Thromboembolism from aortic plaque

INTRODUCTION — Aortic atherosclerotic plaques are a manifestation of systemic atherosclerosis (image 1 and movie 1). They are associated with risk factors for atherosclerotic disease and are more common in patients with coronary artery disease and in older individuals [1-5].

In addition, aortic atherosclerotic plaques are an important cause of systemic embolization [6-9]. Embolic events in the setting of aortic atherosclerosis can occur spontaneously or they can be induced by mechanical interventions including guidewire/catheter manipulation during cardiac catheterization, intraaortic balloon pulsations, and vessel clamping/manipulations during cardiac and vascular surgery [10,11]. The risk of embolism in patients with aortic atherosclerosis is markedly increased for plaques that are mobile and/or protruding, particularly if >4 mm in thickness.

The risk factors, clinical manifestations, detection, and preventive treatment of thromboembolism from aortic plaques are reviewed here. Atheroembolism is discussed separately. (See "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)".)

THROMBOEMBOLISM VERSUS ATHEROEMBOLISM — Thromboembolism from aortic plaques is common, whereas cholesterol crystal embolization is fairly rare. Although there is some overlap, these disorders have characteristic distinguishing features:

●Thromboembolism may occur when an atherosclerotic plaque from large or medium arteries becomes unstable, and superimposed thrombi embolize. The thromboemboli tend to be single and tend to lodge in small or medium arteries, resulting most often in stroke or transient ischemic attack [6-9,12], limb ischemia (upper or lower extremity), renal infarction, intestinal ischemia, or ischemia of other organs [9,13].

●The term atheroembolism is used synonymously with cholesterol crystal embolism, cholesterol embolism, or micro-atheroembolism. These terms refer to arterio-arterial embolism of fragments of atheromatous material originating from an atherosclerotic plaque of the aorta or occasionally other arteries. The result of such embolization is tissue and organ damage produced by multiple small artery occlusions (eg, "blue toe" syndrome, retinal ischemia, renal failure, livedo reticularis, intestinal infarction). (See "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)".)

PATHOLOGY — The material protruding from the aortic wall is typically atheromatous plaque, with the characteristic composition consisting of a lipid pool, a fibrous cap, smooth muscle cell and mononuclear cell infiltration, and varying degrees of calcification [7,14]. Thrombi may be more characteristic of plaques with a high proportion of lipid and with a preponderance of monocytes or macrophages [14]. The mobile component, as seen on transesophageal echocardiography (TEE), is usually thrombus superimposed on the plaque, which has presumably ruptured (movie 2). In contrast, highly calcified plaques may be more stable (ie, less vulnerable and less likely to develop thrombus and embolize) [15]. (See 'Plaque ulceration and mobility' below.)

COMPLEX AORTIC PLAQUE — Atherosclerosis of the aorta is a diffuse process, and many of the individual plaques are complex, which is defined as thickness >4 mm, ulceration, or mobility of a component of the plaque. In one series of patients with complex thoracic aortic plaque, mobile thrombi were seen on transesophageal echocardiography (TEE) in 24 percent [16]. Discovery of complex aortic plaque may occur when TEE is performed as part of the evaluation for an acute stroke or peripheral embolism, or for some unrelated reason.

Association with embolization — Evidence for a cause and effect relationship between complex aortic plaque and embolism comes from the following observations:

●Complex aortic plaque is seen in 2 to 14 percent of patients with a history of stroke or peripheral embolization [3,8,17]. The true prevalence may be underestimated since the plaque that has "caused" the event may have migrated with only the remaining or "residual" plaque present.

●Complex thoracic aortic plaque is seen much more frequently in stroke patients compared with controls without stroke in both TEE and autopsy studies (21 to 27 percent versus 5 to 9 percent) [7,8,12,17].

●Complex thoracic aortic plaques are associated with a high frequency of embolization [9,13,16]. A cohort study compared 42 patients with complex thoracic aortic plaque identified on TEE (and no other detected source of emboli) with matched controls without aortic plaque on TEE [13]. Vascular events (stroke, peripheral embolization) occurred in 33 percent of those with aortic plaque, compared with 7 percent in patients without plaque during a mean follow-up of 14 months.

