Cholesterol embolism syndrome

An aging population requiring invasive vascular imaging and procedures is at increased risk for this syndrome. Learn how to recognize it.


What do the following patients have in common: a 62-year-old man unable to get off the bypass pump after coronary bypass surgery, an elderly man with severe back pain and fever five days after cardiac catheterization, a 60-year-old woman with severe lower body pain on completion of aortogram, and a 74-year-old man with paralysis and bowel infarction immediately following aortogram and aortofemoral bypass grafting?

All are suffering from cholesterol embolism syndrome, or cholesterol crystal embolism syndrome, where debris from atheromatous plaque occludes small arterioles, causing both immediate ischemia and delayed infarction due to intense inflammatory and vasoconstriction resulting in organ dysfunction. The crystals dissolve during routine tissue fixing, leaving biconvex ghosts in the occlusive debris of arterioles. The embolic events are called atheroembolism or atheromatous embolization.

The true incidence of cholesterol embolism syndrome (CES) is unknown, as it is probably underecognized and underdiagnosed due to its protean manifestations. Tissue sections indicate that cholesterol embolisms may be present in 31% of patients with aortic aneurysms, up to 77% of those undergoing abdominal aortic aneurysm repairs, 13%-16% of patients with severe aortic disease, and 1%-2% of patients with mild aortic disease. Twenty-five to 30% of patients having angiography may have atheroembolic events; 2.5%-3% of patients who receive percutaneous coronary transluminal angioplasty vein grafts and 1%-3% of patients undergoing renal artery angioplasty or cardiac catheterization have been reported to have atheroembolism.

Mortality rates vary depending on severity: up to 90% in three months in those with multisystem disease; 16% in those with mild renal failure.

Fibrinoid necrosis and foreign body reaction suggest CES. The diagnosis may be missed if tissue sample depth is inadequate. However, diagnosis is important if efforts to avoid further embolization are to be made.

The differential diagnosis is broad, as CES imitates many other acute or subacute illnesses. These include: mesenteric infarction, myocardial infarction, septic shock, hemorrhagic shock, aortic/arterial occlusion, acute tubular necrosis/interstitial nephritis, endocarditis, hypertensive crisis, pancreatitis, gastrointestinal bleeding, cerebrovascular accident, vasculitis and rhabdomyolysis.

Laboratory findings are nonspecific. Eosininophilia or eosinophiluria may be important clues to CES, occurring in 80%-90% of these patients, but often go undetected.

The risk factors are the same as those for atherosclerotic cardiovascular disease. Typically, only patients with severe aortic disease develop CES after a precipitating factor is introduced. But the syndrome may not manifest for weeks or months, after chronic crystal embolization and inflammatory reactions have occluded enough vessels for an organ to begin to demonstrate detectable dysfunction. Often patients will have had fever, malaise, myalgias, anorexia, or weight loss for weeks before presenting with hyperkalemia, acute renal failure, gastrointestinal bleeding, or stroke. More dramatic presentations result from larger atheroembolic plaque fragments causing acute arterial occlusion, which usually occurs after an invasive vascular procedure.

Renal function is disrupted to some degree in CES in over 80% of patients. Peripheral pulses may be spared in an extremity that appears severely ischemic. The lungs are spared direct embolization of atheromatous debris, but may be affected by the inflammatory cytokines from remote organ injury, resulting in acute lung injury or ARDS.

Treatment is both supportive and preventive. Damaged or failing organs, sepsis, or ARDS are treated with usual methods. Aggressive nutrition support may improve survival, as catabolic lean muscle mass losses are large. Steroids to ameliorate the intense inflammatory reaction have offered mixed success, as have both the initiation and the withdrawal of anticoagulation or antiplatelet agents. Treatment with apheresis, iloprost, statins, colchicine, or combinations of these drugs with steroids have led to improvement in anecdotal reports. Calcium-channel blockers such as nifedipine may reduce vasospasm. Surgical removal of the plaque, by vascular bypass or stent grafting, may reduce the incidence of embolization. Salvage or palliative surgery such as debridement or sympathectomy may help with vasospasm.

The best approach is prevention by recognizing patients at risk. Transesophageal echocardiography, CT, or MRI may be relatively noninvasive methods of imaging the aorta for plaque thickness, mobility, and location. At-risk patients could undergo modified angiographic procedures such as brachial artery approach, as well as minimal aortic manipulation and avoidance of high pressure jets of contrast.

An aging population requiring invasive vascular imaging and procedures is at increased risk of CES. A high level of suspicion is required to identify the syndrome, and diagnosis is often clinical in a patient with risk factors exposed to a precipitating agent within the previous few months. Treatment is supportive and expensive, and outcomes are often poor. It is up to the hospitalist to recognize at-risk patients before they receive an invasive procedure, and to recognize the syndrome before potentially harmful treatments are initiated.