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Original article

Assessing different determinants influencing the death outcome resulting from acute coronary syndrome in patients treated in the coronary unit of the General hospital in Valjevo, and their differences

Aleksandra Filipović1, Janko Janković2
  • Institute of Public Health Valjevo, Valjevo, Serbia
  • University of Belgrade, Faculty of Medicine, Belgrade, Institute of Social Medicine, Serbia

ABSTRACT

Introduction: Cardiovascular diseases are the leading cause of morbidity and mortality in most countries of the world and are responsible for the death of 17.9 million people per year and for 11.8% of total DALYs. In Serbia, acute coronary syndrome (ACS) is the main cause of death among ischemic heart diseases, with a share of 49.9%.

Aim: The aim of the study is to examine the association of various determinants (demographic, anthropometric, biological markers, risk factors, presence of comorbidities, and the pharmacotherapeutic approach) with the death outcome resulting from ACS patients treated at the Coronary Unit, as well as their differences.

Materials and methods: This cross-sectional study included 384 adults with ACS, who were patients of the Cardiology Department with the Coronary Unit of the General Hospital in Valjevo, in 2020. The so-called Coronary Sheet was used as a research instrument. It was created, based on national needs, by the Institute of Public Health of Serbia "Dr. Milan Jovanović Batut", the Institute of Epidemiology, and the Cardiology Society of Serbia. This sheet is in the form of a questionnaire filled out by doctors working at the Coronary Unit, which is then submitted to the Institute of Public Health Valjevo. All respondents gave informed consent for anonymous participation in the research. The obtained data were analyzed using the methods of descriptive and analytical statistics, as well as the methods of univariate and multivariate linear regression.

Results: The total sample consisted of 288 (75%) men and 96 (25%) women. The average age of patients who died of ACS was 72.9 ± 9.8 years, while the average age of patients who did not die of ACS was 65.0 ± 12.0 years. The difference was statistically significant (p < 0.001). Statistically significantly more patients who had lower values of both systolic and diastolic blood pressure, when admitted to hospital, died than those who had somewhat higher values of systolic and diastolic pressure at admission (p < 0.001). The mortality rate was lower for patients with ACS who were prescribed acetylsalicylic acid (p < 0.001), beta blockers (p = 0.003), ACE inhibitors (p < 0.001), and statins (p < 0.001) during hospitalization, while all patients whose therapy included inotropes as one of the drugs died (p < 0.001).

Conclusion: Our research indicates the existence of a link between the examined determinants and the death outcome in patients suffering from ACS. It is necessary to improve the quality of data, maintain relevant and timely medical documentation and records, and continuously improve prevention programs, with the aim of reducing risk factors for the occurrence of ACS.


INTRODUCTION

Cardiovascular diseases are the leading cause of morbidity and mortality, both in developed and developing countries of the world. Globally, every year, 17.9 million people die due to this type of pathology [1]. The main cause of life years lost, both globally and in every individual region of the world, is ischemic heart disease (IHD), followed by cerebrovascular disease (CVD). Cardiovascular diseases (CVDs) are responsible for 11.8% of total disability-adjusted life years (DALYs), and the main disease in this group is IHD, with 5.2% [2]. In fact, the greatest increase in mortality in the world, in the last two decades, was recorded regarding deaths from IHD – in 2019, 8.9 million people died from this disease [3].

The situation in Serbia is no better. Thus, in 2020, cardiovascular diseases were the leading cause of death, with a share of 47.3% [4]. Within the structure of mortality from cardiovascular diseases, in 2020, IHD had a share of 15.9%, while acute coronary syndrome (ACS) was the main cause amongst ischemic heart diseases, and it was responsible for 49.9% of deaths. Standardized mortality rates from ACS were more than 36.1 per 100,000 population, in the territory of the Kolubara District, and together with the mortality rates for three more districts (the Zlatibor District, the Raška District, and the North Banat District), had the highest values in Serbia, in 2020 [5]. In the population of Serbia, 150,886 DALYs are lost yearly, due to IHD [6].

As the most complex form of ischemic heart disease [7], ACS represents a spectrum of clinical manifestations caused by a pathophysiological process, which stems from a rupture or erosion of atherosclerotic plaque in the coronary artery that is accompanied by the development of an intravascular coagulum, which causes acute reduction or complete blockage of blood flow. ACS can manifest as the following: ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), unstable angina pectoris (AP), or sudden cardiac death [5].

Since the burden of cardiovascular diseases is great [8], special attention of the professional community is directed towards preventing risk factors, at least the ones that can be modified, these being the following: excess body weight, arterial hypertension, diabetes mellitus, hyperlipoproteinemia [9]. Research up to date indicate that different levels of obesity and a sedentary lifestyle participate, as significant risk factors, in the development of ACS, as well as in poorer prognosis of disease [10]. Risk of the death outcome resulting from ACS is greater in persons with normal weight with central obesity [11]. As far as arterial hypertension is concerned, it is the leading cause of premature adverse cardiovascular events and carries a two to three times greater risk of ACS in persons suffering from it, as compared to normotensive persons [12]. Studies show that persons suffering from diabetes mellitus who develop ACS, have poorer short-term as well as long-term outcomes, as compared to persons without this comorbidity [13]. Since an elevated lipid blood level is one of the most important factors in the process of atherosclerosis development, decreasing it would contribute to the decrease in morbidity and mortality from IHD, by as much as 40% [14].

In the etiopathogenesis of ACS, unhealthy lifestyles, such as smoking and exposure to stress, play a particularly important role [15],[16]. According to a case-control study carried out in Syria, the probability of the development of acute myocardial infarction (MI) is eight times greater in persons of both sexes who smoke more than 25 cigarettes a day, as compared to persons who have never smoked [17]. The hypothesis that the long-term impact of stressogenic factors on a person causes endothelial dysfunction, and, consequently, the development of ACS, is substantiated by a study showing that patients with higher cardiovascular risk were more exposed to stress [18].

Age, sex, and genetic burden, as unchangeable factors related to each individual, also contribute to the development of acute coronary syndrome [9]. Registered ACS at a younger age in the family anamnesis is an important predisposing factor for the development of ACS, especially when male relatives developing disease before the age of 55 years and female relatives developing disease before the age of 65 are concerned [19],[20]. Studies show that 35 genetic risk variants connected with coronary disease act independently of other risk factors [21]. Observed by sex structure, men carry a higher risk of the development of ACS than women during menopause, while in female patients a somewhat less favorable development of disease with numerous complications and a higher mortality rate from ACS is registered [20],[22]. The Serbia Acute Coronary Syndrome Registry for 2020 shows that the greatest number of deceased patients was amongst the elderly population, i.e., in the age group >75 years, which confirms the thesis regarding the significance of age as an independent risk factor for the development and outcome of ACS [5].