●Aortic plaques are strongly associated with embolic stroke even in patients with atrial fibrillation. This was illustrated in a subset analysis of the Stroke Prevention in Atrial Fibrillation III (SPAF-III) trial in which 134 of 382 patients (35 percent) with atrial fibrillation were identified as having a complex aortic plaque (>4 mm in thickness or mobile) on TEE [18]. The stroke rate at one year was significantly higher for patients with complex aortic plaque (15.8 versus 8.0 and 1.2 percent with simple or no plaque, respectively). Complex aortic plaque was independently associated with a higher risk of embolization [19]. (See "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack", section on 'Aortic atherosclerosis' and "Atrial fibrillation in adults: Use of oral anticoagulants".)

Risk factors for embolization — The likelihood of embolization from aortic plaques and the organs that are affected are related to plaque morphology and location as identified on TEE or computed tomographic (CT) angiography, including plaque thickness, ulceration, mobility, as well as a history of aortic instrumentation.

Plaque thickness — Thicker plaques are more likely to be lipid laden and to have overlying thrombi and embolize [8,9,15,20]. The potential importance of plaque thickness is illustrated by the following two studies [8,9].

●In a case control study, 250 patients with ischemic stroke were compared with 250 controls undergoing TEE for cardiac evaluation. Among patients with stroke, 14.4 percent had plaques >4 mm in thickness in the ascending aorta or aortic arch compared with only 2 percent of controls [8]. Compared with plaque thickness <1 mm, the adjusted odds ratio was 4.2 and 9.1 for plaques 1 to 3.9 mm and >4 mm, respectively.

●A subsequent prospective study from the French Study of Aortic Plaques in Stroke Group included 331 patients with an initial ischemic stroke who underwent TEE [9]. At two to four years of follow-up:

•The incidence of recurrent stroke was 2.8, 3.5, and 11.9 percent per year for patients with plaque thickness <1, 1 to 3.9, and >4 mm, respectively.

•The incidence of all vascular events was 5.9, 9.1 and 26 percent per year for patients with plaque thickness <1, 1 to 3.9 and >4 mm, respectively.

•After adjustment for carotid artery stenosis, atrial fibrillation, peripheral artery disease, and other risk factors, aortic plaques >4 mm were independent predictors of recurrent ischemic stroke (relative risk 3.8; 95% CI 1.8-7.8).

●Similarly, a "shaggy" aorta, defined as greater than 75 percent involvement of thoracic aorta with a plaque thickness of >4 mm, increases overall mortality of both open and endovascular abdominal aortic aneurysm repair compared with controls, likely related to visceral and peripheral embolization [21].

A different conclusion was reached in an analysis from the Stroke Prevention: Assessment of Risk in a Community (SPARC) study, which found that complex aortic plaque (>4 mm or mobile) was not associated with a significant increase in risk of cerebrovascular events after adjusting for age, sex, and other clinical risk factors [22]. The reason for this apparent disparity may be related to patient selection bias.

Plaque ulceration and mobility — In an autopsy study of 500 consecutive patients with cerebrovascular and other neurologic diseases, ulcerated aortic arch plaques were much more common in those with cerebrovascular disease (16.9 versus 5.1 percent in those with other neurologic diseases), particularly in the 28 patients with no other known cause for stroke such as atrial fibrillation (58 percent) [7].

Protruding or pedunculated plaques, compared to flat or layered plaques, are associated with a higher risk of embolic events [13,17,23,24]. This was illustrated in a study of 36 patients with aortic plaque on TEE [23]. The plaque was pedunculated and mobile in 11 patients (31 percent), and layered and immobile in 25 (69 percent). Embolic events occurred more frequently in those with pedunculated plaques (8 of 11 versus 3 of 25 [73 versus 12 percent]). These mobile thrombi can occasionally be very large (movie 2).

Rupture of "soft" plaque at focal areas of the aorta results in pedunculated thrombi formation (movie 3). Thrombus in these plaques can easily embolize to visceral organs.

The mobile component has been shown to be primarily thrombus either by direct examination during aortic or cardiac surgery [25,26] or by pathologic examination of tissue obtained during surgery or at autopsy [27,28]. Resolution of mobile aortic masses with anticoagulation and fibrinolytic therapy lends further support to the role of thrombus [29-31]. (See 'Treatment' below.)

Conversely, the "shaggy" aorta is defined by diffuse, ulcerated plaque arising in the descending thoracic aorta and extending through the visceral segment. The lumen of the aorta is irregular as seen on CT angiography (image 2), and the contents of the plaque are a mix of atheromatous debris with thrombus coating [32].

