Egypt, like many other countries, faces a dual disease burden: a persistently diminishing communicable disease burden and a large and rapidly growing non-communicable diseases burden, such as myocardial ischemia and infarction. However, data on clinical features, risk factors, optimal treatment approach, and outcomes in AMI in Egyptian youth and the middle eastern region were limited compared with older subjects. Thus, this population requires special attention, and developing an approach to the early diagnosis and identification of high-risk patients is a challenge. Therefore, we targeted this population in our study.

With regard to the AMI presentation in the present study, anterior wall MI was the predominant STEMI type in 22 patients (88%) (p=0.035), and consequently, LAD was the most affected vessel (63%). Regarding the extent of CAD, our study showed a predominance of single-vessel disease (VD), which was LAD, followed by two VD and three VD.

A study conducted on 124 patients <40 years presenting with AMI were evaluated. Anterior wall MI was found in 88 patients (71%), denoting that anterior wall MI was the most predominant, with LAD being affected in approximately 2/3 of patients (1).

Another cross-sectional study evaluated 41 STEMI patients and revealed that anterior wall MI was found in 82.9%, with obstructive CAD in 61% of patients due to involvement of LAD in 46.4% (10).

Similarly, a cross-sectional study was conducted on 266 young (≤35 years) patients with clinical diagnosis of AMI. Anterior wall MI was the most common. Most patients showed single VD, followed by double VD. The LAD was the most commonly affected vessel (11).

Regarding the demographic characteristics of the present study population, 95.3% of the patients were men, which was similar to the results obtained by Bhardwaj et al. (1), with 99% being men. Similarly, Incalcaterra et al. (12) found that 91% of the study sample were men. Sinha et al. (13) also found that 91% of the study sample were men, indicating that MI in the young age occurs almost exclusively in men. The male predominance of the study population is accredited to the protective effects of estrogen in preventing the atherosclerotic process, and the dominance of smoking was more common among men, which has been established in various epidemiological studies (14).

A limited percentage of obesity was found among the study group, with a mean BMI of 27.81±2.23 (overweight), whereas the prevalence of obesity (BMI ≥30) was only 8% among the study sample. Obesity was an uncommon risk parameter in many previous studies in young individuals presenting with AMI, with an incidence of 3.3%–0% (15-15).

Bhardwaj et al. (1) showed similar results, with only 4% of patients being obese. However, the results were different from our results in studies by Incalcaterra et al. (12) and Sinha et al. (13), wherein the percentage of obesity in their study samples was 25.1% and 39.1%, respectively. Lakka et al. (18) showed that abdominal obesity was an independent risk factor for acute coronary syndrome (ACS) in middle-aged men, and in addition to smoking, the risk of coronary events increased by 5.5 times.

The majority of patients were smokers (87%), and high-lighting smoking was the most significant risk factor in this age group. Cigarette smoking was the most important risk factor for CAD, with involvement ranging from 60% to 90% (15, 16) in many studies. Similar to previous studies, our study population included 87% smokers (17). It unfavorably promotes all phases of atherosclerosis by accelerating thrombotic process, endothelial dysfunction, and coronary vasoconstriction, initiates pro-inflammatory effects, and eventually generates thrombotic milieu.

The percentage of traditional risk factors, such as DM, hypertension, and dyslipidemia, were documented in the present study sample. DM was found in 22%, which was consistent with the prevalence in the study by Karim et al. (19). A similar prevalence (20.7%) was found by Incalcaterra et al. (12), and a prevalence of 17.2% was detected by Sinha et al. (13). However, the study by Bhardwaj et al. (1) showed that the percentage of DM was much lower, with only 8% of the study population being diabetic.

The percentage of hypertension in the study group was 34.9%, which was quite similar to the study by Bhardwaj et al. (1), with 44.4% of the study sample being hypertensive. A study by Aggarwal et al. (2) showed that the percentage of hypertension in young people with CAD was 26% compared with only 13% in those without CAD.

