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Acute Coronary Syndrome in Young Individuals (<45 years): Etiology, Diagnosis, and Management

Young adults with acute coronary syndrome (ACS) require comprehensive evaluation of both traditional and non-traditional risk factors, with special attention to inflammatory conditions, thrombophilic disorders, and other unique etiologies that differ from older populations. 1

Epidemiology and Clinical Significance

• Young adults with coronary artery disease (CAD) represent a unique subset of patients who remain at risk for prolonged cardiovascular morbidity, recurrent major adverse cardiovascular events (MACE), and loss of quality-adjusted life years 1
• ACS in young individuals accounts for approximately 20% of all ACS cases, with increasing prevalence in recent decades 2
• Males are affected more frequently than females by a ratio of approximately 2:1 1
• Mortality risk is lower compared to older adults, but long-term morbidity and economic burden remain substantial 3

Etiology and Risk Factors

Traditional Risk Factors

• Suboptimal control of traditional risk factors has been associated with a higher incidence of recurrent MACE among young adults 1
• Key modifiable risk factors include:
  • Smoking and vaping (highest attributable risk) 1
  • Diabetes mellitus 1
  • Dyslipidemia, particularly familial hypercholesterolemia (FH) 1
  • Hypertension 1
  • Obesity 1

Non-Traditional Risk Factors

• Chronic inflammatory disease states (e.g., HIV, viral hepatitis, systemic autoimmune diseases) 1
• Thrombophilic disorders (elevated D-dimer, fibrinogen, antithrombin III abnormalities) 1
• Recreational drug use, particularly cocaine 1
• Elevated lipoprotein(a) levels 1
• Genetic factors (e.g., Ch9p21 locus) 1

Non-Atherosclerotic Causes

• Kawasaki disease: late sequelae include coronary artery aneurysm, stenosis, thrombosis, or fistula 1
• Coronary artery anomalies 1
• Spontaneous coronary artery dissection (SCAD), particularly in young women 1
• Myocardial bridging 1
• Coronary vasospasm 1

Clinical Presentation

• Chest discomfort remains the most common presenting symptom (affecting approximately 90% of young adults with ACS) 1, 2
• Young women with ACS may present with more associated symptoms than men (e.g., epigastric symptoms, palpitations, pain in jaw/neck/arms) 1
• Young patients with inflammatory conditions may present with atypical symptoms 1
• Patients with Kawasaki disease may present with thrombosis of coronary aneurysms 1

Diagnostic Evaluation

Initial Assessment

• Electrocardiography should be performed immediately (within 10 minutes of presentation) to distinguish between STEMI and NSTE-ACS 1, 2
• High-sensitivity cardiac troponin measurements are the preferred test to evaluate for myocardial injury 2
• Risk stratification tools should be applied early to determine appropriate management strategy 1

Specialized Testing for Young ACS Patients

• Comprehensive lipid profile including lipoprotein(a) 1
• Inflammatory markers (ESR, CRP) in suspected inflammatory conditions 1
• Thrombophilia screening (D-dimer, fibrinogen, protein C/S, antithrombin III) when appropriate 1
• Toxicology screening for recreational drug use 1

Imaging

• Coronary angiography remains the gold standard for diagnosis 1
• Intravascular ultrasound (IVUS) is particularly important in young ACS patients to:
  • Demonstrate true luminal dimensions
  • Improve stent deployment
  • Detect underlying aneurysmal distortion 1
• Coronary CT angiography or cardiac MRI may help understand the pathophysiology in non-STEMI/unstable angina cases 1

Angiographic Patterns in Young ACS

• Predominantly single-vessel disease compared to multi-vessel disease in older adults 1
• Higher prevalence of non-obstructive coronary artery disease 1
• Thrombotic occlusions with minimal underlying plaque burden 1
• Specific patterns in non-atherosclerotic causes:
  • Coronary aneurysms in Kawasaki disease 1
  • Intimal tears or dissection flaps in SCAD 1

Management Approach

Acute Management

• For STEMI: Rapid reperfusion with primary PCI within 120 minutes reduces mortality from 9% to 7% 2
• For high-risk NSTE-ACS: Prompt invasive coronary angiography and revascularization within 24-48 hours 2
• Special considerations for thrombosed aneurysms in Kawasaki disease:
  • Systemic and intracoronary thrombolytic therapy may be beneficial 1
  • Thrombectomy catheters should be considered to remove thrombus burden 1

Pharmacological Therapy

• Dual antiplatelet therapy and anticoagulation should be promptly initiated 2, 4
• Statin therapy has shown long-term benefit in young patients, particularly those with familial hypercholesterolemia 1
• For Kawasaki disease with coronary aneurysms:
  • Low-dose aspirin for small/medium-sized aneurysms
  • Low-dose aspirin plus anticoagulant therapy for large aneurysms 1

Special Considerations for Subgroups

Young Women with ACS

• Evaluate for pregnancy-related risk factors such as history of hypertensive disorders of pregnancy 1
• Consider oral contraceptive use as a potential risk factor 1
• Higher prevalence of SCAD compared to men 1
• Breast arterial calcification on mammography may provide additional risk stratification 1

Patients with Inflammatory Conditions

• Young patients with systemic inflammatory disorders (SID) have higher risk of all-cause mortality (adjusted HR 1.86) 1
• Less likely to receive guideline-based secondary prevention (76% vs 89% for statins) 1
• Require more aggressive prevention strategies 1

Long-term Management and Follow-up

• Optimization of traditional cardiovascular risk factors is essential 1
• Comprehensive evaluation and treatment of non-traditional risk factors is beneficial in reducing cardiovascular events 1
• Screening for familial hypercholesterolemia and appropriate lipid screening of family members 1
• Longitudinal follow-up with cardiovascular specialists is recommended 1
• Implementation of strategies to optimize medication adherence:
  • Health care access optimization
  • Patient education
  • Motivational interviewing
  • Health information technology tools
  • Reducing barriers to medication access 1

Pitfalls and Caveats

• Young adults with ACS are often undertreated due to perception of lower risk 1
• Non-atherosclerotic causes may be missed if not specifically considered 1
• Patients with inflammatory conditions are at particularly high risk for suboptimal secondary prevention 1
• Standard risk calculators may underestimate risk in young adults 1
• Kawasaki disease sequelae may be missed in adults if childhood diagnosis was not made 1