A 58-year-old African American male presents with cramping of his calves after walking about 2 city blocks; the left calf is cramping worse than the right. It abates when he stops walking, but recurs when he resumes walking. There are no symptoms at rest, but the pain is worsened by a faster pace or going up an incline or stairs and is associated with left forefoot numbness when severe. The pain is not positional and is not present when the patient is sitting or standing without walking. There is no back pain. He is treated for hypertension and dyslipidemia and has a 20-pack-year smoking history.
This patient has intermittent claudication (IC), which is the mildest symptomatic presentation of peripheral arterial disease (PAD). PAD isolated to the femoropopliteal segment is typically asymptomatic (75% of the time) or may present with IC.1 IC is defined classically as reproducible pain in a muscle group brought on by a consistent amount of exercise (eg, a defined distance of walking) and relieved by rest. In the setting of femoropopliteal PAD, the pain is located in the calf muscles and is caused by a hemodynamically significant arterial obstruction that prevents increased blood flow in the setting of calf muscle exercise and decreased vascular resistance. By Ohm’s law (pressure = blood flow × vascular resistance), when resistance drops and flow cannot increase, the result is a decrease in pressure distal to the obstruction and ischemic pain.
The prevalence of PAD in the United States is 4.3%, with between 8 and 12 million people affected. Age is an important risk factor, with a prevalence of >15% in those over age 70 years.2,3 PAD prevalence is expected to rise as the population ages and the rates of diabetes and obesity increase. In 2001, Medicare expenditures for PAD topped $4 billion, with a significant portion of this cost related to revascularization procedures.2,4
Other risk factors for PAD mirror those for coronary artery disease, since the common denominator of the 2 diseases is atherosclerosis. Male sex, tobacco use, hypertension, dyslipidemia, and African American race are all well-established risk factors for PAD and, specifically, IC.5
Although limb morbidity related to IC is relatively benign, overall cardiovascular morbidity and mortality in patients with IC are significant. Overall, 75% of patients with IC will remain stable or improve, whereas 25% may worsen. Only 1% to 3% will progress to critical limb ischemia (defined as rest pain or tissue loss) and less than 2% will progress to major amputation. However, 5-year risk of stroke or myocardial infarction in patients with IC is 20%, and overall 5-year cardiovascular mortality is 10% to 15%.6,7 Thus, perhaps the most important treatment rendered after the diagnosis of IC is not intervention on the limb but risk factor modification to mitigate cardiovascular risk.
Although most patients with IC related to femoropopliteal PAD will complain of the classic symptoms of calf muscle cramping with ambulation, presentation may be heterogeneous. Some patients will complain of sharp, stabbing, or “bone” pains, and generalized fatigue, weakness, or “giving out” of the lower extremity may be described as well. Others will complain of numbness of the feet or a sensation of heaviness. The reproducibility with defined amounts of exercise, however, is typically present and can aid in differentiating true IC from other diagnoses.
On examination, diminished popliteal or pedal pulses in the affected extremity may be noted; bilateral disease is common in PAD. Signs of chronic arterial insufficiency include dependent rubor, thin or shiny skin, and diminished hair and nail growth. Given the significant cardiovascular morbidity associated with IC, a complete neurologic and heart exam is warranted to assess for cerebrovascular and coronary atherosclerosis.
Rarely does isolated femoropopliteal PAD cause critical limb ischemia. However, in patients with additional risk factors for nonhealing lower extremity wounds such as diabetic neuropathy and foot deformity or renal failure, isolated femoropopliteal PAD may contribute to slow or arrested healing.
Atypical presentations of IC may be difficult to interpret. The differential diagnosis includes arthritis, spinal stenosis, nerve root compression, neuropathy, chronic compartment syndrome, and venous claudication. Arthritic pain is common, may be described as aching, and may be related to position or weight bearing rather than exercise. It also centers on joints in the foot or knee. Spinal stenosis or nerve root compression may be associated with back pain, is typically described as sharp and radiating down the lower extremities, and may be relieved with changes in position or weight bearing. Neurologic weakness may be a feature. Neuropathic pain is common in diabetics; is described as a burning, numbness, or paresthesia; and may be associated with hyperesthesias. It is not related to exercise. Chronic compartment syndrome is rare and symptoms include tight, bursting pain, more often in the anterior compartment of the leg, associated with prolonged exercise in a patient without classic PAD risk factors. Venous claudication is also rare and described as a tightness or bursting pain associated with standing upright and walking in a patient perhaps with a history of deep vein thrombosis or venous insufficiency.