Dyslipidemia is considered a major risk factor for CAD in the literature, and our study was concerned with the specific form of dyslipidemia prevalent in this age group. In our study, 44.3% of the study population had low HDL levels, and by stratifying them, 29% of the patients had isolated low HDL levels as the only factor of dyslipidemia, whereas only 3.7% had isolated high LDL levels. The significant prevalence of low HDL level in our study sample matched multiple studies. Among 68 studies involving >300.000 patients in different age groups, HDL was strongly and inversely related to CV events (20).

The study by Bhardwaj et al. (1) showed that the prevalence of low HDL among young adults presenting with AMI was 42.7%, whereas high LDL levels were present in 12.9% only.

The study by Alsheikh-Ali et al. (21) showed consistent results with our study. Approximately 55% of all patients who developed AMI had low HDL-C level, whereas almost half of them already had LDL level within the target range (<100).

The percentage of positive family history for premature CAD was 20% in our study, which was consistent with that by Bhardwaj et al. (1), which was 17.7%. In contrast, a positive family history was present in almost half of patients in both studies by Incalcaterra et al. (12) and Sinha et al. (13). The difference in results can also be explained by a better recall of family history by their study subjects due to better education and medical awareness.

Literature data clearly associated the conventional risk factors with atherosclerosis leading to development of CAD and its complications in young subjects but with different rates and importance of specific risk factors compared with older patients. The PDAY study (22) and Bogalusa Heart study (23) showed that atherogenesis already starts in childhood, and the degree of lipid-rich plaques depends on factors, such as age, HDL level, hypertension, hyperglycemia, obesity, and tobacco smoking. Prospective cohort studies, including the Muscatine study (24) and the Cardiovascular Risk in Young Finns study (25) showed that coronary risk factors recorded in childhood or early adulthood correlated significantly with the carotid artery intima–media thickness and coronary calcium score.

A high proportion of study samples had poor sleeping habits, with approximately half (47.2%) of the subjects having reported sleeping <6 h daily and/or interrupted sleeping and/or snoring problems. The study conducted by Xie et al. (26) concluded that less sleeping time and increased snoring frequency upsurges the AMI risk with a calculated OR of 1.77 compared with the control group. Poor sleeping habits were associated with tramadol addiction in 25% of patients, which could be a possible association with tramadol use rather than a separate independent risk factor.

Exposure to stressful life as assessed by the Holmes–Rahe Questionnaire recorded 9.4%, 3.8%, 59.4%, and 27.4% had low, normal, moderate, and high stress levels, respectively. In addition, 47.5% of patients with both moderate and high stress levels had other risk factors, such as low HDL level and illicit drug use, indicating a consistent result with the study by Bagheri et al. (27), which showed that total psychological stress is correlated with the existence and severity of CAD considerably, but the correlation was not independent.

Histopathological studies have shown that these plaques have more lipid content with relative deficiency of cellular scar tissue and progress more quickly than plaques seen in older patients. These vulnerable plaques are susceptible to rupture that may account for higher prevalence of STEMI at a younger age than chronic stable angina (16). High frequency of stressful life events might have attributed for the instability of the plaque causing its rupture leading to STEMI development.

The present study showed a high proportion of study subjects used tramadol and smoked hash (cannabis).The percentage of tramadol use and hash smoking was 31% and 41%, respectively, with 17% of patients having concomitant hash smoking and tramadol use.

Cannabis is the most commonly used illicit substance worldwide. Approximately 160 million people aged 15–64 years have used cannabis at least once in their life (28). These substances are obtained from Cannabis sativa. The dried leaves and flowers are called marijuana, and the dried resin from the flower’s surface is called hash (hashish in Egypt). Cannabis has been suggested to have pro-coagulant properties. Both CB1 and CB2 receptors have been identified on the platelet cell membrane. It has been revealed in vitro that cannabis upsurges expression of glycoprotein IIb–IIIa and P-selectin in a concentration-dependent manner, which predisposes to platelet aggregation and factor VII stimulation. Cannabis is also hypothesized to have hemodynamic effects that could promote plaque rupture and initiate thrombosis (Fig. 2) (5).

A study was conducted to evaluate the percentage of cannabis users among 1116 young STEMI patients, and their mean age was 26±3.9 years. Substance abuse was infrequent, with 52 patients using cannabis (4.6%), which was lesser than that in our study (13).

