Claudication

Claudication 

Claudication refers to reproducible pain, fatigue, discomfort, or cramping due to vascular origin in a muscle group that is consistently induced by exertion and is relieved with rest.

Claudication results from inadequate blood flow to the target muscle group, which is not able to meet increased metabolic demand, resulting in a supply-and-demand mismatch due to peripheral arterial disease (PAD).

Intermittent vascular claudication is more common in the lower extremities but can also affect the upper extremities.

Synonym

  • Intermittent claudication

Epidemiology & Demographics

  • •Symptomatic claudication in Western countries affects 5% of patients between the ages of 55 and 74.
  • •PAD, which includes both symptomatic claudication and asymptomatic disease, is estimated to affect approximately 40 to 45 million Americans and over 200 million people around the world.
  • •At-risk patients include:
    • 1.All patients age 65 yr or older
    • 2.Age 50 to 64 yr with risk factors for atherosclerosis, including diabetes mellitus, smoking history, hyperlipidemia, hypertension, or family history of PAD
    • 3.Age <50 yr, with diabetes mellitus and one additional risk factor for atherosclerosis
    • 4.Individuals with known atherosclerotic disease in another vascular bed, for example, coronary, carotid, subclavian, renal, mesenteric artery, or abdominal aortic aneurysm (AAA)
  • •Risk factors associated with development of PAD are similar to coronary atherosclerosis (CAD) (odds ratio 2.6) and include increasing age, cigarette smoking (odds ratio 2.7), hypertension (odds ratio 1.6), diabetes mellitus (odds ratio 1.9), and hypercholesterolemia (odds ratio 1.2). 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.Asymptomatic: 20% to 50%
    • 2.Atypical leg pain: 40% to 50%
    • 3.Classic intermittent claudication: 10% to 35%
    • 4.Critical limb ischemia with threatened limb: 1% to 2%

What are the Symptoms of Claudication?

Physical Findings & Clinical Presentation

  • •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.Diminished or absent pedal pulses
    • 2.Bruit over the distal aorta, iliac, or femoral arteries
    • 3.Pallor of the distal extremities and cool to the touch upon elevation
    • 4.Rubor with prolonged capillary refill upon dependent positioning
    • 5.Trophic changes, including hair/nail loss and muscle atrophy
    • 6.Nonhealing ulcers, necrotic tissue, and gangrene
    • 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 the below tables illustrates the differential diagnosis of intermittent claudication.View full size

Distinguishing Characteristics between Pseudoclaudication and Claudication

ClaudicationPseudoclaudication
CharacteristicsLimb cramping, tightness, fatigueSimilar to claudication with numbness
Location of discomfortLower extremity involving buttock, hip, thigh, calf, footSimilar to claudication
Induced by exerciseYesVariable
Reproducible with distance walkedConsistentVariable
Occurs with standingNoYes
Actions which provide reliefStandSit
Time to relief<5 min≥30 min

Differential Diagnosis of Intermittent Claudication

From Swartz MH: Textbook of physical diagnosis, ed 7, Philadelphia, 2014, Saunders.

Intermittent ClaudicationVenous ClaudicationNeurogenic Claudication
Quality of painCrampingAching, heaviness, tightness“Pins and needles” sensation going down the leg, weakness
OnsetGradual, consistentGradual; can, however, be immediateCan be immediate
Relieved byStopping walkingActivity, elevation of legSitting down, stooping, flexion at the waist
LocationMuscle groups (e.g., buttocks, thigh, calf)Entire leg, worse in calfPoorly localized, but can affect whole leg
Legs affectedUsually oneUsually oneOften both
  • Location of pain usually corresponds to analogous anatomy:
    • 1.Buttock and hip: Aortic or iliac disease
    • 2.Thigh: Aorta, iliac, or common femoral artery
    • 3.Upper two thirds of calf: Superficial femoral artery
    • 4.Lower one third of calf: Popliteal artery
    • 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.

What causes Claudication?

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.Other etiologies include neuropathy, musculoskeletal or degenerative disease, compartment or entrapment syndrome, vasculitis, and embolic events.

Differential Diagnosis

  • •Spinal stenosis (neurogenic or pseudoclaudication)
  • •Musculoskeletal disorders: Arthritis or myositis
  • •Degenerative osteoarthritic joint disease, predominantly of the lumbar spine and hips
  • •Chronic compartment or popliteal artery entrapment syndrome
  • •Peripheral neuropathy
  • •Sciatica
  • •Atheromatous embolization and deep venous thrombosis, superficial thrombophlebitis
  • •Vasculitis: Thromboangiitis obliterans, Takayasu, or giant cell arteritis
  • •Symptomatic Baker cyst
  • •Venous claudication
  • •Raynaud phenomenon

How is Claudication diagnosed?

