Comparison of Clinical Profiles, Angiographic Features and Outcomes of Young and Elderly Patients with ST-Segment Elevation Myocardial Infarction

Objective: It is to reveal the differences between clinical, angiographic, in-hospital and one-year follow-up results between young and elderly patients with acute ST-segment elevation myocardial infarction. Materials and Methods: This study was designed retrospectively in two centers. 2891 patients were screened; 260 of which were young. 260 elderly patients were randomly selected among the patients and the differences between both groups were evaluated. Results: The median age of the young patients was 37 (34-39) years and the median age of the elderly patients was 65 (56-73) years, and male gender was dominant in both groups. Young patients were more likely to be admitted with Killip class 1, while older patients were more likely to be admitted with Killip class 2 (P=0.002). Single-vessel disease was more common in young patients (81.0% vs. 46.3%; P<0.001), while multi-vessel disease was more common in the elderly patients (19.0% vs. 53.7%; P<0.001). In one-year follow-up, all-cause hospitalization was lower in younger patients, but there was no significant difference in mortality between elderly and young patients. Conclusion: Young patients presenting with ST-segment elevation myocardial infarction were more frequent smokers, obese and dyslipidemic and although in-hospital outcomes were better than the elderly, one-year mortality was similar to those of the elderly.


INTRODUCTION
ST-segment elevation myocardial infarction (STEMI) is one of the most common causes of emergency room admission and cardiovascular death and therefore currently poses a major burden on healthcare worldwide [1,2]. Although the incidence of acute coronary syndrome has decreased in the elderly population in recent years, unfortunately, there is no decrease in the incidence of STEMI in young people [3]. In some studies, although the short-term prognosis of acute STEMI is favorable in young patients, it has been reported that the long-term prognosis is unfavorable [4]. STEMI, with an increasing incidence in young adults, is an important problem for both the patient and the treating physician [5,6]. In recent studies, it was stated that the prevalence of acute STEMI increased significantly in young people. Therefore, recent studies have focused on the clinical profile, risk factors, treatment and long-term consequences of premature myocardial infarction (MI) in young people [7]. While it is important to have MI at an early age, there is not enough data on the etiology and long-term prognosis of this disease, since the most productive life years of the society are at risk due to this disease. In this study, it was aimed to compare the clinical profiles, risk factors, in-hospital and one-year clinical outcomes of young and old patients with STEMI.

Study population
This study was carried out retrospectively at two centers between June 2015 and June 2020. The study included 260 patients younger than 45 years of age who applied to the emergency department with the diagnosis of acute STEMI and were hospitalized in the coronary intensive care unit who underwent reperfusion therapy. 260 patients older than 45 years who were admitted to the hospital during the study period were randomly selected. The clinical profiles, risk factors, angiographic features, in-hospital and one-year clinical outcome of these patient groups were compared. Demographic information of the patients, age, gender, coronary artery disease (CAD) risk factors, cardiovascular disease histories, laboratory results were obtained from the records in the electronic system of the hospitals. The family histories and one-year results of the patients were learned by telephone call method.

Definitions
In this study, patients were divided into two groups, according to the current European Society of Cardiology guidelines, patients younger than 45 years were defined as "young" and patients older than 45 years were defined as elderly [8]. STEMI was defined according to the 4th universal MI guideline [9]. The type and localization of myocardial infarction were determined according to electrocardiographic (ECG) findings. The patients were divided into two groups according to their body mass index (BMI) (<25 and >25 kg/m2). Patients with a body mass index >25 kg/m2 were defined as obese. Dyslipidemia was defined as serum total cholesterol (TC) ≥200 mg/dl; triglyceride (TG) >150 mg/dl; low-density lipoprotein (LDL) >130 mg/dl; high-density lipoprotein (HDL) <50 mg/dl in men and <40 mg/dl in women; and/or those receiving lipid-lowering therapy [10]. The term re-infarction was defined as the ischemic symptoms lasting 20 minutes or longer and at least one of the following: recurrence of ≥0.1 mV ST-segment elevation in at least two contiguous leads on the ECG, or the appearance of new pathognomonic Q waves, and a 20% or greater increase in cardiac troponin [11]. TIMI thrombus scale was used to evaluate thrombus burden [12]. Then, the TIMI thrombus score was divided into two classes as large thrombus grade (4 and 5) and small thrombus grade (1-3 grade) [13]. Castelli's risk index 1 and 2 (CRI-1 and CRI-2) were defined as TC/HDL-c and LDLc/HDL-c ratios. Inhospital outcomes included left ventricular ejection fraction (LVEF) before discharge, reinfarction, cardiogenic shock, stroke, major bleeding, nonmajor bleeding, blood transfusion and all-cause mortality. One-year clinical outcome was defined as hospitalization for any cause, MI, coronary angiography, cardiovascular death and all-cause death. Patients with the following conditions were excluded from the study: Congenital heart disease, cardiomyopathy, myocarditis, MI due to aortic dissection, Takayasu arteritis or vascular dysplasia, those who did not undergo coronary angiography who had an acute MI during pregnancy and inhospital. The study was approved by the local ethics committee.