The aim of the study is to investigate the influence of different determinants (demographic, anthropometric, biological markers, risk factors, presence of comorbidities, and the pharmacotherapeutic approach) on the death outcome resulting from ACS patients treated at the Coronary Unit of the General Hospital in Valjevo, in 2020, as well as their differences. According to our understanding, studies of this type are carried out mostly at the national level or at the level of larger medical centers, which is why data at the district level are limited. In fact, selecting this topic was motivated by an attempt to correct this situation.

MATERIALS AND METHODS

The study type and sample

The research, which was carried out as a cross-sectional study, included 384 adults with ACS, who received secondary healthcare services, i.e., who were treated at the Cardiology Department with the Coronary Unit of the General Hospital in Valjevo, in the period between January 1, 2020, and December 31, 2020. According to the Decree on the Health Care Institution Network Plan [23], the General Hospital in Valjevo is the only inpatient healthcare facility in the territory of the Kolubara District. Consequently, the Coronary Unit of this hospital provides health services for patients from six municipalities: Valjevo, Lajkovac, Ub, Mionica, Osečina, and Ljig.

Research instrument

The form for reporting persons with acute coronary syndrome – the Coronary Sheet, was used as the research instrument. It was created, based on national needs, by the Institute of Public Health of Serbia "Dr. Milan Jovanović Batut", the Institute of Epidemiology, and the Cardiology Society of Serbia. This sheet is in the form of a questionnaire filled out by doctors working at the Coronary Unit, which is then submitted to the Institute of Public Health Valjevo. The Institute is in charge of maintaining the Regional Acute Coronary Syndrome Registry, which is a part of the comprehensive Serbian Acute Coronary Syndrome Registry [5]. In this way, all ACS patients in the territory of the Kolubara District, treated at the Coronary Unit of the General Hospital in Valjevo, in 2020, were recorded. As it is mandatory to report all ACS cases, as prescribed by the Law on Health Documentation and Records in the Field of Health [24], the response rate was 100%. All respondents gave informed consent for anonymous participation in the research, thus giving consent for the use of the data obtained from the survey.

Variables

The study analyzed the association between demographic and anthropometric variables, biological markers, risk factors, and the application of certain pharmacotherapy with the lethal outcome resulting from ACS. The demographic determinants observed were the following: sex (male/female), age, and type of settlement (urban/rural). The age variable was categorized into the following three groups: I – patients younger than 65 years, II – patients between the age of 65 and 74 years, and III – patients aged 75 years and above. The following anthropometric characteristics were observed: height, weight, and body mass index (BMI). The following biological markers were taken into account: the glucose level, the hemoglobin level, the creatine kinase (Max CK) level, and the level of troponin I. As far as pharmacotherapy is concerned, the following were observed: acetylsalicylic acid, nitrates, inotropes, heparin, low molecular weight heparin (LMWH), beta blockers, angiotensin-converting enzyme inhibitors (ACEI), clopidogrel, and statins. As far as the risk factors are concerned, the following variables were considered: smoking status, hyperlipoproteinemia (HLP), hypertension (hypertensio arterialis – HTA), diabetes mellitus (DM), chest pain. Of the previous and existing conditions, the following were observed: previous acute myocardial infarction (AMI), preexisting bypass, previous percutaneous transluminal coronary angioplasty (PTCA), previous cerebrovascular insult (CVI), peripheral artery disease (PAD), pulmonary diseases, and anemias. As the dependent variable, death form ACS was used, with two outcomes (yes/no).

Statistical data processing methods

The data obtained in this study were analyzed using descriptive and analytical statistical methods. The following descriptive methods were applied: absolute and relative numbers (n, %), measures of central tendency (arithmetic mean, median), and measures of dispersion (standard deviation, percentiles). The following analytical statistical methods were used: tests of difference – parametric (t test) and non-parametric (Pearson’s χ2 test, Fisher's exact test, the Mann–Whitney U test). The choice of test for calculating difference depended on the type of data and type of distribution. Parametric methods were used when distribution was normal, while non-parametric tests were used when the distribution was not normal. Normality of distribution was tested on the basis of descriptive parameters, with tests of normality (the Kolmogorov-Smirnov test and the Shapiro–Wilk test) and with graphical tests (histogram, box plot, Q-Q plot). Logistic regression analysis (univariate and multivariate) was used for analyzing the association between independent variables (age, smoking, BMI, HTA, pulmonary disease, Killip class, glucose, Hgb, acetylsalicylic acid, beta blockers, ACEI, and statins) and the death outcome resulting from ACS, as the dependent variable. The study presents cross-section relationships and 95% confidence intervals, with lower and upper bounds (95% CP) in logistic models. The validity of the model was tested with the Nagelkerke R Squared. The probability value of p < 0.05 was taken as the minimal level of statistical significance.

All data were processed with the SPSS 20.0 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.) software and the R 3.4.2 (R Core Team 2017. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria) software.

RESULTS

The total sample in our study was composed of 288 (75%) men and 96 (25%) women. The average age of the patients was 65.8 ± 12.1 years, with the youngest patient aged 29 and the oldest aged 95 years. The sociodemographic characteristics of the patients, in relation to the lethal outcome, are presented Table 1.

Table 1. Patient sociodemographic characteristics, in relation to death from ACS

Table 1. Patient sociodemographic characteristics, in relation to death from ACS

The average age of the deceased patients was 72.9 ± 9.8 years, while the age of the surviving patients was 65.0 ± 12.0 years, and this difference is statistically significant (p < 0.001). Based on the distribution of patients by age groups (Table 1), it is evident that the oldest patients were most at risk, i.e., they had the highest percentage of lethal outcome. As opposed to age, there was no significant difference in mortality between the sexes. In relation to the type of settlement, the distribution in relation to mortality was identical in both the urban/suburban and rural type of settlement.

Table 2 presents patient anthropometric data and values of arterial blood pressure, in relation to mortality from ACS.

Table 2. Anthropometric data and arterial blood pressure values in patients, in relation to the death outcome from ACS

Table 2. Anthropometric data and arterial blood pressure values in patients, in relation to the death outcome from ACS

Based on the values presented in Table 2, it is evident that the patients of both groups were of similar physical build, and that the deceased patients even had a somewhat lower body weight. On the other hand, blood pressure values were significantly lower in patients who died.

Table 3 presents the distribution of risk factors in patients, in relation to mortality from acute coronary syndrome.

Table 3. Risk factors in patients, in relation to death from ACS

Table 3. Risk factors in patients, in relation to death from ACS

As far as smoking status is concerned, it was determined that the percentage of smokers who died was significantly smaller. However, it should be noted that data on the number of former smokers were not available, which is significant for this population. Patients who had previously experienced chest pain also had a smaller percentage of mortality, however, this difference was not statistically significant. The distribution of the death outcome in relation to HLP, HTA, and DM is very similar and is without statistical significance.

Table 4 presents descriptive statistics for patient laboratory parameters, in relation to mortality from ACS.

