OVERVIEW OF ATHEROSCLEROSIS
- Definition: A chronic inflammatory disorder of arteries characterized by plaque buildup (atheroma) in the arterial walls.
- Clinical Impact:
- May lead to vascular disease (coronary heart disease [CHD], peripheral vascular disease, cerebrovascular disease).
- A major cause of disability and death from occlusive arterial disease.
PATHOPHYSIOLOGY OF ATHEROSCLEROSIS
- Arterial Wall Layers:
- Endothelial layer
- Intima/subendothelial space
- Internal elastic lamina
- Media (smooth muscle cells)
- Adventitia (loose connective tissue)
- Sites of Lesions:
- Arterial regions with turbulent flow (bifurcations, curvatures).
- Common symptomatic locations: proximal left anterior descending coronary artery, proximal renal arteries, carotid bifurcations.
- Initiating Event:
- Chronic endothelial injury or dysfunction.
- Key risk factors damaging endothelium:
- Elevated low-density lipoprotein (LDL)
- Decreased high-density lipoprotein (HDL)
- Oxidant stress (cigarette smoking, hypertension, diabetes)
- Aging
- Fatty Streak Formation:
- LDL (and other apo B100–containing lipoproteins) move from blood into subendothelial space.
- Retention of LDL by charge interactions with proteoglycans.
- LDL oxidation → promotes monocyte chemotaxis.
- Monocytes enter subendothelium, become macrophages, and ingest oxidized LDL → foam cells.
- Clusters of foam cells = fatty streak, which can regress or advance.
- Progression to Fibrous Plaque:
- Further accumulation of foam cells + smooth muscle cells + extracellular matrix.
- Smooth muscle cells proliferate, produce collagen, and form a fibrous cap over a lipid-filled necrotic core.
- Chronic inflammation (monocytes, T cells) continues, releasing cytokines, proteases, and growth factors.
- Complicated Lesions:
- Plaque may rupture or erode:
- Exposes subendothelial tissue → thrombosis formation.
- Microvessels (from vasa vasorum) can rupture within plaque → small hemorrhages.
- Calcification: late event with decreased arterial elasticity.
- Cardiac CT can detect coronary calcification (indicates severity of atherosclerosis).
- Plaque rupture leads to acute ischemic events (e.g., myocardial infarction).
- Plaque may rupture or erode:
RISK FACTORS FOR ATHEROSCLEROSIS
- Hypercholesterolemia (↑ LDL)
- Strong predictor of CHD.
- More than 70% of individuals with premature CHD have hyperlipidemia.
- Serum total cholesterol <160 mg/dL markedly reduces CHD risk.
- Hypertension
- Elevated blood pressure injures endothelium.
- Hypertension control → reduces risk of stroke, heart failure, and CHD events.
- Cigarette Smoking
- Increases vascular inflammation and LDL oxidation → promotes atherosclerosis.
- Major modifiable risk factor.
- Diabetes Mellitus
- Substantially increases atherosclerotic risk.
- Mechanisms: small dense LDL, low HDL, hyperglycemia-induced glycosylation of LDL, etc.
- Others/Associated Factors
- Low HDL, aging, physical inactivity, obesity, insulin resistance.
- Diet high in saturated fats.
CLINICAL COURSE
- Lesion Evolution:
- Initially silent; advanced disease → chronic stable syndromes (e.g., stable angina, intermittent claudication) or acute syndromes (e.g., myocardial infarction, stroke).
- Most plaques remain asymptomatic or cause progressive luminal narrowing.
- Plaque Stabilization vs. Vulnerability:
- Stable plaques: thick fibrous caps, small lipid cores.
- Vulnerable plaques: thin fibrous caps, large lipid cores, high macrophage content.
- Ruptured plaques with superimposed thrombus → acute events and sudden cardiac death.