Patients with IHD can present with chronic artery disease or acute coronary syndromes. Read about the different kinds, their diagnosis and treatment!
Coronary Artery Disease

Image: "Coronary artery disease" by BruceBlaus, License: CC BY 3.0

Definition of Coronary Artery Disease

Ischemic Heart Disease, also referred to as coronary artery disease, is a term used to describe a wide range of clinical conditions in which there is imbalance between oxygen supply and the myocardial demands resulting in ischemia to a portion of the myocardium.

The most common cause of ischemic heart disease is atherosclerosis of epicardial coronary arteries, resulting in partial or complete obstruction with subsequent inadequate perfusion of the myocardium supplied by the involved coronary artery.

Many risk factors have been involved in the pathophysiology of ischemic heart disease, the most common are obesity, high-fat diet, insulin resistance, diabetes and smoking. Risk factors modifications delay the onset of the disease and its progression to later life.

Coronary Artery Disease

Image: “Coronary Artery Disease” by BruceBlaus. License: CC BY 3.0

Epidemiology of Coronary Artery Disease


Ischemic heart disease is one of the leading causes of death worldwide, and considered the most common, serious chronic illness in United States, in which more than 13 million patients are suffering from coronary artery disease. More than 6 million have angina pectoris, and more than 7 million have myocardial infarction. Because of the large increase in the prevalence of IHD worldwide, it’s likely to become the leading cause of death by 2020.

Pathophysiology of Coronary Artery Disease

Angina occurs when there is imbalance between the oxygen supply and the myocardial demand, resulting in myocardial ischemia.

Myocardial oxygen demand

Four major factors determine the oxygen demand of the myocardium:

  1. Heart rate
  2. Systolic blood pressure (after load)
  3. Tension on myocardial wall (preload)
  4. Myocardial contractility

Any clinical condition increases one or more of these factors will increase the myocardial oxygen demand and can result in ischemia, such as extreme tachycardia, hypertension, ventricular hypertrophy.

Myocardial oxygen supply

The capacity of blood in carrying the oxygen to the myocardium is affected by different factors:

  • Hemoglobin and oxygen tension
  • The amount of extracted oxygen from hemoglobin to the tissue, and it is related to 2,3 diphosphoglycerate levels
  • Coronary artery blood flow, which is affected by the following factors:
    • Coronary artery diameter: Coronary atherosclerosis is the most frequent cause of narrowing and obstructing the coronary artery, and the clinical presentation differs according to the extent of obstruction.
    • Coronary artery tone: Coronary vasospasm as in variant or Prinzmetal’s angina, reduces the oxygen supply without significant underlying arthrosclerotic changes.
    • Perfusion pressure: It’s determined by the pressure gradient from the aorta to the coronary artery.
    • Heart rate: Coronary artery flow occurs mainly during diastole, therefore extreme tachycardia will decrease the duration of diastole, and thus will decrease the blood flow into the coronary arteries.

Any clinical condition affects one or more of the previous factors will reduce the myocardial oxygen supply and can result in ischemia.

Risk Factors of Coronary Artery Disease

Since myocardial ischemia develops most commonly as result of obstruction of one or more coronary arteries in form of coronary atherosclerosis, a number of risk factors predispose to this condition.

Coronary Artery Disease

Image: “Coronary Artery Disease.” By BruceBlaus, License: CC BY 3.0

Fixed Risk Factors
Age Risk increases with age, and is rare during childhood except if the patient has familial hyperlipidemia.
Male Sex Men have higher incidence of coronary artery disease than premenopausal women. The incidence of atherosclerosis in women increases after menopause due to deficiency of estrogen hormone.
Family history Positive family history is defined as development of ischemic heart disease in a first-degree relative before the age of 50 years.
Modifiable Risk Factors
Hyperlipidemia High level of cholesterol especially increased low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) is associated with an increased risk of atherosclerosis.
Hypertension Systolic and diastolic hypertension are associated with an increased risk of ischemic heart disease.
Cigarette smoking Number of cigarettes smoked is directly related to the risk of ischemic heart disease. Cessation of smoking reduces the risk by 25 %.
Diabetes mellitus Abnormal glucose tolerance, or diabetes mellitus increases risk of coronary artery disease, and progresses the other risk factors, such as dyslipidemia, obesity and hypertension.
Lack of exercise It’s recommended to exercise regularly for 30 minutes with moderate intensity for 5 days/week.
Obesity Reduction of body weight by exercise and healthy diet decreases risk of ischemic heart disease and controls the diabetes and insulin resistance.
Alcohol Moderate intake of alcohol (1 or 2 drinks/day) is associated with a reduced risk of coronary artery disease. At higher levels, the risk is increased.

