Stable and Unstable Angina

Stable and unstable angina are considered an important symptom of coronary heart disease (CHD) and present with chest pain due to transient myocardial ischemia. These disorders can be a warning sign for the risk of heart attack (MI) in the future. Clinically, stable and unstable angina are differentiated by exacerbating factors, duration of symptoms, and response to rest and medications. Diagnosis is by history and examination, ECG, stress testing with possible additional nuclear medicine imaging, echocardiography, or coronary angiography. Management with lifestyle modifications and aggressive risk factor reduction (of hypertension, diabetes, and hyperlipidemia) is indicated to prevent the risk of progression to MI and death.

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Overview

Definition

  • Stable angina is episodic chest pain due to transient myocardial ischemia resulting from coronary atherosclerosis.
  • Unstable angina: 
    • Worsening of previously stable angina, chest pain at rest, or pain not relieved with nitroglycerin, in the absence of elevated troponin levels
    • Belongs to the spectrum of acute coronary syndrome

Epidemiology

Stable angina: 

  • Occurs in approximately 14% of patients with coronary heart disease (CHD)
  • Experienced by 9.8 million people in the United States annually

Unstable angina:

  • 1 million patients are hospitalized annually in the United States.
  • Incidence is rising.
  • Mean age at presentation: 62 years

Etiology

Angina results from coronary artery disease (CAD):

  • CAD may be microvascular or macrovascular, with atherosclerotic narrowing of coronary arteries and arterioles. 
  • Unstable angina is due to a thrombus that develops on an atherosclerotic plaque, causing ischemia (decreased blood flow).

Risk factors

Cardiac risk factors include: 

  • Smoking
  • Diabetes
  • Hypertension
  • Hyperlipidemia
  • Family history
  • Obesity

Pathophysiology

Angina is a result of mismatched myocardial oxygen demand and oxygen supply.

Myocardial oxygen demand

  • 4 major factors that determine myocardial oxygen demand:
    • HR
    • BP
    • Myocardial wall tension
    • Contractility
  • ↑ Oxygen demand is seen with:
    • Arrhythmias
    • Malignant hypertension
    • Valvular heart disease
    • Fever
    • Hyperthyroidism (thyrotoxicosis)
    • Anemia
    • Congestive heart failure

Myocardial oxygen supply

  • Factors that determine myocardial oxygen supply:
    • Oxygen-carrying capacity of blood, which is determined by:
      • Oxygen tension
      • Hemoglobin concentration
    • Unloading of oxygen from hemoglobin to the tissues
    • Coronary blood flow
  • ↓ Oxygen supply is seen with ↓ coronary artery blood flow due to:
    • Atherosclerosis plus thrombus
    • Vasospasm, with or without atherosclerosis
    • ↑ HR → ↓ diastolic filling → ↓ coronary blood flow
    • ↓ Perfusion pressure, determined by left ventricular end diastolic pressure

Pathogenesis of angina

Ischemia results when oxygen demand is greater than supply: 

  • Results in myocardial ischemia → acidosis and ↓ formation of ATP
  • Loss of integrity of the myocardial membrane → release of chemical substances that stimulate nerve cells within cardiac muscle and around coronary vessels:
    • Lactate
    • Serotonin
    • Bradykinin
    • Histamine
    • Oxygen free radicals
    • Adenosine
  • Platelets release substances that cause aggregation in the area of a stenosis:
    • Serotonin
    • Thromboxane A2
    • 5-Hydroxytryptamine
  • The nerve fibers send a signal of pain → clinical angina:
    • From the heart to the sympathetic ganglia in the spinal cord
    • Up the ascending spinothalamic pathways to the brain

Clinical Presentation

Stable angina

  • Subacute or chronic
  • Chest pain that lasts 2–10 minutes.
  • Exacerbated by exertion
  • Predictable triggers and timing
  • Relieved by rest or nitroglycerin

Unstable angina

  • Acute presentation
  • Chest pain that lasts 10–30 minutes (or more)
  • Occurs at rest or with previously tolerated levels of exertion
  • No predictable pattern
  • Not relieved with rest or nitroglycerin

Common signs and symptoms

  • Substernal chest pain or discomfort: 
    • Described as “pressure”
    • May radiate: 
      • To the neck
      • To the jaw
      • Down the arm
    • Not positional
    • Not reproducible by palpation
    • Not pleuritic
  • Associated symptoms:
    • Dyspnea
    • Palpitations
    • Nausea
    • Diaphoresis
    • Epigastric pain
  • Special considerations:
    • Women and elderly patients may present only with nonclassic symptoms (nausea, diaphoresis).
    • Patients with diabetes (and autonomic neuropathy) may have only associated symptoms without classic chest pain.

