Acute myocardial infarction in very young adults aged 20–29 years: characteristics, predisposing risk factors, and outcomes

In recent years, there is a rising incidence of acute myocardial infarction (MI) in middle-aged patients.1,2 An increase in the rate of premature coronary artery disease (CAD) is often seen above the age 40–45 years, particularly in men. Clinical features, risk factors profile, and coronary angiographic characteristics may be different in young patients compared to those who develop CAD at an older age.3 In addition, although most cases of acute MI are secondary to atherosclerosis with plaque erosion or rupture, additional unique aetiologies for MI may be recognized with the decrease in age of presentation.4,5 Much information is available in the medical literature on the characteristics of premature MI in middle-aged patients.3,6 However, there are limited data on acute MI in very young adults under 30 years of age. These reports mainly stem from populations from South Asia, in whom clinical CAD is prone to occur earlier than in western populations.7 In the present study, we aimed to identify the clinical characteristics, risk factors, aetiologies, and angiographic findings in very young adults aged 20–29 years presenting with a first event of acute MI and evidence of CAD. This study is a single-centre retrospective analysis of the cardiac catheterization database at the Lady Davis Carmel Medical Center, Haifa, Israel. Between the years 2011 and 2022, cardiac catheterization was performed in 30 patients aged 20–29 years; of them, 12 patients had acute MI with angiographic evidence of CAD and were included in the analysis. All were men, with median age of 26.5 years. The most prevalent cardiovascular risk factor was smoking, evident in two-thirds of the patients, with half of the smokers concomitantly using cannabis. In addition, half of the patients had a history of premature coronary disease in first-degree relatives, and a quarter was hypertensive or obese (Table 1). Median LDL cholesterol (LDL-C) was 111 mg/dL (interquartile range 92−145). HDL cholesterol (HDL-C) < 40 mg/dL was observed in a third of the patients. Probable or definite phenotypical diagnosis of familial hypercholesterolaemia was documented in three patients, with peak LDL-C levels >200 mg/dL. In addition, an extremely elevated lipoprotein(a) level (341 nmol/L) was documented in a single patient. Baseline clinical characteristics Continuous data are presented as median (interquartile range). ACS, acute coronary syndrome; HDL-C, HDL cholesterol; LAD, left anterior descending; LDL-C, LDL cholesterol; NSTEMI, non–ST-segment elevation myocardial infarction; OM, obtuse marginal; RCA, right coronary artery; STEMI, ST-segment elevation myocardial infarction; UAP, unstable angina pectoris. Acute ST-segment elevation myocardial infarction (STEMI) was the most common presentation, evident in eight patients (67%), in whom an occluded coronary vessel was observed. The culprit coronary lesion was primarily located at the left anterior descending (LAD) coronary artery (n = 8). Overall, a single-vessel coronary disease was observed in seven patients. Successful percutaneous coronary intervention (PCI) with stent/s implantation was performed in six individuals; two underwent balloon angioplasty alone, and coronary artery bypass graft operation was performed in one patient. In addition, an unsuccessful attempted PCI was performed in a single patient, and in two patients, the decision was to continue with medical therapy without PCI. Intravascular imaging in two patients showed distinct findings. In the first, intravascular ultrasound (IVUS) detected a thrombus in the proximal LAD while optical coherence tomography revealed plaque erosion with red and white thrombi. In the second patient, IVUS identified eccentric atherosclerotic plaques in the right coronary artery. Thrombophilia screening was accomplished in six patients, four of which returned positive. Antiphospholipid syndrome was diagnosed in two subjects, and polycythaemia vera (n = 1) and essential thrombocytosis with methylenetetrahydrofolate reductase (MTHFR) homozygosity and hyperhomocysteinaemia (n = 1) were additional findings. During a median follow-up period of 54 months (interquartile range 12–95 months), two patients were hospitalized with recurrent MI and underwent successful revascularization to a culprit lesion that was not an acute thrombosis or restenosis. Additional patient with thrombophilia died following an acute ischaemic stroke. Our study provides valuable insights. First, acute MI with angiographic evidence of atherothrombotic disease in patients in their twenties is infrequent, with only 12 cases documented over a decade, at a catheterization unit conducting 1700 coronary angiographies annually, in a country classified as having low cardiovascular risk. Importantly, the burden of early modifiable risk factors among these young patients was substantial, with smoking standing out as a prominent predisposing factor. Furthermore, the high concurrent use of cannabis with tobacco smoking may have served as a cardinal risk precipitator for acute MI in young individual, and the interplay between their pathophysiologic mechanisms should be further studied. Smoking control and cessation programmes as well as educating young people about the potential risks associated with substance use should be a priority in the prevention of early cardiovascular disease. The high incidence of family history of premature CAD among young patients with acute MI emphasizes the substantial influence of genetic predisposition at this age group. Genetic dyslipidaemias, specifically familial hypercholesterolaemia and elevated lipoprotein(a), are prevalent in young patients with CAD, highlighting the importance of early screening and drug intervention for inherited lipid disorders.8,9 Moreover, our study indicates that performing a comprehensive assessment for thrombophilia and hypercoagulable disorders in young acute MI patients could yield valuable insights and diagnostic information, with potential therapeutic implications.10 Of note, additional unique aetiologies and mechanisms for acute MI in young patients may be observed, including spontaneous coronary artery dissection (SCAD), embolism, vasospasm, drug and substance induced, vasculitis, autoimmune-related disorders, and additional hypercoagulable states.5 Most young patients with acute MI were found to have a single-vessel CAD, with the common presentation being STEMI with an occluded LAD. The risk for recurrent atherosclerotic events was non-negligible, with one in four patients experiencing additional cardiovascular events over a median follow-up period of 4.5 years. This finding highlights the pronounced severity that may be linked to acute MI at a very young age and underscores the need for intensive secondary prevention strategies and close monitoring. Despite the limitations of a single-centre retrospective design and small sample size, we conclude that acute MI in young individuals 20–29 years of age is rare, but may have distinctive characteristics concerning the aetiologies, predisposing factors, and coronary presentation (Figure 1). The management of young patients presenting with acute MI should be addressed by a multifactorial approach, taking into consideration both modifiable and inherited risk factors and potential non-atherosclerotic and thromboembolic pathogenic causes, enabling early diagnosis and aetiology-directed therapies. Acute myocardial infarction in very young adults: aetiologies and predisposing factors in a single-centre cohort. APLA, antiphospholipid antibodies; CAD, coronary artery disease; MTHFR, methylenetetrahydrofolate reductase. I.N. and B.Z. contributed to the conception, design, acquisition, analysis, or interpretation of data for the work. B.Z. drafted the manuscript. All authors critically revised the manuscript, gave final approval, and agree to be accountable for all aspects of work ensuring integrity and accuracy. None declared. The data sets generated during the current study are not publicly available due to privacy regulations. Data will be shared upon reasonable request to the corresponding author.