Ankle-brachial index (ABI) is the best way to diagnose PAD. An ABI less than 0.9 has excellent sensitivity and specificity for the diagnosis of PAD, and an ABI less than 0.9 or greater than 1.4 is associated with increased risk of cardiovascular events.8,9 In patients with medial calcification, ABI may be falsely elevated, and toe pressures, Doppler waveforms, or pulse volume recordings done in the vascular lab can be useful. Exercise ABIs can uncover occult arterial occlusion in patients with classic IC symptoms but normal resting ABIs. A drop to less than 0.9 or a decrease of more than 20% of baseline with exercise is considered abnormal. Segmental pressures and Doppler waveforms may further localize levels of disease should that help with diagnosis or intervention planning. Additional imaging, including computed tomography angiography (CTA) or magnetic resonance angiography (MRA), is only indicated for procedural planning once intervention has been decided upon.
The diagnosis of PAD implies significant systemic atherosclerotic burden, even in the setting of asymptomatic disease. Thus, treatment of asymptomatic femoropopliteal PAD should be directed toward management of risk factors including smoking, sedentary lifestyle, hypertension, dyslipidemia, and diabetes. Even in the setting of IC, risk factor modification remains the mainstay of treatment, supplemented with cilostazol.
Smoking history has been shown to quantitatively correlate with degree of PAD;10 confers increased risk of amputation, myocardial infarction, and death; and decreases the durability of revascularization.11–13 Thus, smoking cessation is appropriate in all cases of PAD.
Exercise therapy is a mainstay of treatment for IC and provides durable and significant increases in walking ability. Theorized mechanisms of action include enlargement of collateral arterial pathways, angiogenesis, nitric oxide–mediated vasodilation, and rheologic benefits.7 However, patient comorbidities, compliance, and lack of reimbursement for supervised exercise programs conspire to decrease the effectiveness of exercise therapy. The most effective programs are supervised ones to promote compliance, and walking appears to be as effective as other types of activity. Greater than 30-minute sessions, 3 or more sessions per week, and programs longer than 26 weeks have all been shown to confer greater benefit than shorter or less intense programs.14
According to the American College of Cardiology/American Heart Association 2013 guidelines on treatment of cholesterol, most, if not all, patients with PAD will fall into the >7.5% 10-year risk for cardiovascular events category. High-intensity statin therapy (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) with a goal of 50% reduction in low-density lipoprotein (LDL) is indicated for this group.15 National Cholesterol Education Program 2004 recommendations suggested achieving LDL levels <100 mg/dL in patients with PAD.16
Up to 30% of patients with diabetes will have concomitant PAD, with increased risk of amputation likely related to diabetic issues of neuropathy, foot deformity, and susceptibility to trauma and infection. Pharmacologic control of hyperglycemia is critical in the setting of PAD.
After smoking, hyperlipidemia, and diabetes, hypertension has the next highest relative risk for PAD. Optimal medical management of hypertension in PAD patients will decrease risk of cardiovascular events.17,18
Multiple large prospective trials have studied the effect of antiplatelet therapy on cardiovascular risk in PAD, and either aspirin or clopidogrel is indicated in all PAD patients for reduction of cardiovascular risk. Risk reduction with clopidogrel may be increased at the cost of increased bleeding complications. Dual antiplatelet therapy does not seem to confer increased benefit and increases bleeding risk. However, based on the coronary intervention literature, clopidogrel specifically is indicated after peripheral stenting or drug-coated balloon angioplasty to decrease risk of postprocedural thrombosis.7,19
Only 2 medications are US Food and Drug Administration approved to treat symptoms of IC: pentoxifylline and cilostazol. Pentoxifylline reduces blood viscosity and inhibits platelet aggregation and has been shown to increase walking distance.20 Dosage begins at 400 mg 3 times a day and can be increased to 600 mg 3 times a day. Nausea, headache, and hypertension are common side effects.
