Upper extremity atherosclerotic disease

INTRODUCTION — Atherosclerotic disease affecting the upper extremity arteries is common and is most often asymptomatic. However, it can cause exertional pain, ischemic pain, gangrene, or ulceration. Exertional pain is a reproducible discomfort of a defined group of muscles induced by exercise and relieved with rest due to an imbalance between blood flow supply and demand.

An overview of the clinical manifestations, diagnosis, and management of atherosclerotic disease of the upper extremity is presented. Surgical and endovascular techniques for upper extremity revascularization, when indicated, are reviewed separately. (See "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization".)

Peripheral artery disease affecting the lower extremities is discussed in detail separately. (See "Overview of lower extremity peripheral artery disease".)

UPPER EXTREMITY ATHEROSCLEROSIS — Atherosclerosis is the most common cause of stenosis of the proximal arteries supplying the upper extremity. Atherosclerotic disease can affect any of the upper extremity arteries, although the subclavian is by far the most affected artery. Risk factors associated with peripheral atherosclerosis include increased age, hypertension, dyslipidemia, and smoking, among others, and are discussed elsewhere. The prevalence of upper extremity atherosclerotic disease is much lower compared with lower extremities [1]. Males are more commonly affected compared with females. (See "Overview of established risk factors for cardiovascular disease".)

Proximal atherosclerotic disease — In a large study of extracranial arterial disease, the incidence of proximal upper extremity artery occlusive disease (subclavian, innominate artery [brachiocephalic] stenosis/occlusion) was 17 percent [2]. Approximately 30 percent of such patients have subclavian artery stenosis [3], which occurs far more commonly on the left side (>75 percent), possibly due to a more acute origin resulting in accelerated atherosclerosis from increased turbulence [4-9]. Innominate disease is also not infrequent and can lead to right-sided steal symptoms.

Distal atherosclerotic disease — While proximal atherosclerotic disease is more commonly recognized, atherosclerosis is a systemic process involving most arterial locations, including the more distal upper extremity arteries (eg, brachial, radial, ulnar arteries) [10-16]. Patients with diabetes can have more distal atherosclerotic disease, which is more often located in the forearm vessels, especially among those with concurrent chronic kidney disease.

In studies evaluating the radial artery as a possible conduit for coronary artery bypass, for creation of a forearm flap, or for hemodialysis arteriovenous access, atherosclerosis is commonly encountered, with most lesions considered mild to moderate [13-15]. Severe atherosclerotic disease in the arteries below the elbow is indicative of severe widespread atherosclerotic disease. In a review of 28 patients undergoing intervention for severe hand ischemia, 68 percent had coronary artery disease, 86 percent had peripheral artery disease, and 50 percent had undergone major lower limb amputation [12]. Typical presentations include patients on hemodialysis with vascular access dysfunction or symptoms of hand ischemia. Medial calcific arteriopathy may be a compounding factor. (See "Overview of peripheral artery disease in patients with diabetes mellitus".)

Occlusive disease affecting the digital arteries can be due to atherosclerosis, but symptomatic disease is more often related to mechanisms such as embolism from proximal sources (eg, atheroembolism, thromboembolism) or other disease processes (eg, thromboangiitis obliterans, the arteritides, systemic sclerosis) [17]. (See 'Differential diagnosis' below and "Overview of upper extremity ischemia", section on 'Isolated hand symptoms'.)

VASCULAR ANATOMY — The subclavian arteries provide blood flow to the upper extremities. On the left, the subclavian artery originates directly from the aorta distal to the left common carotid artery. On the right, blood flows first through the brachiocephalic trunk (ie, innominate artery), which divides into the right common carotid artery and right subclavian artery. The anatomy of the aortic arch can vary (figure 1) and may include an anomalous origin of the subclavian arteries or retroesophageal position.

The vertebral arteries most often arise bilaterally as the first branch of the subclavian artery. In approximately 6 percent of patients, the vertebral artery, especially on the left, may originate directly from the aortic arch [18]. The subclavian artery passes over the first rib posterior to the anterior scalene muscle (figure 2) and becomes the axillary artery at the lateral margin of the first rib.

