- Clinical science
Coronary artery disease (CAD) is an ischemic heart disease that is most commonly caused by atherosclerosis and the subsequent reduction of blood supply to the myocardium, resulting in a mismatch between myocardial oxygen supply and demand. Acute retrosternal chest pain (angina) is the cardinal symptom of CAD. Other symptoms include dyspnea, dizziness, anxiety, and nausea. Severe ischemia may lead to myocardial infarction (MI). CAD is diagnosed using cardiac stress testing and/or coronary catheterization. Management of CAD involves primary and secondary prevention of atherosclerosis (e.g., weight reduction), antianginal treatment (e.g., beta blockers) and, in severe cases, revascularization (e.g., percutaneous transluminal coronary angioplasty).
- Coronary artery disease (CAD): ischemic heart disease due to narrowing or blockage of coronary arteries, most commonly due to atherosclerosis, resulting in a mismatch between myocardial oxygen supply and demand
- Angina: chest pain caused by myocardial ischemia (necrosis of myocytes has not yet occurred) due to narrowing (e.g., thrombus) or spasm (e.g., Prinzmetal angina) of the coronary artery
- Stable angina: a type of angina that occurs upon exertion, mental stress, and/or exposure to cold and usually subsides within 20 minutes of rest or after administration of nitroglycerin
- CAD is the leading cause of death in the US and worldwide. 
- The lifetime risk of coronary artery disease at age 50 is approx. 50% for men and 40% for women. 
Epidemiological data refers to the US, unless otherwise specified.
- is the most common cause (see “ ”).
Plaque formation and coronary artery stenosis 
- For plaque formation, see “ .”
- Stable atherosclerotic plaque → vascular stenosis → increased resistance to blood flow in the coronary arteries → decreased myocardial blood flow → oxygen supply-demand mismatch → myocardial ischemia
- The extent of coronary stenosis determines the severity of the oxygen supply-demand mismatch and, thus, the severity of myocardial ischemia.
- Severe ischemia results in myocardial infarction (see “ ”).
Coronary flow reserve (CFR): the difference between maximum coronary blood flow and coronary flow at rest (a measure of the ability of the coronary capillaries to dilate and increase blood flow to the myocardium).
- In healthy individuals, the CFR can be up to 4 times higher on exertion than at rest.
- CFR is reduced in individuals with CAD due to vascular stenosis and reduced vascular compliance.
Myocardial oxygen supply-demand mismatch 
- Definition: mismatch between the amount of oxygen the myocardium receives and the amount it requires
- Factors reducing oxygen supply
- Factors increasing oxygen demand
An increased heart rate reduces oxygen supply and increases oxygen demand.
Effect of vascular stenosis on resistance to blood flow 
- The resistance to blood flow within the coronary arteries is calculated using the Poiseuille equation: R = 8Lη/(πr4), where R = resistance to flow, L = length of the vessel, η = viscosity of blood, and r = radius of the vessel.
- Provided the length of the vessel and viscosity of blood remain constant, the degree of resistance can be calculated using the simplified formula: R ≈ 1/r4
Myocardial ischemia 
Reversible ischemia: Tissue is ischemic but not irreversibly dead and, therefore, still potentially salvageable.
- Myocardial stunning: acutely ischemic myocardial segments with transiently impaired but completely reversible contractility
- Hibernating myocardium: a state in which myocardial tissue has persistently impaired contractility due to repetitive or persistent ischemia
- Irreversible ischemia: tissue necrosis (myocardial scars)
- Definition: a phenomenon of vasodilator-induced alteration of coronary blood flow in patients with coronary atherosclerosis resulting in myocardial ischemia and symptoms of angina
- Long-standing CAD requires maximal coronary arterial dilation distal to the stenosis to maintain normal myocardial function.
- In CAD, the affected coronary artery is maximally dilated distal to the stenosis to compensate for the reduced blood flow .
- If a vasodilator (e.g., dipyridamole) is administered, the subsequent vasodilation of healthy vessels causes these to “steal” blood from the stenotic blood vessels, resulting in poststenotic myocardial ischemia.
- Coronary steal is the underlying mechanism of .
- Administration of vasodilators (e.g., dipyridamole) → coronary vasodilation → decreased hydrostatic pressure in the normal coronary arteries → blood shunting back to well-perfused myocardium → decreased flow to the ischemic myocardium → myocardial ischemia downstream to the pathologically dilated vessels → angina pectoris and/or ECG changes
Angina is the cardinal symptom of CAD. Patients with CAD usually become symptomatic when the degree of coronary stenosis reaches ≥ 70%.
