Coronary Heart Disease and Stable Angina

General Principles


  • Coronary artery disease (CAD) refers to the luminal narrowing of a coronary artery, usually due to atherosclerosis. CAD is the leading contributor to ischemic heart disease (IHD). IHD includes angina pectoris, myocardial infarction (MI), and silent myocardial ischemia.
  • Cardiovascular disease (CVD) includes IHD, cardiomyopathy, heart failure (HF), arrhythmia, hypertension, cerebrovascular accident (CVA), diseases of the aorta, peripheral vascular disease (PVD), valvular heart disease, and congenital heart disease.
  • Stable angina is defined as angina symptoms or angina equivalent symptoms that are reproduced by consistent levels of activity and relieved by rest.
  • American Heart Association/American College of Cardiology (AHA/ACC) guidelines provide a more thorough overview of stable IHD.1,2


  • The lifetime risk of IHD at age 40 is one in two for men and one in three for women.
  • There are more than 15 million Americans with IHD, 50% of whom have chronic angina.
  • CVD has become an important cause of death worldwide, accounting for nearly 30% of all deaths and has become increasingly significant in developing nations.3


  • CAD most commonly results from luminal accumulation of atheromatous plaque.
  • Other causes of obstructive CAD include congenital coronary anomalies, myocardial bridging, vasculitis, and prior radiation therapy.


  • Stable angina results from progressive luminal obstruction of angiographically visible epicardial coronary arteries or, less commonly, obstruction of the microvasculature, which results in a mismatch between myocardial oxygen supply and demand.
  • Atherosclerosis is an inflammatory process, initiated by lipid deposition in the arterial intima layer followed by recruitment of inflammatory cells and proliferation of arterial smooth muscle cells to form an atheroma.
    • The coronary lesions responsible for stable angina differ from the vulnerable plaques associated with acute MI. The stable angina lesion is fixed and is less prone to fissuring, hence producing symptoms that are more predictable.4
    • All coronary lesions are eccentric and do not uniformly alter the inner circumference of the artery.
    • Epicardial coronary lesions causing less than 40% luminal narrowing generally do not significantly impair coronary flow.
    • Moderate angiographic lesions (40%–70% obstruction) may interfere with flow and are routinely underestimated on coronary angiograms given the eccentricity of CAD.

Risk Factors

  • Of IHD events, >90% can be attributed to elevations in at least one major risk factor.5
  • Assessment of traditional CVD risk factors includes:
    • Age
    • Blood pressure (BP)
    • Blood glucose (Note: Diabetes is considered an IHD risk equivalent.)
    • Lipid profile (low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides); direct LDL for nonfasting samples or very high triglycerides
    • Tobacco use (Note: Smoking cessation restores the risk of IHD to that of a nonsmoker within approximately 15 years.)6
    • Family history of premature CAD: Defined as first-degree male relative with IHD before age 55 years or female relative before age 65 years
    • Measures for obesity, particularly central obesity; body mass index goal is between 18.5 and 24.9 kg/m2; waist circumference goal is <40 in for men and <35 in for women
  • As of 2013, AHA/ACC guidelines recommend assessing 10-year atherosclerotic cardiovascular disease (ASCVD) risk for patients aged 40–79 years using new race and age-specific pooled cohort equations.7
    • The ASCVD risk calculator is available online (!/calculate/estimate/).
    • If there remains uncertainty about lower risk estimates, high-sensitivity C-reactive protein (≥2 mg/dL), coronary artery calcium score (≥300 Agatston units or ≥75th percentile), or ankle-brachial index (<0.9) may be obtained to revise risk estimates upward.
    • Traditional risk factors noted above should be assessed in patients younger than 40 years and every 4–6 years after 40; 10-year ASCVD risk should be calculated every 4–6 years in patients 40–79 years of age.
    • Lifetime risk can be assessed using the ASCVD risk calculator and may be helpful in the setting of counseling patients about lifestyle modifications.


Primary prevention: See Chapter 3, Preventive Cardiology.

