• A symptom complex resulting from mismatch of myocardial oxygen demand and supply
• Classic angina: A sense of choking or of pressure or heaviness deep to the precordium, usually brought on by exertion or anxiety and relieved by rest
• Anginal equivalent: Exertional dyspnea or exertional fatigue, which results from myocardial ischemia and is relieved by rest or nitroglycerin
• Variant angina: Also referred to as Prinzmetal angina; describes angina occurring at rest in atypical patterns, such as after exercise or nocturnally. Prinzmetal angina is caused by coronary artery spasm and is associated with electrocardiogram (ECG) changes (usually ST elevation) during symptoms.
• Stable angina: Predictable chest discomfort that occurs in a consistent pattern at a certain level of exertion and is relieved with rest or nitroglycerin
• Unstable angina: Pain that is new or is changed in character to become more frequent, more severe, or both. Unstable angina portends myocardial infarction in a certain percentage of patients.
• System(s) affected: Cardiovascular
• Synonym(s): Heberden syndrome

ALERT
Geriatric Considerations

• Patients may be very sensitive to the side effects of medications.

Pediatric Considerations

• Suspect familial dyslipidemias in children presenting with manifestations of coronary artery disease.

Pregnancy Considerations

• Other diagnoses should be excluded and the patient managed closely by an obstetrician or family physician and cardiologist: The metabolic demands of pregnancy will exacerbate symptoms and directly interfere with treatment.

• Predominant age: Most common in middle-age and older men, postmenopausal women
• Predominant sex: Male > Female (before menopause)

Prevalence

• NHANES self-reported data suggest almost 14 million people in the US have diagnosed coronary artery disease (CAD), about half of whom have angina. Prevalence increases with age.
• Men: 7% between 40 and 49 years of age to 22% between 70 and 79 years of age
• Women: 5% between 40 and 49 years of age to 14% between 70 and 79 years of age

• Family history of premature CAD
• Hypercholesterolemia
• Hypertension (HTN)
• Tobacco use
• Diabetes mellitus
• Male gender
• Advanced age

• Discontinue tobacco, adherence to low-fat/low-cholesterol diet, regular aerobic exercise program
• Antilipidemics if indicated by current ATP guidelines or a risk-based approach
• Daily aspirin in those with coronary artery disease and without contraindications

• Atherosclerosis of the coronary arteries
• Coronary artery spasm
• Aortic stenosis
• Hypertrophic cardiomyopathy
• Severe HTN
• Aortic insufficiency
• Primary pulmonary HTN

• Hypercholesterolemia
• Claudication, peripheral vascular disease
• Arterial aneurysms
• Mitral regurgitation
• Papillary muscle dysfunction
• Ventricular aneurysm
• Abdominal aortic aneurysm
• Hypertrophic subaortic stenosis
• Primary hyperthyroidism
• Anemia and other high-output states

• Precordial pressure or heaviness radiating to the back, neck, or arms; brought on by exertion, emotional stress, meals, cold air, or smoking; relieved by rest or nitrates
• Discomfort may radiate to the neck, lower jaw, teeth, shoulders, and inner aspects of the arms or back.
• Discomfort may be described with a clenched fist over the sternum (Levine sign).
• Dyspnea on exertion may present as the only symptom.
• A choking sensation on exertion is a classic symptom.
• Atypical symptoms are more likely in women, elderly, and diabetic patients.

• Quality of any previous anginal episodes and pattern over time
• Underlying history of heart disease or valvular disease
• Family history of myocardial infarction (MI), CAD, sudden death

May see signs of dyslipidemia (xanthomas, xanthelasma), diminished peripheral pulses, carotid bruits

• ECG:
  • May show evidence of ischemia or prior myocardial infarction; other findings are nonspecific, and tracings are frequently normal.
  • Bundle branch block, Wolff-Parkinson-White syndrome, or intraventricular conduction delay may make the ECG unreliable.
• If abnormal ECG, exercise stress treadmill testing (ETT) based on probability is indicated:
  • ETT with imaging via echocardiography or perfusion imaging with sestamibi
  • In patients who cannot tolerate exercise, pharmacologic stress testing should be performed (e.g., Persantine, dobutamine).
  • Women have lower sensitivity and specificity with plain ETT than do men; exercise ECG or nuclear imaging is indicated.
  • In men:
    • Low probability (clinical assessment of pre-test probability low) and EKG normal: ETT without imaging
    • Intermediate probability: ETT with imaging
    • High probability: ETT may be considered prior to angiography, but proceding directly to angiography may also be appropriate without ETT.