Clinical Presentation of Coronary Artery Disease

Patients with ischemic heart disease (IHD) can present with either:

  • Chronic artery disease (CAD), which most commonly presents as stable angina
  • Acute coronary syndromes (ACSs), is a term that encompasses:
    • Unstable Angina (UA)
    • Myocardial infarction:
      • ST-segment Elevation Myocardial Infarction (STEMI)
      • Non-ST-segment Elevation Myocardial Infarction (NSTEMI)

Stable Angina Pectoris

It’s an episodic chest pain due to transient myocardial ischemia. The characteristic chest pain occurs with exertion or exercise (also termed: exertional angina) in a patient with narrow coronary arteries due to fixed atheromatous stenosis.


Diagram of discomfort caused by coronary artery disease

Image: “Diagram of discomfort caused by coronary artery disease. Pressure, fullness, squeezing or pain in the center of the chest. Can also feel discomfort in the neck, jaw, shoulder, back or arm.” By lan Furst. License: CC BY-SA 3.0

Typical patient presents with episodes of chest discomfort, described as a sense of pressure, choking, heaviness or tightness in the chest.

Onset, course and duration

The pain starts gradually, with the intensity increasing and decreasing (crescendo-decrescendo in nature) within minutes, typically lasts 2–5 minutes. It generally does not last for 20 to 30 minutes, unless the patient has acute coronary syndrome.

Site of pain

Ischemic pain is usually described as central substernal discomfort in which patient can’t localize the site of pain, and typically places his hand or clenched fist over the sternum.


The pain radiates to any dermatome from C8 to T4, most often to the left shoulder and left arm (especially the ulnar surface). Also it can radiate to interscapular region, back, epigastrium and lower jaw.

Precipitating and relieving factors

Episodes of angina is provoked by physical exertion and intense emotion, and relieved within minutes by rest and sublingual nitroglycerin.

Associated symptoms

Angina is usually associated with shortness of breath, diaphoresis, dizziness, lightheadedness, and fatigue.


Physical examination is usually unremarkable in patients with stable angina when they are asymptomatic, but clinicians should search for:

  1. Important risk factors: hypertension and diabetes mellitus
  2. Evidence of atherosclerosis at other sites, as carotid bruits and peripheral vascular disease
  3. Evidence of valvular diseases and left ventricular dysfunction


Resting ECG

It is normal between attacks, and may show evidence of previous myocardial infarction. During the pain, reversible ST segment depression or elevation, with or without T-wave inversion, is suggestive of myocardial ischemia.

Exercise ECG

Stress ECG ST Depression

Image: “stress-ecg with st-segment-depression (arrow) beginning at 100 W (column C)” by J. Heuser. License: CC BY-SA 3.0

Ischemia that is not present at rest is detected by provoking of chest pain using treadmill. Planar or down-sloping ST segment depression of 1 mm or more is indicative of ischemia.

Isotope scanning

Thallium scan can show areas of diminished uptake of radioactive isotope by ischemic myocardium at rest or during exercise.


It visualizes the location, number and severity of coronary artery stenosis, and indicated in whom coronary revascularization is being considered.


A) General measures

  1. Life style modification and control the previously mentioned risk factors
  2. Assessment of the extent and severity of atherosclerosis affecting different body organs

B) Medical treatment

1. Antiplatelet therapy: Low-dose aspirin or Clopidgorel (if aspirin intolerant) should be prescribed for all patients.

2. Antianginal therapy:

  • Nitrates:
    • Causes venous and arterial dilatation, thus lowering myocardial oxygen demand by reducing the preload and after load on the heart
    • Sublingual glyceryl trinitrate (GTN) should be taken during attack, relieves the pain within 2–3 minutes
    • Taken prophylactically before strenuous exercise
  • Beta-Blockers:
    • Lower myocardial oxygen demand by reducing heart rate and force of contraction
    • Aim of therapy: relieve angina and ischemia, and reduce mortality and re-infarction rates after myocardial infarction
  • Calcium channel antagonists:
    • Lower myocardial oxygen demand by reducing blood pressure and myocardial contractility

C) Coronary revascularization

It’s more appropriate to start treatment of stable angina initially with the medical treatment. Coronary revascularization should be considered in:

  1. Low exercise capacity or ischemia at low workload
  2. Large area of ischemic myocardium
  3. Impaired LV function with ejection fraction < 40 %

Percutaneous coronary intervention is mainly used in patients with single- or two-vessel disease with suitable anatomy, whereas coronary artery bypass grafting (CABG) is mainly used in patients with three-vessel or left main stem disease.