Statistical Analysis
Continuous data are given as median (Q1 -Q3). Categorical data are given as a percentage (%). Shapiro Wilk's test was used to investigate the suitability of the data for normal distribution. The Mann-Whitney U test was used for the cases with two groups in the comparison of those which did not conform to the normal distribution. Pearson Exact Chi-Square analyzes were used in the analysis of the created cross tables. IBM SPSS Statistics 21.0 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) program was used in the analysis. A value of p<0.05 was accepted as a criterion for statistical significance.

Angiographic findings
In terms of coronary angiographic findings, the duration of fluoroscopy was shorter in the young compared to the elderly (25.06±11 vs. 33.9±12; P<0.001). As a result of coronary angiography performed after STEMI, normal coronary arteries (5.1% vs. 1.2%; P<0.005) and single vessel disease (81.0% vs. 46.3%; P<0.001) was more common in the young, whereas multivessel disease was more common (53.7% vs. 19.0%; P<0.001) in the elderly. When the thrombus burden was examined, there was no significant difference between both groups in terms of small thrombi, while large thrombi (50.4% vs. 33.1%; P<0.001) were significantly more common in the young than in the elderly. Angiographic findings are summarized in table 3 in detail.

In
1-year clinical outcomes, all-cause hospitalizations (43.0% vs. 25.7%; P=0.001) and hospitalizations due to heart failure (HF) (12.7% vs. 5.1%; P=0.005) were more common in the elderly, but there was no difference between both groups in terms of MI, revascularization, stroke, all-cause death and cardiovascular death. In-hospital and one-year outcomes are detailed in Table 4.

