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Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
Synonyms: cholesterol embolism syndrome (CES), cholesterol crystal embolisation (CCE), atheroembolism
See also separate articles Limb Embolism and Ischaemia and 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.
The following six factors are required for the development of cholesterol embolisation syndrome:
- Plaque in a proximal, large-calibre artery (such as the internal carotid artery, the iliac arteries, or the aorta).
- Plaque rupture - which may be spontaneous, traumatic, or iatrogenic.
- Embolisation of plaque debris (containing cholesterol crystals, platelets, fibrin, and calcified detritus).
- Lodging of the emboli in small-to-medium arteries, leading to mechanical occlusion.
- Foreign-body inflammatory response to cholesterol emboli.
- End-organ damage due to mechanical plugging and inflammation.
The lungs are spared from direct damage from cholesterol emboli, but may suffer damage from inflammation.
There are no useful population-based figures. It is probably underdiagnosed. It is an uncommon consequence of a very common disease (atherosclerosis). There is an appreciable background prevalence in the general population, particularly in older, male patients.
A series in patients undergoing cardiac catheterisation found it affected 1.4% of those having the procedure.
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. In a postmortem series, using tissue sections from patients who had abdominal aortic aneurysm repair, up to 77% were found to have cholesterol embolisation.
- Male gender.
- Age >50 years.
- Known atherosclerosis.
- History of hypertension.
- Elevation of C-reactive protein (CRP) before arterial instrumentation.
- Co-existence of mitral valve annular calcification.
It can uncommonly affect those who develop accelerated atheromatous disease due to dyslipidaemia or other causes 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. 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.
Symptoms and signs
Cholesterol embolisation is characterised by a nonspecific acute inflammatory response leading to constitutional symptoms including:
- Nonspecific malaise.
- Acute respiratory distress syndrome (ARDS) due to circulating inflammatory mediators.
- Hypercatabolic state.
Cholesterol emboli originating in the descending thoracic and abdominal aorta may lead to renal failure, gut ischaemia, and emboli to the skeletal muscles and the skin.
Cholesterol emboli originating in the ascending aorta may in addition cause neurological damage that is typically diffuse and due to small infarcts.
Dermatological manifestations (most commonly livedo reticularis and blue toe syndrome) are usually confined to the lower extremities but may extend to the abdomen and the chest.
- Infective endocarditis.
- Causes of gastrointestinal 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 aortic dissection or thoracic aortic dissection.
- De novo acute pancreatitis.
- Multisystem organ failure due to other causes, eg sepsis, cardiogenic shock.
- De novo myocardial infarction (MI).
- Other causes of renal impairment, eg interstitial nephritis, glomerulonephritis, renal vascular disease.
- Severe atheroma of aorto-iliac vessels.
- Cardiogenic shock.
- Secondary hypertension.
- Other causes of malignant hypertension.
- Vasculitides, eg polyarteritis nodosa.
- Deep vein thrombosis.
- Causes of acute neurological dysfunction or delirium.
- Diabetic vascular disease and leg ulcers.
- Necrotising fasciitis.
- FBC reveals leukocytosis in some cases but is nonspecific.
- Eosinophilia (found in early days in 80% patients).
- U&Es 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.
- 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 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 monitor vascular parameters.
- Mechanical ventilation may be needed to treat ARDS.
- Dialysis/plasmapheresis have been used to treat the condition and counteract renal impairment.
- Oral corticosteroids, either alone or in combination with dialysis, have been used, with some anecdotal evidence of benefit.
- 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.
- Acute respiratory distress syndrome (ARDS).
- Catabolism and cachexia.
- MI or impairment.
- Neurological dysfunction.
- Adrenal failure.
- Multi-organ failure and death.
The in-hospital mortality rate was 16% for cholesterol embolisation after cardiac catheterisation in one study. Those with severe multi-organ involvement have a poor outcome with mortality up to 90% at three months. Symptoms and organ dysfunction may subside over time, with dependence on dialysis diminishing or terminating in some cases.
Because cholesterol embolisation syndrome is a manifestation of atherosclerosis, modification of traditional risk factors such as smoking, hypertension and serum cholesterol should be advised strongly. There is some evidence that statin therapy decreases the risk of cholesterol embolisation syndrome.
- 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.
- 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.
Further reading and references
Guidelines for the Management of Dyslipidaemias; European Society of Cardiology (2011)
CVD risk assessment and management; NICE CKS, December 2008 (UK access only)
Kronzon I, Saric M; Cholesterol embolization syndrome. Circulation. 2010 Aug 10122(6):631-41
Fukumoto Y, Tsutsui H, Tsuchihashi M, et al; The incidence and risk factors of cholesterol embolization syndrome, a complication of cardiac catheterization: a prospective study J Am Coll Cardiol. 2003 Jul 16
Kirkland L, Cholesterol Embolism, Medscape, Aug 2011; good general overview
Hasegawa M, Sugiyama S; Apheresis in the treatment of cholesterol embolic disease Ther Apher Dial. 2003 Aug
Koga J, Ohno M, Okamoto K, et al; Cholesterol embolization treated with corticosteroids--two case reports. Angiology. 2005 Jul-Aug