Acute Coronary Syndrome

signs suggestive of ACS

Image: Copyright by MedicoNotes.

Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction

Unstable angina (UA) is characterized by absence of myocardial damage, in contrast to the non-ST-elevation MI (NSTEMI) which presents with evidence of myocardial necrosis.


The diagnosis of UA/NSTEMI depends mainly on the history, abnormalities on ECG and the cardiac biomarkers.

A) History

Chest pain is similar in character to stable angina pectoris, but it is characterized by at least one of the following three features:

  1. It’s severe and of new onset.
  2. It occurs on minimal exertion or even at rest, and lasts longer.
  3. It’ characterized by being more intense and rapidly worsening (crescendo angina), not fully relieved by rest or nitroglycerin.

It’s usually preceded by vigorous exercise or emotional stress which results in imbalance between oxygen supply and myocardial demands.

B) Abnormalities on ECG

  • Transient or persistent ST-segment depression and/or T-wave inversion in 30–50 % of patients.
  • ST segment elevations and Q waves are absent in both UA and NSTEMI
  • ECG can be normal

C) Cardiac biomarkers

Cardiac enzymes are used to differentiate between Unstable Angina (UA) and non-ST-elevation MI (NSTEMI) :

  • Unstable angina → No myocardial damage → thus, normal cardiac enzymes
  • Non-ST-elevation MI (NSTEMI) → evidence of myocardial damage → elevated cardiac enzymes such as CK-MB and troponin I and T (more specific & sensitive marker)


Since initial ECG is not diagnostic, patients with UA/NSTEMI should rest on bed with serial ECG monitoring for any ST-segment deviation until pain resolves on definitive diagnosis is made.

A) Medical treatment

It involves simultaneous administration of anti-ischemic and anti-thrombotic treatment.

1. Anti-ischemic treatment:

  • Nitrates:
    • Sublingual Nitroglycerin , maybe repeated at 3-5 minutes if chest discomfort persists. If no response after 3 doses, consider IV nitroglycerin.
  • Beta-Blockers:
    • Metoprolol is given with a target heart rate: 50-60 beats/minute.
    • If beta-blocker is contraindicated, consider calcium channels blockers (CCBs): verapamil or diltiazem.

2. Anti-thrombotic treatment:

  • Aspirin:
    • High dose (375 mg/day) then lower doses (75 mg/day) for long-term treatment
  • Clopidogrel:
    • As early as possible in addition to aspirin unless there’s risk of bleeding
    • Pretreatment with clopidogrel is recommended prior to PCI
  • Anti-coagulant:
    • In addition to aspirin and clopidogrel, four anticoagulant options are available:
      • Unfractionated heparin (UFH)
      • Low-molecular-weight heparin (LMWH) “enoxaparin”: is superior on UFH with less risk of hemorrhage
      • Fondaparinux: indirect Factor Xa inhibitor, and it is equal in efficacy with enoxaparin but lower risk of bleeding
      • Bivalirudin: direct thrombin inhibitor, and it is equal in efficacy with UFH and LMWH

B) Early invasive strategy

Only high risk patients can benefit from coronary revascularization (PCI or coronary artery bypass grafting):

  • Age > 65 years
  • > 3 CAD risk factors
  • ST deviation
  • > 2 anginal events < 24h
  • Elevated cardiac markers

The outcomes of conservative treatment are similar to invasive treatment in low risk patients, therefore invasive treatment is not recommended in low risk patients.

ST-segment Elevation Myocardial Infarction (STEMI)


Diagnosis of STEMI also depends on history, abnormalities on ECG and the cardiac biomarkers.

A) History

Chest pain is similar in character to stable angina pectoris, but more severe, lasts longer (usually > 20 minutes) and not fully relieved by rest or nitroglycerin.

B) Abnormalities on ECG

ST elevation, followed by T-wave inversion if no reperfusion was achieved, followed by Q-wave development over several hours. The ECG criteria for ST-elevation MI (a, b, or c) are:

  1. ST elevation ≥ 0.1 mV (1 mm) in at least 2 leads of either:
    1. Inferior group: II, III, aVF
    2. Lateral group: I, aVL, V5, V6
  2. ST elevation ≥ 0.2 mV (1 mm) in at least 2 contiguous anterior leads (V1–V4)
  3. New LBBB

C) Cardiac biomarkers

Troponin I and T are more specific than CK-MB cardiac enzymes. Normally, Troponin enzymes are not detectable in the blood of healthy individuals, but they are increased to levels more than 20 times higher than upper reference limit in myocardial infarction (MI).

