Coronary Artery Disease (CAD)

Definition and Epidemiology

Coronary Artery Anatomy

• Left Coronary Artery (LCA/LMCA): Branches into the left anterior descending (LAD) - supplying the LV free wall and interventricular septum - and the left circumflex artery - running along the AV groove.
• Right Coronary Artery (RCA): Supplies the RV free wall and, via the posterior descending artery (PDA), the inferior wall of the LV. In right-dominant systems (most common), the RCA gives rise to the PDA.

Risk Factors

• Hypertension
• Dyslipidemia (elevated LDL, low HDL)
• Diabetes mellitus
• Tobacco use / smoking
• Truncal obesity
• Sedentary lifestyle
• Unhealthy diet

• Age >40 years
• Male sex (or postmenopausal female)
• Family history of premature CAD
• Genetic predisposition (estimated ~40% heritability)

Pathophysiology

Atherosclerosis - The Core Process

1. Endothelial injury triggered by hyperlipidemia, hypertension, smoking, or hyperglycemia.
2. Lipid accumulation - LDL particles penetrate the endothelium and become oxidized, attracting monocytes that differentiate into macrophages and engulf oxidized LDL, forming foam cells.
3. Plaque development - Smooth muscle cells migrate from the media and proliferate. The plaque acquires extracellular matrix components (collagen, proteoglycans), forming a fibrous cap over a lipid-rich necrotic core.
4. Plaque instability - Matrix metalloproteinases (MMPs), produced by macrophages and smooth muscle cells, degrade the fibrous cap. Pro-inflammatory cytokines (IL-1β, TNF-α) amplify this process, increasing plaque vulnerability to rupture.

Three Mechanisms Precipitating Acute Coronary Syndromes

1. Plaque rupture (most common) - The fibrous cap breaks, exposing the thrombogenic core to circulating blood, triggering thrombus formation and potential vessel occlusion.
2. Plaque erosion - The outer endothelial layer is worn away without full rupture; up to one-third of acute MIs result from this mechanism.
3. Calcified nodule - Hard calcified deposits fracture through the fibrous cap, potentially causing sudden luminal obstruction.

Clinical Spectrum

Stable Angina (Chronic CAD)

• Chest pressure, tightness, or heaviness precipitated by exertion or emotional stress, relieved by rest or nitrates within minutes
• Caused by a fixed obstructive lesion reducing flow during demand states
• Canadian Cardiovascular Society (CCS) Classification grades severity (I-IV)

Acute Coronary Syndromes (ACS)

• Unstable Angina (UA): Rest angina >20 min, new-onset severe angina (CCS ≥3), or crescendo angina - cardiac biomarkers normal
• NSTEMI: Similar presentation; cardiac biomarkers elevated, ST depression or T-wave changes on ECG
• STEMI: Complete occlusion; ST elevation on ECG, positive biomarkers, transmural infarction

MI Classification (Fourth Universal Definition)

• Sabiston Textbook of Surgery, p. 2487

Diagnostic Workup

Clinical Assessment

• Detailed history: character, radiation (jaw, left arm), duration, precipitants of chest pain
• Physical examination: S3/S4 gallop, signs of heart failure, bruits

ECG

• Resting ECG: May show ST changes, Q waves (prior MI), LBBB
• ST elevation in contiguous leads: STEMI
• ST depression, T-wave inversions: NSTEMI/UA or ischemia

Cardiac Biomarkers

• High-sensitivity troponin I/T: Preferred biomarker; rises within 1-3 hours, peaks at 12-24 hours, stays elevated for days
• Serial measurements at 0 and 1-3 hours used in accelerated diagnostic protocols

Non-Invasive Imaging

Invasive Evaluation

• Coronary angiography (cardiac catheterization): Defines anatomy, degree of stenosis, and suitability for revascularization - the definitive standard
• FFR/iFR: Physiologic assessment of lesion significance (>50% stenosis that is functionally significant)
• OCT/IVUS: Intracoronary imaging for plaque characterization and stent optimization
• SYNTAX score: Quantifies coronary complexity; guides PCI vs. CABG decision
• STS risk score: Predicts surgical risk
• Sabiston Textbook of Surgery, p. 2487-2490

Management

Medical Therapy (Guideline-Directed Medical Therapy - GDMT)