Clinical Presentation


  • Typical angina has three features: (1) substernal chest discomfort with a characteristic quality and duration that is (2) provoked by stress or exertion and (3) relieved by rest or nitroglycerin.
    • Atypical angina has two of these three characteristics.
    • Noncardiac chest pain meets one or none of these characteristics.
  • Chronic stable angina is reproducibly precipitated in a predictable manner by exertion or emotional stress and relieved within 5–10 minutes by sublingual nitroglycerin or rest.
  • The severity of angina may be quantified using the Canadian Cardiovascular Society (CCS) classification system (Table 4-1).
  • Associated symptoms may include dyspnea, diaphoresis, nausea, vomiting, dizziness, jaw pain, and left arm pain.
  • Female patients and those with diabetes or chronic kidney disease may have minimal or atypical symptoms that serve as anginal equivalents. Such symptoms include dyspnea (most common), epigastric pain, and nausea.
  • The clinician’s assessment of the pretest probability of IHD is the important driver for further diagnostic testing in patients without known CAD and is largely ascertained from the clinical history (Table 4-2). Patients with a low pretest probability (<5%) of CAD are unlikely to benefit from further diagnostic testing aimed at detecting CAD.
Table 4-1: Canadian Cardiovascular Society (CCS) Classification System
CCS 1Angina with strenuous or prolonged activity
CCS 2Angina with moderate activity (walking greater than two level blocks or one flight of stairs)
CCS 3Angina with mild activity (walking less than two level blocks or one flight of stairs)
CCS 4Angina that occurs with any activity or at rest

Anginal symptoms may include typical chest discomfort or anginal equivalents.

Data from Sangareddi V, Anand C, Gnanavelu G, et al. Canadian Cardiovascular Society classification of effort angina: an angiographic correlation. Coron Artery Dis. 2004;15(2):111-114.  [PMID:15024299]

Table 4-2: Pretest Probability of Coronary Artery Disease by Age, Gender, and Symptoms
Age (y)AsymptomaticNonanginal Chest PainAtypical/Probable Angina PectorisTypical/Definite Angina Pectoris

Very low < 5%Low < 10%Intermediate 10%–80%High > 80%

Data from Gibbons RJ, Balady GJ, Bricker JT, et al. (Committee Members). ACC/AHA 2002 guideline update for exercise testing – summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Circulation. 2002;106(14):1883-1892.  [PMID:12356646]

Differential Diagnosis

  • A wide range of disorders may manifest with chest discomfort and may include both cardiovascular and noncardiovascular etiologies (Table 4-3).
  • A careful history focused on cardiac risk factors, physical exam, and initial laboratory evaluation usually narrows the differential diagnosis.
  • In patients with established IHD, always look for exacerbating factors that contribute to ischemia.
  • Any process that reduces myocardial oxygen supply or increases demand can cause or exacerbate angina (Table 4-4).
Table 4-3: Differential Diagnosis of Chest Pain Excluding Epicardial Atherosclerosis
Aortic stenosisAnginal episodes can occur with severe aortic stenosis.
HCMSubendocardial ischemia may occur with exercise and/or exertion.
Prinzmetal anginaCoronary vasospasm that may be elicited by exertion or emotional stress.
PericarditisPleuritic chest pain associated with pericardial inflammation from infectious or autoimmune disease.
Aortic dissectionMay mimic anginal pain and/or involve the coronary arteries.
Cocaine useResults in coronary vasospasm and/or thrombus formation.
AnemiaMarked anemia can result in a myocardial O2 supply–demand mismatch.
ThyrotoxicosisIncrease in myocardial demand may result in an O2 supply–demand mismatch.
Esophageal diseaseGERD and esophageal spasm can mimic angina (responsive to NTG).
Biliary colicGallstones can usually be visualized on abdominal sonography.
Respiratory diseasesPneumonia with pleuritic pain, pulmonary embolism, pulmonary hypertension.
MusculoskeletalCostochondritis, cervical radiculopathy.

GERD, gastroesophageal reflux disease; HCM, hypertrophic cardiomyopathy; NTG, nitroglycerin.

