Intermittent Claudication

Etiology

The risk factors for the development of intermittent claudication are similar to those for atherosclerosis. Modifiable risk factors include smoking, hypertension, dyslipidemias, obesity, metabolic syndrome, and diabetes mellitus. Non-modifiable risk factors include age, male gender, family history, and congenital predisposition. Investigational risk factors include alcohol, radiation, C-reactive protein, infection, homocysteinemia, lipoprotein(a), reduced adiponectin, and fibrinogen.[4][5]

Besides smoking, poor renal function is also deemed a high-risk factor for the development of intermittent claudication.

Epidemiology

In the general population over age 60, intermittent claudication is present in 5% of men and 2.5% of women. Of all patients with peripheral arterial disease, between 10% to 35% will have a presentation of “classic” intermittent claudication. Certain patient groups have a higher incidence of peripheral arterial disease; these include age greater than 70, people who smoke, patients with diabetes between ages 50-69, and those with other atherosclerotic cardiovascular diseases.

Pathophysiology

Intermittent claudication occurs due to atherosclerosis-mediated narrowing of lower extremity vessels. Oxidative injury to the inner layer of endothelial cells is the nidus of atherogenesis. The subsequent dysfunction of endothelial cells promotes localized deposition of oxidized-LDL and synthesis of pro-inflammatory factors. This creates a fibro-inflammatory plaque that propagates as macrophages are recruited and become resident foam cells as they phagocytize the oxidized-LDL. The foam cells form a classic histologic feature called a “fatty-streak.” As the plaque enlarges and matures, surrounding vascular smooth muscles migrate into it, and collagen deposition forms a fibrous cap. The most common location of plaque formation in peripheral arterial disease is in the superficial femoral artery, which may lead to IC symptoms in the calf. Other locations include the aortoiliac bifurcation, producing hip and buttock pain, and the common femoral artery, which can cause thigh or calf claudication.[6]

The resting blood flow in these individuals is similar to healthy adults, but during exercise or physical activity, the blood cannot flow through the areas of obstruction. At the same time, these individuals take a long time to recover from physical activity compared to healthy adults.

History and Physical

The typical presentation of intermittent claudication is lower extremity pain during ambulation that is relieved with rest. The progression of symptoms is gradual. The pain may be localized to the buttocks or the lower leg, depending on the site of occlusion. Patients with aortoiliac disease frequently develop buttock pain.

Physical examination of these patients may show evidence of arterial insufficiency. The affected limb may feel cool and have diminished pulses. The physical examination should include an assessment of femoral, popliteal, dorsalis pedis, and posterior tibial artery pulses. The patient’s presentation should be carefully distinguished from other causes of leg pain like neurogenic pseudoclaudication (spinal stenosis), musculoskeletal pain, and venous claudication associated with leg swelling and varicosities. In general, the presence of strong pedal pulses argues against a diagnosis of intermittent claudication.

If pulses are not palpable, one may have to use a handheld Doppler device.  In general, in healthy people, the blood pressure in the arms and ankles should be about the same. In fact, ankle pressure is slightly higher in most people. The ankle-brachial index should be measured in all individuals. Patients with an ankle-brachial index of less than 0.9 may have some degree of vascular disease.

Evaluation

In addition to a full cardiac and respiratory history and physical exam, certain non-invasive and invasive tests can be performed based on the severity of symptoms. All patients should have a baseline lipid profile, Doppler waveform pulse assessment, and ankle-brachial indices (ABI). An ABI is a ratio of blood pressure at the ankle compared to the arm. An ABI between 0.9-1.3 is normal. Claudication is common in patients with an ABI between 0.4 and 0.9. ABI less and 0.4 suggests more severe peripheral arterial disease, while an ABI greater than 1.3 is associated with non-compressible calcified arteries. In patients with calcified arteries, commonly patients with diabetes, a toe-brachial pressure index (TBI) can be used. The TBI in a healthy patient should be 0.70-0.80. If a symptomatic patient has a normal ABI or TBI, standardized exercise testing can be helpful.

In normal patients, the ABI will increase during exercise. In patients with post-exercise ABI drop of greater than 20%, diagnostic imaging and referral to a vascular specialist are warranted. There are three major classification systems for patients with peripheral arterial disease: Wound/Ischemia/Foot Infection (Wifi), Rutherford, and Fontaine. The older Rutherford and Fontaine systems incorporate intermittent claudication as part of their classification.

