Cholesterol embolism syndrome, shown below, should be suspected in a patient who develops worsening renal function, hypertension, distal ischemia, or acute multisystem dysfunction after an invasive arterial procedure. Atheroemboli may also occur spontaneously. The protean manifestations of this syndrome make the diagnosis challenging. As the population ages, the incidence of cholesterol embolism syndrome will increase.
See the image below.
Cholesterol crystal embolization from upstream coronary artery plaque after percutaneous transluminal coronary angioplasty.
Key components of cholesterol embolism syndrome include the following:
Proximal, large caliber arterial plaque
Plaque rupture with embolization of debris
Mechanical occlusion of small arteries
Intense foreign body inflammation
End organ damage from mechanical obstruction
Inflammatory vascular changes
Any organ system, with the exception of the lungs, may be directly affected. Cholesterol embolism syndrome has 2 mechanisms of action.
In the first, cholesterol crystals spontaneously break off from severely atherosclerotic plaques and shower into downstream organs, occluding arterioles 100-200 micrometers in diameter. The crystals induce an inflammatory body reaction and adventitial fibrosis, which eventually obliterate the vessel lumen. Local vasospastic mediators compound tissue ischemia and produce progressive, irreversible organ damage.
With the second mechanism, larger cholesterol plaques break off and occlude larger arteries, causing tissue infarction with acute organ dysfunction. This can occur after local trauma to the atherosclerotic plaque, such as that caused by angiography or aortic trauma, or it can occur after destabilization of the protective clot overlying the plaque, which can occur as a result of anticoagulation.
Cholesterol crystal embolization occurs from the arterial system, and crystals are trapped in the arterioles where they either immediately occlude the vessels or induce an intense inflammatory response that leads to tissue ischemia. Crystals do not travel to the lungs; however, inflammatory mediators released by ischemic tissue may result in acute lung injury.
Estimates of the incidence of cholesterol embolic disease are usually based on autopsy data. Tissue sections from patients with the following diseases or indicate the incidence of atheroembolic events: aortic aneurysms (31%), abdominal aortic aneurysm repair (up to 77%), severe aortic disease (13-16%), and mild aortic disease (1-2%). Of patients undergoing angiography, 25-30% may have atheroembolic events, while 2.5-3% of patients who receive percutaneous coronary transluminal angioplasty vein grafts and 1.4-3% of patients undergoing renal artery angioplasty or cardiac catheterization have been reported to have clinical signs of atheroemboli. Cholesterol embolism syndrome has been reported as occurring months after thrombolytic therapy for stroke, but the true incidence is unknown.[1, 2]
The mortality rate of acute multisystem organ failure resulting from cholesterol embolism syndrome is 58-90%. Jucgla found an overall incidence of 58% at 15 months, increasing to 65% if visceral organs were involved. Pre-existing chronic renal insufficiency had a relative risk of death of 4.54.
The mortality rate of severe cholesterol embolism is 90% at 3 months.
Mild cases with renal dysfunction with or without skin findings had a mortality of 16%.
Men have a higher risk than women.
Cholesterol embolism is a disease of persons ranging from middle-aged to elderly, with a minimum age of 50 years.
The diagnosis of cholesterol embolism must be considered in patients older than 50 years who have atherosclerotic disease presenting with multisystem dysfunction after undergoing an invasive vascular procedure or receiving an anticoagulant or thrombolytic agent within the past several months. All patients with the classic triad of livedo reticularis, acute renal failure, and eosinophilia should be evaluated for cholesterol embolism, including a funduscopic examination.
Clinicians should be aware that the syndrome may not manifest until chronic crystal embolization and inflammatory changes have occluded enough vessels to create detectable organ damage. Patients may have unexplained fever, weight loss, myalgias, or anorexia for weeks or months after a procedure before presenting with acute renal failure, hyperkalemia, GI bleeding, or stroke.
Any risk factor for atherosclerotic disease is a risk factor for cholesterol embolism.
Preoperative risk factors for cholesterol embolism syndrome after coronary artery bypass surgery include being older than 60 years, hypertension, cerebrovascular disease, aortoiliac disease, and mitral annular calcification. Although the other factors are well known, the association between mitral annular calcification and aortic atherosclerosis was identified only recently.