Table 4. Patient laboratory parameters, in relation to death from ACS

Table 4. Patient laboratory parameters, in relation to death from ACS

The average glucose level was significantly higher in patients who had a death outcome. On the other hand, patients with a lethal outcome had significantly lower levels of hemoglobin. The median maximum CK (Max CK) value was higher in patients with a lethal outcome, although the average values were very similar. Nevertheless, the variability was large enough to make it impossible to confirm the significance of the difference. The same happened with troponin I, where the median values were also very similar. (The average value was extremely large due to individual extreme values). The distribution of anamnestic data on previous and existing patient diseases, in relation to the death outcome resulting from acute coronary syndrome, is presented in Table 5.

Table 5. Previous and existing diseases in patients, in relation to the death outcome from ACS

Table 5. Previous and existing diseases in patients, in relation to the death outcome from ACS

The percentage of patients with the death outcome did not significantly differ in relation to previous and existing diseases. Namely, patients with previous acute myocardial infarction and aortocoronary bypass, as well as patients with previous cerebrovascular insult had a very similar, i.e., almost identical percentage of the death outcome. Previous PTCA and peripheral artery disease were present in only two patients, rendering the difference in percentage irrelevant. Patients in whom pulmonary diseases were recorded had a much higher percentage of lethal outcome, as compared to those without lung disease, however, the number of patients in question was small, which is why statistical significance was not recorded, as could be expected.

The characteristics of patients with acute coronary syndrome, in relation to the death outcome, are presented in Table 6.

Table 6. Characteristics of patients with ACS, in relation to the death outcome

Table 6. Characteristics of patients with ACS, in relation to the death outcome

The greatest number of patients was brought to hospital by emergency services, while a far smaller number of patients came in on their own. Other modes of arrival to hospital were significantly rarer. Mortality was the highest in NSTEMI and STEMI type of myocardial infarction, while unstable AP and MI with left bundle branch block did not result in death. Patients with different localizations of myocardial infarction did not differ significantly with regards to the death outcome. As expected, patients with a higher Killip class had a higher percentage of mortality, and this trend is statistically significant. As far as complications during hospitalization are concerned, arrythmia occurred in two patients, while postinfarct angina, mechanical complications, and reinfarction did not occur in the examined patient sample. Almost all patients who required cardiopulmonary resuscitation died, and this difference is statistically significant.

The distribution of patients with pharmacotherapy, in relation to the death outcome, is presented in Table 7.

Table 7. Pharmacotherapy which the patients received during hospitalization, in relation to death outcome from ACS

Table 7. Pharmacotherapy which the patients received during hospitalization, in relation to death outcome from ACS

The mortality of patients who took acetylsalicylic acid was significantly lower as compared to patients who did not take this medicine. All patients who were given inotropes died. However, these were severe cases where this medication was indicated. Patients who were prescribed beta blockers, ACE inhibitors, and statins had a statistically significantly lower percentage of mortality, as compared to patients who did not receive this medication. There was no statistically significant difference regarding other treatment modalities, in relation to the death outcome. None of the patients had emergency bypass surgery, emergency PTCA, or emergency pacemaker implantation.

Table 8 shows univariate and multivariate models of logistic regression, with the death outcome as the dependent variable.

Table 8. Univariate and multivariate logistic regression models with death outcome as a dependent variable

Table 8. Univariate and multivariate logistic regression models with death outcome as a dependent variable

Modeling was performed in several steps. The univariate model was designed first, with all the predictors whose p values was less than 0.1 in univariate analyses, and for whom it was logical that they should be modeled further. The problem of missing data in the Killip classification (43%), glucose levels (11.7%), and hemoglobin values (7.8%) was overcome by not entering these variables into the multivariate model. Namely, introducing these variables would create the problem of too many missing data, rendering the model invalid. Glucose and hemoglobin levels may vary (glucose may vary on a daily basis), which is why these values were excluded at the very beginning. Thereby, the final multivariate model was lacking 10% of the data.

Based on the results of univariate analysis, age, Killip class, glucose and hemoglobin levels are significant predictors of the death outcome. In the multivariate model (without the above stated parameters, which significantly reduce the sample), the significant predictors are age, ACE inhibitors, and statins. The described variability of the model (Nagelkerke R Squared) is 0.215.

DISCUSSION

This study analyzes the association between demographic and anthropometric variables, risk factors, the presence of comorbidities, and the applied pharmacotherapy with the lethal outcome resulting from ACS, in patients treated at the General Hospital in Valjevo, as well as their differences. Based on the results obtained, an association was determined between certain age groups and the lethal outcome resulting from ACS, i.e., it was established that the percentage of patients with the lethal outcome rose with age, which is why the percentage of deceased patients is the highest in the oldest age group (> 75 years). According to data found in literature, older patients with ACS have less favorable hospital outcomes as compared to younger patients. There is a number of reasons for this: decreased remaining capacity of the body resulting from ageing as a physiological process, the presence of multiple comorbidities, more frequent atypical presentation of the disease, as well as limitations in the application of all pharmacotherapeutic models. The differences in treating older patients with ACS, i.e., the differences in the selection of therapy, are most commonly reflected in the fact that older patients less frequently undergo reperfusion therapies – thrombolysis and primary percutaneous coronary intervention, and in the fact that these patients are less frequently prescribed drugs for secondary prevention, after they are dismissed from hospital, as compared to younger patients [25]. A cohort study carried out on a sample of 10,253 patients with ACS, from 25 European countries, confirms that old age is a significant predictor of increased inhospital mortality resulting from ACS. The percentage of patients undergoing coronarography was in inverse correlation with the increase in age, i.e., this diagnostic procedure was applied in only 13% of patients aged ≥ 85 [26].

In our study, patients with somewhat lower values of body weight (p = 0.056) belonged to the group of patients with ACS with a lethal outcome. It is important to stress that the data on body weight were obtained through anamnesis, which is why the subjectivity of the patients in their responses should be taken into consideration. There is a possibility that somewhat different information would have been obtained had anthropometric data been obtained with measurement.

A study, which included 8,680 multiethnic Asian patients with acute myocardial infarction, in the period between 2011 and 2021, analyzed the following outcome variables on a monthly basis – cardiovascular mortality, all-cause mortality, repeated hospitalization, development of cardiogenic shock, development of cardiac insufficiency, the occurrence of stroke, in patients without standard variable risk factors, as compared to those patients who had them. Unexpectedly, amongst patients who were without modifying risk factors (smoking, hypertension, hypercholesterolemia, and DM), the rates of cardiovascular mortality and cardiogenic shock were higher, as was all-cause mortality, in the five-year period after acute myocardial infarction. Identifying this unusually risky group of patients requires particular attention with respect to the approach to their treatment, especially because of the younger age of these patients [27].