• Aspirin 75-100 mg daily: cornerstone of secondary prevention
• P2Y12 inhibitors (clopidogrel, ticagrelor, prasugrel): used for dual antiplatelet therapy (DAPT) post-ACS/PCI
• A 2025 Lancet meta-analysis found clopidogrel may be superior to aspirin for secondary prevention in certain CAD patients
• A 2025 BMJ individual patient data meta-analysis supports P2Y12 inhibitor monotherapy after PCI over aspirin monotherapy

• High-intensity statins (atorvastatin 40-80 mg, rosuvastatin 20-40 mg): first-line
• Add ezetimibe if LDL-C target not reached; a 2024 meta-analysis in BMC Cardiovascular Disorders showed low/moderate statin + ezetimibe is non-inferior to high-intensity statin monotherapy with better tolerability
• PCSK9 inhibitors for high-risk patients not at LDL-C target

• Beta-blockers: Reduce heart rate and oxygen demand; improve survival post-MI; first-line for stable angina
• Nitrates: Venodilation reduces preload; sublingual GTN for acute relief
• Calcium channel blockers: Used if beta-blockers contraindicated or for vasospastic angina
• Ranolazine: Late sodium current inhibitor; add-on therapy for refractory angina
• Ivabradine: Heart rate reduction in specific patients

• ACE inhibitors/ARBs: Especially post-MI with reduced EF, diabetes, or hypertension
• Mineralocorticoid receptor antagonists: Post-MI with EF <40%
• Anticoagulation: For AF with CAD - warfarin or DOAC; management of antithrombotic therapy in this scenario has been addressed by a 2025 JACC meta-analysis

• Smoking cessation, blood pressure control (target <130/80 mmHg), diabetes management (HbA1c control), Mediterranean diet, regular aerobic exercise, weight management

Revascularization

Percutaneous Coronary Intervention (PCI)

• Balloon angioplasty + stenting (DES preferred over BMS)
• STEMI: Primary PCI is the preferred reperfusion strategy; target door-to-balloon time ≤90 minutes
• NSTE-ACS:
  • Immediate invasive (<2 hours): cardiogenic shock, refractory angina, hemodynamic/electrical instability
  • Early invasive (<24 hours): GRACE score >140
  • Invasive before discharge: Low-intermediate risk patients

Timing of invasive strategy in NSTE-ACS per 2021 ACC/AHA/SCAI guidelines (Sabiston Textbook of Surgery)

Coronary Artery Bypass Grafting (CABG)

• Left main CAD (≥50% stenosis)
• Three-vessel CAD with reduced EF or diabetes
• Complex multivessel disease (high SYNTAX score)
• Patients undergoing concurrent cardiac surgery (valve repair, etc.)

• Left internal mammary artery (LIMA) to LAD: gold standard - superior long-term patency
• Bilateral internal mammary artery (BIMA): improves survival, especially in younger patients
• Radial artery, right IMA, saphenous vein graft (SVG) as additional conduits

• Conventional on-pump CABG (cardiopulmonary bypass with cardioplegic arrest)
• Off-pump CABG (beating heart)
• Minimally invasive direct CABG (MIDCAB)
• Robotic totally endoscopic CABG
• Hybrid coronary surgery (CABG + PCI)

Mechanical Complications of Acute MI

Special Populations

• Females: Often present atypically (dyspnea, fatigue, nausea); higher incidence of MINOCA (MI with non-obstructive coronary arteries); INOCA (ischemia with non-obstructive CAD) is more common
• Diabetic patients: Higher restenosis risk post-PCI; often benefit more from CABG
• Renal disease: Contrast-induced nephropathy risk; dose-adjust antiplatelet/anticoagulant agents
• Elderly (>70 years): Higher surgical risk; careful risk-benefit assessment required
• Pregnant patients: Rare; gestational MI managed on individual basis

Secondary Prevention and Cardiac Rehabilitation

1. Aspirin indefinitely; DAPT for 6-12 months post-DES implantation
2. High-intensity statin therapy with LDL-C goal <55 mg/dL (very high risk)
3. Beta-blocker (if EF reduced or post-MI)
4. ACE inhibitor/ARB
5. Cardiac rehabilitation (exercise training, education, psychological support)
6. Lifestyle modification - smoking cessation, diet, weight, blood pressure, diabetes control

Key Recent Evidence (2024-2026)