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Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)

Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)
Literature review current through: Jan 2024.
This topic last updated: Oct 18, 2023.

INTRODUCTION — Atherosclerotic plaques are a manifestation of systemic atherosclerosis. They are associated with general risk factors for atherosclerotic disease, including age, hypertension, and hypercholesterolemia, and are more common in patients with coronary artery disease [1,2].

Atherosclerotic plaques are an important source of emboli, leading to cerebral (eg, transient ischemic attack, stroke), extremity, or visceral embolization (picture 1) [3-6]. Embolic events can occur spontaneously or can be induced by interventions, including cardiac catheterization, arteriography, peripheral interventions, intraaortic balloon pumping, and cardiac or vascular surgery [7,8].

The general manifestations and treatment of cholesterol crystal embolism, diagnosis, and medical and surgical management will be reviewed. Thromboembolism from unstable aortic plaques is discussed elsewhere. (See "Thromboembolism from aortic plaque".)

Specific considerations related to end-organ ischemia (kidney, gut, extremity) that may result from cholesterol crystal embolus are discussed in separate topic reviews.

ATHEROEMBOLISM VERSUS THROMBOEMBOLISM — Two types of emboli originate from atherosclerotic plaques: thromboemboli and atheroemboli (cholesterol crystal emboli). Although the underlying risk factors may be similar, the two can often be differentiated based upon associated conditions and clinical manifestations. This is an important distinction, since the prognosis and treatment differ. Thromboembolism from complex aortic plaques is common, particularly from thoracic aortic plaques. In comparison, cholesterol crystal embolism is fairly rare but is probably underrecognized given its diverse presentations. (See 'Epidemiology and risk factors' below and "Thromboembolism from aortic plaque".)

Although there is some overlap, these two disorders can be distinguished from each other. Thromboembolism occurs when thrombus, which is usually superimposed on an atherosclerotic plaque, dislodges due to plaque rupture or other forces. The thromboemboli tend to be single and lodge in medium or large arteries. Thromboemboli from aortic atherosclerotic plaque most often result in transient ischemic attack or stroke [3-6]. Acute ischemia of the extremities, intestines, or solid organs (eg, kidney, spleen) can also occur [9].

The term cholesterol crystal embolism is used synonymously with cholesterol embolism or atheroembolism [10]. Cholesterol crystal embolism occurs when atherosclerotic plaque is disrupted and cholesterol crystals within the plaque or portions of the plaque embolize distally. The debris showers into the circulation, partially or totally occluding arterioles that are <200 micrometers in diameter, leading to a myriad of occlusions that typically affect multiple organs. These characteristic sizes of atheroemboli were illustrated in an experimental study using human aortorenal endarterectomy specimens. Following ex vivo "angioplasty" of these specimens, thousands of fragments 20 to 40 micrometers in size, the approximate size of the human afferent arteriole, and hundreds >100 micrometers in size, were collected [11].

EPIDEMIOLOGY AND RISK FACTORS — Cholesterol embolization is most likely to occur in a male patient >50 years of age, with risk factors for atherosclerosis following cardiac catheterization or a vascular procedure. Cholesterol crystal embolism is strongly associated with older age, with the average age being 66 years in a review of 221 published cases [12]. Lighter-skinned individuals may be more often affected, but it is more likely that subtle skin manifestations are not recognized in patients with darker skin tones. (See 'Skin' below.)

The incidence and prevalence of cholesterol crystal embolism are unknown. The published estimates are limited by suboptimal or unclear diagnostic criteria (such as solely relying on elevation of serum creatinine concentration after a procedure) and infrequent biopsy data. The full manifestations of the syndrome are probably rare. (See 'Clinical manifestations' below.)

Cholesterol crystal embolization may arise spontaneously or as the result of instrumentation of the vasculature (eg, cardiac catheterization, arteriography, vascular surgery). The following observations are from some of the studies that have evaluated the incidence or prevalence of cholesterol crystal embolism:

In a review of 519 patients with extensive thoracic aortic plaque on transesophageal echocardiography, cholesterol crystal embolism occurred in 1 percent of patients during a follow-up of more than three years [13].

In a series of 1011 patients who underwent infrarenal aortic and infrainguinal vascular surgery or angiographic manipulation, clinical and pathologic evidence of cholesterol crystal embolism was found in 2.9 percent [14].

Lower rates are seen after cardiac surgery (0.2 percent) [15]. In a prospective observational study of 1786 patients undergoing cardiac catheterization, definite cholesterol crystal embolism was observed in 0.8 percent [16].

In a retrospective review of 493 patients who underwent aortoiliac stent placements, 72 bilateral, the incidence of atheroembolism was 1.6 percent [17].

Many cases of cholesterol crystal embolism are not recognized clinically [18]. This issue was addressed in a prospective study of 60 patients with an acute myocardial infarction, one half of whom were treated with thrombolytic therapy [19]. All patients underwent coronary artery bypass graft surgery (CABG) within one month, and two muscle biopsy specimens and one skin biopsy specimen were obtained at the time of surgery. Seven patients (12 percent) had pathologic evidence of cholesterol crystal emboli in the muscle biopsy specimens, only one of whom had clinically evident disease.

This finding of asymptomatic disease is consistent with the prevalence of cholesterol crystal embolism in autopsy studies in unselected patients that range from 0.7 to 4 percent [15,20]. Even higher rates of cholesterol embolization (up to 75 percent) are reported in retrospective autopsy studies in patients selected for atherosclerotic risk factors or following surgery or instrumentation, but these studies may overestimate the incidence of cholesterol crystal embolism due to selection bias [21].

In addition to asymptomatic disease, it is probable that clinical manifestations of cholesterol crystal embolism are ascribed to other causes. This may be most likely with acute renal failure, where acute kidney injury is much more common than cholesterol crystal embolism, which will not be diagnosed unless tissue is available for pathology if there are no other manifestations of this syndrome [22]. (See 'Renal' below.)

Risk factors for atherosclerosis — Risk factors for developing cholesterol crystal embolism are largely those associated with developing general atherosclerotic disease such as smoking, hypercholesterolemia, hypertension, obesity, and diabetes. The data supporting these associations are discussed in detail separately. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach".)

The "classic" risk factors of hypertension, age, and smoking have been correlated with severe atherosclerotic plaque in the thoracic aorta. This relationship was demonstrated with transesophageal echocardiography (TEE) in a population-based study [23]. Among those with aortic plaque, the odds of having complex plaque increased as systolic blood pressure increased (odds ratio [OR] 1.43 for each 10-mmHg increase, 95% CI 1.10-1.87). Complex aortic plaque also correlated with hypertension treatment, controlling for age and history of smoking.

Risk factors for embolization — The risk of cholesterol crystal embolization is directly related to the severity of atherosclerosis. Any factor that destabilizes atherosclerotic plaque can result in cholesterol crystal embolism. Embolization may be spontaneous or iatrogenic precipitated by vascular manipulation during arteriography or surgery. It was previously estimated that 50 to 60 percent of cases of cholesterol crystal embolization were spontaneous [14,24]. However, the increasing frequency of endovascular manipulations (eg, coronary, aortoiliac, renal) has increased the incidence of iatrogenic embolization [24,25]. In one retrospective review, spontaneous embolism occurred in only 25 percent of patients [26].

Abdominal aortic aneurysms are a known source of cholesterol emboli. In a prospective study of 660 patients with abdominal aortic aneurysm who were followed for 1 to 60 months (mean 15 months), cholesterol crystal embolization was diagnosed in 2.9 percent of the patients [27]. (See "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Limb ischemia'.)

Cholesterol emboli may also originate from nonaortic sources such as the ICA (Hollenhorst plaque) and iliac artery or SFA (blue toe syndrome).

Plaque characteristics and location — The risk of cholesterol crystal embolism in patients with aortic atherosclerosis is markedly increased if transesophageal echocardiography reveals protruding plaques, particularly if ≥4 mm in thickness; ulceration; or superimposed mobile thrombi [5,9,28-33].