Patients with ACS, in whom lower values of arterial blood pressure were measured at admission to the General Hospital in Valjevo, died statistically significantly more frequently than those patients whose blood pressure values where somewhat higher. Lower values of arterial blood pressure at admission were mostly in correlation with a more severe clinical presentation in patients with ACS. They are often the manifestation of cardiogenic shock in the patient, which consequently leads to a less favorable health outcome. Mouhat et al. [28] monitored the values of systolic arterial blood pressure measured in the first 48 hours upon admission, in patients with acute myocardial infarction older than 75 years. The risk of cardiovascular mortality in the one-year follow-up period after AMI was twice higher in patients whose systolic pressure was < 125 mmHg.

When observing only smoking status, it was determined that smokers had a significantly smaller percentage of lethal outcome. This paradox can be explained by the fact that, with regards to patients who stated that they were non-smokers, there was a lack of data on whether they were former smokers or recent smokers, and if they were, how long they had smoked and how many cigarettes they smoked a day. The data on the length of smoking status and the number of cigarettes smoked per day in smokers would also contribute to a clearer understanding. Data found in literature also describes the concept of the smoker’s paradox. According to a meta-analysis carried out in China, which included 2,188 patients with acute myocardial infarction, aged ≤ 45 years, differences regarding adverse cardiovascular outcomes between smokers and non-smokers were not recorded [29].

In patients with ACS who had a death outcome, significantly higher values of blood glucose were recorded, as compared to the survivors, which is in keeping with data from literature. According to the data published in a prospective longitudinal observational cohort study, carried out on a sample of 3,576 patients with ACS, in the Mexican Gulf area [13], significantly higher inhospital mortality, thirty-day mortality, and one-year mortality were recorded in patients with DM, as compared to patients without this comorbidity. One-year mortality was higher by 13.7% in patients with diabetes. A joint study of the American Heart Association and the Chinese Society of Cardiology [30], which included 63,450 patients with ACS, showed that in patients who had diabetes or suspected diabetes, the risk of death from any cause was twice higher, while the risk of death from major adverse cardiovascular and cerebrovascular events was one and a half times higher.

In our study, significantly lower levels of hemoglobin were registered in patients with ACS who belonged to the group with a death outcome. These results are in keeping with a prospective randomized control study, which included 7,781 patients with ACS [31]. In these patients, during inhospital treatment, the decreased levels of hemoglobin (≥3 g/dL) were independently associated with an increased risk of mortality, by as much as two and a half times, during a one-year period. The association between lower levels of hemoglobin, the exacerbation of myocardial ischemia, and the development of major adverse cardiovascular events, in the first 30 days, in patients with ACS, was also recorded in a study by Sabatine et al. [32].

In relation to ACS classification, the death outcome was registered in patients with myocardial infarction with ST elevation (STEMI) and in patients with myocardial infarction without ST elevation (NSTEMI). A prospective study, which analyzed mortality among 1,188 patients with myocardial infarction with ST elevation, myocardial infarction without ST elevation, and unstable angina pectoris, hospitalized at the Tampere University Hospital in Finland, showed that hospital mortality was 9.6%, 13%, and 2.6%, respectively (p < 0.001) [33].

Another determinant which was observed to be associated with an adverse outcome in patients with ACS, in our study, is the Killip class. Namely, with the increase of the Killip class, mortality of patients with ACS also rose, whereby the percentage of deceased patients with Killip class III was 23.1%, while the percentage of deceased patients with Killip class IV was 100%. A study analyzing data pertaining to 26,090 patients with ACS, categorized according to the Killip class, confirmed the association of a higher Killip class with higher patient mortality, after one month and after six months. Although patients with Killip class II, III, and IV made up 11% of the sample, they accounted for as much as 30% of death outcomes in both observational periods [34].

As many as 93.8% of patients with ACS who required manual cardiopulmonary resuscitation died. This is an initially severe clinical presentation in patients with ACS, which is why this result was not surprising. Insight into the results of ten-year follow-up of patient survival in Korea (5,918 patients), regarding patients who required inhospital cardiopulmonary resus citation, due to various causes, shows that the survival rate was 11.7% during hospital stay, and 8% in the first six months of follow-up [35].

It is evident that mortality was lower in patients with ACS who were treated with the following medicaments during their hospital stay: acetylsalicylic acid, beta blockers, ACE inhibitors, and statins. According to the guidelines for treating acute myocardial infarction with ST elevation of the European Society of Cardiology [36], the application of acetylsalicylic acid was indicated, not only acutely, in patients with acute myocardial infarction, but also as long-term prevention of similar adverse ischemic events. As far as beta blockers are concerned, their early intravenous application, in patients with acute myocardial infarction who underwent fibrinolysis, reduces the incidence of acute malignant ventricular arrythmias. Early intravenous application of metoprolol in patients with AMI was connected with the reduction of the size of the infarction , within a period of 5 – 7 days (p = 0.012). Based on evidence available so far, in patients with AMI, the administration of statins should be started as early as possible. A meta-analysis by Ibanez et al. [36] showed that more intensive therapy with statins led to a decreased risk of the death outcome due to the reduction in the level of LDL cholesterol (low density lipoprotein cholesterol). The study showed that the application of ACE inhibitors in the early stage, in patients with acute myocardial infarction with ST elevation, was associated with a reduction in thirty-day mortality.

All patients with ACS who received inotropes during their inhospital treatment (2.6% of the overall sample) had a death outcome. Such a result can be substantiated with the well-known fact that drugs belonging to this group of medications are indicated in patients with the most severe presentation, who already display signs of cardiogenic shock and heart failure. A retrospective cohort study [37] analyzing data from an electronic data base on mortality in 200,859 patients with cardiogenic shock, hospitalized in intensive care units in USA, who received inotropic agents, showed that patients who were given inotropes had significantly higher inhospital mortality rates (24.03%), as compared to patients who did not receive these medicaments (12.40%).

CONCLUSION

In this study, a statistically significant association between different determinants, namely: age, body mass index, the value of arterial pressure, smoking status, levels of glucose and hemoglobin, the Killip class, applied manual cardiopulmonary resuscitation, acetylsalicylic acid, beta blockers, ACE inhibitors, statins, inotropes and the death outcome in patients with acute coronary syndrome, was determined.

Higher mortality was recorded in patients who were older, patients with a lower bodyweight, non-smokers, patients with lower values of arterial blood pressure measured at hospital admission, patients with higher levels of blood glucose and lower levels of hemoglobin, patients with STEMI and NSTEMI, patients with a higher Killip class, as well as patients in whom the application of manual cardiopulmonary resuscitation and inotropes was necessary. On the other hand, lower mortality was recorded amongst patients with ACS, who were given acetylsalicylic acid, beta blockers, ACE inhibitors, and statins.

Understanding and monitoring the health status of the population suffering from ACS is an important element in further planning, organizing, and implementing healthcare for the population of the Kolubara District, with the aim of preserving and improving health. In order to maintain timely recording and improve the quality of data in the Coronary Sheets, it is necessary to strengthen staff capacity by increasing the number of doctors working in the Coronary Unit, increasing the time available for documenting a detailed anamnesis, performing a physical examination, and filling out the Coronary Sheets, as well as by providing additional training for doctors regarding the importance of accurate and relevant medical record keeping.