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

  • •Careful physical examinations include:
    • 1.Measurement of blood pressure in both arms and notation of asymmetry
    • 2.Palpation and recording of carotid pulses, upstroke, amplitude, and presence of bruits
    • 3.Auscultation and palpation of abdomen for bruits, aortic pulsation, and diameter
    • 4.Palpation of brachial, radial, ulnar, femoral, popliteal, dorsalis pedis, and posterior tibial pulses. Pulse intensity should be recorded as follows: 0, absent; 1+, diminished; 2+, normal; 3+, bounding
    • 5.Auscultation of femoral arteries for the presence of bruits.
    • 6.Extremities should be inspected for color, temperature, integrity of the skin, hair loss, and hypertrophic nails
  • •Measurement of resting ankle–brachial index (ABI) should be considered first-line test in patients at risk for PAD.
  • •An ABI is the ratio of higher ankle systolic pressure (between the dorsalis pedis and posterior tibial arteries) of each leg to the higher systolic pressure of either arm (brachial artery).
  • •When measuring ABI, brachial pressures in both arms should be taken to avoid underestimating pressure due to subclavian artery stenosis.
  • •The severity of PAD is based on the resting ABI:
    • 1.Severe PAD: <0.4
    • 2.Moderate PAD: 0.4 to 0.69
    • 3.Mild PAD: 0.70 to 0.90
    • 4.Borderline: 0.91 to 0.99
    • 5.Normal: 1.00 to 1.40
    • 6.Noncompressible: >1.40
  • •ABI ≤0.90 has 75% sensitivity and 86% specificity in the detection of PAD.
  • •A low ABI has been shown to be an independent predictor of mortality.
  • •A high ABI (>1.4) may represent significant PAD caused by arterial wall stiffening. 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 exercise treadmill ABI testing to evaluate for PAD. This can help differentiate claudication from pseudoclaudication. If posttreadmill ABI is normal, alternative causes of leg pain should be considered.
  • •Progression of PAD is considered to have occurred if a decrease in ABI of 0.15 occurs while the patient is on 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, 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.
  • •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.

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 and 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 approximately 4 to 6 wk postprocedure, 6 and 12 mo 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 noniodinated contrast agents, respectively.
  • •Angiography remains the gold standard for diagnosing PAD, particularly below the knee.

Nonpharmacologic Therapy

  • •Smoking cessation is of paramount importance. Smokers and former smokers should be asked about tobacco use status at every visit and offered pharmacotherapy, counseling, and/or referred to smoking cessation programs (Class I, A).
  • •Aggressive risk factor modification for hypertension, dyslipidemia, and diabetes mellitus, including diet, weight loss, and lifestyle counseling, is recommended
  • 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 wk.
  • •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. It typically requires 4 to 6 wk for patients to notice improvement.
  • •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 significantlyimprove 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.
  • •Intermittent mechanical compression appears to be an effective noninvasive treatment alternative for patients with intermittent claudication.

Acute General Treatment

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 Treatment

  • •One antiplatelet agent, either aspirin 81 mg daily or clopidogrel 75 mg daily, should be initiated for symptomatic patients and those undergoing endovascular or surgical revascularization (Class I, A).
  • •Dual antiplatelet therapy is recommended for after infrainguinal stenting and carotid artery stenting for at least 1 mo (Class IIa, C) and single agent afterward.
  • •Asymptomatic patients with PAD (ABI ≤0.90) without claudication symptoms may benefit from the addition of an antiplatelet agent (Class IIa, C), either ASA or clopidogrel, as there is an increased cardiovascular risk in this subgroup.
  • •Statin medications are indicated for all patients with PAD (Class I, A).
    • 1.LDL cholesterol level of less than 100 mg/dl is recommended.
    • 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.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.
  • •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 (Class I, A).
  • •Among patients with intermittent claudication, a single randomized controlled trial has shown a 24-wk treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking times compared with placebo.
  • •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, thiazolidinediones) 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 strongly advised to quit smoking at every visit 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. Its use to improve patency after bypass is uncertain (Class III, A).
  • •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.
  • Revascularization through either a percutaneous or surgical approach is indicated in patients with lifestyle-limiting claudication and inadequate response to goal-directed medical therapy. It is also indicated in those with nonhealing ulcers or gangrene and in select patients with functional disability. Before such revascularization, each patient should have:
    • 1.Participated in a supervised exercise training program and been given goal-directed medical therapy.
    • 2.Received comprehensive risk factor modification, including smoking cessation and optimal management of comorbidities.
    • 3.Significant disability with either the inability to perform normal work or a serious impairment of other activities important to the patient.
    • 4.Lower-extremity PAD lesion anatomy amenable to revascularization defined as low risk with high probability of initial and long-term success.
  • •Common procedures include:
    • 1.Percutaneous balloon angioplasty can be used for long lesions or diffuse disease and has initial success rate of 90% but >60% restenosis rate over 12 mo. Balloon angioplasty combined with stenting is primarily used on discrete stenotic lesions in the iliac or femoropopliteal arteries.
    • 2.Aortoiliofemoral reconstruction or bypass or infrainguinal bypass (e.g., femoropopliteal, femorotibial).
    • 3.Endovascular intervention is recommended as the preferred revascularization technique for iliac and femoropopliteal arterial lesions. In LEVANT II trial, endovascular stenting had greater primary patency rate than balloon angioplasty in patients with claudication at 12 mo.
    • 4.Stenting is an 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.
    • 5.In severe, nonreversible cases with gangrene, amputation may be required.
  • •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 yr or more, and increased mortality rate associated with claudication is usually the result of cardiovascular events rather than limb-related events.