The axillary artery becomes the brachial artery (figure 3) at the lower margin of the teres major muscle. The brachial artery passes between the biceps and triceps muscles accompanied by the ulnar and median nerves adjacent to the humerus and supplies the soft tissues of the arm. In the antecubital fossa, the brachial artery divides (figure 4) into the radial, interosseous, and ulnar arteries to supply soft tissues of the forearm. Distally at the wrist, the ulnar artery and radial artery supply the hand (figure 5).

Collateral circulation — An extensive collateral circulation around the shoulder usually compensates well for stenosis or occlusion of the innominate, subclavian, or axillary arteries (figure 6). Blood flow is maintained to the arm via connections between the superior and inferior thyroid arteries; vertebral arteries, intercostals, superior epigastric and internal thoracic arteries; profunda cervicis and descending branch of the occipital artery; scapular branches of the thyrocervical trunk and the branches of the axillary artery; and the thoracic branches of the axillary artery with the aortic intercostals [19]. Collateral circulation around the elbow (figure 7) also usually compensates for reduced flow at the level of the elbow. The collateral circulation around the elbow includes contributions from the radial recurrent arteries medially, the anterior and posterior ulnar recurrent arteries and the inferior and superior ulnar collateral arteries medially, and the deep brachial and dorsal interosseous arteries.

CLINICAL FEATURES

Presentations — Most patients with upper extremity atherosclerotic disease are asymptomatic and detected only by a finding of asymmetric arm blood pressures or during ultrasound testing in patients with carotid or coronary artery disease. (See 'Physical examination' below.)

When symptoms occur, they can be related to embolism, or to hemodynamic alterations that reduce perfusion to the extremity, the brain, or heart (in patients with coronary artery bypass grafts).

Chronic upper extremity ischemia — Chronic upper extremity ischemia can occur in association with proximal arterial stenosis due to reduced blood flow. Exercise-induced arm pain/fatigue is relatively common in patients with subclavian stenosis, occurring in approximately one-third of patients. More distal arterial occlusions can result in trophic changes or tissue loss, particularly in patients on dialysis using an arteriovenous access. (See "Overview of upper extremity ischemia", section on 'Chronic ischemia'.)

Vascular steal syndromes — Proximal atherosclerotic disease can produce alterations in flow that may produce cerebrovascular symptoms (ie, subclavian steal syndrome) or cardiac ischemia (ie, coronary-subclavian steal syndrome). However, only a minority of patients with proximal stenosis develop such a condition, predominantly because of the extensive collateral network of vessels around the shoulder (figure 6) [1,20-30]. In a study that identified subclavian stenosis/occlusion in 432 of 7881 patients presenting for ultrasound examination of the extracranial neck vessels, only 38 (8.8 percent) experienced symptoms [9]. (See 'Collateral circulation' above and 'Subclavian steal' below and 'Coronary-subclavian steal' below.)

Subclavian steal — Atherosclerotic disease is one of several etiologies that can cause subclavian steal. Because of the stenotic lesion, pressure is lower in the distal subclavian artery [4,31]. As a result, blood flows from the contralateral vertebral artery to the basilar artery and may flow in a retrograde direction down the ipsilateral vertebral artery, away from the brainstem, a phenomenon known as subclavian steal (figure 8) [3,32]. Reversed flow in the vertebral artery serves as an important collateral pathway for the arm in this setting, although it may have negative neurologic effects.

Subclavian steal syndrome refers to the occurrence of cerebrovascular symptoms due to subclavian steal. Patients with documented steal physiology have a low incidence of developing symptoms [2,33]. Left-sided subclavian steal is more prevalent due to the propensity for atherosclerosis on the left, although right-sided steal has also been reported (image 1) [34-36]. The clinical features and diagnostic criterial for subclavian steal syndrome are reviewed separately. (See "Subclavian steal syndrome".)