Univariate logistic regression analysis for factors related to AMI showed that hash smoking (cannabis) was significantly associated with the odds of AMI. The estimated OR (95% CI) of hash smoking was 3.281 (1.313–8.200) (p<0.011).

A large, multi-institutional database retrospective, matched cohort analysis was performed on patients between October 2011 and September 2016. The researchers identified 210,700 patients with cannabis abuse and were compared with 10,395,060 age-matched controls. The 5-year cumulative incidence of MI in the cannabis group was considerably greater than that in the control group [1.28% vs. 0.89%, relative risk (RR), 1.44]. A greater risk was found in the young, with RR of 3.20 and 4.56 individuals aged 25–29 years and 30–34 years (29).

Mittelman et al. (30) evaluated the role of marijuana as an initiator for ACS by conducting a case-crossover study on 3882 patients, and 124 patients had marijuana use in the past year. The authors revealed a raised risk of up to 4.8 times for MI within 1 h of marijuana use. The risk dropped quickly after 1 h. The number of patients who admitted marijuana use was only 3.2% of the whole group. In regular marijuana users, the annual risk of cardiovascular events was augmented by 1.5%–3% (30). Cocaine revealed an OR of 24 compared with 4.8 for marijuana in the study by Mittelman et al. (30). The attributable risk of marijuana was the second lowest among the triggers at 0.8, signifying a low predominance in the population. Although many case reports and in vitro studies conveyed that marijuana might cause platelet stimulation and coronary vasospasm, there is no certain evidence for this suggestion (31).

In the CARDIA (Coronary Artery Risk Development in Young Adults) study, a 15-year longitudinal follow up of 3617 adults was conducted, and no relationship was found between marijuana and cardiovascular risk (32). However, marijuana use was linked to other unhealthy actions, such as high-caloric diet, tobacco smoking, HIV infection, and other illicit drug use, which accounts for poor health consequences. Moreover, other large-sample size, long-term longitudinal studies were unsuccessful to display any statistically substantial escalation in mortality due to cardiovascular events in marijuana users (33, 34). However, marijuana use more than once weekly was accompanied with a threefold increase in mortality in patients who previously had an MI (35).

Although many case reports of ACS after marijuana use have been issued in the literature, assessment of cardiovascular effects of marijuana is complex due to concurrent use of other drugs, such as cocaine, poor quantification, and existence of several chemical compounds in marijuana. Furthermore, there are diverse means of marijuana use that might modify the quantity and types of chemicals consumed. For example, marijuana rolled in tobacco leaves are called blunts, whereas while those rolled in cigarette paper are called joints. Thus, using blunts will yield effects of nicotine in addition to that of marijuana, (36) whereas using joints leads to inhalation of chemicals from the combustion of paper.

Tramadol is used as pain medication in the US and Europe. Tramadol is an atypical opioid that acts centrally to initiate its analgesic effect. It is commonly used in the treatment of moderate to severe pain. It binds to the µ opioid receptors with a low affinity and also inhibits the reuptake of serotonin and norepinephrine. At analgesic doses, it exerts a low risk for development of cardiovascular events. However, tramadol use can predispose to serotonin syndrome, which can initiate cardiac arrhythmia. Cardiac side effects may vary from agitation and palpitations to arrhythmia, conduction abnormalities, and cardiac arrest (6).

In 2018, the Food and Drug Administration has raised a question if tramadol causes ACS; however, well-validated clinical studies evaluating the association between tramadol use and CAD is limited. In contrast with our study, the Nair and Chandy study (40) showed low risk of cardiovascular complication with tramadol use in anesthesia. The main concern raised by the study was tramadol-induced serotonin syndrome, and not CAD, with tramadol use. This factor was not well investigated probably because tramadol is not commonly used as an illicit drug in western countries but used more often as a sedative or in pain management purposes in the short term.

A substantial correlation was established between tramadol use and LAD involvement in our study. However, no statistical significance was found between the use of hash and involvement of any culprit vessel. Unfortunately, a limited number of studies were conducted on that aspect.