Patient Characteristics, Risk Factors, and Disease Outcomes in Young Adults With St-Elevation Myocardial Infarction: Insights From The Kermanshah Acute Coronary Syndrome Registry

Background: Myocardial infarction in younger adults is an understudied research area. Objectives: This paper reports on characteristics, risk factors, and disease outcomes of young adults with St-elevation myocardial infarction (STEMI). Methods: This is a sub-analysis of data from the Kermanshah Acute Coronary Syndrome Registry, including all patients aged ≤ 45 with STEMI (n=247) registered in the registry from June 2017 to June 2019. Results: Patients aged ≤ 45 constituted 10.66% of all patients with STEM; the majority was male (91.8%), and the most common CVD risk factors included: smoking (56.7%), low high-density lipoprotein (55.5%), elevated triglyceride (44.4%), hypertension (38.2%), hypercholesterolemia (38.1%), elevated low-density lipoprotein (26.3%), and obesity (24.3%). Many patients (62.8%) received primary percutaneous coronary intervention (PCI), and in-hospital mortality was low at 0.8%. Conclusions: Younger adults should be screened for CVD risk factors, and are educated and supported to participate in programs that aim to reduce risk through risk factor modication.

The burden of CVD in younger adults has been overlooked due to its lower prevalence; however, AMI at a young age can carry signi cant physical and psychological morbidity and nancial impact for the patient, family, and society. Similar to many other low-and middle-income countries, the prevalence of AMI is high and on the rise in Iran. Iranians develop CVD at relatively younger ages, with the mean age of the patients varying between 54.8 and 60.5 in men and 59.4 and 67.1 in women [13]. This paper reports on characteristics, risk factors, and disease outcomes of young adults ≤45years with ST-segment elevation MI (STEMI).

Methods
This is a sub-analysis of data from the Kermanshah Acute Coronary Syndrome Registry, based in a tertiary referral hospital in Western Iran. The majority of the population in this area has Kurdish background (nearly 80%). Since June 01, 2016, a total of 2341 patients with the diagnosis of STEMI were registered in the registry, of which 247 patients (10.55 %) were aged 45 years or younger and eligible for our analysis.
The registry is sponsored by Kermanshah University of Medical Sciences and is part of the European Observational Registry Program (EORP). Therefore, the data for the registry are collected according to the EROP protocol by two trained nurses. The inclusion criteria include: 1) being hospitalized with the diagnosis of STEMI; 2) being above 18 years and 3) being able to provide informed consent. Patients were excluded from the registry if they were not interested or experienced MI after being admitted to the hospital. Data were collected through patient interviews and a review of their medical records. All collected data were audited for quality and completeness by a trained physician, and defective and/or incomplete cases were corrected by revisiting patients' medical records or patient interviews. A detailed description of the registry's objectives, inclusion and exclusion criteria, type of data, and ethical considerations has been published elsewhere [The citation was removed for blind review]. This study has received approval from the Research Ethics Committee of Kermanshah University of Medical Sciences (The approval number was removed for blind review).

Data analysis
We chose the age cutoff of 45 years for de ning young adults with STEMI based on previous research [15,16]. Data were entered in and analyzed using IBM SPSS Statistics for Windows, version 23.0. Descriptive statistics including, frequencies, percentages, ranges, means, and standard deviations, were used to summarize data. Differences in the mean scores between groups were examined using the independent t-tests.

Results
Two hundred forty-seven patients aged 45 years or younger were entered into the registry between June 04, 2016, and June 10, 2019. The demographic and clinical characteristics of the patients are presented in Table 1. The mean age of this patient cohort was 39.36±5.21, with a range of 19 to 45 years. Sixteen out of 2341 registered patients (0.68%) experienced STEMI at age 30 or younger. The majority of patients were male (91.8%), with no statistically signi cant difference between males and females in terms of age (p=0.250).

