Claudication

Erum Iqbal Bajwa, M.D.
Pranav M. Patel, M.D.

Basic Information

Definition

Claudication refers to reproducible pain, fatigue, or cramping due to vascular origin in a muscle group that is consistently brought on by exertion and is relieved with rest. The pain experienced results from inadequate blood flow to the target muscle group, which is not able to meet increased metabolic demand. Claudication is therefore a supply-and-demand mismatch and is due to peripheral arterial disease (PAD). Intermittent vascular claudication is more common in the lower extremities but can also affect the upper extremities.

Synonyms

Intermittent claudication

ICD-10CM CODES
I70.211	Atherosclerosis of native arteries of extremities with intermittent claudication, right leg
I70.212	Atherosclerosis of native arteries of extremities with intermittent claudication, left leg
I70.213	Atherosclerosis of native arteries of extremities with intermittent claudication, bilateral legs
I70.219	Atherosclerosis of native arteries of extremities with intermittent claudication, unspecified extremity
I70.311	Atherosclerosis of unspecified type of bypass graft(s) of the extremities with intermittent claudication, right leg
I70.312	Atherosclerosis of unspecified type of bypass graft(s) of the extremities with intermittent claudication, left leg
I70.313	Atherosclerosis of unspecified type of bypass graft(s) of the extremities with intermittent claudication, bilateral legs
I70.319	Atherosclerosis of unspecified type of bypass graft(s) of the extremities with intermittent claudication, unspecified extremity
I70.719	Atherosclerosis of other type of bypass graft(s) of the extremities with intermittent claudication, unspecified extremity

Epidemiology & Demographics

•

Symptomatic claudication in Western countries affects 5% of patients between the ages of 55 and 74.
•

Lower-extremity PAD, which includes both symptomatic claudication and asymptomatic disease, is estimated to affect approximately 8.5 million Americans above age 40 yr and 202 million people around the world. This finding demonstrates that a large portion of patients is at risk of developing claudication.
•

Risk factors associated with development of PAD are similar to coronary atherosclerosis (CAD) and include increasing age, cigarette smoking, hypertension, diabetes mellitus, and dyslipidemia. In addition, patients with chronic kidney disease, metabolic syndrome, and elevated levels of C-reactive protein, lipoprotein(a), and homocysteine are at increased risk. Nontraditional risk factors include race/ethnicity, with African American patients being at higher risk. Hispanics also have similar to slightly higher rates of PAD compared to non-Hispanic whites.
•

There is a strong correlation among PAD, CAD, carotid artery stenosis, and generalized cerebrovascular disease. Individuals with known atherosclerotic disease in one vascular bed are likely to have disease in another.
•
The American College of Cardiology/American Heart Association (ACC/AHA) guidelines suggested the following distribution of clinical presentation of PAD in patients 50 yr of age or older:
1. 1.
  
  Asymptomatic: 20% to 50%
2. 2.
  
  Atypical leg pain: 40% to 50%
3. 3.
  
  Classic claudication: 10% to 35%
4. 4.
  
  Critical limb ischemia with threatened limb: 1% to 2%

Physical Findings & Clinical Presentation

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The severity of symptoms varies with degree of PAD, collateral blood supply, and exertional demands.
•
Classic symptoms include exertional calf pain, which limits the patient’s activity and self-resolves with rest within 10 minutes. Claudication can also typically present in the buttock and hip, thigh, calf, or foot, with one or more of the following signs or symptoms, depending on the level and degree of peripheral stenosis:
1. 1.
  
  Diminished or absent pedal pulses
2. 2.
  
  Bruit over the distal aorta, iliac, or femoral arteries
3. 3.
  
  Pallor of the distal extremities and cool to the touch upon elevation.
4. 4.
  
  Rubor with prolonged capillary refill upon dependent positioning.
5. 5.
  
  Trophic changes, including hair/nail loss and muscle atrophy
6. 6.
  
  Non-healing ulcers, necrotic tissue, and gangrene
7. 7.
  
  Weakness, numbness, or heaviness in the lower extremities

•

True vascular claudication must be distinguished from “pseudoclaudication,” which can be caused by severe venous obstruction or insufficiency, chronic compartment syndrome, spinal stenosis, osteoarthritis, and inflammatory muscle diseases. The characteristic features of pseudoclaudication that distinguish it from claudication are summarized in Table 1. Table 2 illustrates the differential diagnosis of intermittent claudication.