- Typically retrosternal chest pain or pressure
- Dizzinesss, palpitations
- Restlessness, anxiety
- Autonomic symptoms (e.g., diaphoresis, nausea, vomiting, syncope)
- Symptoms are reproducible/predictable
- Symptoms often subside within minutes with rest or after administration of nitroglycerin
- Common triggers include mental/physical stress or exposure to cold
- Angina caused by transient coronary spasms (usually due to spasms occurring close to areas of coronary stenosis)
- Not affected by exertion (may also occur at rest)
- Typically occurs early in the morning 
- Highest prevalence in Japanese population (especially young women)
- Average age of onset: 50 years
- Cigarette smoking; use of stimulants (e.g., cocaine, amphetamines), alcohol, or triptans
- Stress, hyperventilation, exposure to cold
- Associated with other vasospastic disorders (e.g., Raynaud phenomenon, migraine headaches) 
- Common atherosclerotic risk factors (except smoking) do not apply to vasospastic angina.
- The 5-year survival rate is > 90% (with treatment). 
- Persistence of symptoms is common.
- History of recurrent angina episodes
- Signs of atherosclerotic vascular disease (e.g., absent foot pulses, carotid bruit)
Clinical assessment of symptomatic patients to predict the probability of CAD, used to:
- Help determine the need for further diagnostic tests
- Guide the selection of best initial diagnostic test
Factors used to estimate the probability of CAD 
The pretest probability takes into consideration:
- Patient's age and sex
Type of chest pain
- Typical angina meets all of the following criteria:
- Atypical angina: meets only 2 of the aforementioned criteria
- Noncardiac chest pain: meets one or none of the aforementioned criteria
|Probability of CAD ||Clinical presentation||Next diagnostic step|
Low (< 10%)
| || |
|High (> 90%)|| |
- Best initial test for all types of chest pain
- Usually normal in stable angina
- ST segment depression or T wave inversion/flattening indicates previous MI or unstable angina and requires further workup (see “”).
Cardiac stress test 
- Best test for assessing patients with an intermediate pretest probability of CAD.
Cardiac exercise stress test: test of choice (preferred over pharmacological testing because exercise can achieve a higher level of strain)
- The patient exercises until the target heart rate is achieved (e.g., on a treadmill).
- Contraindications 
- Acute myocardial infarction with elevated troponin levels and/or ST elevations (within the past 2 days)
- Unstable angina pectoris or ST depressions at rest
- Decompensated heart failure or severe symptomatic stenosis of one or more heart valves
- Acute endocarditis, myocarditis, or pericarditis
- Hemodynamically significant arrhythmias
- Acute thromboembolic disease
- Acute aortic dissection
- Mental or physical impairment to exercise
Cardiac pharmacological stress test: performed if the patient is unable to exercise or has contraindications for exercising
- Positive inotropic/chronotropic substances (e.g., dobutamine) or vasodilators (e.g., dipyridamole or adenosine) are administered to simulate the effect of exercise on the myocardium.
- For adenosine, dipyridamole
- For dobutamine
- If cardiac stress test is performed for primary diagnosis, withhold the following:
- If a cardiac stress test is performed for treatment evaluation, medication can be continued.
Findings in stress-induced ischemia 
- Clinical findings
- (detection method of choice)
Imaging: (echocardiography, myocardial perfusion imaging)
- Used if the patient's resting ECG cannot be interpreted
- Helps distinguish between reversible ischemia and irreversible ischemia
- To detect wall motion abnormalities
- Simultaneous evaluation of ventricular size and functional parameters (e.g., EF) and detection of valvular disorders is possible.
- Radionuclide myocardial perfusion imaging (PET or SPECT): to visualize perfusion 
- Persistent symptoms of angina despite appropriate therapy
- Abnormal results of noninvasive testing
- Ambiguous results on noninvasive procedures and in high clinical suspicion of CAD
- Considered the gold standard of CAD diagnosis since it provides:
The differential diagnoses listed here are not exhaustive.
- All patients: risk factor reduction and antiplatelet drugs (see “Prevention” below)
- Mild CAD: pharmacologic therapy
- Moderate CAD: consider coronary angiography and percutaneous transluminal coronary angioplasty (PTCA)/percutaneous coronary intervention (PCI)
- Severe CAD: coronary angiography and revascularization or coronary artery bypass grafting
Antianginal treatment 
- Goal: reduction of MVO2 (myocardial O2 demand)
- CCBs: indicated if there are contraindications to beta blockers or in addition to beta blockers (if angina or hypertension persist)
Ranolazine: a metabolic modulator that reduces myocardial oxygen demand without altering the heart rate, blood pressure, contractility, and/or end-diastolic volume
- Indication: stable angina that is refractory to first-line treatment
- Mechanism of action
- Side effects
- Combination therapy
|Effects of drugs on MVO2 parameters|
|Parameter||Beta blocker||Nitrates||Combination therapy|
|Heart rate||↓|| |
|Unchanged or slightly ↓|
|End-diastolic volume||Unchanged or ↑||↓||Unchanged or slightly ↓|
- Prognostic factors
- Stable angina
Prevention of atherosclerosis
- See “.”
Special considerations in coronary artery disease 
- Antiplatelet drugs
- Arterial hypertension management
- Diabetes mellitus: maintenance of HbA1c at < 7% levels
- Lifestyle modifications (e.g., weight loss, diet modification)
- See “.”