Plaque location — Although embolization can be a complication of lesions at any site in the aorta, stroke will occur much more commonly with lesions of the ascending aorta and aortic arch. In a review of 250 patients admitted with ischemic stroke who were compared with consecutive controls, the odds ratio for stroke was 13.8 for patients with plaques >4 mm in the aortic arch compared to 1.5 with such lesions in the descending aorta (figure 1) [8]. (See "Stroke: Etiology, classification, and epidemiology", section on 'Embolism'.)

Conversely, complex aortic plaque arising distal to the left subclavian artery may preferentially manifest as visceral, pelvic, or peripheral embolization syndromes [33]. These patients will present with signs of bowel ischemia, flank pain from renal infarction, livido reticularis of the buttocks and thighs, or acute limb ischemia [32]. (See "Acute mesenteric arterial occlusion" and "Embolism to the lower extremities".)

Cardiovascular procedures — Thromboembolism may occur as a complication of invasive cardiovascular procedures (eg, diagnostic catheterization, percutaneous coronary intervention, intraaortic balloon pump, cardiac surgery, endovascular aortic repair) due to dislodging of debris from the aortic wall when a catheter or wire is advanced in a retrograde fashion from the femoral artery [10,11,21,34-38]. Manipulation of the aorta during open cardiac or aortic surgery is also thought to predispose to embolization due to mechanical disruption of the atheroma.

●In a review of 70 patients with aortic plaque ≥5 mm on TEE, the rate of embolic events was 17 percent after cardiac catheterization via the femoral artery [10]. In comparison, there were no embolic events in those (11 patients) catheterized via the brachial route. In addition, embolic events occurred in 5 of 10 patients with complex aortic plaque treated with an intraaortic balloon pump, compared to no events in 12 patients without complex aortic plaque.

●In a review of 130 patients ≥65 years of age undergoing coronary artery bypass grafting, protruding aortic arch plaques were identified in 23 patients (18 percent), 12 of whom had mobile plaques [11]. The risk of stroke was much higher in those with mobile plaques (3 of 12 versus 2 of 118).

●In a series of 3404 patients undergoing cardiac surgery with cardiopulmonary bypass, intraoperative TEE revealed complex aortic arch plaque (≥5 mm thick and/or mobile) in 268 (8 percent) [37]. Stroke occurred in 12 percent of these patients, sixfold higher than the overall intraoperative stroke risk at that institution. Patients who underwent aortic arch atherectomy in an effort to reduce the stroke risk actually had a higher rate of stroke (35 percent). (See 'Surgery' below and "Neurologic complications of cardiac surgery", section on 'Cerebrovascular disease' and "Neurologic complications of cardiac surgery", section on 'Risk factors'.)

Endovascular aneurysm repair is also associated with an increased risk of embolization and decrease in overall survival in patients with aortic plaque compared with patients without diffuse aortic atheroma. Appropriate consideration for the medical risk of open versus endovascular repair should be undertaken for appropriate planning. (See "Complications of endovascular abdominal aortic repair", section on 'Ischemic complications'.)

CLINICAL MANIFESTATIONS — Clinical manifestations depend upon the arterial segment affected by thromboembolism. In the retrospective cohort study of 519 patients with complex thoracic aortic plaque cited above, the most common manifestations were stroke (50 percent), transient ischemic attack (35 percent), and signs and symptoms of peripheral embolization (14 percent) [16]. The discussion of the differential diagnosis of stroke is found elsewhere. (See "Clinical diagnosis of stroke subtypes" and "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)".)

Complex plaques more commonly involve the mid or distal aortic arch or descending aorta and are relatively uncommon in the ascending aorta. This results in a higher likelihood of embolic events involving the left cerebral hemisphere or the peripheral circulation (image 3), rather than embolic events in the innominate artery distribution (eg, right brain) [17]. (See "Clinical features and diagnosis of acute lower extremity ischemia" and "Overview of intestinal ischemia in adults".)

With thromboembolic events, multiple sites may be simultaneously involved (eg, ischemic colitis, acute renal injury, lower extremity ischemia, visual loss), but concurrent embolization is less common compared with cholesterol embolization, which is typically characterized by showers of small emboli. (See "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)".)

Mortality — Mortality associated with complex aortic plaque may be as high as 20 percent within three years [16]. Almost 20 percent of the deaths are attributed to stroke, and an additional 7 percent to other embolic events (eg, intestinal ischemia).

The presence of aortic plaque also worsens outcomes following cardiovascular procedures:

●In-hospital mortality following cardiac surgery was 15 percent overall and as high as 39 percent with intraoperative stroke during cardiopulmonary bypass in one series [37].