Common imaging modalities include non-invasive duplex vascular ultrasound, minimally invasive computed tomography angiography and magnetic resonance angiography, and formal peripheral angiography. Imagining modalities determine the location of the diseased vasculature. Aortoiliac disease is referred to as inflow disease and typically produces symptoms in the thigh or gluteal musculature. Meanwhile, disease below the inguinal ligament commonly produces claudication affecting the calf muscles.[7][8]

Treatment / Management

The guiding principle of treatment for intermittent claudication is that around 1% to 2% of patients with claudication ever progress to limb-threatening ischemia. Under this pretense, initial aggressive treatment strategies are discouraged. Most patients with intermittent claudication can be treated with medical interventions.

Medical management includes smoking cessation, antiplatelet agents, statin therapy, blood pressure modification, glucose control, structured walking programs, and cilostazol. Structured walking programs improve pain-free walking distance better than pharmacologic therapy alone. It is important to note that continued smoking with walking therapy restricts improvement in these patients. A three-month trial of smoking cessation, ambulation, and cilostazol is typically prescribed. Headaches are the most common side-effect of cilostazol and may warrant a dose reduction. Patients undergoing medical management should have frequent follow-ups to assess their symptom relief. Most patients are instructed to walk at least three ten-minute walks daily.

Any patient with intermittent claudication or peripheral arterial disease should also be evaluated for coexisting cardiac disease. If symptoms are worsening despite medical treatment, or if symptoms are considered disabling or lifestyle-limiting, intervention may be considered. Other considerations for invasive procedures may include atherosclerotic lesion characteristics and patient prognosis. Intervention may initially involve minimally-invasive endovascular angioplasty, stenting, or atherectomy.

Percutaneous techniques are typically performed via the femoral artery with the insertion of a sheath with wires and catheters to the diseased region. Lesions that are multifocal, long, or heavily calcified may not be amenable to endovascular repair. In these cases, intervention may ultimately require an endarterectomy or a conduit bypass. The conduit can either be an autogenous vein or prosthetic material. In 2007 the Society for Vascular Surgery developed the Trans-Atlantic Inter-Society Consensus (TASC II) guidelines that can aid physicians in determining whether endovascular or open surgery should be pursued in a patient. The classification identifies lesions as A, B, C, or D based on location, number, length, and severity of the stenosis. The complications of any surgical intervention should also be considered - these include vessel or graft conduit thrombosis, in-stent stenosis or fracture, and infection.[3][9][10](B3)

Differential Diagnosis

The differential diagnosis of intermittent claudication include:

• Sciatica
• Atheroembolic disease
• Venous insufficiency
• Vasculitis

Staging

Current guidelines on peripheral vascular disease include the following:

• Obtain ABI as the first non-invasive test to establish a diagnosis of peripheral vascular disease. If ABI is about 0.9 or normal, recommend an exercise ABI
• Routine screening for peripheral vascular disease in the absence of risk factors is not recommended
• Patients who smoke, patients with diabetes mellitus, and those with abnormal peripheral vascular exams should be screened and risk-stratified for preventive care
• Symptomatic patients should undergo an invasive evaluation to determine the location and grade of obstruction. Some of these patients may benefit from angioplasty or bypass. Endovascular therapy is preferred to surgery
• Educating the patient on the harms of smoking
• Considering statin therapy if the patient has elevated lipids
• Optimizing blood glucose levels
• Managing hypertension with beta-blockers
• Starting antiplatelet therapy - aspirin or clopidogrel
• Encouraging patients to walk regularly

Prognosis

The prognosis of intermittent claudication depends on many factors. For those who continue to smoke, have uncontrolled hypertension or elevated blood glucose, the condition can progress, leading to ischemia, necrosis, and eventually culminate in the amputation of the limb. Besides smoking, two factors that negatively affect prognosis include diabetes mellitus and advanced age. Overall, the survival of patients with intermittent claudication is less than that of age-matched controls. The key reason for the shortened life expectancy is the presence of coronary artery disease. About 5% to 30% of individuals are dead at 10 years, depending on the severity of the vascular disease.

Complications

The complications of intermittent claudication include:

• Lack of exercise endurance
• Prolonged wound healing
• Impotence
• Blue toe syndrome
• Ischemic leg