Cholesterol Emboli

Synonyms: cholesterol embolism syndrome (CES), cholesterol crystal embolisation (CCE), atheroembolism

See also separate articles: Limb Embolism and Ischaemia, Bowel Ischaemia.

Cholesterol crystals and associated components of atheromatous arterial plaques may embolise spontaneously, as a result of vascular instrumentation, or following other destabilisation of the organised thrombotic surface of a plaque. It is predominantly a disease of the older, particularly male population, but can uncommonly affect those who develop accelerated atheromatous disease due to dyslipidaemia or other cause(s) of enhanced vascular risk.

The most common embolic source is the aorta, so it tends to cause disruption of blood supply to the visceral organs and lower extremities. The syndrome should be considered as a cause of deteriorating renal function, worsening hypertension, distal ischaemia or sudden-onset multisystem dysfunction after an invasive arterial procedure. The syndrome can manifest in a myriad of presentations, making diagnosis a challenge.¹ It may directly affect all tissues of the body with the exception of the lungs. However, systemic inflammatory mediators released by cholesterol emboli may affect pulmonary tissues.

There are no useful population-based figures and there is probably much underdiagnosis. It is an uncommon consequence of a very common disease (atherosclerosis), so there is probably an appreciable background prevalence in the general population, particularly in older, male patients. A recent series in patients undergoing cardiac catheterisation found it affected 1.4% of those having the procedure. The in-hospital mortality rate for those affected was 16%.² The syndrome is thought to affect up to 25% of those undergoing angiography, although this may just represent a higher risk population than any inherent risks associated with the procedure.¹ Post mortem series, utilising tissue sections from patients with the following diseases, indicate the incidence of atheroembolic events in these relatively high-risk groups:¹

• Aortic aneurysms – 31%
• Abdominal aortic aneurysm repair – up to 77%
• Severe aortic disease – 13-16%
• Mild aortic disease – 1-2%

Risk factors^1,2

• Male gender
• Age >50 yrs
• Known atherosclerosis
• History of hypertension
• Smoking
• Elevation of C-reactive protein before arterial instrumentation
• Co-existence of mitral valve annular calcification

The syndrome normally occurs in patients aged >50 who are at risk of/known to have atherosclerotic disease. They tend to present with a multisystem disorder after having undergone arterial instrumentation, initiation of anticoagulation or thrombolysis in the preceding few months. A more acute presentation may occur where larger aggregates of cholesterol embolise (see Mechanisms of cholesterol embolisation above).

• Infective endocarditis
• Causes of GI bleeding
• Acute gastritis
• Inflammatory bowel disease
• Abdominal angina due to severe mesenteric atheroma
• Mesenteric infarction
• Adrenal (Addisonian) crisis
• Abdominal trauma
• Biliary or renal colic or other causes of acute abdomen
• Abdominal- or thoracic-aortic dissection
• De-novo acute pancreatitis
• Multisystem organ failure due to other causes, e.g. sepsis, cardiogenic shock
• De-novo MI
• Other causes of renal impairment, e.g. interstitial nephritis, glomerulonephritis, renal vascular disease
• Severe atheroma of aorto-iliac vessels
• Cardiogenic shock
• Secondary hypertension
• Other causes of malignant hypertension
• Vasculitides, e.g. polyarteritis nodosa
• Cellulitis
• Deep vein thrombosis
• Causes of acute neurological dysfunction or delirium
• Diabetic vascular disease and leg ulcers
• Necrotising fasciitis (including Fournier's gangrene affecting the perineum/genitalia)

• FBC reveals leucocytosis in some cases but is non-specific.
• Eosinophilia strongly suggests the diagnosis.^1,2
• U & E nearly always show varying degrees of elevated urea and creatinine.
• Creatine kinase, cardiac enzymes, LFTs and amylase may be elevated.
• Urine microscopy shows hyaline casts and eosinophils (strongly suggestive of the diagnosis).
• Urinalysis may show microscopic haematuria and proteinuria.
• Elevated CRP before arterial instrumentation is a useful predictive factor with an odds ratio of 4.6.²
• Indicators of an excess of inflammatory mediators may be suggested by elevation of ESR, CRP, rheumatoid factor and antinuclear antibodies. Low complement levels may be found.
• Angiography may be considered to look for other causes of vascular compromise and is also a cause of the condition.
• Transoesophageal echocardiography, helical CT angiography and MRI angiography may detect unstable atheromatous disease in the aorta and suggest the diagnosis in conjunction with typical features.
• Tissue biopsy (particularly of the kidney) may be utilised to demonstrate cholesterol crystals within affected tissues.

There are no universally agreed therapies. Treatment is mainly supportive and aimed at ameliorating and seeing the patient through the effects of multi-organ dysfunction or acute respiratory distress syndrome (ARDS). High-dependency interventions such as Swan-Ganz catheterisation may be employed to categorise and monitor vascular parameters. Mechanical ventilation may be needed to treat ARDS. Dialysis/plasmapheresis have been used to treat the condition and counteract renal impairment.⁶ Oral corticosteroids, either alone or in combination with dialysis, have been used, with some anecdotal evidence of benefit.⁷ Optimal nutritional support can help overcome the catabolic, cachectic complications of the illness. Further invasive vascular intervention, anticoagulation and thrombolysis are best avoided as they may worsen the situation with no evidence of benefit. In severe cases, surgical intervention may take the form of aortic atherectomy, aneurysm repair and stent-grafting. Debridement of necrotic tissues may be necessary following acute infarction. Lumbar sympathetic blockade may be used as rescue therapy for critically ischaemic limbs.

• Worsening renal impairment
• Accelerated or malignant hypertension
• Ischaemia and dysfunction of organs and viscera/tissues of peripheral limbs
• Dermatological lesions
• ARDS
• Catabolism and cachexia
• MI or impairment
• Neurological dysfunction
• Adrenal failure
• Multi-organ failure and death

Following a study of patients with the syndrome, after cardiac catheterisation, the in-hospital mortality rate was 16%.² Those with severe multi-organ involvement have a poor outcome with mortality up to 90% at 3 months.¹ Symptoms and organ dysfunction may subside over time, with dependence on dialysis diminishing or terminating in some cases.

• Careful balancing of risks and benefits in patients about to undergo arterial instrumentation who are known to have or are at high risk of atheromatous vascular disease.
• Checking of pre-procedure CRP may be useful as a predictive indicator, and may influence opinion of the risk/benefit balance.
• The use of brachial or radial artery approaches was thought to reduce the risk of the syndrome, but analyses have failed to support this assumption, leading to the conclusion that the aorta is the major embolic source.²
• Surgical techniques, involving careful siting of aortic clamps and gentle manipulation of the aorta during cardiac or aortic surgery, may reduce the incidence of the disease in this high-risk cohort.