CardiologyTier 2Topic

Vascular biology and the pathophysiology of atherosclerosis

Atherosclerosis as inflammation

Atherosclerosis is a chronic inflammatory process of the arterial wall, not simply passive lipid deposition - beginning with endothelial dysfunction and progressing through a well-defined sequence to plaque rupture
Begins in childhood/early adulthood (fatty streaks) in most populations, with clinical events typically decades later

Endothelial dysfunction (from hypertension, smoking, hyperglycaemia, dyslipidaemia) -> increased permeability to LDL -> LDL oxidation in the subendothelial space -> monocyte recruitment/differentiation to macrophages -> foam cell formation (lipid-laden macrophages) -> fatty streak -> fibrous cap formation (smooth muscle migration/proliferation) -> plaque
Vulnerable plaque - thin fibrous cap, large lipid core, active inflammation - prone to rupture regardless of luminal stenosis severity (a haemodynamically "insignificant" plaque can still cause an acute event if it ruptures)
Plaque rupture -> exposed thrombogenic core -> platelet aggregation/thrombus -> acute vessel occlusion (the final common pathway of ACS)

Anatomical imaging (angiography, CT coronary angiogram) quantifies luminal stenosis but does not reliably identify vulnerable (rupture-prone) plaque
Intravascular imaging (IVUS, OCT) can characterise plaque composition directly when needed

Explains why statins reduce cardiovascular events disproportionately to the degree of stenosis regression - they stabilise plaque (reduce inflammation, thicken the fibrous cap) rather than simply shrinking it

Acute coronary syndrome, stroke (carotid plaque rupture), peripheral arterial disease - atherosclerosis as a systemic process affecting multiple vascular beds simultaneously
The systemic nature of atherosclerosis means a patient presenting with disease in one vascular territory (e.g. PAD) has a substantially elevated risk of events in others (coronary, cerebrovascular) - risk assessment and secondary prevention should be systemic, not territory-specific

4 more sections, plus exam facts

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