Additionally, it is necessary to create such public health policies that promote the improvement of prevention programs, with the aim to reduce risk factors for the development of acute coronary syndrome. In order to properly implement such policies, it is necessary to educate both the public and the medical community on this issue, through more active educational work, to continue with similar research, as well as to ensure the continuity of the said activities.

  • Conflict of interest:
    None declared.

Informations

December 2023

Pages 403-420
  • Keywords:
    acute coronary syndrome, death outcome, risk factors
  • Received:
    25 October 2022
  • Revised:
    27 October 2022
  • Accepted:
    30 October 2022
  • Online first:
    25 December 2022
  • DOI:
  • Cite this article:
    Filipović A, Janković J. Assessing different determinants influencing the death outcome resulting from acute coronary syndrome in patients treated in the coronary unit of the general hospital in Valjevo, and their differences. Serbian Journal of the Medical Chamber. 2022;3(4):403-20. doi: 10.5937/smclk3-40807
Corresponding author

Janko Janković
Institute of Social Medicine, Faculty of Medicine, University of Belgrade, Serbia
15 Dr Subotića Street, 11000 Belgrade, Serbia
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


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9. Lapcević M, Vuković M. Faktori rizika za hronicna nezarazna oboljenja: dvansestonediljna prospektivna studija [Risk factors for chronic noncontiguous diseases: twelve-week prospective study]. Srp Arh Celok Lek. 2004 NovDec;132(11-12):414-20. Serbian. doi: 10.2298/sarh0412414l. [CROSSREF]

10. Babić Z, Zeljković I, Pintarić H, Vrsalović M, Jelavić MM, Mišigoj-Duraković M. The role of anthropometric parameters and physical activity level in patients with acute coronary syndrome admitted to the intensive cardiac care unit. Acta Clin Croat. 2021 Jun;60(2):201-8. doi: 10.20471/acc.2021.60.02.05. [CROSSREF]

11. Wan J, Zhou P, Wang D, Liu S, Yang Y, Hou J, et al. Impact of Normal Weight Central Obesity on Clinical Outcomes in Male Patients with Premature Acute Coronary Syndrome. Angiology. 2019 Nov;70(10):960-8. doi: 10.1177/0003319719835637. [CROSSREF]

12. Kringeland E, Tell GS, Midtbø H, Igland J, Haugsgjerd TR, Gerdts E. Stage 1 hypertension, sex, and acute coronary syndromes during midlife: the Hordaland Health Study. Eur J Prev Cardiol. 2022 Feb 19;29(1):147-54. doi: 10.1093/ eurjpc/zwab068. [CROSSREF]

13. Shehab A, Bhagavathula AS, Al-Rasadi K, Alshamsi F, Al Kaab J, Thani KB, et al. Diabetes and Mortality in Acute Coronary Syndrome: Findings from the Gulf COAST Registry. Curr Vasc Pharmacol. 2020;18(1):68-76. doi: 10.2174/15 70161116666181024094337. [CROSSREF]

14. Ministarstvo zdravlja Republike Srbije. Republička stručna komisija za izradu i implementaciju vodiča u kliničkoj praksi, Odbor za lipide Endokrinološke sekcije Srpskog lekarskog društva, Udruženje za aterosklerozu Srbije, Agencija za akreditaciju zdravstvenih ustanova Srbije. Nacionalni vodič dobre kliničke prakse za dijagnostikovanje i lečenje lipidskih poremećaja 5/11. [Internet]. 2012. Dostupno na: https://www.zdravlje.gov.rs/view_file.php?-file_id=673&cache=sr [HTTP]

15. Snaterse M, Scholte Op Reimer WJ, Dobber J, Minneboo M, Ter Riet G, Jorstad HT, et al. Smoking cessation after an acute coronary syndrome: immediate quitters are successful quitters. Neth Heart J. 2015 Dec;23(12):600-7. doi: 10.1007/s12471-015-0755-9. [CROSSREF]

16. Steptoe A, Kivimäki M. Stress and cardiovascular disease. Nat Rev Cardiol. 2012 Apr 3;9(6):360-70. doi: 10.1038/nrcardio.2012.45. [CROSSREF]

17. Hbejan K. Smoking effect on ischemic heart disease in young patients. Heart Views. 2011 Jan;12(1):1-6. doi: 10.4103/1995-705X.81547. [CROSSREF]

18. Stajić D, Đonović N. Kardiovaskularne bolesti – faktori rizika. Med Čas (Krag). 2016;50(2):43-8. [CROSSREF]

19. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation. 2001 Nov 27;104(22):2746-53. doi: 10.1161/hc4601.099487. [CROSSREF]

20. Ministarstvo zdravlja Republike Srbije. Nacionalni komitet za izradu Vodiča kliničke prakse u Srbiji, Radna grupa za kardiovaskularne bolesti. Nacionalni vodič kliničke prakse. Preporuke za prevenciju ishemijske bolesti srca. [Internet]. 2002. Dostupno na: https://www.zdravlje.gov.rs/view_file.php?-file_id=678&cache=sr

21. Roberts R. Genetics of coronary artery disease. Circ Res. 2014 Jun 6;114(12):1890-903. doi: 10.1161/CIRCRESAHA.114.302692. [CROSSREF]

22. Graham G. Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes. Clin Med Insights Cardiol. 2016 Feb 8;10:1-10. doi: 10.4137/ CMC.S37145. [CROSSREF]

23. Službeni glasnik RS, br. 42/06, 119 /07, 84/08, 71/09, 85/09, 24/10, 6/12, 37/12, 8/14, 92/15, 111/17, 114/17 – ispr, 13/18, 15/18 – ispr, 68/19, 5/20, 11/20, 52/20, 88/20, 62/21, 69/21, 74/21, 95/21. Uredba o Planu mreže zdravstvenih ustanova. [Internet]. Dostupno na: https://www.paragraf.rs/propisi/uredba_o_planu_mreze_zdravstvenih_ustanova.html [HTTP]

24. Službeni glasnik RS, br. 123/2014-2, 106/2015-65, 105/2017-32, 25/2019- 3 -dr. zakon. Zakon o zdravstvenoj dokumentaciji i evidencijama u oblasti zdravstva RS. [Internet]. Dostupno na: https://www.paragraf.rs/propisi/zakon-o-zdravstvenoj-dokumentaciji-i-evidencijama-u-oblasti-zdravstva.html [HTTP]

25. Simms AD, Batin PD, Kurian J, Durham N, Gale CP. Acute coronary syndromes: an old age problem. J Geriatr Cardiol. 2012 Jun;9(2):192-6. doi: 10.3724/ SP.J.1263.2012.01312. [CROSSREF]