Identifying patients at risk and making efforts to minimize aortic wall trauma help reduce the chance of cholesterol embolism. The risk for a patient developing cholesterol embolism may be reduced by using a brachial or axillary approach in patients known to have severely ulcerated aortic plaque, using soft flexible catheters, and avoiding high-pressure jets of contrast material.
The actual cholesterol crystals are dissolved during fixation, leaving intra-arterial biconvex ghosts. Often, the crystals are missed because the depth of the tissue sample is inadequate. If these ghosts are absent, the diagnosis still may be inferred by fibrinoid necrosis, as depicted in the image below, and a foreign-body reaction in tissues commonly involved by atheromatous emboli in a patient with consistent clinical findings. Exuberant adventitial fibrosis contributes to vessel lumen occlusion.
See the image below.
Necrosis of the abdominal wall in a patient with cholesterol embolism syndrome who received anticoagulation.
Hemodynamic monitoring, including pulmonary artery catheterization, may be helpful for fluid and vasopressor adjustments.
If ARDS occurs, mechanical ventilation may be required for a prolonged period.
Dialysis should be started when indicated because patients can recover limited renal function.
Aggressive nutritional and metabolic support is essential because these patients often lose considerable lean body mass to ongoing catabolism.
Further invasive vascular procedures and anticoagulant or thrombolytic therapies should be avoided. If they are unavoidable, downstream protection devices to trap atheromatous debris after stenting or angioplasty are suggested.
Surgical therapy, such as aortic aneurysm resection, may be necessary to remove the source of atheroembolic material. Stent-grafting may be less invasive method to reduce risk of embolization.
Damaged tissue should be protected and allowed to demarcate for several months. Surprisingly, a majority of the damage may recover. Necrotic tissue should be debrided, and establishing vascular access for dialysis also may be necessary.
In severe cases, lumbar sympathetic block (rarely, surgical sympathectomy) has been used to avoid impending lower extremity tissue loss resulting from intense vasoconstriction.
Medical therapy is not particularly successful in patients with cholesterol embolism syndrome. Vasodilator therapy with calcium channel blockers may help relieve the local ischemia resulting from vasospasm, but angiotensin-converting enzyme (ACE) inhibitors should not be used because of their negative effects on renal afferent arterioles and the glomerular filtration rate. Patients presumed to have vasculitis have been treated with high-dose steroids and antiinflammatory agents, with anecdotal reports of recovery. However, steroids may predispose patients to infectious, metabolic, and nutritional complications and difficulties with wound healing. The use of anticoagulants is controversial because anticoagulants and thrombolytics have been shown to induce atheroemboli. Anecdotal reports of treatment with apheresis, iloprost, statin, colchicine, or combinations of these drugs with steroids report improvement in some cases.
If an invasive radiologic procedure is necessary, the risk of inducing cholesterol embolism must be considered. If the patient is at high risk, with known or suspected severe aortic atherosclerosis or aortic aneurysm, the Judkins (ie, brachial) or a radial artery approach may be used for introducing the catheter into the aorta. However, some investigators found the approach made no difference, leading them to suspect the ascending aorta as a major source of atheroemboli.
Gentle handling of the severely diseased aorta during cardiac or aortic surgery can reduce the risk of cholesterol embolism. Careful clamping techniques and careful selection of aortotomy sites may minimize disruption of the atherosclerotic plaque.
Patients with multisystem cholesterol embolism syndrome have a poor prognosis. As many as 90% die within 3 months.
Cholesterol crystal showers can become stabilized, leaving patients with varying degrees of organ dysfunction. Renal function can recover if no further insults occur, even to the degree that dialysis can be discontinued. However, patients remain at risk for recurrence of emboli.
Lisa Kirkland, MD, FACP, CNSP, MSHA, Assistant Professor, Department of Internal Medicine, Division of Hospital Medicine, Mayo Clinic; ANW Intensivists, Abbott Northwestern Hospital
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Travis J Phifer, MD, Chief, Division of Vascular Surgery, Professor, Department of Surgery and Radiology, Louisiana State University Health Sciences Center in Shreveport
Disclosure: Nothing to disclose.
Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy
Disclosure: Nothing to disclose.
Vincent Lopez Rowe, MD, Professor of Surgery, Program Director, Vascular Surgery Residency, Department of Surgery, Division of Vascular Surgery, Keck School of Medicine of the University of Southern California