Lab

• Total cholesterol: Frequently elevated
• High density lipoprotein (HDL) cholesterol: Frequently reduced
• Low density lipoprotein (LDL) cholesterol: Frequently elevated
• CRP: Most useful for those individuals at intermediate risk of developing coronary artery disease (10–20% over 10 years by Framingham risk criteria) in whom an elevated CRP may suggest an increased likelihood of benefit from statin therapy)

Imaging

• Stress ECG
• Stress scintigraphy

Diagnostic Procedures/Other

• Definitive evaluation requires coronary arteriography for confirmation and delineation of coronary disease and direction of interventional therapy or surgery. Coronary artery stenting has proven very effective, with restenosis rates (in skilled hands) often < 10%, eliminating need for surgery in many cases.
• Surgery in CAD not amenable to angioplasty, and stenting has proven to have a long-term benefit.

Pathological Findings
Atherosclerosis of the coronary arteries

• Esophagitis (GERD)
• Esophageal spasm
• Peptic ulcer disease
• Gastritis or nonulcer dyspepsia
• Cholecystitis
• Costochondritis
• Pericarditis
• Aortic dissection
• Pleurisy
• Pulmonary embolus
• Pulmonary HTN
• Pneumothorax
• Radiculopathy
• Shoulder arthropathy
• Psychological: Anxiety and panic disorders

First Line

• Aspirin: 81–325 mg/d
• β-blockers are effective in reducing heart rate, decreasing oxygen consumption, and reducing angina:
  • Atenolol 25–100 mg/d, metoprolol 25–100 mg b.i.d., or bisoprolol 2.5–10 mg/d
  • Adjust doses according to clinical response. Aim to maintain resting heart rate of 50–60 beats per minute.
  • Side effects are infrequent but include fatigue, exercise intolerance, erectile dysfunction, and exacerbation of peripheral vascular and chronic obstructive pulmonary disease.
• Nitroglycerin 0.4 mg SL is the most effective therapy for acute anginal episodes:
  • May repeat 2–3 times over a 10–15-minute period; if no relief, the patient should seek immediate medical attention.
• Long-acting nitrates (mononitrates or transdermal nitrates):
  • Should be used with a drug-free interval of 10–14 hours to prevent tolerance
  • Tachyphylaxis occurs rapidly.
  • Preload reduction and coronary vasodilatation
  • Side effects: Headaches and hypotension tend to clear with continued usage.
  • A β-blocker or calcium channel blocker should be used in conjunction with the nitrates during the drug-free interval.
  • Caution patients not to use in conjunction with oral medicine for erectile dysfunction, such as sildenafil (Viagra).
• Long-acting calcium channel blockers: Verapamil 160–480 mg/d, or diltiazem 90–360 mg/d, or nifedipine 30–120 mg/d, or amlodipine 5–20 mg/d. Drug of choice for variant angina. The various agents have their own individual side effects (i.e., verapamil, constipation; nifedipine, peripheral edema). Use amlodipine in patients with low ejection fraction.
• HMG CoA reductase inhibitors (e.g., simvastatin, atorvastatin, pravastatin, lovastatin) for hypercholesterolemia: Most clearly beneficial for secondary prevention, as in those patients with angina (in contrast, the number needed to treat to prevent myocardioal infarction [MI] is in the hundreds for patients with risk factors but without known CAD, over 5 years). These drugs decrease incidence of symptomatic CAD and reduce both myocardial infarction and death from MI. LDL target levels below 100 mg/dL for established CAD.
• ACE inhibitors (ramipril 10 mg) in patients with CAD or other vascular disease, (1)[B] and particularly those with diabetes or left ventricular (LV) systolic dysfunction (1)[A], have been shown to reduce both cardiovascular death and MI.
• Heparin: Low-molecular-weight heparin should be initiated in patients hospitalized with unstable angina.
• Glycoprotein IIb/IIIa receptor antagonists (Integrilin): Used in patients hospitalized with unstable angina just prior to cardiac catheterization if stenting anticipated.
• Clopidogrel is indicated for most patients with unstable angina/ACS (300-mg load, then 75 mg/d)
• Combination therapy may be used (especially nitrates plus calcium antagonists, with or without β-blockers).
• Contraindications:
  • Sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis) with nitrates should be avoided due to the risk of hypotension and possible death.
• Precautions: Avoid verapamil and diltiazem with compromised ventricular function (LV ejection fraction < 40%), especially in conjunction with β-blockers.
• Significant possible interactions:
  • Combination therapies may impair LV function and precipitate heart failure.
  • β-blockers and calcium channel blocker: May combine to produce symptomatic heart block, although either class of drug may act alone in producing this side effect.
• Niacin may worsen glucose intolerance (clinical implication uncertain).