●Complex fenestrated endovascular aortic repair (FEVAR) with evidence of increased aortic thrombus volume on preoperative CT angiography significantly increased incidence of mesenteric ischemia [38]. Among patients developing embolic mesenteric ischemia during FEVAR, 80 percent died as a result of the disease.

●The presence of complex aortic plaque predicts a decreased overall survival after abdominal aortic aneurysm (AAA) repair regardless of technique [21]. This effect is likely secondary to both acute morbidity and mortality from intraoperative embolization of organs as well as being a marker for worse overall atherosclerotic burden.

DETECTION — Imaging techniques that have been used to detect aortic plaques include transesophageal echocardiography (TEE), computed tomographic (CT) angiography, magnetic resonance angiography and transthoracic echocardiography (TTE). (See 'Complex aortic plaque' above.)

TEE is the procedure of choice for the detection and measurement of thoracic aortic plaques, particularly when present in the ascending or proximal descending thoracic aorta, and for cardiac sources of embolization (movie 1 and movie 2). It is moderately invasive, usually requiring conscious sedation, but has a very low complication rate. The discovery of a complex aortic plaque (>4 mm thick, or mobile, ulcerated, or pedunculated) may occur when TEE is performed as part of the evaluation for an acute stroke, peripheral embolism, or for some unrelated reason. If concern for complex aortic plaque is raised during TEE/TTE, follow-up evaluation with CT or MR angiography is warranted prior to any aortic procedure to aid in planning. (See "Echocardiography in detection of cardiac and aortic sources of systemic embolism".)

The accuracy of TEE in detecting and characterizing aortic plaque was illustrated in a study in which TEE was performed during surgery in 31 patients undergoing repair of an aortic aneurysm or dissection; tissue samples were examined pathologically [27]. TEE and pathologic evaluation were in agreement in distinguishing minimal intimal thickening from more severe plaques in 93 percent of the 62 aortic segments examined. TEE also had a high sensitivity and specificity for the detection of thrombus (91 and 90 percent, respectively).

In some patients with thromboembolism from aortic plaque, transthoracic echocardiography may demonstrate the plaques [39]. However, its sensitivity is limited since resolution is insufficient for measuring the prognostically important plaque thickness.

CT angiography is the modality of choice for surgical planning in cases of known or suspected atheromatous aorta. MR angiography may be an alternative for those in whom intravenous contrast is contraindicated. CT angiography provides information about the quality of the aortic wall and allows for qualification of the embolic potential of the plaque by appearance, as well as quantification using scales of luminal irregularity and calculation of thrombus volume [38]. Based on location, placement of clamps or guidewires can be planned preoperatively and techniques used to protect branch vessels during repair to limit embolization.

TREATMENT — Noncoronary atherosclerotic disease is a coronary heart disease risk equivalent, and, as such, all patients with established atherosclerotic aortic plaque, including those who are asymptomatic, should be aggressively treated to prevent future cardiovascular events. These therapies include antithrombotic therapy (aspirin, clopidogrel), lipid-lowering therapy (eg, statins), blood pressure control, smoking cessation, and in patients with diabetes, glycemic control. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

A separate issue is whether specific therapy might prevent a first or recurrent embolization from atherosclerotic plaques in the aorta. Both medical and surgical approaches have been evaluated.

Whether specific medical therapy might prevent a first or recurrent embolization from atherosclerotic plaques in the aorta remains controversial. The mainstays of medical treatment are antiplatelet therapy and HMG-CoA reductase (statin) administration. The role of anticoagulation is reserved for plaques with a majority of thrombotic component as opposed to complex atheromatous plaques.

Antithrombotic therapy — In addition to appropriate lifestyle modification consistent with overall cardiovascular care, we suggest the following medical regimen, which is generally consistent with guideline recommendations [40-42]:

Discrete recommendations for antiplatelet or anticoagulation therapies are generally lacking. This is likely due to the variable composition of the layers of aortic plaques. Classic "shaggy" aortas with diffuse plaque consisting of mostly cholesterol and calcific debris with a lining of thrombus along the flow channel are best treated as overall cardiac risk. In addition to high-intensity statin therapy, aspirin and a secondary platelet aggregation inhibitor are warranted. Some have speculated that anticoagulation in these patients may destabilize the thrombus along the flow channel and predispose to increased embolic events [32,43].