Table 4-4: Conditions That May Provoke or Exacerbate Ischemia/Angina Independent of Worsening Atherosclerosis
Increased Oxygen DemandDecreased Oxygen Supply
  • Hyperthermia
  • Hyperthyroidism
  • Sympathomimetic toxicity (i.e., cocaine use)
  • Hypertension
  • Anxiety
  • Anemia
  • Sickle cell disease
  • Hypoxemia
    • Pneumonia
    • Asthma exacerbation
    • Chronic obstructive pulmonary disease
    • Pulmonary hypertension
    • Pulmonary fibrosis
    • Obstructive sleep apnea
  • Pulmonary embolus
  • Sympathomimetic toxicity (i.e., cocaine use, pheochromocytoma)
  • Hyperviscosity
  • Polycythemia
    • Leukemia
    • Thrombocytosis
    • Hypergammaglobulinemia
  • Hypertrophic cardiomyopathy
  • Aortic stenosis
  • Dilated cardiomyopathy
  • Tachycardia
    • Ventricular
    • Supraventricular
  • Aortic stenosis
  • Elevated left ventricular end-diastolic pressure
  • Hypertrophic cardiomyopathy
  • Microvascular disease

Modified from Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012;60(24):e44-e164  [PMID:23182125]. Copyright © 2012 American College of Cardiology Foundation and the American Heart Association, Inc. With permission.

Diagnostic Testing

  • General diagnostic testing
    • A resting ECG can be helpful in determining the presence of prior infarcts or conduction system disease and may alert the clinician to the possibility of CAD in patients with chest pain.
    • A transthoracic echocardiogram (TTE) can be useful in determining presence of left ventricular (LV) dysfunction or valvular heart disease that may affect the management and diagnosis of IHD. TTE can also be used to assess for resting wall motion abnormalities that may be the result of prior MI.
    • Evidence of vascular disease or prior MI on the diagnostic testing modalities noted above should raise the pretest probability of IHD in patients presenting with chest pain.
  • Stress testing overview
    • All stress testing requires (1) a cardiovascular stress and (2) a way of evaluating cardiac changes consistent with ischemia. The latter is always done with continuous ECG; however, it can be done either with or without an imaging modality.
    • Many stress testing modalities provide not only detection of ischemia/CAD but also prognostic information based on the burden of ischemia.
    • Table 4-5 provides an overview of the sensitivity and specificity for each stress and imaging modality along with advantages and disadvantages for the clinician to consider.
  • Stress testing indications
    • See the ACCF 2013 Multimodality Appropriate Use Criteria for the Detection and Risk Assessment of Stable Ischemic Heart Disease8 for a comprehensive list of the indications for stress testing.
    • The following are some of the more common indications:
      • Patients without known CAD:
        • Patients with anginal symptoms who are intermediate risk
        • Asymptomatic intermediate-risk patients who plan on beginning a vigorous exercise program or working in a high-risk occupation (e.g., airline pilot)
        • Atypical symptoms in patients with a high risk of IHD (i.e., diabetes or vascular disease patients)
      • Patients with known CAD:
        • Post-MI risk stratification (see section on ST-segment elevation MI)
        • Preoperative risk assessment if it will change management prior to surgery
        • Recurrent anginal symptoms despite medical therapy or revascularization
  • Contraindications to stress testing
    • Acute MI within 2 days
    • Unstable angina not previously stabilized by medical therapy
    • Cardiac arrhythmias causing symptoms or hemodynamic compromise
    • Symptomatic severe aortic stenosis
    • Symptomatic HF
    • Acute pulmonary embolus, myocarditis, pericarditis, or aortic dissection
  • Stress modalities
    • Exercise stress testing
      • The stress modality of choice for evaluating most patients of intermediate risk for CAD (see Table 4-2).
      • Bruce protocol: Consists of 3-minute stages of increasing treadmill speed and incline. BP, heart rate, and ECG are monitored throughout the study and the recovery period.
      • The ECG portion of the study is considered positive if:
        • New ST-segment depressions of >1 mm in multiple contiguous leads
        • Hypotensive response to exercise
        • Sustained ventricular arrhythmias are precipitated by exercise
      • The Duke Treadmill Score provides prognostic information for patients presenting with chronic angina (Table 4-6).