TABLE1 Characteristic Features of Pseudoclaudication That Distinguish It from Claudication

	Claudication	Pseudoclaudication
Characteristics	Limb cramping, tightness, fatigue	Similar to claudication with numbness
Location of discomfort	Lower extremity involving buttock, hip, thigh, calf, foot	Similar to claudication
Induced by exercise	Yes	Variable
Reproducible with distance walked	Consistent	Variable
Occurs with standing	No	Yes
Actions which provide relief	Stand	Sit
Time to relief	<5 min	≥30 min

TABLE2 Differential Diagnosis of Intermittent ClaudicationFrom Swartz, MH: Textbook of physical diagnosis, ed 7, Philadelphia, 2014, Saunders.

	Intermittent Claudication	Venous Claudication	Neurogenic Claudication
Quality of pain	Cramping	Aching, heaviness, tightness	“Pins and needles” sensation going down the leg, weakness
Onset	Gradual, consistent	Gradual; can, however, be immediate	Can be immediate
Relieved by	Stopping walking	Activity, elevation of leg	Sitting down, stooping, flexion at the waist
Location	Muscle groups (e.g., buttocks, thigh, calf)	Whole leg	Poorly localized, but can affect whole leg
Legs affected	Usually one	Usually one	Often both

•
Location of pain usually corresponds to analogous anatomy:
1. 1.
  
  Buttock and hip: aortic or iliac disease
2. 2.
  
  Thigh: aorta, iliac, or common femoral artery
3. 3.
  
  Upper two thirds of calf: superficial femoral artery
4. 4.
  
  Lower one third of calf: popliteal artery
5. 5.
  
  Foot: tibial or peroneal artery
•

Asymptomatic PAD is typically diagnosed by screening studies (exercise ankle brachial index, lower-extremity ultrasound) or incidentally on physical exam. Patients who are at significant risk for PAD often have multiple comorbidities that can alter their presentation. In the PARTNERS program report, 47% of those with a new diagnosis of PAD had no history of leg symptoms, 47% had atypical symptoms, and only 6% had classic symptoms.
•

Symptoms of intermittent claudication classically start distally within a muscle group (below the stenosis) and then ascend with continued activity.
•

Rest pain that occurs with leg elevation and is paradoxically relieved by walking may suggest severe PAD.
•

Critical limb ischemia may present as tissue ulceration and gangrene, which require prompt intervention.

Etiology

The primary cause of claudication is peripheral atherosclerosis, resulting in a stenosis that impedes blood flow beyond the level necessary to meet the metabolic demand of limb muscles first with activity and then ultimately at rest.

Diagnosis

Differential Diagnosis

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Spinal stenosis (neurogenic or pseudoclaudication)
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Musculoskeletal disorders: arthritis or myositis
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Degenerative osteoarthritic joint disease, predominantly of the lumbar spine and hips
•

Chronic compartment or popliteal artery entrapment syndrome
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Peripheral neuropathy
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Atheromatous embolization and deep venous thrombosis
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Vasculitis: thromboangiitis obliterans, Takayasu, or giant cell arteritis
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Symptomatic Baker cyst
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Venous claudication

Workup

History and physical findings suggest the diagnosis of claudication and noninvasive studies help confirm the diagnosis.

•

Measurement of resting ankle–brachial index (ABI) should be considered first-line test in patients at risk for PAD.
•
At-risk patients include:
1. 1.
  
  Patients with exertional leg symptoms
2. 2.
  
  Nonhealing lower-extremity wounds
3. 3.
  
  Asymptomatic patients 50 yr or older with a history of smoking or diabetes
4. 4.
  
  Patients younger than age 50 yr with diabetes and an additional cardiovascular risk factor (smoking, dyslipidemia, hypertension, or homocysteinemia)
5. 5.
  
  All patients age 65 yr or older
•

During the initial assessment, patients with PAD should undergo noninvasive blood pressure measurement in both arms at least once; may be repeated at least once every 5 yr.
•

An ABI is the ratio of highest ankle systolic pressure to the highest brachial systolic pressure of either arm. A normal ABI is 1.00 to 1.40. A low ABI has been shown to be an independent predictor of mortality.
•
The severity of PAD is based on the resting ABI. The absolute value of the ABI is reported to 2 decimal places.
1. 1.
  
