Differences in Clinical Nature and Outcome Among Youth and Older Patients Suffering from an Acute Coronary Syndrome

Objective: Acute coronary disease (ACS) is an acute regional reduction in coronary blood ow. Pathophysiology, clinical appearance, risk factors and clinical outcomes may vary between younger and older patients. The purpose of this study was to assess these factors in patients less than 45 years of age compared to older adults admitted with a ACS diagnosis. Patients and methods: Retrospective chart review study of ACS patients admitted between 2015 and 2020. Results: Overall, 652 patients were enrolled. Of these, 109 patients (16.7%) were under 45, with a mean age of 38 ± 7. Younger patients showed a higher rate of palpitation (23.9% versus. 13.6%; P = 0.019). A positive smoking history and a family history of CAD were seen more often in younger patients (42.2% vs. 27.3%, P < 0.001; 22.9% vs. 9.4%, P < 0.001, respectively). Older patients had greater renal impairment with higher creatinine (median = 1.10 mg /dl (range, 0.3-13.0) vs. 1.0 (0.3-19.0; p = 0. 001), BUN (median = 16.0 (mange, 0.9-141.0) vs 12.0 (0.9-49.0); P < 0.001)). Younger patients had higher levels of LDL and total cholesterol (median 138c. 115; p < 0.001) and cholesterol (median 209 vs. 178.5; p < 0.001). Hospital mortality was 0.9% in younger patients versus 7.4% in older patients (P=0.004). Conclusion: Palpitations, smoking, family history, higher LDL levels, and total cholesterol levels were more in than 45 with ACS. Impaired renal function, hypertension, and diabetes were more in older patients with ACS.


Background
Cardiovascular disease, which includes coronary heart disease and stroke, is the leading cause of death and disease burden globally.1 Acute coronary syndrome (ACS) is characterized by acute local reduction in blood ow to the myocardium, also known as ischemia.2 Ischemic heart disease may present with a variety of symptoms e.g. a symptom complex called acute coronary syndrome (ACS), which may lead to a diagnosis of one of unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), or ST-segment elevation myocardial infarction (STEMI). The former is a clinical diagnosis, whereas the latter two are diagnosed from the abnormalities seen on the EKG, possibly complemented by serum enzyme assays e.g. of troponin C.3 Atherosclerosis is a chronic in ammatory process of the arterial wall, and although it starts early in life, it takes years to be of serious pathological severity, so that young people do not present with ACS very often.4,5 However, in recent years, coronary artery disease (CAD) has been affecting younger patients, which raises concern due to the accompanying results of premature morbidity and mortality. Patients less than 45 years of age represent 6-10% of cardiac infarctions in the United States. [5][6][7] Smoking was found to be the prevailing risk factor and was frequently found along with coronary events in young patients.8,9 ACS presents with similar clinical features irrespective of age 9 The main presenting symptom is chest pain in both the young as well as in the elderly.10 It is also important to note that the severity and presentation of the diseases caused by atherosclerosis seem to differ between men and women in their different stages of life.11 For example, men are more likely to develop advanced coronary artery disease (CAD) in all age groups.12 The aim of this study was to assess the demographic characteristics, cardiovascular risk factors, and complications in young adults below the age of 45 years compared to older adults who were admitted with a diagnosis of ACS at King Fahd University Hospital between 2015 and 2020.

Setting
The study was conducted at King Fahad Hospital of the University (KFHU), a tertiary care university teaching hospital with 600 beds in the Eastern Province of Saudi Arabia. It is a retrospective study that was conducted using medical records of all ACS patients admitted between 2015 and 2020.
Demographic data, presenting symptoms, risk factors, and clinical outcomes were obtained. The local institutional research body approved this study.

Target Population
We recruited all patients who were diagnosed with ACS based on the international classi cation of diseases version 10 ICD-10, including younger adult patients (from 18-45 years old) and older patients (above 45-year-old). We excluded patients labelled DNR (do not resuscitate), and incomplete patient le.

Study design
A descriptive retrospective study was conducted with the sample size determined by the number of patients in King Fahd Hospital of the University in Al-Khobar city, and this was a total of 652 patients. All methods were performed in accordance with STROBE guidelines and regulations of cohort studies.

Statistical analysis
All categorical variables were represented by frequency as percentages, and were analyzed using chisquared and Fisher's exact tests. Continuous variables were represented by median with range because the data did not follow the normal distribution. The Mann-Whitney U test was used for the comparison between the two groups. All analyses were performed using SPSS (21 version). A P value of less than 0.05 was considered signi cant by Kruskal-Wallis test.

Results
A total of 652 patients were enrolled in this study. Of these, 109 (16.7%) patients were less than 45 years of age. The mean age was 38 ± 7 vs. 60 ± 11 years in the young and old groups, respectively (P < 0.001). Table 1 shows that younger patients had a higher frequency of palpitations (23.9% vs. 13.6%; P = 0.019).