A correlation between complex plaque seen on two-dimensional transesophageal echocardiography (2D-TEE) and embolization phenomena was first noted in 1990 [31]. Subsequent 2D-TEE studies found that complex plaques may give rise to either cholesterol crystal emboli or thromboemboli (image 1 and movie 1). In a few case reports, cholesterol crystal embolism to the skin and kidneys was proven by biopsy in patients with complex plaques in the descending thoracic aorta on 2D-TEE [32,33]. In another report, transesophageal echocardiography demonstrated mobile particulate matter in transit from a complex plaque in a patient who subsequently died after multisystem involvement from cholesterol crystal embolism (image 2) [34].

Plaque in the aortic arch is implicated as a risk factor for cerebral embolization. However, data are conflicting. In longitudinal population-based studies in nonselected individuals, complex aortic atherosclerosis does not appear to be associated with an increased risk of primary stroke [35].

However, most reports evaluating secondary stroke risk have found that complex aortic atherosclerosis is a risk factor for recurrent stroke. This may be due to selection bias as the studies linking aortic atheroma and secondary stroke were usually performed in patients referred for TEE to evaluate a cardiac source of emboli rather than in a random population sample.

Mechanistically, aortic plaque may be both a source of cerebral emboli and a marker of generalized atherosclerosis. Studies of aortic arch plaque have found a 12 to 14 percent risk of cerebral embolization, particularly when the plaque is ulcerated or mobile. On the other hand, aortic plaque may be a marker of aging, and age is an independent predictor of cerebrovascular events [36].

Atherosclerotic plaque in the thoracic aorta is typically associated with distal embolization (abdominal organs, lower extremities). However, retrograde flow from complex descending thoracic aortic plaques may also be a source of cranial or upper extremity embolization. In a study of 94 patients using transesophageal echocardiography, retrograde diastolic flow reached the left subclavian artery in 60 percent, the left common carotid artery in 26 percent, and the brachiocephalic trunk in 14 percent [37].

The abdominal aorta and iliac arteries are commonly identified as a source for lower extremity cholesterol crystal embolization. In one surgical series of 62 patients, the aorta or iliac arteries were identified angiographically as the embolic source in 80 percent of patients [24].

Atherosclerotic plaque in the femoral, popliteal, or subclavian arteries may also be a source of extremity embolization.

Instrumentation — Iatrogenic embolism is typically related to cardiovascular manipulation during arteriography, stenting, or surgery [38,39]. Surgical procedures may disrupt atherosclerotic plaque as vessels are dissected, cross-clamped, or as an arteriotomy is made. Trauma is an unusual cause [24].

Arteriography is a more common iatrogenic cause than surgery, accounting for as many as 85 percent of iatrogenic cases [14]. The source of the emboli in a review of 29 patients was the abdominal aorta (16 patients), iliac arteries (7 patients), and femoropopliteal arteries (6 patients) [14]. Patients with atherosclerotic renal artery stenosis often have diffuse atherosclerosis and are at a relatively high risk for cholesterol crystal embolism after renal arteriography, with an overall incidence of approximately 2 percent [40].

The effect of arterial manipulation has been illustrated in several studies [16,41-43]. In a prospective series of 1000 patients who underwent percutaneous coronary interventions, guiding catheter placement was associated with visible scraping of debris from the walls of the aorta in more than one half of the patients [43]. Clinical cholesterol crystal embolism was not seen, however, as ischemic events were not associated with visualization of debris in the catheter. Similarly, in reviews of renal artery angioplasty and stenting, grossly visible material (cholesterol crystals, atheromatous material, and thrombus) was retrieved from the embolic protection filter in 45 to 60 percent of cases [44,45]. (See "Clinical presentation, evaluation, and treatment of renal atheroemboli".)

Anticoagulation/thrombolytic therapy — Cholesterol crystal embolism has been reported after the use of thrombolytic agents or anticoagulants (eg, heparin, warfarin, direct factor Xa inhibitors, direct oral anticoagulants) [46,47]. However, a causal relationship between the use of these medications and cholesterol crystal embolism has not been established, and based on available evidence, the overall risk appears to be low.

In the 40 years since the introduction of thrombolytic therapy, a total of 30 cases as a complication of thrombolysis have been reported; 28 patients received a thrombolytic agent for acute myocardial infarction and 2 patients for deep venous thrombosis [48,49]. These case reports gave the impression that there might be a causal relationship between thrombolysis and cholesterol crystal embolism. However, there is no evidence to suggest that lysis of thrombus overlying atherosclerotic plaque leads to plaque destabilization and atheroembolism. There are no large-scale clinical trials that specifically addressed the issue of cholesterol crystal embolism in the setting of thrombolytic therapy. One small study of 60 patients found no differences in the rate of cholesterol crystal embolism between the patients who received thrombolysis and those who did not. The presence or absence of cholesterol crystal embolism in this study was based upon skin and muscle biopsies [19]. However, given the low incidence of embolism and the small number of patients in the study, a significant difference may not have been detectable.

Cholesterol crystal embolism has also been blamed on therapy with anticoagulant drugs, particularly heparin or warfarin, with plaque hemorrhage as the putative precipitating factor [50,51]. However, it is unclear if cholesterol crystal embolism was caused by anticoagulants, or it simply occurred in patients who happened to be on anticoagulation therapy. Trials that have randomly assigned patients with documented aortic plaque identified by transesophageal echocardiography to anticoagulant therapy have not identified an increased risk for atheroembolism [13,16,52,53]. Thus, the putative risk associated with anticoagulation therapy appears to be low.

CLINICAL MANIFESTATIONS — The variability in clinical manifestation is related to the location of the embolic source, extent of embolization, whether there is partial or complete occlusion of the affected vessels, and the presence or absence of preexisting disease in the affected vascular bed (eg, peripheral artery disease).

Atheroemboli from the aortic arch typically embolize to the brain, eye, or upper extremity while descending thoracic or abdominal aortic plaque causes gastrointestinal or lower extremity symptoms and signs. Retrograde embolization from the thoracic aorta can also occur. (See 'Plaque characteristics and location' above.)

The presenting symptoms of cholesterol crystal embolism may be subtle and nonspecific. As an example, 21 percent of patients in a review of 221 cases presented with systemic symptoms of fever, myalgias, headache, and weight loss [12]. Often there is a delay between the embolic event and subsequent symptoms. In a review of histologically proven cholesterol embolization, skin signs developed more than 30 days after a precipitating event in 50 percent of patients [54].

More dramatic clinical presentations are generally due to a diffuse showering of larger, atheromatous debris originating from usually aortic plaque. The emboli may lodge into the renal, mesenteric, pelvic, carotid, coronary, or extremity vascular beds [55]. Classic manifestations include "blue toe syndrome," livedo reticularis, acute or subacute renal failure, and intestinal ischemia. Other manifestations include gastrointestinal bleeding and pancreatitis.

Skin — Skin findings are the most common clinical sign of cholesterol crystal embolism, occurring in 34 percent of patients in one systematic review [12]. In this study, the most frequent findings included livedo reticularis (16 percent), gangrene (12 percent), cyanosis (10 percent), skin ulcer (6 percent), purpura or petechiae (5 percent), and firm, painful erythematous nodules (3 percent) [12]. Splinter hemorrhages have also been described as a possible cutaneous manifestation of cholesterol crystal embolization [56]. Gangrene and ulcerations typically affect the toes but may extend to more proximal portions of the lower extremities. (See "Management of chronic limb-threatening ischemia".)

These classic skin findings in cholesterol crystal embolism commonly occur in areas where the arterial pulse is palpable since the embolization is to smaller arteries [12,54,57]. However, the arterial pulse may not be palpable in patients who also have underlying peripheral artery disease. (See "Noninvasive diagnosis of upper and lower extremity arterial disease" and 'Treatment' below.)

Cholesterol crystal embolization to the skin of the genitalia is rare but, when it occurs, can lead to severe scrotal or penile skin loss [58-60]. This devastating complication has been reported following open and, more recently, endovascular repair of abdominal aortic aneurysm [60].