      • When exercise testing is combined with imaging (e.g., echocardiography), and the test is normal at the target heart rate for age, the risk of infarction or death from CVD is <1% annually in patients with no prior history of IHD.
      • In patients who cannot exercise and require pharmacologic testing, the annual risk of infarction or death in a normal study, doubles (i.e., 2% per year). This underscores the inability to perform physical activity as a marker of increased cardiovascular risk.
  • Pharmacologic stress testing
    • In patients who are unable to exercise, pharmacologic stress testing may be preferable.
    • Pharmacologic stress is preferred in patients with left bundle branch block (LBBB) or a paced rhythm on ECG. This is due to the increased incidence of false-positive stress tests seen with either exercise or dobutamine infusion.
    • Dipyridamole, adenosine, and regadenoson are vasodilators commonly used in conjunction with myocardial perfusion scintigraphy. Relative ischemia across a coronary vascular bed is elucidated as healthy vessels dilate more than diseased vessels with fixed obstruction. This in turn leads to relative changes in perfusion that are reflected in the postvasodilator images.
    • Dobutamine is a positive inotrope commonly used with echocardiographic stress tests and may be augmented with atropine to achieve target heart rate for age.
  • Stress testing with imaging
    • Recommended for patients with the following baseline ECG abnormalities:
      • Preexcitation (Wolf-Parkinson-White syndrome)
      • LVH
      • LBBB or paced rhythm
      • Intraventricular conduction delay
      • Resting ST-segment or T-wave changes
      • Patients unable to exercise or who do not have an interpretable ECG at rest or with exercise
      • May be considered in patients with high pretest probability of IHD who have not met the threshold of invasive angiography
  • Imaging modalities
    • Myocardial perfusion imaging (MPI): Both PET (positron emission tomography) and SPECT (single-photon emission tomography) use tracers that emit radiation detected by a camera in conjunction with exercise or pharmacologic stress. PET has better contrast and spatial resolution than SPECT, but PET is much more expensive and less widely available. Perfusion imaging compares rest perfusion to stress perfusion images to discern areas of ischemia or infarct. It can be limited by body habitus, breast attenuation, and quality of the acquisition and processing of images. Severe CAD may cause balanced reduction in perfusion and an underestimation of ischemic burden.
    • Echocardiographic imaging: Exercise or dobutamine stress testing can be performed with echocardiography to aid in the diagnosis of CAD. Echocardiography adds to the sensitivity and specificity of the test by revealing areas with wall motion abnormalities. The technical quality of this study can be limited by imaging quality (i.e., obesity).
    • Magnetic resonance perfusion imaging: MRI sequences obtained with contrast and vasodilator stress testing (and very rarely exercise testing) provides viability assessment without additional testing, as well as evaluation for other causes of myocardial dysfunction that may mimic IHD (i.e., sarcoidosis or infiltrative cardiomyopathies). Can be performed in patients with implanted cardiac devices (i.e., defibrillators and pacemakers).
Table 4-5: Diagnostic Accuracy of Common Stress Testing Modalities in Patients Without Known Ischemic Heart Disease
Test TypeSensitivitySpecificityAdvantagesDisadvantages
  • Easy to perform
  • Inexpensive
  • Less diagnostic accuracy, especially in women
  • No viability assessment
  • Gather other important information on diastolic function, valvular disorders, and pulmonary pressures
  • Can assess viability with pharmacologic stress
  • Limited by image quality
  • Diagnostic accuracy reduced with resting wall motion abnormalities
Pharmacologic (dobutamine)85%–90%79%–90%
Nuclear Perfusion Imaging
  • More sensitive for small areas of ischemia/infarct
  • Very accurate ejection fraction assessment
  • Easy to compare to prior studies
  • Significant radiation
  • May underestimate severe balanced ischemia
  • No other valve or other structural information
  • Viability may require separate testing
Pharmacologic (adenosine, regadenoson, or dobutamine)82%–91%75%–90%
Cardiac MRI
  • Excellent assessment of viability
  • Anatomic detail of heart and great vessels superb
  • Expensive
  • Requires closed MRI
  • Exercise option not typically available