  Abnormal: ABI at rest ≤0.90
2. 2.
  
  Borderline: ABI 0.9-0.99
3. 3.
  
  Normal: 1.00-1.40
4. 4.
  
  Noncompressible >1.40
•

Segmental systolic pressures are measured at the level of the thigh, calf, ankle, metatarsal, and toes. Normally, successive segments have <20 mm Hg difference in pressures. If the gradient is >20 mm Hg, a significant stenosis is suspected in the interval vascular segment.
•

ABI >1.4 may represent significant PAD caused by heavy calcification. In such cases, measuring a toe–brachial index (TBI) can increase the sensitivity of testing, as highly calcified arteries are incompressible and may have an elevated ABI. A toe–brachial index <0.7 is considered abnormal and diagnostic of PAD.
•

Borderline resting ABI (>0.90 and ≤1.40) in patients with exertional leg symptoms should undergo treadmill ABI testing to evaluate for PAD. This can help differentiate claudication from pesudoclaudication. If posttreadmill ABI is normal, alternative causes of leg pain should be considered. If no treadmill is available, the pedal plantarflexion ABI test is a reasonable alternative.
•

Progression of PAD is considered to have occurred if a decrease in ABI of 0.15 occurs while the patient is in treatment.
•

If a patient has a history concerning for PAD but a normal ABI, and if the clinician is concerned about a potential false-negative finding, performing an exercise stress ABI can potentially demonstrate lower-extremity PAD.
•

If after exercise an ABI reading decreases by more than 20% or an ankle pressure decreases by 30 mm Hg, the patient should be considered to have significant PAD.

Imaging Studies

•

Duplex ultrasound can be used to assess occlusion location, length, and patency of the distal arterial system or prior grafts; it is a good choice for initial imaging.
•

Ultrasound is an excellent noninvasive modality for surveillance monitoring after revascularization.
•

In patients with prior infrainguinal venous bypass grafts, the long-term patency should be evaluated at regular intervals using a duplex ultrasound. The 2016 AHA/ACC guidelines recommend routine surveillance using a duplex ultrasound at approximately 4 to 6 weeks postprocedure, 6 months and 12 months after graft placement, and then yearly.
•

Magnetic resonance angiography (MRA) and CT angiography (CTA) are effective for imaging of the aorta and peripheral lower-extremity arteries above the knee. MRA has almost replaced catheter-based angiography, with 90% sensitivity and 97% specificity in identification of hemodynamically significant stenosis in the lower extremities.
•

MRA and CTA are useful to define the anatomy and assist in planning percutaneous and surgical revascularization; however, the utility of each is decreased by necessity of gadolinium contrast and non-iodinated contrast agents, respectively.
•

CTA of occlusive aortoiliac disease with fractional flow reserve (FFR) has been correlated with invasive angiographic evaluation with FFR and demonstrated, although in a small sample of people the correlation is excellent. One may then surmise that the patients could benefit from noninvasive CTA to plan and evaluate any potential areas of disease amenable to revascularization.
•

Angiography (Fig. 1) remains the gold standard for diagnosing PAD, particularly below the knee.

FIG.1

Angiogram of the distal abdominal aorta and iliac arteries demonstrates an occluded left common

Treatment

Nonpharmacologic Therapy

•

Smoking cessation is of paramount importance. Smokers and former smokers should be asked about tobacco use status on each visit. Assistance and counseling for smoking cessation should be addressed thoroughly.
•

Aggressive risk factor modification for hypertension, dyslipidemia, and diabetes mellitus, including diet, weight loss, and lifestyle counseling, is recommended (Fig. 2)

FIG.2

Algorithm for revascularization in the management of claudication. ACE, Angiotensin-converting enzyme; BP, blood pressure; HbA_1c, hemoglobin A_1c; LDL, low-density lipoprotein; PAD, peripheral arterial disease.

From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.
•

Supervised exercise training should be performed as a first-line therapy for a minimum of 30 to 45 minutes, in sessions performed at least 3 times per week for a minimum of 12 weeks.
•

Supervised exercise training programs under direct supervision in a hospital or outpatient facility and structured exercise are recommended for all patients with PAD. This has been shown to increase maximal walking distance, pain-free walking distance, and the 6-minute walking distance. This treatment modality should be attempted prior to revascularization attempts.
•

Structured or home-based walking exercise program may be considered as an alternative treatment modality, but it has not been shown to be as efficacious. It can be combined with group-mediated cognitive behavioral intervention that can significantly improve endurance and physical activity for patients unable or unwilling to participate in supervised exercise training.
•

Lifestyle therapy in conjunction with exercise can be as or more effective than pharmacologic therapy and in some cases more effective than stent revascularization, as shown by the CLEVER Study.
•

Intermittent pneumatic compression may hold promise as an adjunctive therapy.