Livedo reticularis — Livedo reticularis is a reticulated, mottled, or erythematous skin discoloration that blanches on pressure. It may be red or blue, and even ulcerated, depending on the degree of blood flow compromise and oxygen desaturation through the affected area. Livedo reticularis is not specific for atheroembolism and has an extensive differential diagnosis. In patients with cholesterol crystal embolization, livedo reticularis is usually bilateral and is typically found on the feet and lower legs (picture 2 and picture 3) but may extend toward the thighs, buttocks, and back. Upper extremities are less commonly involved. Atheroembolism involving the breast has also been reported [61].

In patients undergoing abdominal aortic aneurysm repair, livedo reticularis may appear on the back and the buttocks due to cholesterol embolization into the branches of the internal iliac arteries.

Blue toe syndrome — Although cholesterol crystal embolization is often referred to as the "blue toe syndrome" (picture 4), blue skin discoloration is less common than other skin findings. In the overall population of patients with cholesterol embolization syndrome, skin manifestations are seen in only approximately one third of such patients, and of these, blue toes are present in 10 to 15 percent [12,18,54]. The blue toe syndrome may be considered as a specific manifestation of retiform purpura (picture 5 and picture 6). (See "Approach to the patient with retiform (angulated) purpura".)

In a retrospective review of 78 patients with cutaneous manifestations of cholesterol crystal embolization, blue toes were noted in 14 percent of the patients. More common skin manifestations were livedo reticularis (49 percent), gangrene (35 percent), cyanosis (28 percent), and ulceration (17 percent) [54].

In another study of 221 patients, skin manifestations were present in 75 patients. Of these 75, blue toes were observed in 11 patients [12].

Renal — Acute kidney injury is a common manifestation of cholesterol crystal embolism [26,62]. Acute kidney injury is present in 25 to 50 percent of cases [12,15,24,63]. Renal disease most often occurs after invasive vascular procedures but can occur spontaneously. In such patients, the diagnosis may be difficult to establish without biopsy unless other manifestations of crystal embolism are present.

Because the cholesterol crystal emboli are irregularly shaped and nondistensible and typically do not completely occlude larger vessels, the renal manifestations are those of distal parenchymal ischemia usually manifested as a bland sediment rather than renal infarction as seen with thromboemboli, which present with flank pain, hematuria that may be gross, and markedly elevated serum lactate dehydrogenase (image 3). The characteristics of renal involvement are discussed in detail separately (picture 7A-B). (See "Clinical presentation, evaluation, and treatment of renal atheroemboli".)

When acute kidney injury occurs after arteriography, the primary differential diagnosis is contrast nephropathy and cholesterol crystal embolism. Unless there are other signs of cholesterol crystal embolism, the two disorders are distinguished by differences in the clinical course. Contrast nephropathy typically begins to recover within three to five days, while cholesterol crystal embolism shows at best an incomplete recovery, and there may be a stuttering course with further showers of cholesterol crystals. (See "Contrast-associated and contrast-induced acute kidney injury: Clinical features, diagnosis, and management".)

Although not a common manifestation of cholesterol crystal embolism, rhabdomyolysis has been reported in association with massive cholesterol crystal embolism and can lead to heme-pigment-associated acute kidney injury [64]. Rhabdomyolysis presents with elevated serum muscle enzymes (including creatine kinase), red to brown urine due to myoglobinuria if there is persistent renal function, and electrolyte abnormalities. Peak serum creatine kinase levels depend upon the volume of muscle breakdown and the muscle mass of the patient. (See "Clinical features and diagnosis of heme pigment-induced acute kidney injury".)

Gastrointestinal — Atheroembolism to the mesenteric circulation most commonly involves the colon, small bowel, and stomach [65-68]. The pancreas, liver, and gallbladder also may be affected [69]. (See "Overview of intestinal ischemia in adults" and "Colonic ischemia".)

Gastrointestinal manifestations include abdominal pain, diarrhea, and, in approximately 10 percent of patients, bleeding [12,68,70]. Bleeding may originate from any site in the gastrointestinal tract, including the stomach [71]. Other manifestations of cholesterol crystal embolism include necrotizing pancreatitis, focal hepatic cell necrosis, and acalculous necrotizing cholecystitis. Intestinal infarction has a poor prognosis, with reported mortality rates ranging from 38 to 81 percent [12,72].

Upper endoscopic findings of nonspecific entities such as gastritis may be erroneously diagnosed [71]. A definitive diagnosis can only be established by examination of a biopsy specimen.

Central nervous system — Central nervous system manifestations of atheroembolism may include amaurosis fugax, transient ischemic attack (TIA), stroke, confusional state, headache, dizziness, or organic brain syndrome. Embolization to the spinal cord is rare but can lead to lower extremity paralysis.

Transient ischemic attack/stroke — Transient ischemic attack due to atheroembolic debris is more commonly associated with carotid atherosclerotic disease, and carotid thrombosis or thromboembolism can lead to hemispheric stroke. (See "Stroke: Etiology, classification, and epidemiology", section on 'Embolism'.)

There are conflicting data regarding the stroke risk associated with aortic atherosclerosis [4,5,35,73-78]. Large protruding plaques in the aortic arch, particularly mobile plaques, in our opinion, are an important cause of brain pathology. In one retrospective review of 29 patients with cholesterol emboli in the brain identified on autopsy, encephalopathy presumably due to ischemia was the predominant clinical finding and was most likely due to bilateral diffuse embolization from the identified aortic plaque disease [79].

In clinical longitudinal population studies in unselected patients, complex aortic atherosclerosis does not appear to be associated with an increased risk for primary ischemic stroke [35,75,76]. However, most studies have found that complex aortic atherosclerosis is a risk factor for recurrent stroke [4,5,77,78].

The range of findings is illustrated by the following studies:

A prospective study examined the frequency and thickness of atherosclerotic plaques in the ascending aorta and proximal arch in 250 patients admitted to the hospital with ischemic stroke and 250 consecutive controls, all over the age of 60 years [5]. Atherosclerotic plaques ≥4 mm in thickness were found in 14 percent of patients compared with 2 percent of controls, and the odds ratio for ischemic stroke among patients with such plaques was 9.1 after adjustment for atherosclerotic risk factors. In addition, aortic atherosclerotic plaques ≥4 mm were much more common in patients with brain infarcts of unknown cause (relative risk 4.7).

In contrast, a population-based study of 1135 subjects who had transesophageal echocardiography (TEE) found that complex atherosclerotic plaque (>4 mm with or without mobile debris) in the ascending and transverse aortic arch was not a significant risk factor for cryptogenic ischemic stroke or TIA after adjusting for age, sex, and other clinical risk factors [75]. However, there was an association between complex aortic plaque and noncryptogenic stroke. The investigators concluded that complex aortic arch debris is a marker for the presence of generalized atherosclerosis.

Methodologic differences are a potential explanation for the discrepant results of these reports assessing the risk of ischemic stroke related to aortic atherosclerosis, as the earlier case-control studies may have been skewed by selection and referral bias. However, many patients with aortic atherosclerosis also have cardiac or large artery lesions, a problem that may confound purely epidemiologic studies.

Ocular signs — Hollenhorst plaques are bright, refractile lesions in the retina indicative of cholesterol crystal embolization from a proximal atherosclerotic source (picture 8) [80,81].

The most common proximal source is the carotid artery [82,83]. In a review of 130 patents with Hollenhorst plaque or retinal artery occlusion (amaurosis excluded), 61 percent complained of ocular symptoms, including eye pain, blurred vision, or other atypical visual symptoms [84]. Of the 98 patients who underwent carotid duplex, all had some evidence of carotid stenosis ipsilateral to the ocular findings, but the degree of stenosis was less than 60 percent in 90 of the 130 patients. Over a mean of 22 months, no patient suffered from a transient ischemic attack (including amaurosis fugax) or stroke. Evaluation of the more central vasculature was performed in approximately 20 percent of the patients, and, although some minor valvular problems were found, a cardiac or aortic source for the retinal findings was not found.

