid it.
Diabetes Mellitus (DM) and hypertension are related and may increase the risk of cardiovascular diseases [15] . As many as 32.3% of DM patients have cardiovascular and stroke complications which later became the leading mortality cause among them [16] . Even though DM patients have 2-4 times higher risk of cardiovascular diseases, recent studies showed that most DM patients are at low risk of cardiovascular complications [17] .  [18] . At the same time, another study stated that dyslipidemia and CHD are unrelated [19] . Indian research said that individuals with a history of hypertension are at five times higher risk of CHD [20] . The longer an individual suffers from hypertension, the higher their risk of CHD is [21] . However, another study conducted in West Sumatra concluded that there is no significant relation between hypertension and CHD [22] .

Determining risk factors based on laboratory results
is very important. This is because laboratory data collection can objectively show the relationship between risk factors and ACS occurrence.
Dyslipidemia can be determined by measuring blood lipid concentration [23] . Diabetes mellitus can be determined by measuring blood glucose level and HbA1c level [24] . In comparison, hypertension can be determined by measuring the patient's blood pressure [25] . Examinations of HDL-C, total/HDL-C, and triglycerides/HDL-C have been proven to have a relationship in showing the risk of heart disease [26] . A Framingham study mentioned that LDL-C, triglyceride, and HDL-C are the strongest predictors of atherosclerosis [27] .
The prevalence of ACS has increased each year significantly [5] . This increase will undoubtedly cause various impacts, one of which is the loss of an individual's productive time. The loss of adequate time will indeed correlate to other problems, including social and economic issues. Therefore, this study is conducted to understand the profile of the major risk factors of ACS so that it can be used both as additional information and/or as epidemiological data. This study is proposed to September 2021 | Vol 2 | Article 2 provide medical personnel with an overview regarding the management of ACS so that it can reduce the mortality rate of ACS or coronary heart disease in general. This study can also provide an overview of the risk factors of coronary heart disease to the community. It is hoped that the description can be followed up by the people in the community by taking various preventive measures as early as possible so that, in the end, it can reduce the incidence of CHD in the future.

Material and Methods
This study used a retrospective descriptive method to analyze the patients' electronic medical records

Results
This is a retrospective study in which data was

Diabetes Mellitus
In this study, 116 (60%) patients were found to have type 2 diabetes mellitus, while the blood glucose level of 78 (40%) patients was found to be normal.

History of Smoking
This study found that 101 (52%) patients have a history of smoking while 93 (48%) patients do not.  [28] which stated that coronary heart disease is most common among people between 51-60 years old with a percentage of 42.6%. The result is also similar to a study by Nadasya, et al in 2019 [29] which stated that coronary heart disease is most common among people between 50-60 years old with a percentage of 58%. Iskandar conducts another study which is in line with this study, et al in 2015 [30]  Age is one of the risk factors that might cause CHD.
Generally, the risk of CHD increases with age, especially if they are also exposed to other risk factors [34] . Individuals 40-60 years old will have an increased risk of CHD due to their history of disease and degenerative process of the blood vessels. Both processes can increase the risk of myocardial infarction up to 5 folds [35] . Another study mentioned that people older than 65 years old have a higher risk of CHD due to the degenerative process, which might alter the heart and blood vessels. The changes might decrease the heart's contractility, especially with effort. Moreover, the degenerative process will also increase the stiffness of blood vessels so that it will increase the risk of atherosclerotic plaque formation, which will lead to CHD [36] . September 2021 | Vol 2 | Article 2  [6] which stated that ACS is more often to be found in males with 199 patients (67%) than in females with 101 patients (33%), thus making the male to female patients' ratio to be 2:1.
A study by Nohair et al in 2017 [31] also stated a comparable result that coronary heart disease was found in 157 (67%) male patients and in 76 (33%) female patients, thus making the male to female patients' ratio to be 2:1. Another study by Shabana et al. in 2020 [37] stated that coronary heart disease is more likely to be found in males with 290 (58%) patients than in females with 210 (42%) patients, making the male to female patients' ratio to be 1.2:1. Previous studies already mentioned that the difference in male to female CHD incidence is due to the different number of collected samples.
However, in general, the aforementioned studies agreed that male is still the majority of CHD patients.
Age plays a role as one of the major risk factors of CHD development. A study found that in >45 years of age, males have a higher tendency to develop CHD while females will have an increased risk of CHD after 55 years old, which is also known to be the period of menopause in most females. Some previous studies also found that the prevalence, incidence, and mortality of CHD are higher in males than in females [36] . Another study also found that the development of cardiovascular diseases in females tends to be 7-10 years later than in males.
This might be due to the effect of endogenous estrogen in the fertile female, which will inhibit atherosclerotic formation [37] . Estrogen has some advantages and effects in inhibiting atherosclerotic plaque formation, vasodilatation, blood pressure regulation, antioxidant properties, and inflammatory process, reducing the risk of CHD [38] . The postmenopausal female has 1.5 higher risks of CHD compared to the female who has not undergone menopause [39] . However, a study by Ghani in 2016 [32]  (overweight) is more likely to be found in males, whilst a BMI of ≥30 kg/m2 is more likely to be found in females [36] .
Hypertension also became a contributing risk factor in 98 (51%) patients with ACS in this study, while 96 (49%) other patients do not have hypertension.
A survey by Shabana et al in 2010 [35]  Hypertension is one of the risk factors which contribute to ACS by causing oxidative and mechanical stress on the blood vessels' wall [10] .
Hypertension will cause endothelial damage and atherosclerotic plaque formation. In addition, hypertension also makes the plaque unstable so that it falls off quickly. If left protracted, hypertension will cause left ventricular hypertrophy due to increased heart load [41] . If the high blood pressure is sustained for a long time, endothelial cells damage will occur. Reactive Oxygen Species (ROS) formed by normal blood vessels' wall acts as signals that regulate the vessels' contraction and relaxation. In the case of endothelial damage, ROS will become uncontrollable, thus will lead to oxidative stress. Production of ROS will activate COX-1 to produce prostanoid, leading to endothelial dysfunction, which will further increase and worsen atherosclerotic plaque formation and susceptibility [42] . Atherosclerotic plaque formation will disrupt the blood flow to the myocardium, which in turn will provoke symptoms of angina pectoris, coronary insufficiency, and myocardial infarction more often than in normal patients [40] . Hypertension can also increase the stiffness of the blood vessels if left for a longer time. Hypertension has various causes; other risk factors that correlate with hypertension are consuming high-fat diets and smoking [43] .  [35] which result showed that in 500 patients with ACS, 255 (51%) of them were found to have dyslipidemia, however there are some differences in lipid profile distribution among those patients. In Shabana's study [35] , 250 (80%) patients with ACS have hypercholesterolemia, 400 (80%) patients have hypertriglyceridemia, 320 (64%) patients have low HDL-C level, and 260 (52%) patients have high LDL-C level. A study by Nohair et al in 2017 [31] also showed slight differences as this study focused on the increase of LDL-C level and the decrease of HDL-C level from baseline. The study used 233 samples and concluded that 192 (82%) patients have high LDL-C levels while 71 (30%) patients have low HDL-C levels [31] .
Dyslipidemia is the second most common risk factor of heart disease [44] . Primarily, CHD incidence is correlated to LDL-C level and inversely proportional to HDL-C level. LDL-C (Low-Density Lipoprotein-Cholesterol) is known as bad cholesterol.
Therefore, a high level of LDL-C will cause the thickening of the wall of blood vessels through atherosclerotic plaque formation. Various studies using animals and clinical trials concluded that hyper-LDL-C is the major risk factor of CHD [45] .
Epidemiological studies found that people with high LDL-C levels are 3 times more at risk of CHD than September 2021 | Vol 2 | Article 2 normal people [45] . Furthermore, a high LDL-C level will speed up atherosclerotic plaque formation.

