Endothelial injury, lipid entry, foam cells, fatty streak, then fibrous plaque
Mnemonic
“Fatty streak, plaque, rupture, thrombus”, the sequence in four steps:
- Endothelial injury from shear stress, smoking, hypertension, hyperglycaemia or dyslipidaemia
- LDL enters and is oxidised; monocytes migrate in and become foam cells, forming the fatty streak, which is present even in children
- Smooth muscle migrates from the media and lays down collagen, forming the fibrous cap over a lipid core: the mature atheromatous plaque
- Plaque rupture exposes thrombogenic material, triggering platelet aggregation and thrombosis
“It is the rupture, not the stenosis, that causes the infarct.” That is the single most important idea: the plaques that rupture are often less than 50 per cent stenotic, which is why an infarct can be the first symptom and why statins work by stabilising plaques rather than by unblocking arteries.
Vulnerable plaques have a thin cap, a large lipid core and heavy inflammation; stable plaques have thick fibrous caps and calcification.
Sites follow turbulent flow: branch points, the abdominal aorta, coronary and carotid bifurcations.
Expansion
- Endothelial injury or dysfunction from smoking, hypertension, hyperlipidaemia, diabetes and turbulent flow at branch points
- LDL enters the intima and is oxidised
- Monocytes adhere, enter and become macrophages, engulfing oxidised LDL to become foam cells
- Fatty streak, present even in children and reversible
- Smooth muscle migrates from media to intima and lays down collagen, forming a fibrous cap over a lipid-rich necrotic core
- Complicated plaque: calcification, ulceration, haemorrhage into the plaque, thrombosis, aneurysm formation
Distribution follows haemodynamic stress: abdominal aorta, coronary arteries, popliteal arteries, internal carotid and circle of Willis.
The key clinical concept is the vulnerable plaque: a thin fibrous cap, a large lipid core and heavy inflammatory infiltrate. Such a plaque may cause little stenosis yet rupture and occlude the vessel abruptly. This is why acute coronary syndromes often occur in vessels that were not critically narrowed, and why statins reduce events partly by stabilising plaques rather than by reversing stenosis.