ATHEROSCLEROSIS


Definition:

A progressive inflammatory disorder of arterial wall i.e. characterized by focal lipid-rich deposits of atheroma that remain clinically silent until they become large enough to impair arterial perfusion / until ulceration / disruption of lesion results in thrombotic occlusion / embolization of affected vessel.

Risk factors:

1) Major constitutional risk factors

  • Age
  • Sex more in men
  • Genetic factors
  • Familial & racial factors

2) Major acquired risk factors

  • Hyperlipidemia
  • HTN
  • Smoking
  • Diabetes mellitus

3) Minor risk factors

  • Obesity
  • Exogenous hormones like oral contraceptives
  • Endogenous estrogen deficiency
  • Physical inactivity
  • Stress full life style
  • Environmental influences
  • Heavy alcohol

Pathophysiology:

1) Early atherosclerosis

  • Fatty streaks @ altered arterial shear stress
  • Abnormal endothelial function
  • Development of inflammation
  • Inflammatory cells mainly monocytes binds to receptors of endothelial cells
  • Migrate into intima
  • Take up oxidized LDL from plasma
  • Lipid laden foam cells or macrophages
  • Extracellular lipid pool in intima, foam cells die, release of contents
  • Cytokines, growth factors released, smooth muscle cells migration into intima & change form contractile to a repair phenotype in attempt to stabilize atherosclerotic lesion
  • Formation of atherosclerotic plaque

2) Advanced atherosclerosis

  • In established atherosclerotic plaque macrophages mediate inflammation & smooth muscle cells promote repair
  • If inflammation predominates plaque becomes active/unstable & may be complicated by ulceration & super added thrombosis
  • Cytokines by activated macrophages & may cause inflammation of smooth muscle cells overlying plaque to become senescent
  • Thinning of fibrous capsule
  • Any breach in integrity of plaque will expose contents to circulatory blood
  • Platelet aggregation & thrombosis that extends in to atheromatous plaque & arterial lumen

Clinical effects:

  • Depends on size, type of arteries
  • Slow luminal narrowing causing ischemia & atrophy
  • Sudden luminal occlusion causing infarction and necrosis
  • Propagation of plaque by formation of thrombi, emboli
  • Formation of aneurysmal dilatation & eventual rupture

Diagnosis:

  • Angiography
  • Blood test
  • ECG/EKG
  • Chest x-ray to check heart size
  • Echocardiography

Prevention:

Primary prevention

2 complementary strategies

1) Population strategy

  •  Risk factors in whole population through diet & life style
  •  Advice on smoking / average cholesterol / exercise / diet / obesity

    2) Targeted strategy
  •  Treat high risk
  •  Consider absolute risk of atheromatous CVS disease
  •  Anti hypertensive, lipid lowering therapy
  •  Appropriate treatment

Secondary prevention

  • In whom evidence of atheromatous vascular disease e.g. peripheral vascular disease / MI offered a variety of treatment.

Energetic correction of risk factors like smoking, HTN, hypercholesterolemia.