Coronary Artery Disease (CAD)

Definition & Epidemiology

Pathophysiology

Atherosclerosis: Injury-Response Model

1. Endothelial Injury: Risk factors (hyperlipidemia, hypertension, smoking, diabetes) damage endothelial cells, causing expression of leukocyte adhesion molecules and release of chemokines (e.g., MCP-1). Increased permeability allows LDL particles and leukocytes to enter the subendothelial space.
2. Response to Injury: Monocyte-derived macrophages engulf oxidized LDL and transform into foam cells — the hallmark of the early "fatty streak" lesion. Cytokines (TNF-α, IL-1, IL-6, IL-8, IL-18) and growth factors recruit further inflammatory and smooth muscle cells. Over time, foam cells + extracellular lipid form a necrotic core surrounded by smooth muscle cells and a collagen-rich fibrous cap.
3. Plaque Progression → Luminal Narrowing: Progressive atheroma narrows the arterial lumen, creating an imbalance between myocardial oxygen supply and demand.
4. Vulnerable Plaque & Rupture: Inflammatory mediators and proteolytic enzymes thin the fibrous cap; rupture triggers platelet aggregation and acute thrombosis — the culprit event in most acute coronary syndromes. — Barash's Clinical Anesthesia, 9e, p. 3383–3384

Risk Factors

Clinical Spectrum

Silent CAD → Stable Angina → Unstable Angina → NSTEMI → STEMI → Sudden Cardiac Death
                          ↑_____________Acute Coronary Syndromes (ACS)______________↑

1. Stable Angina Pectoris

• Mechanism: Fixed stenosis causing demand ischemia (supply-demand mismatch with exertion)
• Symptoms: Retrosternal chest tightness/pressure, radiation to left arm/shoulder/jaw; relieved by rest or nitroglycerin; triggered by exertion, cold, stress
• Prognosis: ~2% average annual mortality (only twice age-matched controls)
• ECG: ST depression during episodes; normal at rest

2. Unstable Angina (UA)

• Angina at rest
• New-onset severe angina
• Crescendo angina (increasing frequency, severity, or duration with less provocation)
• Troponins are negative (distinguishes from NSTEMI)

3. NSTEMI

• Same presentation as UA but with elevated troponins (myocardial necrosis confirmed)
• No ST elevation on ECG (may show ST depression, T-wave changes)
• 30-day mortality 10–20% despite treatment

4. STEMI

• Complete occlusion of a coronary artery → transmural infarction
• ST elevation in ≥2 contiguous leads (or new LBBB)
• Medical emergency requiring immediate reperfusion (primary PCI preferred)

Prinzmetal (Variant) Angina

• Caused by coronary artery spasm (with or without fixed stenosis)
• Occurs at rest, often in early morning, may awaken patient from sleep
• ST elevation (not depression) during episodes
• More common in women
• Treatment: calcium channel blockers (first-line); nitrates also effective; beta-blockers contraindicated in pure vasospasm — Swanson's Family Medicine Review, p. 119

Diagnosis

Treatment

Three Pillars

1. Medical Therapy
2. Percutaneous Coronary Intervention (PCI)
3. Coronary Artery Bypass Grafting (CABG)

Medical Therapy

• Aspirin + P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) = DAPT
• Anticoagulation: unfractionated heparin or LMWH (enoxaparin)
• Consider GPIIb/IIIa inhibitor for high-risk patients
• Early invasive strategy (cardiac catheterization) — Swanson's Family Medicine Review, p. 119–120

PCI (Percutaneous Coronary Intervention)

• Balloon angioplasty + drug-eluting stent (DES) placement
• Success rate >90% per stenosis; complication rate ~4%
• Does not reduce overall mortality vs. medical therapy in stable CAD
• Does improve symptoms and reduces need for medication
• Drug-eluting stents dramatically reduced restenosis (previously up to 40%)
• 2025 ACS Guideline update: Intracoronary imaging (IVUS/OCT) during complex PCI upgraded from Class IIa → Class I recommendation

CABG (Coronary Artery Bypass Grafting)

• Left main stem disease (≥50% stenosis)
• 3-vessel CAD
• 2-vessel disease with proximal LAD involvement
• Diabetic patients with multivessel disease

Revascularization Decision Summary

Single-vessel CAD (non-LAD) → Medical therapy OR PCI
Proximal LAD / 2-vessel → PCI or CABG (anatomy-dependent)
3-vessel CAD / Left main → CABG preferred (especially with ↓EF or diabetes)
STEMI → Primary PCI within 90 minutes (door-to-balloon time)

Secondary Prevention

2025 ACS Guideline — Key Updates

• Intracoronary imaging (IVUS/OCT) during PCI for complex lesions: upgraded to Class I
• Ticagrelor monotherapy (≥1 month post-PCI) as a bleeding-reduction strategy
• PPI use recommended for patients at GI bleeding risk on DAPT
• In patients requiring long-term anticoagulation after PCI: aspirin discontinuation at 1–4 weeks with continuation of P2Y12 inhibitor (preferably clopidogrel)

• Barash's Clinical Anesthesia, 9e, pp. 3382–3390
• Swanson's Family Medicine Review, pp. 119–120
• Sabiston Textbook of Surgery
• 2025 ACC/AHA/ACEP/NAEMSP/SCAI ACS Guideline — Circulation & JACC