The Aortic Arch Related Cerebral Hazzard (ARCH) trial was a prospective randomized trial of adults with nondisabling ischemic stroke, transient ischemic attack, peripheral embolism, and at least 4 mm atherosclerotic plaque in the thoracic aorta on transesophageal echocardiography [44]. Subjects were randomly assigned to aspirin (75 to 150 mg daily) plus clopidogrel 75 mg daily or warfarin (international normalized ratio 2.0 to 3.0). The trial was stopped prematurely after enrollment of 349 patients due to poor recruitment and lack of ongoing funding. For the warfarin group, the time in the therapeutic range was 67 percent. After a median follow-up of 3.4 years, the primary endpoint (composite of ischemic stroke, myocardial infarction, peripheral embolism, vascular death, or hemorrhagic stroke) occurred significantly less frequently for patients receiving aspirin plus clopidogrel compared with those receiving warfarin (7.6 versus 11.3 percent). Vascular deaths occurred in no patients in the aspirin plus clopidogrel arm and 3.4 percent in the warfarin arm. Major hemorrhage occurred in 2.3 percent of the aspirin plus clopidogrel and 3.4 percent in the warfarin arm. These differences were not statistically significant.

With regards to stroke from more focal ascending aortic plaques, a beneficial effect of anticoagulation with warfarin was suggested by several uncontrolled studies of primary and secondary atherosclerosis prevention [18,29,45,46]. These studies demonstrated a significant risk of stroke in patients with aortic plaque who were not treated with adequate warfarin therapy. The SPAF-III trial compared adjusted-dose warfarin (to maintain an international normalized ratio [INR] of 2 to 3) to low-dose warfarin (INR 1.2 to 1.5) plus aspirin for the prevention of stroke in 1044 patients with atrial fibrillation with at least one thromboembolic risk factor (heart failure or left ventricular fractional shortening ≤25 percent, previous thromboembolism, systolic blood pressure >160 mmHg, or female >75 years of age) [45]. A subset patients (n = 382) underwent observational TEE; in each treatment group, 35 percent of patients had complex aortic plaque (>4 mm, mobile, ulcerated or pedunculated), of which approximately one half were in the ascending or transverse aorta [18]. At a mean follow-up of 1.1 years, the incidence of stroke in patients with complex aortic plaque was 4 percent in those treated with adjusted-dose warfarin (median INR 2.3) compared with 16 percent for those on fixed low-dose warfarin plus aspirin. The risk reduction (75 percent) was the same as in the entire study population, but the absolute benefit was greater (12 versus 6 percent) because patients with complex plaque were at higher risk [45].

No data have been reported regarding the role of direct oral anticoagulants (eg, dabigatran, rivaroxaban, apixaban, edoxaban) in the management of aortic atheroma, and these agents are not recommended for this purpose.

Statin therapy — Statins are reasonable in all patients with complex aortic plaque, as well as patients with simple plaque and a history of otherwise unexplained stroke or peripheral embolism, since such plaques represent systemic atherosclerosis. Statins have a variety of potentially beneficial mechanisms, including anti-inflammatory properties that may be beneficial for those with aortic plaques.

●For patients with no contraindications (ie, low risk of major bleeding) with stroke and complex aortic plaque (≥4 mm thick and/or atheroma with a mobile component), or without stroke but atheroma with a mobile component, high-intensity statin therapy plus dual antiplatelet therapy is warranted.

●The optimal approach for patients without stroke and simple plaque (<4 mm without a mobile component) or diffuse atheromatous plaques ("shaggy" aorta) is controversial because the data are limited. High-intensity statin plus aspirin or clopidogrel 75 mg daily (monotherapy) is likely adequate.

We suggest using the same targets recommended for the secondary prevention of coronary artery disease. (See "Overview of secondary prevention of ischemic stroke" and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

The efficacy of statin therapy in reducing the risk of embolic events in patients with thoracic aortic atherosclerosis has been evaluated in observational studies and small trials. In the previously cited retrospective analysis of 519 patients (64 percent of whom had a history of coronary heart disease), statin therapy was associated with a significant 17 percent absolute reduction in thromboembolic events (12 versus 29 percent in patients not treated with a statin) [16]. This apparent clinical benefit probably reflects, at least in part, stabilization or even regression of aortic plaque, which some have attempted to evaluate using imaging studies [47-56]. In one trial, thickness of thoracic and abdominal aortic plaque was measured using magnetic resonance imaging following 12 months of statin therapy [47]. Patients were randomly assigned to receive 20 mg atorvastatin daily, 400 mg etidronate daily, or both drugs daily. Maximal wall thickness of the thoracic aorta was reduced by 13.8 percent with combination therapy and 12.3 percent in the atorvastatin groups, compared with only 2.2 percent in the etidronate group. Maximal vessel wall thickness of the abdominal aorta was significantly reduced in the combination therapy group compared with the atorvastatin group, or etidronate (11.4 versus 0.9 and 5.5 percent, respectively). Although these results are interesting, there was no correlation between observed changes in aortic wall thickness and clinically significant embolic events [48]. Thus, the impact of these wall thickness changes on potential future clinical or even subclinical events is unknown.