Cholesterol embolization resulting in Hollenhorst plaques can occur following arteriography or cardiac catheterization, vascular surgery, or trauma. The mere finding of Hollenhorst plaques in a patient presenting with suspected cholesterol embolization syndrome should not be used to confirm that the acute clinical presentation is due to cholesterol emboli. A finding of Hollenhorst plaque may represent a prior event [85,86]. In one study, serial funduscopic examination found persistence of Hollenhorst plaques for over one year [83]. Moreover, approximately one third of patients who have Hollenhorst plaques are asymptomatic. Thus, additional evaluation may be needed to confirm the diagnosis of acute cholesterol embolization syndrome. (See 'Diagnosis' below.)

Other — Other vascular beds including coronary, pulmonary, prostate, thyroid, and adrenal glands may rarely be affected with diagnosis often established at autopsy [87].

DIAGNOSIS — A diagnosis of cholesterol crystal embolization should be highly suspected in a patient with known atherosclerotic disease and a classic history: the development of renal failure, abdominal pain or diarrhea, typical skin findings or a finding of Hollenhorst plaques of the retina following arteriography, cardiac catheterization, vascular surgery, or trauma to the abdomen. (See 'Clinical manifestations' above.)

Laboratory testing is generally nonspecific and may show elevations in the white blood cell count, decreased red blood cell count, or thrombocytopenia. Inflammation markers including elevated erythrocyte sedimentation rate, C-reactive protein and fibrinogen have been associated with atheroembolism [16]. Other abnormalities may include transient hypocomplementemia and eosinophilia.

Because there is an association between occlusive diseases in large peripheral arteries and cholesterol crystal embolization to smaller arteries, patients with extremity embolism should undergo noninvasive vascular testing to identify the presence of hemodynamically significant proximal peripheral artery disease. Even when a stenotic peripheral artery may not be the source of cholesterol crystal embolism, arterial revascularization may improve clinical outcomes. (See 'Vascular intervention' below.)

Specific abnormalities may indicate end-organ dysfunction such as increased creatinine or eosinophiluria if the kidneys are involved [88-91], increased amylase with pancreatic (and possibly bowel) involvement, elevated transaminases with hepatic involvement, or elevated creatine kinase and myoglobinuria with sufficient muscle involvement.

Imaging — Plaques in the aorta can be visualized, characterized, and quantified by a variety of imaging techniques; however, the index plaque that is the cause of the cholesterol crystal embolization is rarely determined. The diagnosis is more difficult in patients without typical clinical features, particularly if cholesterol crystal embolism has occurred spontaneously. However, the identification of complex aortic plaque or multiple ischemic strokes on imaging studies may permit a presumptive diagnosis to be made [5,29,30].

Plaques can be simple or complex (image 4). Simple plaques are characterized by wall thickness <4 mm and the absence of mobile components. Complex plaques are ≥4 mm in thickness and may exhibit irregular borders, ulceration, and mobile components that represent superimposed thrombus. Complex plaques are associated with an increased propensity for embolization. (See 'Plaque characteristics and location' above.)

Transesophageal echocardiography, primarily two-dimensional (2D) transesophageal echocardiography (TEE), is the first-line diagnostic modality to identify a thoracic aortic source of atheroembolism. Real-time three-dimensional transesophageal echocardiography (3D-TEE) provides very detailed information on aortic plaque location and morphology (picture 9 and movie 2). Transthoracic echocardiography, abdominal ultrasound, and endoscopic ultrasound (image 5) of the upper gastrointestinal tract have occasionally incidentally identified atherosclerotic plaques in the thoracic or abdominal aorta.

Compared with TEE, computed tomography (CT) (image 6 and movie 3) and magnetic resonance imaging (MRI) (image 7) are less invasive and more complete evaluations of the extent of atherosclerosis in the aorta. CT and MRI have several advantages over TEE [92,93]. These radiologic techniques are better than TEE for imaging aortic branches. In addition, they can image the entire abdominal aorta. In comparison, only the very proximal abdominal aorta between the diaphragm and the ostium of the superior mesenteric artery can be seen with TEE.

Conventional arteriography has low sensitivity for detection of plaques and often fails to identify plaques detected by other imaging techniques and should be avoided given the potential disruption of atherosclerotic debris with instrumentation [94]. (See 'Instrumentation' above.)

Radiologic studies of the brain may help suggest the diagnosis in demonstrating multiple small ischemic lesions. (See "Neuroimaging of acute stroke".)

Biopsy and pathologic findings — Biopsy is the only definitive means of confirming the diagnosis of cholesterol embolization syndrome. Thus, biopsy should be performed whenever the diagnosis is in doubt and when the specimen can safely be obtained from the patient. Histopathologic examination of amputated body parts or embolectomy specimens for cholesterol emboli pose no additional risk to the patient and should be performed if the diagnosis is suspected. Skin and skeletal biopsies are less invasive than renal and gastrointestinal biopsies.

The histologic hallmark of cholesterol crystal embolism is the presence of "ghosts" of cholesterol crystals or cholesterol clefts within arterioles, since the cholesterol crystals are dissolved during tissue fixation (picture 7A-B). The cholesterol clefts are crescentic (with pointed ends) or elongated ovoid spaces present in small or medium-sized arteries or arterioles. Inflammatory or fibrous intimal proliferation develops rapidly and may be the cause for vascular occlusion and resultant ischemic tissue damage [95].

Cholesterol clefts have also been demonstrated in the pulmonary arteries of patients with cholesterol crystal embolism. Since pulmonary arterial atherosclerosis is rare (eg, in end-stage Eisenmenger syndrome), the crystals presumably pass through the systemic capillary bed into the venous system and lungs. In a case report, cholesterol crystal emboli were seen in 25 percent of the small pulmonary arteries in a patient with atheroembolic disease [96].

Differential diagnosis — The diagnosis is often difficult to establish when the presenting symptoms and signs of cholesterol crystal embolism are subtle and nonspecific. Cholesterol crystal embolism needs to be distinguished from thromboembolism given differences in treatment. (See "Thromboembolism from aortic plaque", section on 'Clinical manifestations'.)

Because of its many differing effects, cholesterol crystal embolism may be included as one of the "great imitators," (such as tuberculosis, brucellosis) given its often nonspecific symptoms, leading it to be confused with a number of other diseases, including vascular diseases such aortic dissection, and tumors such as left atrial myxoma, lymphoma, and renal cell carcinoma [55]. The differential diagnosis includes many systemic illnesses, including cyanotic congenital heart disease, secondary syphilis, and pheochromocytoma [72].

There is also an extensive differential diagnosis of livedo reticularis that includes Raynaud's phenomenon, vasculitis (polyarteritis nodosa, systemic lupus, dermatomyositis, leukocytoclastic angiitis, rheumatoid vasculitis, thromboangiitis obliterans), infection (syphilis or tuberculosis), cryoglobulinemia, antiphospholipid syndrome, and polycythemia vera. A familial form called Sneddon's syndrome is seen in association with cerebrovascular disease.

There is also an extensive differential diagnosis for retiform purpura. (See "Approach to the patient with retiform (angulated) purpura".)

Among patients who develop acute kidney injury, particularly if the sediment is relatively bland, the differential renal diagnosis includes contrast nephropathy and acute kidney injury, both of which are typically reversible. (See "Clinical presentation, evaluation, and treatment of renal atheroemboli".)

TREATMENT — Treatment for cholesterol embolization comprises managing cardiovascular risk factors, management of end-organ ischemia, and prevention of recurrent embolization.

Cardiovascular risk factor management — Patients with cholesterol crystal embolism should be aggressively treated for secondary prevention of cardiovascular disease [97]. These modalities include aspirin, statins, blood pressure control, cessation of smoking, and, in patients with diabetes, glycemic control. (See 'Lipid-lowering therapy' below and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Managing ischemic manifestations — The management of the microvascular obstruction leading to end-organ ischemia varies depending upon the vascular bed affected but is primarily supportive with measures to control pain and lessen inflammation.

The inflammatory reaction that results from cholesterol crystal embolization is essentially a foreign body reaction to the cholesterol crystals that are resistant to breakdown by macrophages. Arterioles that are not immediately occluded may occlude as a chronic inflammatory infiltrate fills the lumen. Given this pathologic mechanism, various anti-inflammatory and antithrombotic agents have been used to lessen the inflammatory reaction and to prevent thrombosis.