Coronary-subclavian steal — A coronary-subclavian steal has been described in patients who have undergone prior coronary artery bypass surgery (CABG) using the internal mammary artery (IMA) [37-39]. In the presence of a hemodynamically significant subclavian artery stenosis proximal to the origin of the ipsilateral IMA, flow through the IMA may reverse and steal flow from the coronary circulation with upper extremity exercise causing symptoms (figure 9) .

Patients who have had a prior cardiac bypass who present with a measurable blood pressure difference in the upper extremities in the setting of chest pain should be evaluated for coronary-subclavian steal. Coronary artery and graft angiography will demonstrate retrograde flow in the involved IMA [40].

Identification of a significant subclavian artery stenosis prior to CABG can prevent this important problem [41,42]; however, there is little guidance concerning screening. The prevalence of subclavian artery stenosis is approximately 5 percent in patients referred for coronary artery bypass grafting [43,44]. Patients identified with high-grade subclavian artery stenosis should be treated (percutaneously or surgically) prior to CABG [41]. In one review, complications, mortality, and symptom recurrence were similar for patients with symptomatic subclavian lesions who required coronary artery bypass, using a combined or staged approach to revascularization [42].

Thromboembolism — Acute thrombosis or embolism from atherosclerotic plaque can cause peripheral ischemia distally leading to acute extremity symptoms [45]. Physical signs may involve the entire extremity with classic symptoms (ie, pain, pallor, pulselessness, coolness of the extremity [ie, poikilothermia], paresthesia, paralysis) or be limited to the more distal circulation. When collateral circulation is insufficient to compensate, minor sensory deficits develop as a sign of early nerve dysfunction; major sensory or motor loss indicates advanced ischemia. (See "Overview of upper extremity ischemia", section on 'Acute ischemia' and "Embolism to the upper extremities".)

Atherosclerotic disease of the proximal vasculature can also be a source of embolism, causing transient cerebrovascular ischemia or stroke affecting the anterior or posterior cerebral circulation [46]. (See "Stroke: Etiology, classification, and epidemiology", section on 'Embolism'.)

Physical examination

Blood pressure differential — A difference in brachial systolic blood pressure between the affected and normal arm of at least 10 mmHg indicates a significant proximal stenosis. A systematic review identified 20 studies evaluating blood pressure differentials in the upper extremity [47]. In noninvasive studies, a pooled difference of ≥15 mmHg or more was associated with a significant stenosis with high specificity (specificity 96 percent, 95% CI 94-98). A large pressure differential of >40 mmHg between the upper extremities is more commonly associated with symptoms and the need for treatment. (See "Overview of upper extremity ischemia".)

If a blood pressure difference is identified, we repeat the blood pressure measurement in both arms to confirm the finding. In a small cohort study of cardiac surgery patients, approximately 40 percent with a systolic pressure differential in the arm of 15 mmHg or more had a subclavian stenosis [48]. The authors also reported that 10 percent of those without a difference in blood pressure also had subclavian artery stenosis. However, this finding may reflect an inadequate pressure measurement technique.

The blood pressure differential in the upper extremity can be confirmed in the vascular laboratory. (See "Noninvasive diagnosis of upper and lower extremity arterial disease", section on 'Upper extremity segmental pressures'.)

Vascular examination — Simultaneous palpation of both radial artery pulses may disclose a decrease in amplitude and delay in arrival on the affected side, but this may be difficult to appreciate in the absence of an obvious blood pressure differential (waveform 1).

It is important to examine the subclavian arteries in the supraclavicular fossa using palpation (pulse character and thrills) and auscultation for paraclavicular bruits. The carotid arteries in the neck should also be carefully examined for evidence of occlusive arterial disease. Auscultation over the suboccipital region for vertebral artery bruits should also be performed.

Approximately 6 percent of patients with asymptomatic neck bruits have a significant lesion on duplex scanning [34,49]. In one prospective study, among 500 patients with asymptomatic neck bruits, 9 percent had subclavian stenosis [49]. None of the patients had exertional upper extremity pain but approximately half had evidence of subclavian steal physiology.

Evaluate the skin of the hands and nail beds for signs of atheroembolism from atherosclerotic lesions, which may cause blue fingers, livedo reticularis, digital ischemia, ulceration, or splinter hemorrhages under the nail beds. (See "Embolism to the upper extremities".)