HDL-C (High-Density Lipoprotein-Cholesterol) is
known as good cholesterol, which is in charge of transporting fat from circulation to the liver. Various studies suggest that the lower the HDL-C level, the more likely an individual is to have CHD. HDL-C level can be increased by stopping smoking, doing physical exercises, and lowering body weight [46].
Triglycerides are the type of fat consisting of three types of fats: saturated fats, monounsaturated fats, and polyunsaturated fats. A high level of triglycerides is a risk factor for CHD. Triglycerides play a role in increasing blood viscosity. Therefore, the higher the triglycerides level, the more viscous the blood will be [46] . A study by Ginsberg in 2004 [47] concluded that people with triglycerides levels of  [32] . Another study by Nohair et al in 2020 [31] also showed that among 233 patients, only 24 (10.3%) patients have a history of type-2 diabetes mellitus.
Diabetes mellitus is one of the risk factors of coronary heart disease. People with diabetes mellitus tend to have an earlier onset of tissue degeneration process and endothelial dysfunction.
These processes will cause the thickening of the capillary and coronary basement membrane, which will cause the narrowing of the blood flow to the heart [49] . The high blood glucose level in patients with diabetes mellitus will cause the glucose to attach to the wall of the blood vessels. The attached glucose will then be oxidized and reacted, forming Advanced Glycosylated End-products (AGEs). If this happens continuously, the walls of the blood vessels will be damaged. The damaged vessels' wall will cause lipid to accumulates inside the blood vessels, which will later form atherosclerotic plaque [50] . Furthermore, in diabetic patients, there will be an increase in blood viscosity which will correlate to the rise of atherosclerosis and might lead to coronary heart disease [32] . Adults with diabetes mellitus are 2-4 times more at risk of developing CHD than normal adults [51] . analysis from that study also suggested that smokers have a 4-5 increased risk of CHD compared to non-smoker [53] . However, a study by Iskandar et al in 2015 [30] suggested that 33 (55%) patients with CHD do not have a history of smoking.
A study by Shabana [35] also suggested that 353 (70.6%) patients with CHD do not have smoking history.
Smoking correlates to endothelial dysfunction, inflammatory process, lipid modification, and altered anti-thrombotic and pro-thrombotic factors [42] .
Smoking can provoke atherogenesis through its direct effect on the arterial wall, carbon dioxide on the smoke, which will cause arterial hypoxia, nicotine, and its mobilization effects of catecholamine, which will cause thrombocyte reaction, and the glycoprotein of the cigarette, which might cause arterial wall hypersensitivity [54] .
Cigarettes affect hypertension by stimulating the sympathetic nervous system, causing endothelial damage, and increasing the stiffness of blood vessels [42] .