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).

RISK FACTORS FOR ATHEROSCLEROSIS

  1. 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.
  2. Hypertension
    • Elevated blood pressure injures endothelium.
    • Hypertension control → reduces risk of stroke, heart failure, and CHD events.
  3. Cigarette Smoking
    • Increases vascular inflammation and LDL oxidation → promotes atherosclerosis.
    • Major modifiable risk factor.
  4. Diabetes Mellitus
    • Substantially increases atherosclerotic risk.
    • Mechanisms: small dense LDL, low HDL, hyperglycemia-induced glycosylation of LDL, etc.
  5. 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.

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