Discussion
Acute coronary syndrome (ACS) in young adults is a rare entity, but it does occur. It is important to assess the clinical features, risk factors, and outcomes, which may be due to the primary disease or may be secondary as complications, so that measures to prevent further episodes of ACS can be undertaken.
In this study, the cutoff point that we used to de ne young patients was 45 years. It was determined based on the results of similar studies in Thailand, Singapore, Israel, and California. 13,14 Other studies have de ned the young age to be under 40 years, including studies from Japan, Poland, Germany, Australia, New Zealand, and the USA. 14 Our ndings are as follows: First, 109 patients who had ACS were younger than 45 years with a mean age of 38 ± 7. Second, regarding risk factors, as expected, older patients had a higher frequency of hypertension, diabetes, and a history of CAD. On the other hand, they had less frequent history of smoking and family history of ACS, which were higher among younger patients. Furthermore, a recent retrospective cohort study of two academic institutions suggests an increased likelihood of encountering ACS with a family history of hypercholesterolemia. 15 In previous studies, the most crucial risk factor for the development of ACS in young adults was smoking.
The literature reports that 82% of young patients who suffered from ACS were smokers. An interesting nding was reported by Huang and colleagues who found that the rate of smoking in patients aged ≤ 35 years and who suffered from MI was signi cantly higher than in patients > 65 years of age who suffered from the same condition.
All of these ndings suggest that a history of smoking and family history of cardiovascular disease are risk factors in young patients with ACS ( Fig. 1), which is consistent with the ndings of other studies. 16,17,18 A study in Thailand reached the same conclusion, where it was discovered that the most common risk factor of ACS in patients aged < 45 years of age was smoking. 13 A different study found that patients whose parents developed cardiovascular disease of early onset had an increased risk of cardiovascular disease. 19 Smoking is a major risk factor for ACS in young patients for multiple reasons. Both quantity and duration of smoking quicken the development of atherogenic cardiovascular disease. 20,21 Furthermore, smoking also alters the defensive response of the immune system against vascular damage, which is characterized by an increase in oxidative in uence on lipid peroxidation, endothelial cell dysfunction, and generation of foam cells in the tunica media. 21,22 It also leads to increased platelet aggregation, disrupts the metabolic activities of lipoproteins, and tends to reduce HDL cholesterol. 21,22 Cigarette smoking is linked to increased levels of in ammatory markers. During the acute phase of the in ammatory process, C-reactive protein is elevated, white blood cells and brinogen are increased, and serum albumin is decreased. 20,21,22 Smoking can also increase myocardial load due to stimulation by catecholamines and reduce consumption of O2 due to inhalation of carbon monoxide, which may cause tachycardia, vasoconstriction of blood vessels, and which may modify the permeability of the vessel wall. 21,22 Primary and secondary prevention speci cally are important in this subset of patients. In addition, one study has shown that diabetes mellitus was more prevalent in younger adults. Acute coronary syndrome is clinically similar in both young patients and the elderly, and this has been emphasized by several authors. 9,23−26 However, in our study, we found that palpitations occurred more frequently in younger adults.
In addition, some laboratory parameters including creatinine, and BUN, were higher in older patients, but HGB, LDL, and cholesterol levels were higher among younger patients. This result was similar to those of previous studies.
In terms of length of stay, other studies have shown that older patients with ACS had longer hospital stays. 27, 28 on the other hand, in our study, the length of stay was not signi cantly different between the two age groups. In our study, in-hospital mortality was 7.4% among older patients and 0.9% among younger patients. Our ndings align with those of a recent cohort of Junjie Yang et al., which have demonstrated equity among younger and older adults in terms of short-and long-term outcomes. 29 Potential limitations of our study include the fact that our selected design was retrospective. However, our sample size was reasonably large (652 cases), which in our opinion reduced information bias and therefore strengthened the results.

Conclusion
Palpitations, positive smoking history, positive family history, and higher lipid pro le were more prevalent in adults younger than 45 years old with ACS than in older ones. Impaired renal function, hypertension, and diabetes were more common in older patients with ACS. Younger patients seem to have a better outcome in terms of mortality with no difference in length of hospital stay. We wish to acknowledge the King Fahd Hospital of the University administrators and staff for providing much needed assistance throughout the course of this research.

Disclosure:
The author reports no con icts of interest in this work. Data availability: The datasets generated during and analysed during the current study are not publicly available due to the privacy of research participants but are available from the corresponding author on reasonable request Funding: This research did not receive any speci c grant from funding agencies in the public, commercial, or forpro t sectors. The patient is 42 years old, suffering from atypical chest pain. He's overweight, and his lab results came back positive for dyslipidemia. Cardiac CT scan performed to evaluate the presence of coronary heart disease. An ECG-gated cardiac CT acquisition was performed using an ECG-modulated radiation dose. A sublingual nitroglycerin tablet given three minutes prior to the procedure. (a) The left anterior descending artery presents a benign diffuse disease with moderate calci cation and no apparent obstructive lesions (arrow). However, the presence of calci cation impedes an accurate evaluation of stenosis. (b) The left ventricle is slightly dilated, the left ventricular volume at the end of diastolic is 211 ml, and the volume at the end of systole is 114 ml. The calculated ejector fraction is 46 percent. An organized small wallmounted apical clot was displayed (arrow), which denotes an infarction of the old LAD territory with an organized old LV apical clot. There is an akinese of the medium and distal septum and the major part of the apex (not shown).