DISCUSSION
In this retrospective study performed in two centers evaluating 520 patients including 260 young and 260 elderly, patients aged ≤45 years constituted 9% of the total study population and male gender was more dominant (83.8%). More than half (65.1%) of the young patients were smokers, one-third (34.5%) had dyslipidemia and 23.1% had a history of CAD in their first-degree relatives, and also 25% of the youth were obese. Low density lipoprotein cholesterol in the blood values taken in the first 24 hours were found to be higher in young patients, while HT, DM and kidney failure were higher in the elderly. Castelli risk index (CRI) 1 and 2 were found to be higher in young patients than in the elderly. Although the in-hospital outcomes of patients aged ≤45 were better, there was no difference in mortality in the one-year follow-up compared to patients aged >45 years. Although there is not enough data on the incidence of acute MI in young people, it has been reported to be between 4-10%. In our study, the incidence of MI was found to be 9%, which is consistent with other studies, although it is higher than the Norwegian registry study [14]. Because the definition of acute MI has changed a few times over the past decade and various studies have used different inclusion criteria, it is difficult to compare incidence rates through different time periods and in different populations [15,16]. The clinical presentation of CAD in patients younger than 45  years old may differ from that in older patients. Typical chest pain, which is the first symptom of acute MI, was more common in the young than in the elderly, consistent with previous studies [6,17]. While young people were mostly admitted with Killip class 1, the elderly were admitted more with Killip class 2, 3 or 4. In previous studies, it was stated that elderly patients were more likely to present with HF symptoms due to the prevalence of advanced CAD and low LVEF [18][19][20].
In young people with acute MI, it is common to have multiple risk factors and the majority of these patients are reported to have at least one traditional cardiovascular risk factor [21,22].
Smoking is the most preventable universal cause of death by leading to the initiation and progression of atherosclerosis [23]. Smoking cessation greatly reduces the risk of CAD and there are striking results reporting that giving up before age 40 reduces the risk of death by 90% [23]. Consistent with previous studies, in our study, the rate of smoking was higher in young people than in the elderly (43.4% versus 65.1%) [7,24,25]. These data explain the importance of smoking cessation over early MI [26]. Low density lipoprotein cholesterol and TG values were found to be higher in young people than in the elderly, while HDL was found to be lower in this study, as well. These results were consistent with previous studies [27,28]. High TG and low HDL levels, which characterize the dyslipidemia aspect of the metabolic syndrome, have a significant role in the development of atherosclerosis and coronary heart disease. In addition, BMI>25 kg/ m2 was also significantly higher in the young than in the elderly in this study. All these results show that it is important to carefully examine young patients in terms of metabolic syndrome, which is one of the most important causes of CAD and atherosclerosis [29]. In previous studies, it has been reported that CRI is an important risk index in terms of CAD and cardiovascular outcomes in the elderly and in patients with DM [30,31]. However, there is no information regarding its importance in young people with CAD. Although it has been reported that LDL increases with age in some previous studies [14], it has been shown that LDL value is higher in young people in recent studies.
In this study, both CRI 1 and CRI 2 were found to be higher in young people. Of course, the results of our study may not be sufficient to predict future clinical outcomes of CRI alone. Larger prospective studies are required on this subject.
The relationship between a positive family history and early CAD and increased plaque burden is well known. In our study, 1 out of every 5 young patients had a positive family history, and it was significantly higher in younger patients than in patients aged >45 years. Although this rate was reported as 10% in some previous studies, the results of our study were similar to those of most recent studies [23,32].
Consistent with the results of previously reported studies, in our study, normal coronary (5.1%) and single vessel disease (81.0%) were more common in patients aged ≤ 45 years, while multi-vessel disease (53.7%) was dominant in patients aged >45 years [20,23,29,32,33]. In the meanwhile, similar to the results of previous studies, in our study, left anterior descending artery (LAD) was the most common involved artery (58.1%) in the young, so was the right coronary artery (RCA) (40.6%) in the elderly [20,34]. In addition, the thrombus load was significantly higher in young patients than in the elderly, and therefore more thrombus aspiration was performed in young patients. This result can be attributed to the fact that younger patients with acute MI are more prone to thrombus formation. Consistent with our study, a high thrombus burden was reported in young patients in the study of Shalaby et al. [7].
Under the light of clinical outcomes, the outcomes of our study are similar to previous studies in terms of in-hospital clinical outcomes, but differ in one-year mortality ( Table 4). As in this study, in previous studies, young patients with acute MI had a better prognosis than the elderly in terms of length of stay in the intensive care unit, in-hospital cardiogenic shock, HF and mortality. These results can be attributed to the earlier admission of young patients to the hospital, fewer co-morbidities, more frequent single vessel involvement and less frequent severe atherosclerosis [20,35,36]. Previous data suggest that younger patients with MI have a relatively favorable short and long-term prognosis compared with older patients. However, some studies have shown an alarming 15% reduction in survival at 7 years, after 5 years of MI [37][38][39]. In a recent study, in which the age of 35 was taken into account, it was shown that there was no significant difference in prognosis between both groups in a 4-year follow-up [39]. In our study, in terms of one-year results, while young patients were more advantageous in terms of all-cause hospitalization and hospitalization due to HF, there was no statistically significant difference between elderly and young patients in terms of mortality. In a study published by Fach A et al. in 2019, only a few of 277 young MI patients achieved the risk control goals planned for long-term follow-up after MI. The target level was achieved in 14.8% for body mass index and 27% for LDL level, and the results were shown to be even worse in the follow-up [40]. One of the reasons why the mortality result in our study differs from previous studies can be explained by the progressively worsening of MI prognosis in younger patients over time compared to the past. Another reason may be the small number of patients included in the study and the fact that 43 patients could not be reached during one-year follow-up.
Our study has some limitations. Firstly, it is a retrospective study with most of the patients' data from hospital records. Secondly, the patients were divided into two groups and the control group was randomly selected from the entire patient population as the number of young patients. Third, conditions such as genetic diseases and spontaneous coronary artery dissection, which are among the most important etiologies of acute MI at an early age, could not be evaluated due to the retrospective nature of the study.

CONCLUSION
Young patients presenting with STEMI were more frequent smokers, obese and dyslipidemic. These patients also had greater thrombus burden and a greater prevalence of single vessel disease. In addition, one-year mortality outcomes were similar to those in the elderly although in-hospital outcomes were better in younger patients. These results highlight the importance of smoking cessation, weight loss programs and health education, especially for the population of this age.

Author contribution
Study conception and design: BM; data collection: SM and BM; analysis and interpretation of results: BM; draft manuscript preparation SM and BM. All authors reviewed the results and approved the final version of the manuscript.