There are no large trials evaluating anti-inflammatory therapies for treating cholesterol crystal embolism. Isolated reports in small numbers of patients using steroids [98-103], iloprost [104,105], and LDL apheresis [106-108] have shown modest success.

The inflammatory nature of cholesterol crystal embolism results in pain that is often out of proportion to the apparent degree of tissue ischemia, and pain management is of critical importance. (See "Pain control in the critically ill adult patient" and "Approach to the management of chronic non-cancer pain in adults".)

For patients with significant muscle inflammation, aggressive saline hydration is important to reduce the risk of acute kidney injury associated with myoglobinuria. Other treatments may include bicarbonate or mannitol. The prevention and treatment of heme-pigment-induced acute kidney injury is discussed in detail elsewhere. (See "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)".)

Preventing recurrent embolization — The optimal treatment to prevent recurrent cholesterol crystal embolization is not clear. Secondary prevention seems warranted, particularly since aortic plaques ≥4 mm in size appear to be associated with an increased risk of recurrent stroke [6,109,110]. In patients whose cholesterol embolization syndrome was precipitated by instrumentation (such as arteriography, cardiac catheterization, or vascular surgery), any further invasive imaging or treatment should be avoided unless absolutely necessary. Noninvasive ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) should replace the invasive techniques whenever possible. When arterial cannulation is absolutely necessary, alternative access routes should be considered (eg, cardiac catheterization via radial artery approach in a patient with extensive plaques in the descending thoracic aorta).

Lipid-lowering therapy — Statin therapy may decrease the risk of future embolization. Statins lower LDL cholesterol and have a variety of other effects, one of which appears to be plaque stabilization. In a retrospective study of 519 patients with severe thoracic aortic plaque cited, statin therapy was associated with a significantly lower rate of recurrent stroke and thromboembolization [13]. However, the number of patients with atheroembolization was too small (five) for subset analysis. On multivariate analysis, the protective effect seen with statin therapy was not present for patients taking warfarin or antiplatelet agents. Specific lipid-lowering therapy regimens may affect atherosclerotic plaque in the thoracic versus the abdominal aorta differently [111]. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Dyslipidemia' and "Thromboembolism from aortic plaque", section on 'Statin therapy'.)

Antithrombotic therapy — Anticoagulant therapy for the treatment of cholesterol crystal embolism remains controversial [112]. Although it seems intuitive that anticoagulation would improve arterial patency, the obstruction is mostly due to the atheroembolic debris and the inflammatory reaction it incites, and not thrombus. Another important consideration is the association between anticoagulant and antithrombotic therapy and the development of cholesterol crystal embolism; however, due to paucity of data, a causal relationship between cholesterol crystal embolism and anticoagulation and/or thrombolytic therapy can be neither proven nor refuted with certainty. (See 'Anticoagulation/thrombolytic therapy' above.)

There are no randomized trials that have evaluated the role of antithrombotic therapy in patients with aortic atheroma [109,113]. Nonrandomized retrospective studies have shown a benefit of oral anticoagulation over aspirin in patients with mobile thrombi in the aortic arch. Based on this low-quality evidence, the 2012 American College of Chest Physicians (ACCP) guidelines panel suggested oral anticoagulation or antiplatelet agents for patients with cryptogenic stroke and mobile aortic arch thrombi [113]. (See "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)", section on 'Treatment'.)

However, the 2012 ACCP guidelines stated that the hemorrhagic complications may outweigh the benefits of anticoagulation [113]. Other studies have not shown a benefit to anticoagulation. In a retrospective review of 519 patients with complex plaque, cholesterol crystal embolism occurred in only 5 (1 percent) during a follow-up of more than three years [13]. The risk was similar in the patients treated (2 of 206) and not treated with warfarin (3 of 313). This rate is similar to that noted in the Stroke Prevention in Atrial Fibrillation (SPAF-III) trial (1 of 134 warfarin-treated patients), most of whom had severe atherosclerotic plaques on transesophageal echocardiography [52,53].

In our practice, we do not routinely use anticoagulants in patients who are diagnosed with cholesterol crystal embolism unless they have other indications for anticoagulation (such as atrial fibrillation or mechanical prosthetic valve). Definitive recommendations regarding the use of anticoagulant in this context should await the results of an ongoing randomized trial comparing oral anticoagulant with antiplatelet therapy in patients with thoracic aortic plaque.

It is important to emphasize that the package insert for warfarin explicitly states that warfarin therapy may increase the risk of cholesterol crystal embolism and that discontinuation of warfarin is recommended when cholesterol crystal embolism is observed [114].

Plaque removal or exclusion — Given the poor outcomes associated with cholesterol crystal embolism, surgical plaque removal (endarterectomy) or exclusion of the plaque (ligation and bypass, endovascular exclusion) may be indicated if a clear embolic source is identified, the source is surgically accessible, and the patient is an appropriate candidate for surgery. Patients with lower extremity symptoms and an infrarenal source for embolism may have more favorable outcomes [115].

In a prospective study of 100 patients who underwent surgery over a 12 year period following identification of the embolic source, occlusive aortoiliac disease (47 patients) and small aortic aneurysms (20 patients) were the most commonly identified embolic sources [116].

The most common surgical treatment was aortic bypass. Other procedures included aortoiliac endarterectomy with patching, femoral or popliteal endarterectomy, and infrainguinal or upper extremity bypass. (See "Management of chronic limb-threatening ischemia" and "Upper extremity atherosclerotic disease" and "Lower extremity surgical bypass techniques".)

In this study, the reported outcomes were:

Postoperative mortality – 11 percent (all had a suprarenal aortic thrombus preoperatively)

Survival rates at one, three, and five years – 89, 83, and 73 percent, respectively

Toe and leg amputations – 9 and 10 percent, respectively

Hemodialysis – 10 percent

Recurrent emboli – 5 percent within eight months of surgery with no further emboli over the next three years

In another surgical series of 62 patients who underwent surgery at one institution, bypass grafts were inserted in 42 patients after exclusion of the native diseased artery, 20 had endarterectomies (6 of them with bypass grafts), and 5 were treated medically [24]. The 30-day mortality rate was 5 percent. "Minor" amputation was required in 19 patients (31 percent), and major leg amputation in 2 patients. Limb salvage was possible in 86 of 88 limbs. There were no postoperative embolic incidents in the involved limbs during a mean follow-up of 20 months.

Covered stents — More recently, covered stents and endografts have been used to exclude the involved arterial segment in a small number of patients with aortic or iliac artery sources of cholesterol crystal embolism [27,117]. The disadvantage of this technique compared with open surgery is a greater risk for recurrent embolization related to the intraluminal manipulation of guidewires [17]. Definitive recommendations for the use of covered stents are not possible at this time.

Vascular intervention — For patients with lower extremity cholesterol embolism and a hemodynamically significant proximal stenosis (that may or may not be the source of embolism), arterial revascularization can restore normal pressures, improve distal perfusion, and may improve pain. (See 'Managing ischemic manifestations' above.)

Surgical (eg, bypass) or endovascular (eg, stent) management may be appropriate depending on the location of the obstruction. Percutaneous angioplasty and stenting, mostly of the iliac and femoral arteries, have been performed in a small number of patients without causing recurrent embolization [116,118]. The decision on whether to perform revascularization in patients with cholesterol embolization syndrome should also take into account the severity and duration of ischemic symptoms. (See "Approach to revascularization for claudication due to peripheral artery disease".)

PROGNOSIS — The prognosis in medically treated patients with cholesterol crystal emboli is poor, in part because of severe underlying atherosclerosis [119]. Acute, in-hospital mortality was 16 percent (4 of 25) in one series [16], but mortality rates may be as high as 80 percent when cases that are diagnosed post-mortem are included [12].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute extremity ischemia".)

SUMMARY AND RECOMMENDATIONS

Atheroembolism – Atheroembolism, also known as cholesterol crystal embolism or cholesterol embolism, refers to arterio-arterial embolism of cholesterol crystals or small pieces of atheromatous material originating from an atherosclerotic plaque usually from the aorta but occasionally from other arteries. Cholesterol crystal embolism results in partial or total occlusion of small arteries, leading to tissue or organ ischemia. (See 'Introduction' above.)