26. Rosengren A, Wallentin L, Simoons M, Gitt AK, Behar S, Battler A, et al. Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey. Eur Heart J. 2006 Apr;27(7):789-95. doi: 10.1093/eurheartj/ehi774. [CROSSREF]

27. Kong G, Chew NWS, Ng CH, Chin YH, Lim OZH, Ambhore A, et al. Prognostic Outcomes in Acute Myocardial Infarction Patients Without Standard Modifiable Risk Factors: A Multiethnic Study of 8,680 Asian Patients. Front Cardiovasc Med. 2022 Mar 29;9:869168. doi: 10.3389/fcvm.2022.869168. [CROSSREF]

28. Mouhat B, Putot A, Hanon O, Eicher JC, Chagué F, Beer JC, et al.; Observatoire des Infarctus de Côte d'Or Survey. Low Systolic Blood Pressure and Mortality in Elderly Patients After Acute Myocardial Infarction. J Am Heart Assoc. 2020 Mar 3;9(5):e013030. doi: 10.1161/JAHA.119.013030. [CROSSREF]

29. Liu Y, Han T, Gao M, Wang J, Liu F, Zhou S, et al. Clinical characteristics and prognosis of acute myocardial infarction in young smokers and non-smokers (≤ 45 years): a systematic review and meta-analysis. Oncotarget. 2017 Sep 20;8(46):81195-81203. doi: 10.18632/oncotarget.21092. [CROSSREF]

30. Zhou M, Liu J, Hao Y, Liu J, Huo Y, Smith SC Jr, et al.; CCC-ACS Investigators. Prevalence and in-hospital outcomes of diabetes among patients with acute coronary syndrome in China: findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project. Cardiovasc Diabetol. 2018 Nov 27;17(1):147. doi: 10.1186/s12933-018-0793-x. [CROSSREF]

31. Leonardi S, Gragnano F, Carrara G, Gargiulo G, Frigoli E, Vranckx P, et al. Prognostic Implications of Declining Hemoglobin Content in Patients Hospitalized With Acute Coronary Syndromes. J Am Coll Cardiol. 2021 Feb 2;77(4):375-88. doi: 10.1016/j.jacc.2020.11.046. [CROSSREF]

32. Sabatine MS, Morrow DA, Giugliano RP, Burton PB, Murphy SA, McCabe CH, et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation. 2005 Apr 26;111(16):2042-9. doi: 10.1161/01. CIR.0000162477.70955.5F. [CROSSREF]

33. Nikus KC, Eskola MJ, Virtanen VK, Harju J, Huhtala H, Mikkelsson J, et al. Mortality of patients with acute coronary syndromes still remains high: a follow-up study of 1188 consecutive patients admitted to a university hospital. Ann Med. 2007;39(1):63-71. doi: 10.1080/08037060600997534. [CROSSREF]

34. Khot UN, Jia G, Moliterno DJ, Lincoff AM, Khot MB, Harrington RA, et al. Prognostic importance of physical examination for heart failure in non-ST-elevation acute coronary syndromes: the enduring value of Killip classification. JAMA. 2003 Oct 22;290(16):2174-81. doi: 10.1001/jama.290.16.2174. [CROSSREF]

35. Park IY, Ju YS, Lee SY, Cho HS, Hong JI, Kim HA. Survival after in-hospital cardiopulmonary resuscitation from 2003 to 2013: An observational study before legislation on the life-sustaining treatment decision-making act of Korean patients. Medicine (Baltimore). 2020 Jul 24;99(30):e21274. doi: 10.1097/MD.0000000000021274. [CROSSREF]

36. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al.; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018 Jan 7;39(2):119-77. doi: 10.1093/eurheartj/ ehx393. [CROSSREF]

37. Gao F, Zhang Y. Inotrope Use and Intensive Care Unit Mortality in Patients With Cardiogenic Shock: An Analysis of a Large Electronic Intensive Care Unit Database. Front Cardiovasc Med. 2021 Sep 21;8:696138. doi: 10.3389/ fcvm.2021.696138. [CROSSREF]


REFERENCES

1. WHO. Health Topics. Cardiovascular diseases. [Internet]. 2019. Dostupno na: https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1 [HTTP]

2. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, et al. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol. 2017 Jul 4;70(1):1-25. doi: 10.1016/j.jacc.2017.04.052. [CROSSREF]

3. WHO. The top 10 causes of death. [Internet]. 2020. Dostupno na: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death [HTTP]

4. Institut za javno zdravlje Srbije „Dr Milan Jovanović Batut“. Zdravstveno-statistički godišnjak Republike Srbije 2020. [Internet]. 2021. Dostupno na: https://www.batut.org.rs/download/publikacije/pub2020.pdf [HTTP]

5. Institut za javno zdravlje Srbije „Dr Milan Jovanović Batut“. Incidencija i mortalitet od akutnog koronarnog sindroma u Srbiji 2020. [Internet]. 2021. Dostupno na: https://www.batut.org.rs/download/publikacije/AKS2020.pdf [HTTP]

6. Jankovic S, Vlajinac H, Bjegovic V, Marinkovic J, Sipetic-Grujicic S, Markovic-Denic L, et al. The burden of disease and injury in Serbia. Eur J Public Health. 2007 Feb;17(1):80-5. doi: 10.1093/eurpub/ckl072. [CROSSREF]

7. Ministarstvo zdravlja Republike Srbije. Republička stručna komisija za izradu i implementaciju vodiča dobre kliničke prakse. Nacionalni vodič dobre kliničke prakse za dijagnostikovanje i lečenje ishemijske bolesti srca 2/11. 2012. [Internet]. Dostupno na: https://www.zdravlje.gov.rs/view_file.php?-file_id=670&cache=sr

8. Van Camp G. Cardiovascular disease prevention. Acta Clin Belg. 2014 Dec;69(6):407-11. doi: 10.1179/2295333714Y.0000000069. [CROSSREF]

9. Lapcević M, Vuković M. Faktori rizika za hronicna nezarazna oboljenja: dvansestonediljna prospektivna studija [Risk factors for chronic noncontiguous diseases: twelve-week prospective study]. Srp Arh Celok Lek. 2004 NovDec;132(11-12):414-20. Serbian. doi: 10.2298/sarh0412414l. [CROSSREF]

10. Babić Z, Zeljković I, Pintarić H, Vrsalović M, Jelavić MM, Mišigoj-Duraković M. The role of anthropometric parameters and physical activity level in patients with acute coronary syndrome admitted to the intensive cardiac care unit. Acta Clin Croat. 2021 Jun;60(2):201-8. doi: 10.20471/acc.2021.60.02.05. [CROSSREF]

11. Wan J, Zhou P, Wang D, Liu S, Yang Y, Hou J, et al. Impact of Normal Weight Central Obesity on Clinical Outcomes in Male Patients with Premature Acute Coronary Syndrome. Angiology. 2019 Nov;70(10):960-8. doi: 10.1177/0003319719835637. [CROSSREF]