Surgery — The role of surgical therapy to prevent embolization in patients with aortic plaque is not clearly defined. Randomized trials and large observational studies suggest that, among patients with atherosclerosis who undergo coronary artery bypass graft surgery (CABG), the rate of stroke is reduced with minimally invasive off-pump CABG. The use of intraoperative ultrasound (epicardial or transesophageal echocardiography) to direct the sites of aortic manipulation also may be beneficial. (See "Intraoperative transesophageal echocardiography for noncardiac surgery".)

Among patients undergoing cardiac surgery, prophylactic replacement of the aortic arch and aortic arch atherectomy are other procedures that have been evaluated. Aortic arch replacement may be beneficial [57], but prophylactic atherectomy may result in worse outcomes. In one report, aortic arch atherectomy was performed during surgery in 268 patients with >4 mm aortic plaque to reduce the stroke risk [37]. However, these patients had a higher rate of stroke than those in whom atherectomy was not performed (35 versus 12 percent).

Aortic arch atherectomy has been performed with good results in the rare younger patient who is a good operative candidate [25,26]. However, this should be considered an experimental approach. We have had mixed results with this approach and only consider atherectomy when the plaque is highly mobile and very large or there has been further growth despite medical therapy.

Endovascular stenting — Endovascular stent-grafting to manage atheroembolic disease has been reported primarily for descending thoracic and abdominal aortic sources [58-63]. The stent-graft is positioned overlying the atheromatous plaque to exclude it from the circulation, thus preventing subsequent embolization. A case report describes the successful deployment of a thoracic stent-graft to manage a thoracic aortic atheromatous lesion that was the source for massive distal embolization [64]. The endovascular approach is an attractive option for patients who are poor candidates for surgery; however, potential disadvantages include the potential for iatrogenic embolization due to manipulation of catheters in the region of the lesion, and complications related to intravenous contrast.

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

●Thoracic aortic atherosclerotic plaques are an important potential source of systemic emboli (thromboembolus, atheroembolus), leading to stroke, transient ischemic attack, and embolization to visceral and peripheral arterial circulation. The clinical manifestations of thromboembolism depend upon the location of the plaque. (See 'Introduction' above and 'Complex aortic plaque' above and 'Clinical manifestations' above.)

●The risk of thromboembolism in patients with aortic atherosclerosis is markedly increased when there is complex plaque, which is defined as thickness >4 mm or ulceration or mobility of a component of the plaque. (See 'Complex aortic plaque' above.)

●All patients with aortic atherosclerosis with or without a history of otherwise unexplained stroke or peripheral embolism should be treated for secondary prevention of cardiovascular disease. These therapies include antiplatelet therapy (eg, aspirin or clopidogrel), lipid-lowering therapy (eg, statin), blood pressure control, smoking cessation, and, in patients with diabetes, glycemic control. The benefit of antithrombotic therapy for aortic arch plaque with or without stroke is uncertain. (See 'Treatment' above and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

•For patients with stroke and complex aortic plaque (≥4 mm thick and/or atheroma with a mobile component), or patients without stroke but atheroma with a mobile component, dual antiplatelet therapy plus high-intensity statin therapy is warranted.

•The optimal approach for patients without stroke and simple plaque (<4 mm without a mobile component) or diffuse atheromatous plaques ("shaggy" aorta) is controversial because the data are limited. Aspirin or clopidogrel (monotherapy) plus high-intensity statin is likely adequate.

•Although the optimal low density lipoprotein cholesterol target or statin dose intensity is unknown for this population, we believe that using targets similar to those recommended for the secondary prevention of coronary artery disease is appropriate. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk" and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

●Prophylactic surgery for the management of atherosclerotic plaque has been performed, but there is no evidence of benefit. Among patients undergoing cardiac surgery or aortic surgery at risk for aortic atherosclerosis, intraoperative ultrasound may be beneficial to help to guide sites of aortic manipulation or clamping. For secondary prevention, endovascular stent-grafting may be feasible in patients who have had an embolic event. (See 'Surgery' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Emile R Mohler, III, MD (deceased), who contributed to an earlier version of this topic review.