Physical examination

  • Patients with stable angina usually have an unremarkable exam.
  • Patients with unstable angina may have any (or none) of these findings:
    • ↑ BP
    • ↑ HR
    • S3 or S4 heart sounds
    • New mitral regurgitation murmur
    • Change in intensity of existing murmurs

Diagnosis

Initial evaluation

  • ECG: 
    • Done during an episode of chest pain
    • May be normal (or show nonspecific changes) in both types of angina
    • May show transient evidence of subendocardial ischemia: 
      • ST-segment depression 
      • T-wave flattening
      • T-wave inversion
  • Lab tests: cardiac enzymes (e.g., troponin) are normal in stable and unstable angina.
  • Chest X-ray: often ordered to evaluate for other causes of chest pain

Stress testing

Indicated for patients at risk (intermediate pretest probability) of CAD who are clinically stable.

  • Exercise stress test is indicated if the patient is able to walk for an adequate time.
  • Pharmacologic or chemical stress test is indicated if a patient cannot physically complete an exercise test.
  • Nuclear medicine imaging may be added to detect perfusion abnormalities, especially in middle-aged women, who have a higher rate of false positives on exercise stress testing. 
  • Stress echocardiography: 
    • Preferred if there are baseline ECG abnormalities such as left bundle branch block.
    • Evaluates:
      • Wall motion abnormalities due to ischemia
      • Valvular function; useful for undiagnosed murmurs
      • Left ventricular ejection fraction (important in patients with signs or symptoms of heart failure)

Advanced imaging

  • Coronary CT angiography may be used in patients who cannot undergo stress testing.
  • Cardiac angiography is indicated for unstable patients or after abnormal stress testing:
    • Gold standard
    • Evaluates for occlusion in the major coronary arteries
    • Indicated in patients with a history of prior MI and ongoing chest pain
    • Evaluates left ventricular systolic function
    • Can also provide management (stenting during the procedure, if indicated)

Comparison within acute coronary syndrome

The following table compares unstable angina, NSTEMI, and STEMI based on clinical features, ECG, and laboratory findings:

Table: Comparison within acute coronary syndrome
DiagnosisClinical featuresECG findingsLaboratory findings
Unstable anginaIschemic chest pain that occurs at rest or with previously tolerated levels of exertion
  • None
  • STD
  • TWI
Normal troponin
NSTEMIProlonged ischemic chest pain in any setting
  • None
  • STD
  • TWI
Elevated troponin
STEMIProlonged ischemic chest pain in any setting
  • STE
  • New LBBB
Elevated troponin
LBBB: left bundle branch block
STD: ST-segment depressions
TWI: T-wave inversions
STE: ST-segment elevations

Management

The goals in treating patients with stable and unstable angina are to make an accurate diagnosis, assess the extent of CAD, relieve pain and other symptoms, and prevent MI.

  • Acute symptom management of angina:
    • Sublingual nitroglycerin
    • Treat underlying exacerbating factors:
      • Anemia
      • Hypertension
      • Tachyarrhythmia
      • Hyperthyroidism
      • Hypoxemia
      • Valvular heart disease
  • CAD risk factor reduction with the treatment of:
    • Hypertension
    • Hyperlipidemia (statin therapy)
    • Diabetes
    • Obesity
    • Smoking cessation
    • Healthy diet (such as the Mediterranean diet)
    • Regular exercise
  • Antiplatelet therapy: 
    • Aspirin
    • Clopidogrel, or similar agents, if intolerance or contraindication to aspirin
  • Manage chronic angina with antianginal medications:
    • Beta-blockers: ↓ myocardial oxygen demand
    • Long-acting nitrates: cause venodilation → ↓ preload and myocardial oxygen demand
    • Long-acting calcium channel blockers
    • Ranolazine for refractory symptoms
  • Patients with stable angina need follow-up visits with every 6–12 months.
  • In addition to the above measures, patients with unstable angina may require:
    • Hospitalization
    • Anticoagulation (heparin or low-molecular-weight heparin)
  • Invasive management with cardiac angiography is based on risk stratification: 
    • Indications:
      • Angina refractory to pharmacologic therapy
      • Unstable arrhythmias
      • Depressed ejection fraction
      • New mitral regurgitation
      • Cardiogenic shock
    • This can determine candidates for revascularization:
      • Coronary artery bypass surgery
      • Percutaneous coronary intervention with stenting