Acute General Rx

Revascularization by an endovascular or surgical approach is usually reserved for patients with symptoms refractory to medical therapy or those with impending critical limb ischemia.

Chronic Rx

•

Aspirin 75 to 325 mg daily is standard therapy.
•

Thienopyridine medications such as clopidogrel 75 mg daily may be considered as an alternative to aspirin, especially for those intolerant of aspirin.
•

Current data do not support combination treatment with aspirin and clopidogrel (CHARISMA trial).
•

Asymptomatic patients with PAD (ABI ≤0.90) without claudication symptoms may benefit from the addition of an antiplatelet agent, either ASA or clopidogrel, as there is an increased cardiovascular risk in this subgroup.
•
Hydroxymethyl glutaryl (HMG) coenzyme-A reductase inhibitor (statin) medications are indicated for all patients with PAD.
1. 1.
  
  LDL cholesterol level of less than 100 mg/dl is recommended.
2. 2.
  
  A goal LDL cholesterol level of less than 70 mg/dl is recommended for patients with PAD and high risk for coronary atherosclerotic disease.
3. 3.
  
  Although new lipid guidelines have been published, the guidelines did not specifically address patients with PAD; therefore, the numerical targets can be considered. In those unable to reach the targets, a reduction in LDL >50% should be approached at a minimum.
•
Antihypertensive therapy with beta-adrenergic blocking drugs and/or ACE inhibitors should be administered to all hypertensive patients with PAD to reduce the risk of MI, stroke, congestive heart failure, and cardiovascular death.
1. 1.
  
  In non-diabetics, the target blood pressure is <140 mm Hg systolic over 90 mm Hg diastolic.
2. 2.
  
  In diabetics or patients with chronic renal disease, the target blood pressure is <130 mm Hg systolic over 80 mm Hg diastolic.
3. 3.
  
  Recent hypertension guidelines have raised the targets for some diseases; however, they do not address the higher risk posed by multiple comorbidities.
•

Cilostazol 100 mg bid may be used in conjunction with aspirin or clopidogrel. It has been shown to increase walking distance by 50% to 67% in symptomatic patients.
•

Among patients with intermittent claudication, a single randomized controlled trial has shown a 24-week treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking times compared with placebo. Furthermore, the use of ACE inhibitors may be considered in patients with PAD to reduce the risk of cardiovascular events compared with ARBs, as their effect has not been studied.
•

Pentoxifylline is not effective for treatment of claudication. In a review of 24 studies with over 3000 participants, results remained unclear, and a randomized control trial showed no difference between pentoxifylline and placebo; thus this is not recommended as a treatment for claudication.
•

In patients with type II diabetes, a secondary analysis of the BARI 2D trial showed that an insulin-sensitizing approach (metformin, glitazones) reduces the risk of developing PAD when compared to insulin-providing therapy (glipizide, insulin). These patients also have lower rates of revascularization and amputation.
•

Patients who are tobacco smokers should be advised at every visit to quit smoking and offered either varenicline or bupropion along with nicotine replacement therapy in the absence of any contraindications. Patients with PAD should avoid tobacco smoke exposure at work, at home, and in public places.
•

Anticoagulation should not be used to reduce the risk of cardiovascular ischemic events in patients with PAD, as there is increased morbidity with no mortality benefit (WAVE trial). Its use to improve patency after bypass is uncertain.
•

Novel agents, such as protease-activated receptor-1 (e.g., vorapaxar), added to existing antiplatelet therapy may have some benefit in decreasing acute limb-related ischemic events; however, its association with a risk of moderate to severe bleeding makes its benefits uncertain at this time. There was no cardiovascular benefit demonstrated in symptomatic PAD.
•

Fig. 3 summarizes the nonoperative management of claudication.

FIG.3

Nonoperative management of claudication. CT, Computed tomographic; MR, magnetic resonance; TASC, TransAtlantic Inter-Society Consensus class.