Second Line

• Current ATP guidelines support the use of lipid-lowering drugs in patients with unfavorable lipid profiles and suspected or documented CAD, with or without symptoms (2)[A].
• Consider adding clopidogrel to ASA for severe diffuse CAD. The use of clopidogrel is indicated after stent placement for at least 9 months to significantly reduce restenosis rates.

General Measures

• The patient’s symptoms should be brought under control medically. If symptoms are unstable, hospitalization is warranted.
• Treatment goal involves reducing myocardial oxygen demand or increasing oxygen supply.
• Noninvasive testing often is indicated as a means of stratifying the patient’s risk for an event that might impair myocardial function.
• Quit smoking.
• Minimize emotional stress.
• Weight reduction in obese patients (3)[C]

Relaxation/stress reduction therapy may help reduce anginal episodes.

Coronary artery bypass graft surgery, angioplasty, stent placement, atherectomy in selected cases

Initial Stabilization
Emergency medical services (EMS) activation if chest discomfort unimproved or worsening 5 minutes after 2–3 nitroglycerin doses (4)[C]:

• EMS to initiate IV, O2, and monitor
• Aspirin administration if acute coronary syndrome suspected and not previously taken or contraindicated

Admission Criteria
Unstable symptoms warrant hospitalization for evaluation and treatment.

• Activity as tolerated after consulting physician
• Exercise program after physician’s approval; very effective if consistent

Patient Monitoring

• Depends on the frequency and severity of the complaints
• Hospitalization is indicated in patients diagnosed with unstable angina.

Low-fat, low-cholesterol, low-salt diet. "Mediterranean" diet may be ideal.

• Variable; depends on the extent of CAD as well as LV function
• Annual overall mortality is 3–4%.

• Related to myocardial damage occurring during infarction
• Arrhythmia
• Cardiac arrest
• Congestive heart failure (CHF)

Algorithms: Chest Pain; Chest Pain/Acute Coronary Syndrome

• 413.9 Other and unspecified angina pectoris
• 413.1 Prinzmetal angina
• 411.1 Intermediate coronary syndrome

• 194828000 Angina (disorder)
• 87343002 Prinzmetal angina (disorder)
• 233819005 Stable angina (disorder)
• 4557003 Preinfarction syndrome (disorder)

• Retain a high index of suspicion for angina in those women and the elderly with CAD risk factors in whom the "typical" presentation may not be present. Suggestive symptoms may include dyspnea, fatigue, and pain or discomfort in nonthoracic locations, and may not be exertional.
• Optimal medical regimens for angina usually include a beta-blocker, ACE inhibitor, statin, aspirin, and/or clopidogrel. Additionally, nitrates and calcium channel blockers may be useful.

Philip P. Lobstein, MD

1. Yusuf S, Sleight P, Pogue J et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:145-53  [PMID:10639539]
2. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-97  [PMID:11368702]
3. Gibbons RJ, Abrams J, Chatterjee K et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). Circulation. 2003;107:149-58  [PMID:12515758]
4. Antman EM, Anbe DT, Armstrong PW et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation. 2004;110:588-636  [PMID:15289388]