Risk factors – Risk factors for atheroembolism include patient factors such as hypertension, advancing age, smoking, hypercholesterolemia, obesity, and diabetes. Anatomic factors associated with the aortic atherosclerotic plaque, such as plaque thickness ≥4 mm, plaque ulceration, or the presence of mobile debris, increase the risk for embolization. (See 'Epidemiology and risk factors' above.)

Clinical manifestations – The clinical manifestations are variable and relate to the location of the embolic source, extent of embolization, whether there is partial or complete occlusion of the affected vessels, and the presence or absence of preexisting disease in the affected vascular bed (eg, peripheral artery disease). Clinical manifestations include but are not limited to (see 'Clinical manifestations' above):

Hollenhorst plaques in the retina

Transient ischemic attack or cerebral infarction

Signs of intestinal ischemia

Development of renal failure

Skin changes such as livedo reticularis

Blue toe syndrome or other signs of digital ischemia

Diagnosis – The clinical diagnosis of cholesterol crystal embolism should be suspected in patients with any of the listed clinical manifestations and known atherosclerotic disease, particularly following arteriography, cardiac catheterization, vascular surgery, or trauma to the abdomen. The diagnosis is more difficult in patients who do not have these features, particularly if cholesterol crystal embolism has occurred spontaneously.

Vascular imaging – The presence of complex aortic plaque on imaging studies supports the diagnosis. Atherosclerotic plaques can also be seen using transthoracic echocardiography, abdominal ultrasound, and endoscopic ultrasound of the upper gastrointestinal tract. (See 'Imaging' above.)

Laboratory examination – Laboratory testing is generally nonspecific but may indicate the effects of end-organ ischemia (eg, increased lactate).

Biopsy – A definitive diagnosis depends upon pathologic specimens. Biopsy should be performed whenever the diagnosis is in doubt and when the specimen can safely be obtained from the patient. The histologic hallmark of cholesterol crystal embolism is the presence of "ghosts" of cholesterol crystals or cholesterol clefts within arterioles. (See 'Biopsy and pathologic findings' above.)

Treatment – The treatment of cholesterol crystal embolism is medical, primarily consisting of risk factor reduction, pain control, and maintaining euvolemia. Statin therapy is indicated as part of risk factor reduction and appears to reduce the rate of recurrent embolism. (See 'Treatment' above.)

We suggest not routinely anticoagulating patients who are diagnosed with cholesterol crystal embolism (Grade 2C). Anticoagulation with heparin, warfarin, and use of thrombolytic therapy are all associated with the development of cholesterol embolism, although a causal relationship has never been demonstrated. However, patients with another indication for anticoagulation, such as thromboembolism or deep vein thrombosis, should be treated. (See 'Managing ischemic manifestations' above.)

Vascular intervention - Surgical or endovascular treatment may be indicated if a clear embolic source is identified, the source is anatomically suitable, and the patient is an appropriate candidate for surgery. For patients who meet these criteria, we suggest surgical or endovascular treatment to remove or exclude the embolic source (Grade 2C). (See 'Vascular intervention' above.)

Prognosis – The prognosis in patients with cholesterol crystal embolism correlates with the degree of the underlying atherosclerosis and is overall poor. (See 'Prognosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Itzhak Kronzon, MD, FACC, FAHA, FASE, who contributed to an earlier version of this topic review.