12. Kringeland E, Tell GS, Midtbø H, Igland J, Haugsgjerd TR, Gerdts E. Stage 1 hypertension, sex, and acute coronary syndromes during midlife: the Hordaland Health Study. Eur J Prev Cardiol. 2022 Feb 19;29(1):147-54. doi: 10.1093/ eurjpc/zwab068. [CROSSREF]

13. Shehab A, Bhagavathula AS, Al-Rasadi K, Alshamsi F, Al Kaab J, Thani KB, et al. Diabetes and Mortality in Acute Coronary Syndrome: Findings from the Gulf COAST Registry. Curr Vasc Pharmacol. 2020;18(1):68-76. doi: 10.2174/15 70161116666181024094337. [CROSSREF]

14. Ministarstvo zdravlja Republike Srbije. Republička stručna komisija za izradu i implementaciju vodiča u kliničkoj praksi, Odbor za lipide Endokrinološke sekcije Srpskog lekarskog društva, Udruženje za aterosklerozu Srbije, Agencija za akreditaciju zdravstvenih ustanova Srbije. Nacionalni vodič dobre kliničke prakse za dijagnostikovanje i lečenje lipidskih poremećaja 5/11. [Internet]. 2012. Dostupno na: https://www.zdravlje.gov.rs/view_file.php?-file_id=673&cache=sr [HTTP]

15. Snaterse M, Scholte Op Reimer WJ, Dobber J, Minneboo M, Ter Riet G, Jorstad HT, et al. Smoking cessation after an acute coronary syndrome: immediate quitters are successful quitters. Neth Heart J. 2015 Dec;23(12):600-7. doi: 10.1007/s12471-015-0755-9. [CROSSREF]

16. Steptoe A, Kivimäki M. Stress and cardiovascular disease. Nat Rev Cardiol. 2012 Apr 3;9(6):360-70. doi: 10.1038/nrcardio.2012.45. [CROSSREF]

17. Hbejan K. Smoking effect on ischemic heart disease in young patients. Heart Views. 2011 Jan;12(1):1-6. doi: 10.4103/1995-705X.81547. [CROSSREF]

18. Stajić D, Đonović N. Kardiovaskularne bolesti – faktori rizika. Med Čas (Krag). 2016;50(2):43-8. [CROSSREF]

19. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation. 2001 Nov 27;104(22):2746-53. doi: 10.1161/hc4601.099487. [CROSSREF]

20. Ministarstvo zdravlja Republike Srbije. Nacionalni komitet za izradu Vodiča kliničke prakse u Srbiji, Radna grupa za kardiovaskularne bolesti. Nacionalni vodič kliničke prakse. Preporuke za prevenciju ishemijske bolesti srca. [Internet]. 2002. Dostupno na: https://www.zdravlje.gov.rs/view_file.php?-file_id=678&cache=sr

21. Roberts R. Genetics of coronary artery disease. Circ Res. 2014 Jun 6;114(12):1890-903. doi: 10.1161/CIRCRESAHA.114.302692. [CROSSREF]

22. Graham G. Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes. Clin Med Insights Cardiol. 2016 Feb 8;10:1-10. doi: 10.4137/ CMC.S37145. [CROSSREF]

23. Službeni glasnik RS, br. 42/06, 119 /07, 84/08, 71/09, 85/09, 24/10, 6/12, 37/12, 8/14, 92/15, 111/17, 114/17 – ispr, 13/18, 15/18 – ispr, 68/19, 5/20, 11/20, 52/20, 88/20, 62/21, 69/21, 74/21, 95/21. Uredba o Planu mreže zdravstvenih ustanova. [Internet]. Dostupno na: https://www.paragraf.rs/propisi/uredba_o_planu_mreze_zdravstvenih_ustanova.html [HTTP]

24. Službeni glasnik RS, br. 123/2014-2, 106/2015-65, 105/2017-32, 25/2019- 3 -dr. zakon. Zakon o zdravstvenoj dokumentaciji i evidencijama u oblasti zdravstva RS. [Internet]. Dostupno na: https://www.paragraf.rs/propisi/zakon-o-zdravstvenoj-dokumentaciji-i-evidencijama-u-oblasti-zdravstva.html [HTTP]

25. Simms AD, Batin PD, Kurian J, Durham N, Gale CP. Acute coronary syndromes: an old age problem. J Geriatr Cardiol. 2012 Jun;9(2):192-6. doi: 10.3724/ SP.J.1263.2012.01312. [CROSSREF]

26. Rosengren A, Wallentin L, Simoons M, Gitt AK, Behar S, Battler A, et al. Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey. Eur Heart J. 2006 Apr;27(7):789-95. doi: 10.1093/eurheartj/ehi774. [CROSSREF]

27. Kong G, Chew NWS, Ng CH, Chin YH, Lim OZH, Ambhore A, et al. Prognostic Outcomes in Acute Myocardial Infarction Patients Without Standard Modifiable Risk Factors: A Multiethnic Study of 8,680 Asian Patients. Front Cardiovasc Med. 2022 Mar 29;9:869168. doi: 10.3389/fcvm.2022.869168. [CROSSREF]

28. Mouhat B, Putot A, Hanon O, Eicher JC, Chagué F, Beer JC, et al.; Observatoire des Infarctus de Côte d'Or Survey. Low Systolic Blood Pressure and Mortality in Elderly Patients After Acute Myocardial Infarction. J Am Heart Assoc. 2020 Mar 3;9(5):e013030. doi: 10.1161/JAHA.119.013030. [CROSSREF]

29. Liu Y, Han T, Gao M, Wang J, Liu F, Zhou S, et al. Clinical characteristics and prognosis of acute myocardial infarction in young smokers and non-smokers (≤ 45 years): a systematic review and meta-analysis. Oncotarget. 2017 Sep 20;8(46):81195-81203. doi: 10.18632/oncotarget.21092. [CROSSREF]

30. Zhou M, Liu J, Hao Y, Liu J, Huo Y, Smith SC Jr, et al.; CCC-ACS Investigators. Prevalence and in-hospital outcomes of diabetes among patients with acute coronary syndrome in China: findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project. Cardiovasc Diabetol. 2018 Nov 27;17(1):147. doi: 10.1186/s12933-018-0793-x. [CROSSREF]

31. Leonardi S, Gragnano F, Carrara G, Gargiulo G, Frigoli E, Vranckx P, et al. Prognostic Implications of Declining Hemoglobin Content in Patients Hospitalized With Acute Coronary Syndromes. J Am Coll Cardiol. 2021 Feb 2;77(4):375-88. doi: 10.1016/j.jacc.2020.11.046. [CROSSREF]

32. Sabatine MS, Morrow DA, Giugliano RP, Burton PB, Murphy SA, McCabe CH, et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation. 2005 Apr 26;111(16):2042-9. doi: 10.1161/01. CIR.0000162477.70955.5F. [CROSSREF]

