Angina Pectoris

Definition

Types / Classification

1. Stable (Typical) Angina

• Most common form
• Caused by chronic stenosing coronary atherosclerosis creating a fixed reduction in coronary perfusion relative to myocardial demand
• Provoked predictably by physical activity, emotional excitement, or psychological stress; does NOT occur at rest
• Character: crushing or squeezing substernal sensation, radiating to the left arm or jaw
• Relieved by rest (within 1-5 min) or sublingual nitroglycerin
• Duration typically 2-5 minutes - Harrison's Principles of Internal Medicine 22E

2. Prinzmetal (Variant) Angina

• Caused by coronary artery spasm (vasospasm)
• Occurs at rest, unrelated to physical activity, heart rate, or blood pressure
• Can occur in vessels with or without significant atherosclerosis
• ST elevation (rather than depression) during episodes
• Responds promptly to vasodilators (nitrates, calcium channel blockers)
• Beta-blockers are NOT indicated (may worsen spasm in pure vasospastic disease) - Katzung's Basic and Clinical Pharmacology

3. Unstable Angina

• Increasingly frequent, prolonged (>20 min), or severe angina
• Precipitated by progressively lower levels of exertion or occurs at rest
• Associated with plaque disruption, superimposed thrombosis, distal embolization, and/or vasospasm
• A harbinger of MI - considered an acute coronary syndrome (ACS) and a medical emergency
• High risk of complete vascular occlusion - Robbins Cotran Pathologic Basis of Disease

4. Special Patterns

• Coronary microvascular dysfunction (formerly "Syndrome X"): typical angina symptoms with normal epicardial coronary vessels; both types show diminished coronary fractional flow reserve
• Silent ischemia: particularly common in elderly and diabetic patients (diabetic neuropathy); may present as dyspnea, nausea, diaphoresis, fatigue, or no symptoms at all - Katzung's, Robbins

Epidemiology

• Males constitute ~70% of all patients with angina pectoris (even higher proportion under age 50)
• Angina in women may present atypically (less frequently described as classic "crushing" chest pain)
• Nearly 10 million people in the USA have angina pectoris - Goldman-Cecil Medicine
• Global burden: cardiovascular disease is the leading cause of death worldwide, accounting for ~18 million deaths in 2019

Pathophysiology

Oxygen Supply-Demand Mismatch

• Demand angina: increased MVO₂ (exertion, emotion) in the setting of fixed coronary stenosis
• Supply angina: diminished oxygen delivery due to vasospasm (Prinzmetal) or dynamic stenosis - Goldman-Cecil Medicine

Coronary Blood Flow

• Coronary flow occurs primarily during diastole (drops to near zero in systole)
• Flow is directly proportional to aortic diastolic pressure and inversely proportional to coronary vascular resistance
• Endothelial dysfunction impairs vasodilation, reducing coronary flow reserve - Katzung

Clinical Features

Symptoms

• Character: heaviness, pressure, squeezing, smothering, or choking - rarely described as sharp or frank "pain"
• Location: central substernal; patient places a hand over the sternum (sometimes a clenched fist = Levine's sign)
• Radiation: either shoulder, ulnar aspects of forearm/hand, back, interscapular region, root of neck, jaw, teeth, epigastrium
• Duration: typically 2-5 minutes for stable angina
• NOT located below the umbilicus or above the mandible
• Radiation to the trapezius muscles is NOT typical of angina - suggests pericarditis instead
• Crescendo-decrescendo pattern (not at maximal intensity at the onset)
• Threshold variability: some patients have fixed threshold (coronary stenosis with fixed supply); others have variable threshold (vasomotor tone fluctuates - worse in the morning, in cold, after meals) - Harrison's 22E

Precipitants

• Physical exertion (exercise, hurrying, sexual activity)
• Emotional stress (anger, fright, frustration)
• Cold exposure
• Heavy meals
• Tachycardia
• Nocturnal angina (angina decubitus): may occur during sleep due to episodic tachycardia, change in respiratory pattern, or recumbency-related increase in intrathoracic blood volume → increased LV end-diastolic volume → increased wall tension → increased MVO₂

Atypical Features

• In women and diabetic patients, angina may be atypical in location and not strictly related to exertion
• Equivalents: dyspnea, nausea/vomiting, palpitations, diaphoresis, fatigue

CCS Functional Classification of Angina

Investigations

Resting ECG

• May be normal between episodes in stable angina
• During ischemia: ST depression (stable/unstable angina), ST elevation (Prinzmetal)
• May show evidence of prior MI (Q waves)

Exercise Stress Testing

• Establishes ischemic threshold in METs (metabolic equivalent tasks)
• Allows practical exercise prescription (keeping below ischemic threshold)

Imaging

• Nuclear perfusion imaging (SPECT/PET): perfusion defects on stress vs. rest images indicate ischemia
• Echocardiography with stress: wall motion abnormalities during ischemia
• Coronary CT angiography: anatomy of coronary stenosis
• Coronary angiography: definitive anatomic assessment; guides revascularization decisions - Harrison's 22E