NSTEMI vs STEMI — Complete Comparison

The Core Distinction

Pathophysiology

• STEMI: Thrombus is completely occlusive → abrupt cessation of flow in an epicardial artery → transmural necrosis progressing in a "wave-front" from endocardium to epicardium. Necrosis begins in as little as 15–20 minutes; partial salvage achievable if reperfused within 3–6 hours.
• NSTEMI: Thrombus is partially occlusive (or complete occlusion with good collateral supply) → subendocardial ischemia/necrosis. Less immediate threat to full-thickness myocardium but still causes cell death (hence positive troponin). — Goldman-Cecil Medicine, p. 654

ECG Differences in Detail

STEMI ECG Criteria

• ST elevation ≥2 mm (0.2 mV) in V2–V3 in men; ≥1.5 mm in women
• ≥1 mm in ≥2 other contiguous chest or limb leads
• Reciprocal ST depression in opposite leads (e.g., inferior STEMI shows elevation in II, III, aVF with depression in aVL/I)
• Hyperacute T waves may precede ST elevation in earliest phase
• Evolution: ST elevation → T-wave inversion → pathologic Q waves (irreversible necrosis)
• New LBBB = STEMI equivalent

1. Early Acute (minutes–hours): Hyperacute T waves → convex "tombstone" ST elevation
2. Evolved Acute (hours–days): ST elevation regresses, T-wave inversion, Q waves form
3. Chronic (weeks–months): Q waves persist, ST returns to baseline — Goldman-Cecil Medicine, p. 655

NSTEMI ECG Findings

• ST depression (horizontal or downsloping) in precordial leads
• T-wave inversion (deep symmetrical — "Wellens pattern" with proximal LAD involvement)
• Nonspecific ST-T changes
• Normal ECG (~30% of cases — diagnosis rests on troponin)
• No ST elevation and no pathologic Q waves (by definition)

Biomarkers

• Diagnosis of MI requires acute rise and/or fall of troponin with at least one value above the 99th percentile upper reference limit + clinical evidence of ischemia. — Goldman-Cecil Medicine, p. 655
• UA vs NSTEMI distinction: same presentation, but UA has negative troponins (no necrosis).

Clinical Presentation

• Chest pain: Persistent (>10–20 min), heavy retrosternal pressure, radiation to left arm/jaw/shoulder — not relieved by rest or nitroglycerin
• Associated symptoms: Diaphoresis, nausea, vomiting, dyspnea, weakness
• Silent MI: ~20% of MIs are painless; more common in elderly, women, and diabetics
• Autonomic signs: anterior MI → sympathetic activation (tachycardia, hypertension, diaphoresis); inferior MI → vagal activation (bradycardia, hypotension)

Infarct Territories by Culprit Artery

Management: The Critical Difference

The key principle: STEMI = emergent reperfusion NOW. NSTEMI = risk-stratified invasive approach within hours to days.

STEMI Management

• 12-lead ECG
• Aspirin 325 mg (chewed)
• IV access, oxygen (if SpO₂ <90%), cardiac monitoring
• Nitroglycerin (unless contraindicated — hypotension, recent sildenafil use, inferior MI with RV involvement)
• Morphine 2–4 mg IV for refractory pain (use cautiously — may mask symptoms)
• Beta-blocker (oral, within 24 hrs) if no HF, cardiogenic shock, or bradycardia

• Chest pain relief
• ≥50% reduction of ST elevation at 60–90 min
• Reperfusion arrhythmia (accelerated idioventricular rhythm) → Absence = rescue PCI required

• DAPT: Aspirin + P2Y12 inhibitor (ticagrelor or prasugrel preferred over clopidogrel)
• Anticoagulation: UFH or bivalirudin (with PCI); LMWH or fondaparinux (with fibrinolysis)
• Complete revascularization: Non-culprit lesions amenable to PCI should be treated (reduces CV death/MI); timing = before discharge or staged outpatient

• Malignant arrhythmias (VF, VT) — peak risk first 24–48 hrs
• Mechanical complications: free wall rupture, papillary muscle rupture (MR), VSD
• RV infarction (inferior STEMI): treat with IV fluids, avoid nitrates
• LV function assessment (echo) before discharge

NSTEMI Management

• Aspirin + P2Y12 inhibitor (DAPT)
• Anticoagulation: LMWH (enoxaparin), UFH, fondaparinux, or bivalirudin
• Beta-blocker (oral)
• High-intensity statin
• ACE inhibitor / ARB
• Nitroglycerin for ongoing pain

• Refractory ischemia / ongoing chest pain
• Cardiogenic shock or hemodynamic instability
• Life-threatening arrhythmias
• Acute HF / pulmonary edema
• Mechanical complications

• Very high risk → Immediate angiography (<2 hrs)
• High risk (positive troponin, new ST changes, GRACE >140) → Early invasive (<24 hrs)
• Intermediate risk → Invasive within 24–72 hrs
• Low risk → Consider non-invasive testing first (conservative strategy)

Side-by-Side Summary Table

Key Mnemonic

"No ST elevation? No fibrinolysis. Risk-stratify and go invasive within hours." "ST elevation? Time is muscle — primary PCI within 90 minutes."

• Goldman-Cecil Medicine, International Edition, pp. 654–657
• Washington Manual of Medical Therapeutics, pp. 155–158
• Harrison's Principles of Internal Medicine, 22e
• 2025 ACC/AHA/ACEP/NAEMSP/SCAI ACS Guideline