Patients with an abnormal upper extremity examination may also have clinical findings consistent with lower extremity peripheral artery disease (PAD; eg, claudication symptoms, reduced lower extremity pulses, ankle-brachial index ≤0.9). (See "Noninvasive diagnosis of upper and lower extremity arterial disease".)

An analysis of several large patient cohorts reported subclavian stenosis in 6 percent of men and 9.7 percent of women who had lower extremity PAD. By comparison, less than 2 percent of individuals without lower extremity PAD had subclavian stenosis [5].

DIAGNOSIS — Upper extremity atherosclerotic disease may be suspected based on clinical features (exertional pain, differential blood pressures, distal embolization, steal syndromes), but the diagnosis requires the demonstration of an atherosclerotic stenosis or occlusion on vascular imaging (duplex ultrasound, angiography). For symptomatic patients, it is also important to confirm that the location and severity of the lesion is sufficient to be the cause of the patient's symptoms is also necessary.

Duplex ultrasound — Duplex ultrasound of extracranial cerebrovascular and upper extremity arterial circulation is the first-line imaging modality for the detection of upper extremity atherosclerotic disease. Duplex ultrasound also demonstrates steal physiology if present. (See "Noninvasive diagnosis of upper and lower extremity arterial disease", section on 'Duplex ultrasound'.)

For patients with suspected upper extremity atherosclerotic disease, duplex ultrasound will often identify the specific site and severity of stenosis or occlusion [50]. The waveform distal to a proximal stenosis will be blunted. If the vessel is occluded, no blood flow will be seen, but collateral vessels may be apparent.

For the subclavian artery, a peak systolic velocity (PSV) >240 cm/second predicted significant (>70 percent) subclavian artery stenosis [51]. Using these values, the sensitivity and specificity was 90.9 and 82.5 percent, respectively. In a later review, optimal cutoff values were PSV ≥340 cm/second and PSV ratio ≥3 in predicting ≥70 percent stenosis [50]. Duplex ultrasound is also highly accurate for the assessment of significant extracranial carotid artery occlusive disease.

Duplex also demonstrates reversal of flow in the ipsilateral vertebral artery (image 2), if present. The likelihood of finding reversed flow in the vertebral artery increases with increasing severity of subclavian artery stenosis. Among patients with subclavian stenosis who have yet to demonstrate retrograde flow, a continuum of changes in the pulse contour of antegrade vertebral artery waveforms manifesting largely in the systolic portion of the cardiac cycle appears to represent the earliest signs [52]. The cardinal feature is the transient sharp decrease in blood flow velocity at peak systole. Recognition of these early changes may identify patients at risk for the eventual development of the subclavian steal syndrome [53,54]. In patients with moderate subclavian artery stenosis (approximately 50 percent narrowing), flow reversal in the vertebral artery is constant in 56 percent and intermittent in 36 percent. When severe stenosis (>80 percent narrowing) of the proximal subclavian artery is present, 65 percent of patients have constant flow reversal in the ipsilateral vertebral artery, and 30 percent have intermittent flow reversal (ie, "to-and-fro" waveform pattern on duplex) [33,55].

While not commonly needed or routinely performed, a reactive hyperemia test can be performed during ultrasound examination to uncover occult or intermittent subclavian steal [56-58]. To do this, a blood pressure cuff is applied to the ipsilateral extremity and inflated to at least 20 mmHg above systolic pressure for three to four minutes. This produces ischemia and compensatory vasodilation distal to the cuff. After cuff deflation, blood flow will increase in the upper extremity, and for patients with an otherwise asymptomatic subclavian stenosis, reversal of blood flow in the ipsilateral vertebral artery may be observed with ultrasound and symptoms may be provoked [52].

Angiography — Computed tomography (CT) angiography is indicated in symptomatic patients with upper extremity atherosclerotic disease who have abnormal findings on duplex ultrasound to confirm and grade any stenotic lesions or when ultrasound is nondiagnostic. CT angiography can also reveal other anatomic abnormalities or pathology such as thrombosis, aneurysm, and vasculitis [9,59,60].

