Write a Review
x
Feedback Cardiology

Atherosclerosis – Risk Factors, Pathogenesis, CF, Prophylaxis

  • Can affect any artery in the body – middle/large vessels only

Risk factors

  • Physical inactivity
  • Obesity
  • Alcohol
  • Poor diet
  • Social factors
  • Age and sex
  • Family history – e.g. HTN, hyperlipidemia, DM
  • Smoking
  • HTN
  • Hypercholesterolemia
  • DM

Pathogenesis

  • Progressive systemic inflammatory disorder of arterial wall
  • Characterised by focal lipid-rich deposits of atheroma in arterial wall
    • Remain clinically silent until large enough to impair tissue perfusion
    • Or until ulceration/disruption of lesions results in thrombotic occlusion or distal embolisation of the vessel
  • CF depends on the site of the lesion

Early atherosclerosis (no symptoms)

  • Fatty streaks occur at sites of stress – e.g. bifurcations.
    • Associated with endothelial dysfunction
  • Develop when inflam cells (monocytes) bind to receptors expressed by endothelial cells
    • They migrate into intima, take up oxidised LDL and become lipid-laden macrophages (AKA foam cells)
  • Foam cells die and release their contents – appear as extracellular lipid pools in intimal space
  • Damaged endothelium, monocytes and macrophages produce cytokines and GFs – causes smooth muscle cells to migrate from tunica media to intima
    • Attempt to stabilise the plaque by covering the lipid core by smooth muscles cells and matrix
    • If successful, the stable plaque will remain asymptomatic until large enough to occlude lumen

Advanced atherosclerosis (symptoms present)

  • In an established plaque, macrophages mediate inflam and SMCs promote repair
  • If inflam predominates, the plaque becomes unstable – can be complicated by ulceration/thrombosis
  • Activated macrophages release – IL-1, TNF-α, IFN-γ, PDGFs
    • Causes SMCs lying over the plaque to become senescent
    • Results in thinning of the protective fibrous cap – makes lesion vulnerable to mechanical stress
      • Can result in erosion, fissuring or rupture of the plaque
  • Breach in integrity of plaque exposes it to blood
    • Can trigger platelet aggregation and thrombosis
    • Leads to obstruction or distal embolisation – resulting in infarction/ischemia of affected organ

Clinical features

  • Clinically silent for decades
  • Symptoms usually start after 4th decade
  • CFs are due to complications and depend on site of narrowing
    • Coronary arties – angina, SOB, sweating, light-headedness, arrhythmias
    • Carotid a. – weakness, confusion, difficult speech, stroke
    • Peripheral a. – limb numbness, claudication
    • renal a. – stenosis, hypoperfusion

Prophylaxis

Primary prevention – in a healthy but at-risk population

  • Population strategy – modify RFs of whole pop through diet and lifestyle advice
  • Targeted strategy – identify and treat high risk people

Secondary prevention – patients who already have evidence of atheromatous vascular disease

  • Correction of modifiable risk factors
  • Statin therapy
  • Target BP of 140/85 mmHg
  • Aspirin + ACEi – for patients with evidence of vascular disease

Target lipids (mmol/l)

  • Total <4
  • LDL <2.5
  • HDL >1

Feedback