Cholesterol Embolization Syndrome

David Goldemund M.D.
Updated on 10/01/2024, published on 13/05/2023


  • cholesterol embolization occurs when small pieces of cholesterol plaque break off from the arterial walls and block small and medium-sized arteries, which can lead to tissue damage
    • large arteries, especially the aorta and its branches, are the usual source of emboli in elderly patients with advanced atherosclerosis
    • embolization is often associated with intravascular procedures, cardiac surgery, and vascular surgery
  • it differs from the more common artery-to-artery thromboembolism, in which thrombi formed on the surface of an atherosclerotic plaque embolize into the peripheral circulation
  • symptoms may include skin discoloration, pain, and organ dysfunction
Cholesterol embolization syndrome


  • atherosclerotic plaques in in mid-size and large arteries (aorta, CCA, ICA, pelvic arteries)   → atherosclerotic plaques classification
    • plaque formation results from a long-term process of lipid particle deposition in the vessel wall, accompanied by a cellular and inflammatory response
    • complex plaques are characterized by a thickness of ≥ 4 mm and an irregular, often exulcerated surface. Blood clots (thrombi) occur on the surface of these lesions to varying degrees and extents, frequently associated with atheroembolism and thromboembolism
  • plaque rupture can occur, leading to the release of atheroma masses and cholesterol crystals (spontaneous, traumatic, iatrogenic) and their embolization to peripheral segments
    • iatrogenic – during cardiac catheterization, cardiac surgery, angioplasty
    • with advancements in catheterization techniques, the incidence of cholesterol embolization is decreasing
    • the incidence of cholesterol embolization during renal artery catheterization procedures is reported to be as high as 30%. This condition typically presents as asymptomatic or may involve a transient increase in urea and creatinine levels
  • embolization to small and medium-sized vessels, resulting in their occlusion
  • systemic inflammatory response to cholesterol emboli
    • may result in local endothelial proliferation with intimal fibrosis, leading to narrowing or permanent occlusion of the affected artery
  • organ damage can occur caused by artery occlusion with hypoperfusion and inflammatory response

Clinical presentation

  • clinical presentation depends on the extent of the target organ damage
  • kidneys, gastrointestinal tract (GIT), brain, skin, and lower limb muscles are the most commonly affected
  • brain damage – focal or diffuse embolization, resulting in stroke or encephalopathy
  • retinal embolization – amaurosis fugax or permanent retinal damage
    • detection of Hollenhorst plaques confirms the diagnosis
  • nephropathy – in addition to embolization, contrast-induced nephropathy (CIN) may contribute to renal injury during interventional procedures
  • GIT – intestinal ischemia with abdominal pain, bleeding from ulcerations, and mucosal erosions is most common; acute pancreatitis or acalculous necrotizing cholecystitis are less frequent
  • skin manifestations  – typically affecting the legs, rarely the trunk and upper extremities
    • common skin symptoms include livedo reticularis (marbled skin, reddish patches), gangrene, cyanosis, ulcerations, nodules, and purpura
    • blue toe syndrome – may also be a manifestation of vasculitis, hypercoagulable and hyperviscosity syndrome, and endocarditis
Retinal cholesterol embolization (Hollenhorst crystals)
Skin cholesterol embolization

Diagnostic evaluation

  • the clinical manifestation of cholesterol embolization syndrome is nonspecific and consists of a combination of end-organ lesions and a systemic inflammatory response
    • cholesterol crystals trigger an inflammatory response (fever, fatigue, anorexia)
    • laboratory findings commonly include leukocytosis, anemia, and thrombocytopenia, as well as an increase in ESR and CRP levels
  • the syndrome should be considered in elderly patients with documented organ manifestations of advanced atherosclerosis, acute renal injury/hepatitis, hypereosinophilia, and skin manifestations such as livedo reticularis or “blue toe syndrome”. Particularly if they have undergone interventional or surgical procedures on large vessels before clinical presentation
  • imaging techniques – enables visualization, quantification, and characterization of atherosclerotic lesions
    • CT+CTA / MRI+MRA
      • assessment of extra- and intracranial arteries (incl. ascending aorta and aortic arch) to identify plaque burden, ulcerations, thrombus presence, etc.)   Exulcerated plaque (CTA, ultrasound)  Aortic atherosclerosis on CTA
      • assessment of parenchymal damage
    • neurosonology
      • detects atherosclerotic changes in extra- and intracranial cerebral arteries
      • monitoring of spontaneous and provoked embolizations during interventional procedures; method can not distinguish cholesterol microemboli from thrombi
    • TEE (can assess aortic arch atherosclerosis) Different types of aortic atherosclerotic lesions on TEE
  • direct confirmation of atheroma embolization
    • skin or renal biopsy with evidence of atheroma emboli
    • plaques/crystals in the retina
      • Hollenhorst plaque – yellowish, typically located at an arterial bifurcation  Hollenhorst plaque
      • DDx: calcium plaque from cardiac valves, which is whiter than Hollenhorst plaque and usually gets stuck at more proximal retinal arteriolar branch segment   Calcium embolus


Treatment of underlying atherosclerosis and prevention of further embolization

Symptomatic therapy and management of organ-specific complications

  • address neurological complications such as stroke or encephalopath with standard protocols for stroke management, including thrombolytics if indicated
    • the benefit of thrombolysis is questionable, but concomitant thrombolysis-sensitive atherothrombotic embolization cannot be excluded
  • wound care and management of skin ulcers and gangrene
  • manage intestinal ischemia, bleeding, or other GIT complications with supportive care, blood transfusions, and sometimes surgery when indicated
  • monitor renal function closely, and if necessary, consider dialysis for severe cases
  • pain management


  • primary prevention of atherosclerosis in high-risk patients, including controlling risk factors and ensuring proper perioperative care to minimize the risk of embolization during medical procedures

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Cholesterol Embolization Syndrome