  1. Fazio GP, Redberg RF, Winslow T, Schiller NB. Transesophageal echocardiographically detected atherosclerotic aortic plaque is a marker for coronary artery disease. J Am Coll Cardiol 1993; 21:144.
  2. Matsuzaki M, Ono S, Tomochika Y, et al. Advances in transesophageal echocardiography for the evaluation of atherosclerotic lesions in thoracic aorta--the effects of hypertension, hypercholesterolemia, and aging on atherosclerotic lesions. Jpn Circ J 1992; 56:592.
  3. Tunick PA, Kronzon I. Atheromas of the thoracic aorta: clinical and therapeutic update. J Am Coll Cardiol 2000; 35:545.
  4. Amarenco P, Duyckaerts C, Tzourio C, et al. The prevalence of ulcerated plaques in the aortic arch in patients with stroke. N Engl J Med 1992; 326:221.
  5. Amarenco P, Cohen A, Tzourio C, et al. Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. N Engl J Med 1994; 331:1474.
  6. French Study of Aortic Plaques in Stroke Group, Amarenco P, Cohen A, et al. Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke. N Engl J Med 1996; 334:1216.
  7. Karalis DG, Quinn V, Victor MF, et al. Risk of catheter-related emboli in patients with atherosclerotic debris in the thoracic aorta. Am Heart J 1996; 131:1149.
  8. Katz ES, Tunick PA, Rusinek H, et al. Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass: experience with intraoperative transesophageal echocardiography. J Am Coll Cardiol 1992; 20:70.
  9. Tunick PA, Rosenzweig BP, Katz ES, et al. High risk for vascular events in patients with protruding aortic atheromas: a prospective study. J Am Coll Cardiol 1994; 23:1085.
  10. Kronzon I, Saric M. Cholesterol embolization syndrome. Circulation 2010; 122:631.
  11. Hiramoto J, Hansen KJ, Pan XM, et al. Atheroemboli during renal artery angioplasty: an ex vivo study. J Vasc Surg 2005; 41:1026.
  12. Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: a review of 221 cases in the English literature. Angiology 1987; 38:769.
  13. Tunick PA, Nayar AC, Goodkin GM, et al. Effect of treatment on the incidence of stroke and other emboli in 519 patients with severe thoracic aortic plaque. Am J Cardiol 2002; 90:1320.
  14. Sharma PV, Babu SC, Shah PM, Nassoura ZE. Changing patterns of atheroembolism. Cardiovasc Surg 1996; 4:573.
  15. Doty JR, Wilentz RE, Salazar JD, et al. Atheroembolism in cardiac surgery. Ann Thorac Surg 2003; 75:1221.
  16. 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; 42:211.
  17. Lin PH, Bush RL, Conklin BS, et al. Late complication of aortoiliac stent placement- atheroembolization of the lower extremities. J Surg Res 2002; 103:153.
  18. Jucgla A, Moreso F, Muniesa C, et al. Cholesterol embolism: still an unrecognized entity with a high mortality rate. J Am Acad Dermatol 2006; 55:786.
  19. Blankenship JC, Butler M, Garbes A. Prospective assessment of cholesterol embolization in patients with acute myocardial infarction treated with thrombolytic vs conservative therapy. Chest 1995; 107:662.
  20. Cross SS. How common is cholesterol embolism? J Clin Pathol 1991; 44:859.
  21. THURLBECK WM, CASTLEMAN B. Atheromatous emboli to the kidneys after aortic surgery. N Engl J Med 1957; 257:442.
  22. Mayo RR, Swartz RD. Redefining the incidence of clinically detectable atheroembolism. Am J Med 1996; 100:524.
  23. Agmon Y, Khandheria BK, Meissner I, et al. Independent association of high blood pressure and aortic atherosclerosis: A population-based study. Circulation 2000; 102:2087.
  24. Baumann DS, McGraw D, Rubin BG, et al. An institutional experience with arterial atheroembolism. Ann Vasc Surg 1994; 8:258.
  25. Scolari F, Ravani P, Pola A, et al. Predictors of renal and patient outcomes in atheroembolic renal disease: a prospective study. J Am Soc Nephrol 2003; 14:1584.
  26. Scolari F, Ravani P, Gaggi R, et al. The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors. Circulation 2007; 116:298.
  27. Carroccio A, Olin JW, Ellozy SH, et al. The role of aortic stent grafting in the treatment of atheromatous embolization syndrome: results after a mean of 15 months follow-up. J Vasc Surg 2004; 40:424.
  28. Nickol J, Richards T, Mullins J. Cholesterol Embolization Syndrome From Penetrating Aortic Ulcer. Cureus 2020; 12:e8670.
  29. Tunick PA, Perez JL, Kronzon I. Protruding atheromas in the thoracic aorta and systemic embolization. Ann Intern Med 1991; 115:423.
  30. Karalis DG, Chandrasekaran K, Victor MF, et al. Recognition and embolic potential of intraaortic atherosclerotic debris. J Am Coll Cardiol 1991; 17:73.
  31. Tunick PA, Kronzon I. Protruding atherosclerotic plaque in the aortic arch of patients with systemic embolization: a new finding seen by transesophageal echocardiography. Am Heart J 1990; 120:658.
  32. Coy KM, Maurer G, Goodman D, Siegel RJ. Transesophageal echocardiographic detection of aortic atheromatosis may provide clues to occult renal dysfunction in the elderly. Am Heart J 1992; 123:1684.
  33. Koppang JR, Nanda NC, Coghlan C, Sanyal R. Histologically confirmed cholesterol atheroemboli with identification of the source by transesophageal echocardiography. Echocardiography 1992; 9:379. http://onlinelibrary.wiley.com/doi/10.1111/j.1540-8175.1992.tb00481.x/abstract (Accessed on November 10, 2010).
  34. Freedberg RS, Tunick PA, Kronzon I. Emboli in transit: the missing link. J Am Soc Echocardiogr 1998; 11:826.
  35. Meissner I, Khandheria BK, Sheps SG, et al. Atherosclerosis of the aorta: risk factor, risk marker, or innocent bystander? A prospective population-based transesophageal echocardiography study. J Am Coll Cardiol 2004; 44:1018.
  36. Tunick PA, Kronzon I. Atherosclerosis of the aorta: a risk factor, risk marker, or an innocent bystander? J Am Coll Cardiol 2005; 45:1907; author reply 1907.
  37. Harloff A, Simon J, Brendecke S, et al. Complex plaques in the proximal descending aorta: an underestimated embolic source of stroke. Stroke 2010; 41:1145.
  38. Tanaka H, Yamana H, Matsui H, et al. Proportion and risk factors of cholesterol crystal embolization after cardiovascular procedures: a retrospective national database study. Heart Vessels 2020; 35:1250.
  39. Pandit AK, Ohshima T, Kawaguchi R, et al. Cholesterol Embolization Syndrome After Carotid Artery Stenting Associated with Delayed Cerebral Hyperperfusion Intracerebral Hemorrhage. World Neurosurg 2020; 142:274.
  40. Rudnick MR, Berns JS, Cohen RM, Goldfarb S. Nephrotoxic risks of renal angiography: contrast media-associated nephrotoxicity and atheroembolism--a critical review. Am J Kidney Dis 1994; 24:713.
  41. Nishi T, Tokuda Y, Tanaka A, et al. Cholesterol Crystal Embolization After Transcatheter Aortic Valve Replacement. Circ Rep 2020; 2:701.
  42. Khan AM, Jacobs S. Trash feet after coronary angiography. Heart 2003; 89:e17.
  43. Keeley EC, Grines CL. Scraping of aortic debris by coronary guiding catheters: a prospective evaluation of 1,000 cases. J Am Coll Cardiol 1998; 32:1861.
  44. Holden A, Hill A, Jaff MR, Pilmore H. Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy. Kidney Int 2006; 70:948.
  45. Edwards MS, Craven BL, Stafford J, et al. Distal embolic protection during renal artery angioplasty and stenting. J Vasc Surg 2006; 44:128.
  46. Muller-Hansma AHG, Daemen-Gubbels CRGM, Schut NH. Cholesterol embolisms as possible adverse drug reaction of direct oral anticoagulants. Neth J Med 2018; 76:125.
  47. Oka H, Kamimura T, Hiramatsu Y, et al. Cholesterol Crystal Embolism Induced by Direct Factor Xa Inhibitor: A First Case Report. Intern Med 2018; 57:71.
  48. Glassock RJ, Ritz E, Bommer J, et al. Acute renal failure, hypertension and skin necrosis in a patient with streptokinase therapy. Am J Nephrol 1984; 4:193.
  49. Hitti WA, Wali RK, Weinman EJ, et al. Cholesterol embolization syndrome induced by thrombolytic therapy. Am J Cardiovasc Drugs 2008; 8:27.
  50. Nevelsteen A, Kutten M, Lacroix H, Suy R. Oral anticoagulant therapy: a precipitating factor in the pathogenesis of cholesterol embolization? Acta Chir Belg 1992; 92:33.
  51. Hyman BT, Landas SK, Ashman RF, et al. Warfarin-related purple toes syndrome and cholesterol microembolization. Am J Med 1987; 82:1233.
  52. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Ann Intern Med 1998; 128:639.
  53. Blackshear JL, Zabalgoitia M, Pennock G, et al. Warfarin safety and efficacy in patients with thoracic aortic plaque and atrial fibrillation. SPAF TEE Investigators. Stroke Prevention and Atrial Fibrillation. Transesophageal echocardiography. Am J Cardiol 1999; 83:453.
  54. Falanga V, Fine MJ, Kapoor WN. The cutaneous manifestations of cholesterol crystal embolization. Arch Dermatol 1986; 122:1194.
  55. Olin JW. Other Peripheral Arterial Diseases. In: Goldman: Cecil Textbook of Medicine, 21st ed, WB Saunders, Philadelphia 2000. p.362.
  56. Turakhia AK, Khan MA. Splinter hemorrhages as a possible clinical manifestation of cholesterol crystal embolization. J Rheumatol 1990; 17:1083.
  57. Donohue KG, Saap L, Falanga V. Cholesterol crystal embolization: an atherosclerotic disease with frequent and varied cutaneous manifestations. J Eur Acad Dermatol Venereol 2003; 17:504.
  58. Rosansky SJ. Multiple cholesterol emboli syndrome. South Med J 1982; 75:677.