33. Nikus KC, Eskola MJ, Virtanen VK, Harju J, Huhtala H, Mikkelsson J, et al. Mortality of patients with acute coronary syndromes still remains high: a follow-up study of 1188 consecutive patients admitted to a university hospital. Ann Med. 2007;39(1):63-71. doi: 10.1080/08037060600997534. [CROSSREF]

34. Khot UN, Jia G, Moliterno DJ, Lincoff AM, Khot MB, Harrington RA, et al. Prognostic importance of physical examination for heart failure in non-ST-elevation acute coronary syndromes: the enduring value of Killip classification. JAMA. 2003 Oct 22;290(16):2174-81. doi: 10.1001/jama.290.16.2174. [CROSSREF]

35. Park IY, Ju YS, Lee SY, Cho HS, Hong JI, Kim HA. Survival after in-hospital cardiopulmonary resuscitation from 2003 to 2013: An observational study before legislation on the life-sustaining treatment decision-making act of Korean patients. Medicine (Baltimore). 2020 Jul 24;99(30):e21274. doi: 10.1097/MD.0000000000021274. [CROSSREF]

36. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al.; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018 Jan 7;39(2):119-77. doi: 10.1093/eurheartj/ ehx393. [CROSSREF]

37. Gao F, Zhang Y. Inotrope Use and Intensive Care Unit Mortality in Patients With Cardiogenic Shock: An Analysis of a Large Electronic Intensive Care Unit Database. Front Cardiovasc Med. 2021 Sep 21;8:696138. doi: 10.3389/ fcvm.2021.696138. [CROSSREF]

1. WHO. Health Topics. Cardiovascular diseases. [Internet]. 2019. Dostupno na: https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1 [HTTP]

2. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, et al. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol. 2017 Jul 4;70(1):1-25. doi: 10.1016/j.jacc.2017.04.052. [CROSSREF]

3. WHO. The top 10 causes of death. [Internet]. 2020. Dostupno na: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death [HTTP]

4. Institut za javno zdravlje Srbije „Dr Milan Jovanović Batut“. Zdravstveno-statistički godišnjak Republike Srbije 2020. [Internet]. 2021. Dostupno na: https://www.batut.org.rs/download/publikacije/pub2020.pdf [HTTP]

5. Institut za javno zdravlje Srbije „Dr Milan Jovanović Batut“. Incidencija i mortalitet od akutnog koronarnog sindroma u Srbiji 2020. [Internet]. 2021. Dostupno na: https://www.batut.org.rs/download/publikacije/AKS2020.pdf [HTTP]

6. Jankovic S, Vlajinac H, Bjegovic V, Marinkovic J, Sipetic-Grujicic S, Markovic-Denic L, et al. The burden of disease and injury in Serbia. Eur J Public Health. 2007 Feb;17(1):80-5. doi: 10.1093/eurpub/ckl072. [CROSSREF]

7. Ministarstvo zdravlja Republike Srbije. Republička stručna komisija za izradu i implementaciju vodiča dobre kliničke prakse. Nacionalni vodič dobre kliničke prakse za dijagnostikovanje i lečenje ishemijske bolesti srca 2/11. 2012. [Internet]. Dostupno na: https://www.zdravlje.gov.rs/view_file.php?-file_id=670&cache=sr

8. Van Camp G. Cardiovascular disease prevention. Acta Clin Belg. 2014 Dec;69(6):407-11. doi: 10.1179/2295333714Y.0000000069. [CROSSREF]

9. Lapcević M, Vuković M. Faktori rizika za hronicna nezarazna oboljenja: dvansestonediljna prospektivna studija [Risk factors for chronic noncontiguous diseases: twelve-week prospective study]. Srp Arh Celok Lek. 2004 NovDec;132(11-12):414-20. Serbian. doi: 10.2298/sarh0412414l. [CROSSREF]

10. Babić Z, Zeljković I, Pintarić H, Vrsalović M, Jelavić MM, Mišigoj-Duraković M. The role of anthropometric parameters and physical activity level in patients with acute coronary syndrome admitted to the intensive cardiac care unit. Acta Clin Croat. 2021 Jun;60(2):201-8. doi: 10.20471/acc.2021.60.02.05. [CROSSREF]

11. Wan J, Zhou P, Wang D, Liu S, Yang Y, Hou J, et al. Impact of Normal Weight Central Obesity on Clinical Outcomes in Male Patients with Premature Acute Coronary Syndrome. Angiology. 2019 Nov;70(10):960-8. doi: 10.1177/0003319719835637. [CROSSREF]

12. Kringeland E, Tell GS, Midtbø H, Igland J, Haugsgjerd TR, Gerdts E. Stage 1 hypertension, sex, and acute coronary syndromes during midlife: the Hordaland Health Study. Eur J Prev Cardiol. 2022 Feb 19;29(1):147-54. doi: 10.1093/ eurjpc/zwab068. [CROSSREF]

13. Shehab A, Bhagavathula AS, Al-Rasadi K, Alshamsi F, Al Kaab J, Thani KB, et al. Diabetes and Mortality in Acute Coronary Syndrome: Findings from the Gulf COAST Registry. Curr Vasc Pharmacol. 2020;18(1):68-76. doi: 10.2174/15 70161116666181024094337. [CROSSREF]

14. Ministarstvo zdravlja Republike Srbije. Republička stručna komisija za izradu i implementaciju vodiča u kliničkoj praksi, Odbor za lipide Endokrinološke sekcije Srpskog lekarskog društva, Udruženje za aterosklerozu Srbije, Agencija za akreditaciju zdravstvenih ustanova Srbije. Nacionalni vodič dobre kliničke prakse za dijagnostikovanje i lečenje lipidskih poremećaja 5/11. [Internet]. 2012. Dostupno na: https://www.zdravlje.gov.rs/view_file.php?-file_id=673&cache=sr [HTTP]

15. Snaterse M, Scholte Op Reimer WJ, Dobber J, Minneboo M, Ter Riet G, Jorstad HT, et al. Smoking cessation after an acute coronary syndrome: immediate quitters are successful quitters. Neth Heart J. 2015 Dec;23(12):600-7. doi: 10.1007/s12471-015-0755-9. [CROSSREF]

16. Steptoe A, Kivimäki M. Stress and cardiovascular disease. Nat Rev Cardiol. 2012 Apr 3;9(6):360-70. doi: 10.1038/nrcardio.2012.45. [CROSSREF]

17. Hbejan K. Smoking effect on ischemic heart disease in young patients. Heart Views. 2011 Jan;12(1):1-6. doi: 10.4103/1995-705X.81547. [CROSSREF]

18. Stajić D, Đonović N. Kardiovaskularne bolesti – faktori rizika. Med Čas (Krag). 2016;50(2):43-8. [CROSSREF]

19. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation. 2001 Nov 27;104(22):2746-53. doi: 10.1161/hc4601.099487. [CROSSREF]

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