Laboratory

• CBC, fasting lipid profile, fasting glucose/HbA1c, renal function, thyroid function, ECG
• Troponin (to exclude MI in acute presentations)

Management

1. Non-Pharmacological / Risk Factor Modification

• Lifestyle: reduce energy requirements in the morning, after meals, in cold weather; reduce activity speed
• Exercise: regular isotonic exercise below the ischemic threshold (<80% of heart rate at ischemia on stress test); improves exercise tolerance and has psychological benefit
• Smoking cessation: accelerates atherosclerosis, increases thrombosis and plaque instability, raises MVO₂
• Diet: low in saturated and trans-unsaturated fatty acids, caloric restriction for weight loss
• Weight management: obesity worsens diabetes, hypertension, and hyperlipidemia

2. Anti-Ischemic Pharmacotherapy

Nitrates

• Mechanism: nitric oxide (NO) release → guanylyl cyclase activation → smooth muscle relaxation → (1) systemic venodilation → reduced preload → reduced LV end-diastolic volume/pressure → decreased wall tension and MVO₂; (2) dilation of epicardial coronary vessels; (3) increased collateral flow
• Sublingual nitroglycerin: onset within minutes; used for acute relief; duration 15-30 min
• Long-acting nitrates (isosorbide dinitrate/mononitrate, transdermal nitroglycerin patches): prophylaxis; require nitrate-free intervals to avoid tolerance
• Bioavailability issue: oral nitroglycerin/isosorbide dinitrate have <10-20% bioavailability due to extensive hepatic first-pass metabolism; sublingual route avoids this - Katzung

Beta-Blockers (First-line for chronic stable angina)

• Mechanism: reduce heart rate, contractility, and blood pressure → reduce MVO₂; also increase diastolic perfusion time (bradycardia)
• Target resting HR: 55-60 bpm; exertional HR: 100 bpm
• Preferred in patients with prior MI (mortality benefit)

Calcium Channel Blockers

• Mechanism: reduce heart rate and contractility (non-dihydropyridines: verapamil, diltiazem); cause coronary and peripheral vasodilation
• First-line for Prinzmetal/vasospastic angina (along with nitrates)
• Useful when beta-blockers are contraindicated (severe COPD, peripheral vascular disease, certain arrhythmias)
• Can be combined with beta-blockers when monotherapy is insufficient
• Dihydropyridines (amlodipine, nifedipine): mainly vasodilators, less chronotropic effect

Anti-Platelet Therapy

• Aspirin (75-100 mg/day): first-line in all patients without contraindications; reduces risk of MI and coronary death
• Clopidogrel: when aspirin is contraindicated

Statins / Lipid-Lowering

• High-intensity statins in all patients with documented or suspected CAD
• Target LDL-C <55 mg/dL (using statins, ezetimibe, and/or PCSK9 inhibitors) - Goldman-Cecil Medicine

ACE Inhibitors / ARBs

• Indicated in all CAD patients with diabetes or LV systolic dysfunction
• Also beneficial in CAD with other vascular disease (evidence-based)
• Not routine for all stable angina patients without these comorbidities (evidence is less clear)

Additional / Second-Line Agents

• Ranolazine: inhibits late sodium current → reduces intracellular Ca²⁺ overload → reduces ischemia without significantly altering HR or BP; useful when HR-reducing agents are not tolerated
• Ivabradine: selective sinus node If-channel inhibitor (heart rate lowering); for patients in sinus rhythm with HR >70 already on maximum tolerated beta-blocker
• Rivaroxaban 2.5 mg twice daily added to aspirin: evidence in favor (reduces MI, stroke, cardiovascular death in high-risk stable CAD) - Goldman-Cecil Medicine

3. Revascularization

PCI (Percutaneous Coronary Intervention)

• Balloon angioplasty ± drug-eluting stent placement
• Relieves symptoms; indicated for significant stenosis (>70%) with ischemia
• In stable angina, a 2026 systematic review and meta-analysis found that PCI vs. optimal medical therapy provides symptom relief but no clear mortality advantage in stable CAD (Upreti et al., 2026)

CABG (Coronary Artery Bypass Grafting)

• Preferred for left main disease, three-vessel disease (especially with LV dysfunction), diabetes with multivessel disease
• Mortality benefit over medical therapy in high-risk anatomic subsets

Drug Therapy Summary by Angina Type

Key Points to Remember

1. Angina pain is referred pain - it does NOT arise from the myocardium itself but from afferent nerve fibers stimulated by ischemia-released metabolites
2. Radiation to the trapezius = think pericarditis, NOT angina
3. Sharp, fleeting, or prolonged localized left submammary ache is rarely ischemic
4. Nitrate tolerance is a real phenomenon - always prescribe a nitrate-free interval
5. Beta-blockers are the cornerstone of chronic stable angina management (especially post-MI)
6. Calcium channel blockers are first-line for Prinzmetal angina; beta-blockers may worsen vasospasm
7. LDL-C target is now <55 mg/dL in established CAD (PCSK9 inhibitor era)