  59. Quintart C, Treille S, Lefebvre P, Pontus T. Penile necrosis following cholesterol embolism. Br J Urol 1997; 80:347.
  60. Zhang WW, Chauvapun JP, Dosluoglu HH. Scrotal necrosis following endovascular abdominal aortic aneurysm repair. Vascular 2007; 15:113.
  61. Zaveri S, Price LZ, Tupper H, Tadros RO. Atheroembolism to the Breast. Ann Vasc Surg 2020; 64:411.e17.
  62. Mittal BV, Alexander MP, Rennke HG, Singh AK. Atheroembolic renal disease: a silent masquerader. Kidney Int 2008; 73:126.
  63. Scolari F, Ravani P. Atheroembolic renal disease. Lancet 2010; 375:1650.
  64. Sarwar S, Al-Absi A, Wall BM. Catastrophic cholesterol crystal embolization after endovascular stent placement for peripheral vascular disease. Am J Med Sci 2008; 335:403.
  65. Grassia R, Manotti L, Pasin F. An Unusual Storm Within the Gastroduodenal Tract. Gastroenterology 2016; 151:243.
  66. Tian M, Matsukuma KE. Cholesterol crystal embolism to the gastrointestinal tract: a catastrophic case. Autops Case Rep 2019; 9:e2018082.
  67. Kadoya Y, Zen K, Takigami M, et al. Multiple Small Bowel Perforations Associated With Cholesterol Crystal Embolization After Transcatheter Aortic Valve Replacement. JACC Cardiovasc Interv 2020; 13:1831.
  68. Ben-Horin S, Bardan E, Barshack I, et al. Cholesterol crystal embolization to the digestive system: characterization of a common, yet overlooked presentation of atheroembolism. Am J Gastroenterol 2003; 98:1471.
  69. Moolenaar W, Lamers CB. Cholesterol crystal embolization to liver, gallbladder, and pancreas. Dig Dis Sci 1996; 41:1819.
  70. Moolenaar W, Lamers CB. Gastrointestinal blood loss due to cholesterol crystal embolization. J Clin Gastroenterol 1995; 21:220.
  71. Bourdages R, Prentice RS, Beck IT, et al. Atheromatous embolization to the stomach: an unusual cause of gastrointestinal bleeding. Am J Dig Dis 1976; 21:889.
  72. Abdelmalek MF, Spittell PC. 79-year-old woman with blue toes. Mayo Clin Proc 1995; 70:292.
  73. Maekawa K, Shibata M, Nakajima H, et al. Cholesterol Crystals in Embolic Debris are Associated with Postoperative Cerebral Embolism after Carotid Artery Stenting. Cerebrovasc Dis 2018; 46:242.
  74. Caplan LR. The aorta as a donor source of brain embolism. In: Brain embolism, Caplan, LR, Manning, WJ (Eds), Informa Healthcare, New York 2006. p.187.
  75. Petty GW, Khandheria BK, Meissner I, et al. Population-based study of the relationship between atherosclerotic aortic debris and cerebrovascular ischemic events. Mayo Clin Proc 2006; 81:609.
  76. Russo C, Jin Z, Rundek T, et al. Atherosclerotic disease of the proximal aorta and the risk of vascular events in a population-based cohort: the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study. Stroke 2009; 40:2313.
  77. Cohen A, Tzourio C, Bertrand B, et al. Aortic plaque morphology and vascular events: a follow-up study in patients with ischemic stroke. FAPS Investigators. French Study of Aortic Plaques in Stroke. Circulation 1997; 96:3838.
  78. Di Tullio MR, Russo C, Jin Z, et al. Aortic arch plaques and risk of recurrent stroke and death. Circulation 2009; 119:2376.
  79. Ezzeddine MA, Primavera JM, Rosand J, et al. Clinical characteristics of pathologically proved cholesterol emboli to the brain. Neurology 2000; 54:1681.
  80. Gonzalez-Castellon M, Kadakia P, Willey J, et al. Teaching video neuroimages: Hollenhorst plaque. Neurology 2013; 81:e60.
  81. HOLLENHORST RW. Significance of bright plaques in the retinal arterioles. JAMA 1961; 178:23.
  82. Chawluk JB, Kushner MJ, Bank WJ, et al. Atherosclerotic carotid artery disease in patients with retinal ischemic syndromes. Neurology 1988; 38:858.
  83. Bunt TJ. The clinical significance of the asymptomatic Hollenhorst plaque. J Vasc Surg 1986; 4:559.
  84. Dunlap AB, Kosmorsky GS, Kashyap VS. The fate of patients with retinal artery occlusion and Hollenhorst plaque. J Vasc Surg 2007; 46:1125.
  85. Wijman CA, Babikian VL, Matjucha IC, et al. Cerebral microembolism in patients with retinal ischemia. Stroke 1998; 29:1139.
  86. Babikian V, Wijman CA, Koleini B, et al. Retinal ischemia and embolism. Etiologies and outcomes based on a prospective study. Cerebrovasc Dis 2001; 12:108.
  87. Kitamura N, Sasabe E, Kitaoka H, Yamamoto T. Unilateral necrosis of the tongue caused by embolisation of cholesterol crystals. Br J Oral Maxillofac Surg 2018; 56:340.
  88. Thadhani RI, Camargo CA Jr, Xavier RJ, et al. Atheroembolic renal failure after invasive procedures. Natural history based on 52 histologically proven cases. Medicine (Baltimore) 1995; 74:350.
  89. Cosio FG, Zager RA, Sharma HM. Atheroembolic renal disease causes hypocomplementaemia. Lancet 1985; 2:118.
  90. Kasinath BS, Lewis EJ. Eosinophilia as a clue to the diagnosis of atheroembolic renal disease. Arch Intern Med 1987; 147:1384.
  91. Wilson DM, Salazer TL, Farkouh ME. Eosinophiluria in atheroembolic renal disease. Am J Med 1991; 91:186.
  92. Tunick PA, Krinsky GA, Lee VS, Kronzon I. Diagnostic imaging of thoracic aortic atherosclerosis. AJR Am J Roentgenol 2000; 174:1119.
  93. Tenenbaum A, Garniek A, Shemesh J, et al. Dual-helical CT for detecting aortic atheromas as a source of stroke: comparison with transesophageal echocardiography. Radiology 1998; 208:153.
  94. Khatri IA, Mian N, Alkawi A, et al. Catheter-based aortography fails to identify aortic atherosclerotic lesions detected on transesophageal echocardiography. J Neuroimaging 2005; 15:261.
  95. Warren BA, Vales O. The ultrastructure of the stages of atheroembolic occlusion of renal arteries. Br J Exp Pathol 1973; 54:469.
  96. Case records of the Massachusetts General Hospital. Weekly Clinicopathological Exercises. Case 11-1996. A 69-year-old man with progressive renal failure and the abrupt onset of dyspnea. N Engl J Med 1996; 334:973.
  97. Smith SC Jr, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 2006; 113:2363.
  98. Mann SJ, Sos TA. Treatment of atheroembolization with corticosteroids. Am J Hypertens 2001; 14:831.
  99. Motegi S, Abe M, Shimizu A, et al. Cholesterol crystal embolization: skin manifestation, gastrointestinal and central nervous symptom treated with corticosteroid. J Dermatol 2005; 32:295.
  100. Matsumura T, Matsumoto A, Ohno M, et al. A case of cholesterol embolism confirmed by skin biopsy and successfully treated with statins and steroids. Am J Med Sci 2006; 331:280.
  101. Koga J, Ohno M, Okamoto K, et al. Cholesterol embolization treated with corticosteroids--two case reports. Angiology 2005; 56:497.
  102. Yücel AE, Kart-Köseoglu H, Demirhan B, Ozdemir FN. Cholesterol crystal embolization mimicking vasculitis: success with corticosteroid and cyclophosphamide therapy in two cases. Rheumatol Int 2006; 26:454.
  103. Fabbian F, Catalano C, Lambertini D, et al. A possible role of corticosteroids in cholesterol crystal embolization. Nephron 1999; 83:189.
  104. Elinav E, Chajek-Shaul T, Stern M. Improvement in cholesterol emboli syndrome after iloprost therapy. BMJ 2002; 324:268.
  105. Minatohara K. Renal failure associated with blue toe syndrome: effective treatment with intravenous prostaglandin E-1. Acta Derm Venereol 2006; 86:364.
  106. Hasegawa M, Sugiyama S. Apheresis in the treatment of cholesterol embolic disease. Ther Apher Dial 2003; 7:435.
  107. Tamura K, Umemura M, Yano H, et al. Acute renal failure due to cholesterol crystal embolism treated with LDL apheresis followed by corticosteroid and candesartan. Clin Exp Nephrol 2003; 7:67.
  108. Muso E, Mune M, Fujii Y, et al. Significantly rapid relief from steroid-resistant nephrotic syndrome by LDL apheresis compared with steroid monotherapy. Nephron 2001; 89:408.
  109. Kronzon I, Tunick PA. Aortic atherosclerotic disease and stroke. Circulation 2006; 114:63.
  110. Fujimoto S, Yasaka M, Otsubo R, et al. Aortic arch atherosclerotic lesions and the recurrence of ischemic stroke. Stroke 2004; 35:1426.
  111. Kawahara T, Nishikawa M, Kawahara C, et al. Atorvastatin, etidronate, or both in patients at high risk for atherosclerotic aortic plaques: a randomized, controlled trial. Circulation 2013; 127:2327.
  112. Igarashi Y, Akimoto T, Kobayashi T, et al. Performing Anticoagulation: A Puzzling Case of Cholesterol Embolization Syndrome. Clin Med Insights Case Rep 2017; 10:1179547616684649.
  113. Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e601S.
  114. http://packageinserts.bms.com/pi/pi_coumadin.pdf (Accessed on October 20, 2010).
  115. Keen RR, McCarthy WJ, Shireman PK, et al. Surgical management of atheroembolization. J Vasc Surg 1995; 21:773.
  116. Renshaw A, McCowen T, Waltke EA, et al. Angioplasty with stenting is effective in treating blue toe syndrome. Vasc Endovascular Surg 2002; 36:155.
  117. Kumins NH, Owens EL, Oglevie SB, et al. Early experience using the Wallgraft in the management of distal microembolism from common iliac artery patholology. Ann Vasc Surg 2002; 16:181.
  118. Matchett WJ, McFarland DR, Eidt JF, Moursi MM. Blue toe syndrome: treatment with intra-arterial stents and review of therapies. J Vasc Interv Radiol 2000; 11:585.
  119. Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005; 352:20.
Topic 8184 Version 26.0

References

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