Complementary & Alternative Medicine

  • •A meta-analysis found that over 12 to 24 wk, 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).
  • •Acupuncture has shown some improvement in symptom relief and functional capacity in small studies but mainly in neurogenic claudication or mild peripheral arterial disease.

What is the Prognosis?

  • •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.
  • •Among patients with claudication, 70% to 80% remain with stable claudication, 10% to 20% with worsening symptoms, and critical limb ischemia in 1% to 2% in 5 yr. The risk for nonfatal cardiovascular event is 20% and death is 15% to 30%.
  • •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 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 patients with threatened limb loss, rest pain, nonhealing 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.
  • •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

  • •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 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.

Seek Additional Information

  • Aboyans V., et al.: 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper, and lower extremity arteries. Endorsed by: the European Stroke Organization (ESO), the Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J 2018; 39 (9): pp. 763-816.
  • Ahimastos A.A., et al.: Effect of ramipril on walking times and quality of life among patients with peripheral artery disease and intermittent claudication: a randomized controlled trial. JAMA 2013; 309 (5): pp. 453-460.
  • Anderson J.L., et al.: Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61 (14): pp. 1555-1570.
  • Crawford F., et al.: Ankle brachial index for the diagnosis of lower limb peripheral arterial disease. Cochrane Database Syst Rev 2016; 9 (CD010680):
  • Gerhard-Herman M.D., et al.: 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017; 69: pp. 1465-1508.
  • Hamburg N., et al.: Exercise rehabilitation in peripheral artery disease functional impact and mechanisms of benefits. Circulation 2011; 123 (1): pp. 87-97.
  • Kithcart A.P., Beckman A.J.: ACC/AHA versus ESC guidelines for diagnosis and management of peripheral artery disease: a JACC guideline comparison. J Am Coll Cardiol 2018; 72 (22): pp. 2789-2801.
  • Lyu X., et al.: Intensive walking exercise for lower extremity peripheral arterial disease: a systematic review and meta-analysis. J Diabetes 2016; 8 (3): pp. 363-377.
  • McDermott M.M., et al.: Home-based walking exercise intervention in peripheral artery disease: a randomized clinical trial. JAMA 2013; 310 (1): pp. 57-65.
  • Murphy T.P., et al.: Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease: six-month outcomes from the claudication: exercise versus endoluminal revascularization (CLEVER) study. Circulation 2012; 125: pp. 130-139.
  • Oka H., et al.: A comparative study of three conservative treatments in patients with lumbar spinal stenosis: lumbar spinal stenosis with acupuncture and physical therapy study (LAP study). BMC Complement Altern Med 2018; 18 (1): pp. 19.
  • Olin J.W., et al.: Peripheral artery disease: current insight into the disease and its diagnosis and management. Mayo Clin Proc 2010; 85 (7): pp. 678-692.
  • Oresanya L., et al.: Systemic review and meta-analysis of high-pressure intermittent limb compression for the treatment of intermittent claudication. J Vasc Surg 2018; 67: pp. 620-628.
  • Qi Z., et al.: Acupuncture combined with hydrotherapy in diabetes patients with mild lower-extremity arterial disease: a prospective, randomized, nonblinded clinical study. Med Sci Monit 2018; 24: pp. 2887-2900.
  • Rantner B., et al.: The fate of patients with intermittent claudication in the 21st century revisited- results from the CAVASIC Study. Sci Rep 2017; 8: pp. 45833.
  • Treat-Jacobson D., et al.: Implementation of supervised exercise therapy for patients with symptomatic peripheral artery disease: a science advisory from the American Heart Association. Circulation 2019; 140 (13): pp. e700-e710.
  • US Preventive Services Task Force, Curry S.J., et al.: Screening for peripheral artery disease and cardiovascular disease risk assessment with the ankle-brachial index: US Preventive Services Task Force Recommendation Statement. JAMA 2018; 320 (2): pp. 177-183.
  • Ward E., et al.: CT FFR can accurately identify culprit lesions in aorto-iliac occlusive disease using minimally-invasive techniques. Ann Vasc Surg 2016; 34: pp. 18.
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