From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.
•
Revascularization through either a percutaneous or surgical approach is indicated in patients with refractory rest pain or claudication that is lifestyle limiting. It is also indicated in those with non-healing ulcers or gangrene and in select patients with functional disability. Before such revascularization, each patient should have:
1. 1.
  
  Participated in a supervised exercise training program and been given goal-directed medical therapy
2. 2.
  
  Received comprehensive risk factor modification, including smoking cessation and optimal management of comorbidities
3. 3.
  
  Significant disability with either the inability to perform normal work or a serious impairment of other activities important to the patient
4. 4.
  
  Lower-extremity PAD lesion anatomy amenable to revascularization, defined by a low risk and a high probability of initial and long-term success
Common procedures include:
1. 1.
  
  Aorto-iliofemoral reconstruction or bypass or infrainguinal bypass (e.g., femoropopliteal, femorotibial).
2. 2.
  
  Percutaneous balloon angioplasty, often with stenting, is primarily used on discrete stenotic lesions in the iliac or femoropopliteal arteries.
3. 3.
  
  Endovascular intervention is recommended as the preferred revascularization technique for iliac and femoropopliteal arterial lesions.
4. 4.
  
  Stenting is effective primary therapy for common and external iliac artery stenosis and occlusions. However, it is not recommended in the femoral, popliteal, or tibial arteries due to a low success rate except to salvage suboptimal balloon dilation.
•

Endovascular procedures should not be performed in patients with PAD solely to prevent progression to critical limb ischemia, as reported rates of amputation or progression to critical limb ischemia are <10% to 15% over 5 years or more, and increased mortality rate associated with claudication is usually the result of cardiovascular events rather than limb-related events.

Complementary & Alternative Medicine

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A meta-analysis found that over 12 to 24 weeks, Ginkgo biloba increased pain-free walking distance by 34 m compared with placebo, although the benefit is not well established according to ACC/AHA guidelines.
•

Naftidrofuryl, a serotonin receptor inhibitor, available in Europe and other parts of the world, has shown some efficacy in improving claudication symptoms.
•

Estrogen replacement therapy, propionyl-L-carnitine, L-arginine, oral vasodilators, prostaglandins, and chelation therapy are ineffective in the treatment of intermittent claudication.
•

B-complex vitamin supplementation to lower homocysteine levels for prevention of cardiovascular events in patients with PAD is not recommended (HOPE-2 trial).

Disposition

•

It is unusual for intermittent claudication to progress to ischemic leg or limb loss, especially with aggressive use of conservative treatments, risk factor modification, exercise, and smoking cessation.
•

The 5-yr risk for development of ischemic ulceration in patients treated for diabetes and with ABI <0.5 was 30% compared with only 5% in patients without either characteristic.
•

A screening duplex ultrasound for abdominal aortic aneurysm (AAA) is recommended for patients with symptomatic PAD.
•

All patients with PAD should receive annual influenza vaccination based on observational studies that have demonstrated a reduced cardiovascular event rate.

Referral

Consultation with physicians specializing in vascular medicine is recommended for the patient with threatened limb loss, rest pain, non-healing ulcers, functional disability from pain, and gangrene.

Pearls & Considerations

•

Approximately 70% of patients with peripheral vascular disease will have concomitant coronary artery disease.
•

Beta-blockers may worsen claudication symptoms in some patients, although their underuse is associated with excess cardiovascular death. Patients with intermittent claudication are less likely to receive beta-blocker therapy after a myocardial infarction. Those who do not receive post-MI beta-blockers have at least a threefold higher mortality.
•

Patients with peripheral vascular disease may benefit from secondary cardiovascular prevention with clopidogrel versus aspirin more so than other high-risk patients (CAPRIE trial).
•

Often, PAD can be asymptomatic or with atypical symptoms, and a thorough history, physical exam, and clinical suspicion based on medical comorbidities may help guide therapy before lifestyle-limiting claudication or limb ischemia develops.

Comments

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Claudication is a marker for generalized atherosclerosis. Patients have a higher risk of death from cardiovascular events than from limb loss. Patients with PAD experience diminished overall quality of life similar to patients with diagnosed coronary artery or cerebrovascular disease.
•

The ABI is more closely associated with exercise tolerance and severity of disease in persons with PAD rather than intermittent claudication or other leg symptoms.

Ferri – Claudication