Troponins Rises within 4–8 hours Remain elevated for 7–10 days
CK-MB Rises within 4–8 hours Returns to normal by 48–72 hours

Note: Troponins can’t detect a reinfarction occurring few days after the first one because they remain elevated for 7–10 days, in contrast to CK-MB which returns to normal level within 2–3 days and therefore can be used to identify a new ischemic event in a patient with a new episode of pain.


Management of patients in with suspected ST-Elevation MI in emergency department should focus on relieving the ischemic pain, identification of candidates urgent reperfusion therapy and avoidance the discharge of patient with suspected STEMI.

  • Patient should be admitted immediately in hospital with ECG rhythm monitoring due to risk of sudden death.
  • Take targeted history and examination.
  • Intravenous access and blood sample for cardiac markers.

A) Immediate treatment:

  • Aspirin: should be administered immediately
  • Sublingual glyceryl trinitrate, repeat if no effect in 5 min
  • Begin oxygen by nasal cannula or mask if hypoxia is present
  • Intravenous opiates (such as Morphine)
  • Beta-Blocker (if no contraindication) for ongoing chest pain, hypertension, tachycardia

B) Reperfusion therapy:

1. Primary percutaneous coronary Iintervention (primary PCI):

Primary PCI refers to angioplasty and/or stenting without preceding fibrinolysis, and it is more effective and preferred on IV fibrinolysis, especially when:

  1. Diagnosis is doubt
  2. Cardiogenic shock is present
  3. Increased risk of bleeding
  4. Symptoms have been present for > 3 hours

2. Fibrinolysis:

IV fibrinolysis is indicated if :

  1. Primary PCI is not available, or
  2. Delay to PCI would be > 1 hour longer than initiation of fibrinolysis

Before starting fibrinolytic drugs, assess for contraindications:

  • Prior intracranial bleeding
  • Intracranial malignancy or vascular malformation
  • Ischemic stroke or head trauma in previous 3 months
  • Aortic dissection
  • Active bleeding (with exception of menses)
  • Internal bleeding in previous 4 weeks
  • Severe hypertension (systolic > 180 or diastolic > 110)
  • Prolonged (> 10 min) CPR chest compressions
  • INR ≥ 2.0 on warfarin, or known bleeding diathesis
  • Pregnancy

Coronary angiography after fibrinolysis (rescue PCI ) is indicated in:

  • Failure of reperfusion (as evidenced by < 50 % resolution of ST segment elevation > 90 min after completion of fibrinolytic treatment)
  • Spontaneous recurrent ischemia in hospital
  • High risk features: e.g., extensive ST-segment elevation, signs of heart failure and hypotension (systolic blood pressure < 100 mmHg)


Several prognostic indicators determine the outcome of ischemic heart disease (IHD):

  1. Function of the left ventricle: increased left ventricular end-diastolic pressure, increased ventricular volume and reduced ejection fraction are associated with poor prognosis
  2. Location and severity of coronary artery stenosis: stenosis of left main left anterior descending coronary artery are associated with greater risk and poor prognosis
  3. Number and severity of risk factors: large number of risk factors for atherosclerosis are associated with increased risk of myocardial infarction with worse prognosis

Review Questions

The solutions are located below the references.

1. A patient with a recent myocardial infarction (MI), few days after hospital admission, started to suffer from a new episode of chest pain. Which cardiac marker is appropriate to ask for this patient?

  1. Troponins I and T
  2. CK-MB
  3. Myoglobin
  4. LDH

2. A patient came to Emergency Department with a typical ischemic chest pain. The ECG shows: ST-segment depression with T-wave inversion, and cardiac markers is negative. The most probable diagnosis is…

  1. …stable Angina.
  2. …unstable Angina.
  3. …ST-Segment Elevation Myocardial Infarction (STEMI).
  4. …non-ST-Segment Elevation Myocardial Infarction (NSTEMI).

3. IV fibrinolysis is preferred to be given in a patient with ST-Elevation MI if:

  1. symptoms have been present for > 3 hours.
  2. cardiogenic Shock.
  3. increased risk of bleeding.
  4. delay to PCI would be >1 hour longer than initiation of fibrinolysis.
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