Contrast-enhanced magnetic resonance (MR) angiography combined with phase-contrast MR imaging characterizes the majority of supra-aortic arteries with excellent image quality and diagnostic values comparable to CT angiography or conventional catheter-based arteriography for detection of arterial stenoses [61,62]. MR angiography is also accurate and reliable for patients with subclavian stenosis [63]. Flow reversal in the vertebral artery ipsilateral to a subclavian stenosis is inferred from presence of vertebral artery patency on three-dimensional contrast-enhanced MR but absence of flow on time-of-flight localizer images [64]. In addition to evaluation of the extracranial vessels, MR also provides detailed anatomic information of the intracranial cerebrovascular circulation. Pitfalls in using MR to evaluate the subclavian artery include the possibility of overestimating the severity of stenosis and the inability to discriminate near-complete from complete arterial occlusion.

Digital subtraction arteriography is generally not needed to establish a diagnosis, but when performed prior to endovascular intervention, concurrent intracranial atherosclerotic disease and anomalies of the circle of Willis can also be identified.

DIFFERENTIAL DIAGNOSIS — Atherosclerosis is the most common cause of ischemic upper extremity disease (table 1), but upper extremity ischemia (acute or chronic) can be caused by other large artery diseases such as arterial injury, arterial dissection, thrombosed aneurysm, atheroembolism, thromboembolism, thromboangiitis obliterans, fibromuscular dysplasia, arteritis (eg, Takayasu disease, giant cell arteritis), and repetitive arterial injury (thoracic outlet syndrome, crutch injury) [65,66]. (See "Overview of upper extremity ischemia".)

Patients who present with a differential blood pressure in the setting of acute chest pain should be evaluated for an acute aortic syndrome (eg, aortic dissection, aortic intramural hematoma). (See "Clinical features and diagnosis of acute aortic dissection".)

MANAGEMENT

Cardiovascular risk reduction — Upper extremity atherosclerotic disease is associated with an increased risk of overall mortality and mortality related to cardiovascular disease. Upper extremity atherosclerotic disease has also been frequently associated with atherosclerosis involving other large vessels, particularly the carotid, coronary, and lower extremity arteries.

●In one systematic review, blood pressure differentials in the upper extremity (≥15 mmHg or more) were associated with increased cardiovascular mortality (four cohorts; hazard ratio [HR] 1.7, 95% CI 1.1-2.5) and all-cause mortality (HR 1.6, 1.1-2.3) [47].

●A study using baseline and longitudinal data for three cohorts (1778 participants recruited from two noninvasive vascular laboratories and one community dwelling) over a mean of 9.8 years [67]. Subclavian stenosis predicted total and cardiovascular disease mortality independent of cardiovascular risk factors and cardiovascular disease identified at baseline.

Risk management and therapies to improve outcomes in patients with peripheral artery disease and for secondary prevention of cardiovascular disease are discussed in detail separately. (See "Overview of lower extremity peripheral artery disease", section on 'Risk factor modification' and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

When to intervene

Asymptomatic — Revascularization is uncommonly needed in patients with asymptomatic proximal upper extremity disease but may be warranted prior to coronary artery bypass grafting that will use an internal mammary artery graft or in selected hemodialysis patients to allow the creation or preservation of an upper extremity hemodialysis access.

Symptomatic — For symptomatic patients, vascular intervention is required for those with:

●A threatened upper extremity (eg, acute limb ischemia, chronic limb-threatening ischemia) to restore perfusion, alleviate symptoms, and heal any ulcers

●Significant cardiac symptoms related to coronary-subclavian steal syndrome

●Embolization (cerebral, peripheral) from the lesion to exclude it from the circulation and prevent future ischemia

●End-stage kidney disease to allow the creation or preservation of upper extremity hemodialysis access

Revascularization in patients with subclavian steal syndrome is controversial. Whether the identified subclavian steal physiology is the principal cause of reported neurologic symptoms may be difficult to determine. As a result, the approach to revascularization in these patients is individualized. (See "Subclavian steal syndrome", section on 'Atherosclerotic subclavian steal syndrome'.)