Hospital arrival
Patients' rst contacts with medical professional were as follows: most patients (79.8%) were directly transported to the ED by a private vehicle, 30(12.1%) visited a general practitioner rst, and 20(8.1%) called the emergency services. Only 26 (10.5%) arrived at the hospital by ambulance, and 76(30.8%) patients were rst admitted to a non-PCI center and later transferred to a PCI center (Table 1). Patients' clinical characteristics are summarized in Table 2. All patients presented with chest pain (100%), 46(18.6%) had a heart rate that was not within the normal range of 60-100 beats per minutes (bpm), 192(78%) had a systolic blood pressure either below or above the normal range of 90-119 mmHg, and 38.2% were hypertensive (SBP≥14). The mean earliest ejection fraction was 41.67±7.65, which dropped to 39.80±8.66 at later stages; 27.5% of patients experienced a decline in ejection fraction (<40%) in the early stage. The Killip classi cation in the majority of patients (96%) was I, indicating no sign of heart failure. Most patients (96.8%) had at least one coronary artery with more than 50% stenosis, and 22% had three coronary arteries with above 50% stenosis. The culprit artery was identi able in 97.8% of patients who underwent angiography; the most common culprit artery was the left anterior descending artery (58.1%), followed by the right coronary artery (25.1%). Over 53% of MIs were anterior, including anterior, anteroseptal, extensive anterior, and anterolateral, while the remaining (46.6%) were inferior, lateral, lateral inferior, or posterior. Atrial brillation was present in the rst ECG of 3 (1.2%) patients.   (Table 3).   [19], a rate that the authors believed was unexpectedly high. Other similar studies in Iran report AMI admission rates at 8.6% and 6.8% for adults ≤45 [13]. These results suggest that AMI in younger adults occurs at a high rate in Iran. Internationally, evidence also suggests a steady increase in AMI admissions among young adults, particularly in young women over the recent decade [20][21][22]. These trends may suggest that cardiovascular risk-reducing programs have not been able to reach young adults effectively. Factors such as low socioeconomic status, limited access to quality health care, substance abuse [23], and underestimation of CVD risk [24] can contribute to this growing burden of CVD among this population group.
In our study, nearly 92% of the patients who developed STEMI at 45 or younger were male. This proportion is much higher than the reported three times higher incidence of MI in males vs. females, including all age groups [25]. In other similar studies, men constituted 91% (15) and 90% (16) of younger adult patients with AMI [18,26]. In a study that included very young patients (aged ≤30), men constituted 95% of the patients [27]. These results suggest that the gender gap in MI incidence is more remarkable in younger ages, i.e., women are particularly protected against cardiovascular disease at younger ages.
The most common CVD risk factors were smoking, low HDL, elevated triglyceride, hypertension, hypercholesterolemia, elevated LDL, and obesity. This nding is most consistent with the results of previous research from other countries (16, 24,26,27). In addition, lower HDL was a common risk factor in our study (55.5%), which is similar to the study by Chua et al., who found that low HDL was common among younger patients with STEMI (26). This nding indicates that the role of lower HDL in developing STEMI in younger adults needs focused investigation.
However, some patients in our study were unaware of their CVD risk factors; more speci cally, 23.6% were not aware that they were hypertensive, 19.1% did not know that they had high blood cholesterol levels, and 2.1% were not aware of their diabetes. Only 8 (3.2%) patients did not have any of the main CVD risk factors. The actual number of the risk factors is likely to be even higher, as the study did not assess the family history of CVD or physical activity level. Further, there were some missing data. To our knowledge, no previous study has investigated CVD risk factors among younger adults with STEMI in Iran; however, a systematic review of the prevalence of AMI revealed that smoking, hypertension, diabetes mellitus, and hypercholesterolemia are the common AMI risk factors in this country irrespective of age and type of MI [13].
Overall, these ndings indicate that many MI cases in young adults could have been prevented if their risk factors had been identi ed earlier and modi ed through behavior change, such as smoking cessation, following up healthy diet control, physical activity, or medication therapy [28]. Screening CVD risk factors in young adults and effective management of the risk factors can result in signi cant health gains in the population by detecting subclinical disease, reducing the risk of the onset of the disease, and slowing disease progression and development of complications [29]. Unfortunately, a lack of knowledge and awareness of CVD risk factors and underestimating personal CVD risk hinder the timely management of CVD risk, particularly among younger adults [30].
The proportion of patients who arrived at the hospital by ambulance was only 10.5%. This rate is alarmingly low and consistent with previous studies in Iran; Seyed Mohammadzad et al. (2010) reported that only 15% of patients with MI admissions in the city of Urmia, Iran arrived at the hospital by ambulance. This rate is even lower than 17% reported by a study conducted in the Middle East [31], while in the United Kingdom (UK) about two-third of all AMI patients [32], in Australia 58.4% [33], and in New Zealand 73% are transferred to hospital by ambulance. A lack of knowledge about the ambulance services and symptoms of heart attack was identi ed as signi cant barriers to using ambulance services in Iran (Seyed Mohammadzadeh et al., 2010). Evidence suggests that arriving by ambulance results in timely treatment, shorter decision-to-balloon time, and symptom onset-to-balloon time [34], factors that can have a signi cant impact on MI outcomes [35].
In our study, the left anterior descending artery was identi ed as the most common culprit artery (58.1%), followed by the right coronary artery (25.1%). This nding is consistent with previous research ndings [27,36,37]. Primary PCI was conducted on 62.8% of the patients, while the remaining eligible missed the opportunity to receive the gold standard treatment for STEMI due to technical issues, lack of facilities, patient refusal, or the need for CABG. The rate of PCI in our study is slightly lower than the international statistics. Previous studies from Italy [26] and [27] and India reported that primary PCI was performed on 75% and 71.6% of patients≤ 45 with STEMI, respectively. This proportion was 74.8% in the US, including patients under 60 years old [38].
In-hospital mortality in our study was 0.8%, which is lower than reported death rates in other studies. For example, the in-hospital death rate in patients aged ≤ 30 years with STEMI was 2.8% in a study in India [27]; 5% in patients aged ≤ 35 years with STEMI in Spain [39], and 3.75% in patients aged <60 years with STEMI in the US.

Limitations
The main limitation of this study is that the value of some variables relied on patients' memories. In addition, patients were predominantly Kurdish, which is a minority group in Iran. Also, some data were to be collected from patients' medical record, which was not available after their discharge, resulting in missing data.

Conclusion
This study suggests that STEMI occurs at a higher rate in younger adults (≤45) in western Iran. Gender gap in the incidence of STEMI is larger in younger ages. Smoking, low HDL, elevated triglyceride, hypertension, hypercholesterolemia, elevated LDL, and obesity were common CVD risk factors in younger adults with STEMI. To reduce the risk of STEMI, younger adults should be screened for these risk factors, and they are educated and supported to participate in programs that aim to reduce CVD risk through risk factor medication. The role of lower HDL in developing STEMI in younger adults needs focused investigation. In this study, a small percentage of patients arrived at the hospital by ambulance; public knowledge about MI symptoms needs to be improved, and the ambulance services in medical emergencies encouraged. This research also suggests that clinical management of younger patients with STEMI was good in western Iran, with nearly 63% of patients receiving primary PCI and in-hospital mortality rates at a lower level.

Declarations
Ethics approval and consent to participate: This study has received approval from the Research Ethics Committee of Kermanshah University of Medical Sciences (The approval number was removed for blind review). All participants consented to the research.
Consent for Publication: All authors consented for publication.
Availability of data and material: Data will be made available if requested.
Competing interests: There is no con ict of interest in relation to this research.