THE CONTEXT
Coronary artery disease produces different clinical syndromes according to whether the dominant process is fixed stenosis, thrombosis, supply–demand imbalance or myocardial damage.
Angina and myocardial infarction
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Stable angina results from ischaemia due to fixed atheromatous stenosis of one or more coronary arteries.
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Unstable angina involves ischaemia caused by dynamic partial or complete coronary obstruction following plaque rupture or erosion with superimposed thrombosis.
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Type 1 myocardial infarction involves myocardial necrosis caused by acute coronary occlusion following plaque rupture or erosion with superimposed thrombosis.
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Type 2 myocardial infarction involves a mismatch between myocardial blood supply and demand. Fixed atheromatous obstruction combined with high myocardial demand can cause this mismatch.
Other clinical manifestations
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Heart failure reflects myocardial dysfunction due to infarction or ischaemia.
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Arrhythmias arise from altered conduction due to ischaemia or infarction.
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Sudden death may result from ventricular arrhythmia, asystole or massive myocardial infarction.
Inflammation, cap failure and thrombosis
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Macrophages mediate inflammation in established plaques, whereas smooth muscle cells promote repair. Predominant inflammation makes a plaque active or unstable.
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Activated macrophages release mediators including interleukin-1, tumour necrosis factor-alpha, interferon-gamma, platelet-derived growth factors and matrix metalloproteinases.
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These mediators cause intimal smooth muscle cell senescence and degradation of collagen cross-links. The protective fibrous cap thins and becomes vulnerable to mechanical stress, erosion, fissuring and rupture.
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A breach exposes plaque contents to blood, triggering platelet aggregation and thrombosis within the plaque and arterial lumen.
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Local obstruction or distal embolisation can cause organ ischaemia or infarction. This mechanism underlies acute coronary syndromes and also contributes to lower limb ischaemia and stroke.