Differential Diagnosis

  • Myocardial infarction: ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation. Clinical presentation is most commonly with chest pain, but may be atypical. Diagnosis is by clinical history, ECG, and elevated cardiac enzymes. Management includes oxygen, pain control, antiplatelet therapy, anticoagulation, beta-blockers, and possibly percutaneous coronary intervention or thrombolytic therapy.
  • Vasospastic angina: uncommon cause of chest pain due to transient coronary artery spasms. The clinical presentation of vasospastic angina is characterized by spontaneous episodes of chest pain due to a transient decrease in blood flow to the epicardial arteries. Diagnosis is made by clinical history, normal exam, and ECG. Cardiac enzymes and PCI are usually normal. Management includes the prevention of vasospasm with calcium channel blockers and the relief of angina with nitrates. 
  • Aortic dissection: due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall, often associated with hypertension. Patients with aortic dissection often present with acute, tearing chest or back pain. Diagnosis is made by CT imaging. Type A dissections (in the ascending aorta) are a surgical emergency because of the risk of imminent rupture. Type B dissections (in the descending aorta) can often be managed medically with beta-blockers and calcium channel blockers.
  • Pulmonary embolism: presents with pleuritic pain, dyspnea, tachycardia, and occasionally chest pain. Risk factors for pulmonary embolism are prolonged immobilization, oral contraceptives or estrogen therapy, smoking, and obesity. Diagnosis of venous thromboembolism is made by CT. ECG may be normal or may show ST-segment changes. Management is urgent, with anticoagulation to prevent further propagation of the clot.
  • Pericarditis: inflammatory disorder of the pericardium resulting in chest pain that is usually constant and may manifest with diffuse ST-segment elevation on ECG. Etiologies can be infectious (usually viral), post-MI, due to medications, or due to malignancy. Treatment is supportive if viral or with management of the underlying cause.
  • Costochondritis: due to inflammation of the cartilage in the rib cage. Costochondritis presents with chest pain that is reproducible on palpation. It may be due to trauma, strain, or viral infection. Diagnosis is made clinically and by the exclusion of coronary disease with appropriate testing. Treatment is with local measures and NSAIDs.
  • Esophageal spasm: painful contraction of the esophagus that can present with severe, intermittent chest pain. Diagnosis is by ruling out cardiac causes of chest pain, esophageal manometry, and a barium swallow study. Management may include antispasmodic medications and, in some cases, surgery.
  • Anxiety or panic disorder: characterized by sudden attacks of fear/anxiety with or without an appropriate stimulus. Patients may report chest pain, palpitations, dyspnea, and other associated symptoms. Diagnosis is made by excluding cardiac causes of chest pain, and management is with psychotherapy therapy or medication.

References

  1. Chaudhary, I. (2020). Microvascular angina: angina pectoris with normal coronary arteries. UpToDate. Retrieved May 24, 2021, from https://www.uptodate.com/contents/microvascular-angina-angina-pectoris-with-normal-coronary-arteries
  2. Mahler, S.A. (2021). Angina pectoris: chest pain caused by fixed epicardial coronary artery obstruction. UpToDate. Retrieved May 24, 2021, from https://www.uptodate.com/contents/angina-pectoris-chest-pain-caused-by-fixed-epicardial-coronary-artery-obstruction
  3. Simons, M., Alpert, J.S. (2020). Acute coronary syndrome: terminology and classification. UpToDate. Retrieved May 24, 2021, from https://www.uptodate.com/contents/acute-coronary-syndrome-terminology-and-classification
  4. Goyal, A., Zeitser, R. (2021). Unstable angina. StatPearls. Retrieved May 24, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK442000/
  5. Gillen, C., Goyal, A. (2020). Stable angina. StatPearls. Retrieved June 13, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK559016/
  6. Sweis, R.N., Jivan, A. (2020). Unstable angina (acute coronary insufficiency; preinfarction angina; intermediate syndrome). MSD Manual Professional Version. Retrieved June 13, 2021, from https://www.msdmanuals.com/professional/cardiovascular-disorders/coronary-artery-disease/unstable-angina
  7. Tan, W., Moliterno, D.J. (2020). Unstable angina. In Yang, E.H. (Ed.), Medscape. Retrieved June 13, 2021, from https://emedicine.medscape.com/article/159383-overview
  8. Alaeddini, J., Shirani, J. (2018). Angina pectoris. In Yang, E.H. (Ed.), Medscape. Retrieved June 13, 2021, from https://emedicine.medscape.com/article/150215-overview

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