Intervention for proximal disease — Selection of the most appropriate intervention (surgical, endovascular) is individualized based on anatomic factors (eg, lesion severity, location, calcification, proximity to the vertebral artery), the presence of concomitant ipsilateral carotid disease, and the patient's overall medical status.

For symptomatic proximal stenosis or occlusion, options include surgical and percutaneous transluminal angioplasty and stenting [68-70]. Surgical revascularization is more durable compared with endovascular intervention. However, percutaneous angioplasty/stenting may be associated with less perioperative morbidity. Techniques for proximal upper extremity revascularization are reviewed separately. (See "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization".)

●Endovascular intervention – High-quality data are limited and a 2022 systematic review found no randomized trials comparing angioplasty alone with stenting for subclavian artery stenosis [68]. However, retrospective studies suggest that endovascular intervention in the subclavian artery is safe with low morbidity and mortality; one study of 110 patients who had percutaneous transluminal angioplasty reported a 3.6 percent combined stroke and death rate [71]. Immediate technical success is greater than 93 percent of patients, with failures usually related to an inability to cross occluded lesions [72-74]. Five-year primary patency rates are approximately 85 percent [73]. In a single-center retrospective review of 167 patients with left subclavian artery stents who were being evaluated for coronary artery bypass, stent patency rates were 75.2 percent at 10 years [75]. Freedom from reintervention for the target vessel and sustained resolution of ischemic symptoms is observed in most patients (>95 percent) [71,73,74,76-78]. Whether angioplasty alone has inferior outcomes compared with angioplasty and stenting depends on the nature of the lesion being treated [79,80]. Angioplasty alone has inferior outcomes when recanalizing occlusive subclavian lesions. (See "Surgical and endovascular techniques for aortic arch branch and upper extremity revascularization", section on 'Angioplasty/stenting'.)

●Surgical revascularization – Extra-anatomic revascularization (eg, carotid-subclavian bypass [81,82], subclavian-carotid transposition [83]) are the most common form of surgical revascularization for proximal stenosis. As with angioplasty and stenting, high-quality data from randomized trials are lacking. Overall patency rates of 95 percent at one year, 86 percent at three years, and 73 percent at five years have been reported [84]. Procedures using the common carotid artery as the donor vessel generally have high patency rates at five years compared with those using the contralateral subclavian or axillary arteries (83 versus 46 percent) [84]. Axillo-axillary bypass is an alternative method of extra-anatomic revascularization that can be used in high-risk surgical patients [85].

Significant (>70 percent) recurrent stenosis or obstruction following subclavian revascularization occurs in approximately 10 percent of patients. In a review of 114 patients, assisted primary patency and freedom from recurrent symptoms was worse in patients presenting with arm ischemia compared with those presenting with cardiac or posterior circulation symptoms at five years [86]. Recurrent lesions are typically treated with repeat angioplasty; however, surgery may be required in up to 5 percent of patients [71]. Patients with a continuous (compared with intermittent) subclavian and coronary artery steal may have a higher risk of subclavian artery restenosis following endovascular intervention [87].

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: Occlusive carotid, aortic, renal, mesenteric, and peripheral atherosclerotic disease".)

SUMMARY AND RECOMMENDATIONS

●Upper extremity atherosclerosis – Although symptoms due to peripheral artery disease (PAD) are more common in the lower extremities, upper extremity exertional pain, pain at rest, and sometimes tissue loss may also manifest in the upper extremities due to atherosclerotic disease, which is predominantly related to disease in the subclavian artery, but distal vessels can also be affected. (See 'Upper extremity atherosclerosis' above.)

●Arterial anatomy – The subclavian arteries provide blood flow to the upper extremities. On the left, the subclavian artery originates directly from the aorta distal to the left common carotid artery. On the right, blood flows first through the innominate artery, then into the right subclavian artery. The collateral circulation around the shoulder (figure 6) and elbow (figure 7) is usually sufficient to provide flow around a focal stenosis in proximal vasculature. (See 'Vascular anatomy' above.)