All diagnostic accuracies unadjusted for referral bias.1,2

aVasodilator stress only; dobutamine has sensitivity of 83% and specificity of 86%.

Table 4-6: Exercise Stress Testing: Duke Treadmill Score
Duke Treadmill Score (DTS) = Minutes exercised – [5 × maximum ST-segment deviation] – [4 × angina score]. Angina score: 0 = none, 1 = not test limiting, 2 = test limiting
5Annual mortality 0.25%Low-risk study
−10 to 4Annual mortality 1.25%Intermediate-risk study
<–10Annual mortality >5%High-risk study

In general, β-blockers, other nodal blocking agents, and nitrates should be discontinued prior to stress testing.9

Diagnostic Procedures

  • Coronary angiography
    • The gold standard for evaluating epicardial coronary anatomy because it quantifies the presence and severity of atherosclerotic lesions, which has prognostic value.
    • Coronary angiography is invasive and associated with a small risk of death, MI, CVA, bleeding, arrhythmia, and vascular complications. Therefore, it is reserved for patients whose risk–benefit ratio favors an invasive approach such as:
      • ST-segment elevation MI (STEMI) patients
      • Most unstable angina (UA)/non–ST-segment elevation MI (NSTEMI) patients
      • Symptomatic patients with high-risk stress tests who are expected to benefit from revascularization
      • Class III and IV angina despite medical therapy (see Table 4-1)
      • Survivors of sudden cardiac death or those with serious ventricular arrhythmias
      • Signs or symptoms of HF or decreased LV function
      • Angina that is inadequately controlled with medical therapy for the patient’s lifestyle
      • Previous coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)
      • Suspected or known left main (≥50% stenosis) or severe three-vessel CAD
      • To diagnose CAD in patients with angina who have not undergone stress testing due to a high pretest probability of having CAD (see Table 4-2)
    • Can be used to evaluate patients who are suspected of having a nonatherosclerotic cause of ischemia (e.g., coronary anomaly, coronary dissection, radiation vasculopathy).
    • Functional significance of intermediate stenotic lesions (50%–70% narrowing) can further be assessed by fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR).
      • Both FFR and iFR are calculated by determining the ratio of pressure distal to the coronary obstruction to that of the aortic pressure (flow) using slightly different methods.
        • An FFR ≤ 0.8 or iFR ≤ 0.89 is considered flow limiting, and PCI decreases the need for urgent revascularization for UA or MI, as well as risk of recurrent MI.10
        • Whether PCI in stable IHD improves cardiovascular outcomes or symptoms compared to medical therapy is controversial.11
          • An early invasive strategy did not reduce death, death from cardiovascular causes, MI, or a composite of the three in stable IHD.12 These patients did have decreased angina and improved quality of life.
            • Patients with recent acute coronary syndrome (ACS), severe angina, left main disease, or left ventricular ejection fraction (LVEF) < 35% were excluded.
            • Physiological studies (FFR) were performed in only 20% of cases, and use of intravascular imaging (intravascular ultrasound, optical coherence tomography) was not reported.
              • The use of physiological studies and intravascular imaging is associated with better outcomes in PCI.13,14
            • 21% of patients assigned to a conservative strategy eventually underwent revascularization.
          • PCI for stable IHD did not improve survival, but was associated with decreased nonprocedural MI, unstable angina, and angina in a meta-analysis. However, there was an increased incidence of procedural MI.15
    • Measurement of LV filling pressures (diastolic function) and aortic and mitral valve gradients, assessment of regional wall motion and LV function, and assessment for certain aortopathies can be accomplished by placing a catheter in the LV cavity or aorta directly and making the appropriate pressure measurements and/or injection of contrast.
    • Contrast-induced nephropathy (CIN) occurs after 24–48 hours in up to 5% of patients undergoing coronary angiography. In most patients, creatinine returns to baseline within 7 days.16 The following are considerations in the prevention of CIN:
      • The volume of contrast media used should be minimized.
      • All patients should receive some CIN prophylactic therapy: oral hydration, IV hydration, held IV diuretics, and statin therapy have proven benefit.
      • We recommend a 3 mL/kg bolus of normal saline at least 6 hours prior to the procedure with a 1 mL/kg continuous infusion rate until procedure start.
      • N-Acetyl-L-cysteine has no advantage over simple hydration for prevention of CIN.
  • Coronary CT angiography
    • A noninvasive technique used to establish a diagnosis of CAD. Like cardiac angiography, it exposes the patient to both radiation and contrast material.
    • Uses arterial phase contrast CT images to evaluate coronary stenosis. Where available, a proprietary software package can calculate intracoronary hemodynamics akin to FFR.
    • CT has a high negative predictive value, so it is better suited to rule out disease for symptomatic patients with a low pretest probability for CAD, such as a patient with repeated emergency room admissions for chest pain or patients with equivocal stress test results.
      • The 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain gives CT a class I indication for use in intermediate risk patients with acute chest pain, without known CAD, to exclude obstructive CAD.17
    • May assist in identification of congenital anomalies of the coronary arteries.
    • Due to diminished study quality, it is not useful in patients with extensive coronary calcification (e.g., elderly, or advanced CKD), coronary stents, or small-caliber vessels.

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