Cilostazol is a phosphodiesterase inhibitor and has evolved into the medication of choice for IC. The mechanism of action is incompletely understood, but it is believed to inhibit platelet aggregation and induce vasodilation.21 Dosage starts at 50 mg twice a day and can be increased to 100 mg twice a day. Treatment lengths of up to 4 weeks may be necessary to gauge response. Headache seems to be the most common side effect, and as with other phosphodiesterase inhibitors, it is contraindicated in heart failure. Cilostazol has been shown to be superior to pentoxifylline in a prospective trial that also showed no difference between pentoxifylline and placebo.22
Procedural intervention for IC should be reserved for cases where smoking cessation, exercise therapy, risk factor modification, and cilostazol fail. The Society for Vascular Surgery recommends a 3-month trial of medical therapy and suggests the use of pentoxifylline in the event that cilostazol is not tolerated or does not improve symptoms.23
Furthermore, procedural intervention should only be considered in cases of a solid diagnosis of IC, with significant functional impairment or adverse effect on quality of life. Determination of the degree of functional impairment or impact on quality of life should be individualized and largely based on the perception of the patient. A very active patient or one who depends on ambulation for work may report significant functional impairment with “mild” IC, whereas a sedentary patient may easily tolerate the same level of disease. Regardless, if procedural intervention is considered, it is critical that patients be counseled about the risks and durability of intervention and that only symptoms specific to arterial insufficiency may be impacted. The latter is important in cases of atypical IC symptoms or in cases where multiple factors in addition to arterial insufficiency may be contributing to lower extremity symptoms, as these will not be improved. Patients whose medical comorbidities prevent significant ambulation or pose serious procedural risk, such as severe cardiopulmonary disease, paralysis, morbid obesity, or bedridden status, should not be offered procedural intervention. As discussed earlier, the natural history of IC is generally benign, and risk of major amputation in IC is extremely low. Thus, amputation prevention is not an appropriate indication for procedural intervention in IC, and durable benefit combined with low risk are prerequisites to any procedural intervention for IC.
As mentioned earlier, it is rare for isolated femoropopliteal PAD to cause rest pain or tissue loss, although it may be implicated in slow healing in patients with additional risk factors for nonhealing lower extremity wounds such as diabetic neuropathy and foot deformity or renal failure. Estimating the impact of revascularization in these difficult patients may be assisted by the use of the Society for Vascular Surgery WIfI scale, which considers wound characteristics, extent of infection, and degree of ischemia in calculating amputation risk.24
Once intervention is decided upon, consideration must be given to the method of revascularization. Each type of intervention, whether endovascular or surgical, has specific indications, advantages, and risks. Often, catheter angiography at the time of intervention will be the first anatomic imaging, but preprocedural CTA or MRA may be performed. Anatomic characteristics of the arterial disease discovered at imaging will also play a role in selecting an intervention.
There is a paucity of contemporary, large-scale, prospective, randomized data comparing endovascular and surgical revascularization for IC or isolated femoropopliteal PAD. Although almost 10 years old, the Trans-Atlantic Inter-Society Consensus II (TASC II) document, an international multidisciplinary opinion consensus document, offers some guidance when selecting endovascular versus surgical revascularization.8 The specific recommendations made in the document may be approaching obsolescence, but the principles behind them remain valid. In general, endovascular interventions remain relatively low risk compared to surgery and can be accomplished with outpatient or shorter hospital stays and minimal recovery times for patients. Shorter femoropopliteal lesions and stenoses are more durably and effectively treated with endovascular procedures compared to longer lesions and total occlusions. Surgical bypass is likely more durable for many femoropopliteal lesions (Figure 35-1), particularly longer ones and total occlusions, but incurs more perioperative cardiac and wound-related morbidity (Figure 35-2), requires longer hospitalizations, and may be associated with a longer return to function. Endovascular treatment of common femoral, profunda, and popliteal disease remains controversial, and anatomic and patient characteristics such as severe calcification and concomitant diabetes and renal failure confer decreased patency for all interventions, whether endovascular or surgical. This chapter will not consider multilevel disease, which often can be addressed by treating the more proximal lesion in the setting of IC, nor will it discuss tibial disease, rest pain, or tissue loss. Tibial intervention for IC is not advised.
Figure 35-1
A shorter chronic total superficial femoral artery occlusion successfully treated with primary self-expanding stent.
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