●Clinical features

•No symptoms – Most patients with upper extremity atherosclerotic disease have few to no symptoms because of the robust collateral circulation. Those with proximal atherosclerotic disease may manifest with a significant difference in brachial systolic blood pressure (>15 mmHg differential) between the affected and normal extremity, and for many, the finding is incidental. (See 'Clinical features' above and 'Physical examination' above.)

•Symptoms – When symptoms do occur, exertional arm pain or posterior circulation symptoms (eg, dizziness, vertigo) are most common. However, evidence of distal thromboembolism, acute limb ischemia, or more severe chronic ischemic symptoms (eg, rest pain) can occur. In some patients, stenosis or occlusion proximal to the origin of the vertebral artery can cause reversal of flow in the vertebral artery, which in association with cerebrovascular symptoms is referred to as subclavian steal syndrome (figure 8). In patients with an internal mammary artery (IMA) bypass graft to the heart, a coronary steal syndrome can similarly occur (figure 9). (See 'Clinical features' above.)

•Physical examination – On physical examination, in addition to a blood pressure differential, patients may exhibit reduced distal pulses in the affected upper extremity and a thrill or bruit overlying the affected vasculature.

●Diagnosis – For patients with suspected upper extremity atherosclerotic disease, duplex ultrasound is the first-line imaging study to identify and quantify the severity of any stenoses. Duplex ultrasound can also demonstrate reversal of flow in the ipsilateral vertebral artery if present. If needed, angiography that includes the aortic arch vessels and intracranial vessels can be accomplished with CT, MR, or occasionally, digital subtraction arteriography. (See 'Diagnosis' above.)

●Differential diagnosis – Atherosclerosis is the most common cause of ischemic upper extremity disease (table 1), but other causes include other large artery vascular diseases such as arterial injury, arterial dissection, thrombosed aneurysm, atheroembolism, thromboembolism, fibromuscular dysplasia, arteritis (eg, giant cell arteritis, Takayasu disease, giant cell arteritis), and repetitive arterial injury. (See 'Differential diagnosis' above.)

●Risk reduction – Upper extremity atherosclerotic disease is a marker for atherosclerotic disease in other arterial beds (eg, carotid, coronary, lower extremity arteries) and is associated with an increased risk of morbidity and mortality. All patients with atherosclerotic disease benefit from secondary prevention measures such as smoking cessation, control of hypertension, lipid modification, and antiplatelet therapy. (See 'Cardiovascular risk reduction' above.)

●When to intervene – (See 'When to intervene' above.)

•For most asymptomatic patients, no specific intervention is generally necessary, other than cardiovascular risk reduction. However, intervention may be needed prior to coronary artery bypass grafting that will use an IMA graft or in selected hemodialysis patients to allow the creation or preservation an upper extremity hemodialysis access.

•For symptomatic patients, in addition to cardiovascular risk reduction, vascular intervention is required for those with:

-A threatened upper extremity (eg, acute limb ischemia, chronic limb-threatening ischemia) to restore perfusion, alleviate symptoms, and heal any ulcers

-Significant cardiac symptoms related to coronary-subclavian steal syndrome

-Embolization (cerebral, peripheral) related to the lesion to prevent future ischemia

-End-stage kidney disease to allow the creation or preservation of upper extremity hemodialysis access

●Choice of intervention – Selection of the most appropriate intervention (surgical, endovascular) is individualized based upon anatomic factors (eg, lesion severity, location, calcification, proximity to the vertebral artery), the presence of concomitant ipsilateral carotid disease, and the patient's overall medical status. For proximal lesions (subclavian artery, innominate artery), extra-anatomic reconstruction is more durable compared with endovascular intervention. However, percutaneous angioplasty/stenting may be associated with less perioperative morbidity. (See 'Intervention for proximal disease' above.)

ACKNOWLEDGMENTS

The UpToDate editorial staff acknowledges Neal R Barshes, MD, MPH, FACS, who contributed to earlier versions of this topic review.

The UpToDate editorial staff also acknowledges Emile R Mohler, III, MD (deceased), who contributed to earlier versions of this topic review.