Peripheral Atherosclerosis

(Arteriosclerosis Obliterans)

Occlusion of blood supply to the extremities by atherosclerotic plaques (atheromas).

Etiology and Pathophysiology

Progressive peripheral atherosclerosis is a common, age-related disease; its development parallels that of atherosclerosis in the coronary and cerebral vessels. The pathologic process begins many years before clinical findings are apparent, and the disorder develops slowly and insidiously.

Risk factors for peripheral atherosclerosis include cigarette smoking, diabetes mellitus, hyperlipidemia, hypertension, polycythemia, a family history, hyperhomocysteinemia, age, and, in women, early hysterectomy and oophorectomy. Any disorder that increases the Hct (eg, polycythemia) increases the resistance to blood flow and the shearing force against vessel walls, resulting in intimal injury. This injury promotes atheroma formation. Poorly controlled diabetes mellitus also leads to intimal injury and the buildup of atheromas. High levels of homocysteine directly injure vessel walls.

How smoking damages the arteries is still unclear, but carbon monoxide and the metabolites of smoke components probably are toxic to the intima. Nicotine, a direct arterial vasoconstrictor, decreases distal blood flow. The incidence of limb amputation is 10 times higher in those who continue to smoke after developing arterial occlusion than in those who quit.

Symptoms and Signs

Most patients with peripheral atherosclerosis, including the elderly, have no symptoms. Almost 70% of a vessel's lumen must be occluded before the disease can be clinically recognized.

The cardinal and most specific symptom of peripheral atherosclerosis is intermittent claudication (pain, tightness, or weakness in an exercising muscle). Claudication occurs during walking (not during sitting or standing still), forcing a person to halt because walking is too painful, and is relieved in < 5 minutes by rest. The pain is most often described as squeezing and almost always occurs in the calf; if the aortoiliac artery is occluded, pain usually occurs in the hip and buttocks.

The distance at which claudication occurs tends to be constant but may change over time. Cold and windy weather, inclines, and rapid walking may shorten the distance. Using canes or crutches does not improve walking distance, because muscle function is normal until hypoxia occurs.

Less specific symptoms of peripheral atherosclerosis--numbness, paresthesias, coldness, and pain during rest--relate to the foot's cutaneous circulation. Foot or toe numbness that occurs during walking suggests arterial disease and results from maximal vasodilation of muscle arterioles, with stealing of blood flow from the skin.

A sense of coldness that has recently increased, that occurs in only one limb, or that persists after sleep suggests arterial insufficiency. However, a sense of coldness is very common among the elderly and does not necessarily indicate arterial insufficiency; it may be secondary to vasoconstriction instead.

Elderly patients who are relatively sedentary and do not walk far enough to induce claudication may present with foot pain at rest or even gangrene. Foot pain at rest is a dire symptom, indicating that blood flow capacity is reduced to < 10% of normal. The pain is paresthetic and burning, most severe distally, and typically worse at night, preventing sleep.

Gangrene first appears as nonblanching cyanosis (ecchymosis), followed by blackening and mummification of the involved part. In patients with peripheral neuropathy (eg, that due to diabetes), dependent rubor and subsequent gangrene may occur without pain.

Wounds often heal poorly, and the skin is prone to breakdown. Skin breakdown can progress quickly to cellulitis and deeper infections.

In Leriche's syndrome, the aortoiliac artery becomes occluded, but the distal vessels are usually patent. Symptoms are hip claudication and impotence secondary to hypotension in the internal iliac arteries. The syndrome is uncommon among the elderly, because they usually have multiple diffuse atherosclerosis and multiple areas of occlusion.

Diagnosis

Absence of peripheral pulses strongly suggests peripheral atherosclerosis. The posterior tibial pulse is always present in healthy persons, although it may be difficult to feel if the patient has edema or prominent malleoli. It is best palpated with the patient supine and the examiner on the same side as the pulse. Meticulous palpation under the medial malleolus is necessary; dorsiflexing and everting the foot slightly may help move the artery into a more superficial position. The dorsalis pedis artery pulse is absent in about 5% of healthy persons. The popliteal pulse is the most difficult to feel; the patient should be supine and relaxed, with the knee slightly flexed. The artery may be located posteriorly, laterally, or medially in the popliteal space. Very deep palpation may be necessary if the patient is obese.

Determination of pulse strength is subjective and depends on the pulse pressure, extremity's girth, patient's age, and examiner's sensitivity. With age, the pulse of arteries that remain patent tends to become more prominent, because the media loses smooth muscle and elastic tissue, predisposing the arteries to ectasia. The upstroke of the pulse wave is more important than the amplitude. Bruits heard over the femoral arteries indicate aortoiliac disease.

Doppler ultrasonography can be used to assess pulses, but it cannot prove that pulsatile flow is adequate. It may detect a signal when the vessel's systolic blood pressure is as low as 30 mm Hg. Thus, the procedure is usually performed with a blood pressure cuff. The pressure at which the Doppler signal disappears is the systolic blood pressure. Blood pressure in the leg is considered low if it is lower than the pressure in the upper extremities or if it decreases during exercise.

Temperature differences between the toes of each foot and changes in skin color are important. To determine whether color changes, the examiner elevates the foot above heart level for 20 seconds and then lowers the foot to the dependent position: Pallor lasting > 30 seconds or rubor (a homogeneous violaceous color) appearing after 20 seconds indicates that normal blood flow capacity is < 10%. Rubor may require 1 to 2 minutes to reach its maximum. It is more pronounced in the toes and extends proximally for various distances. A severely ischemic foot may appear pale even when horizontal. Prolonged pallor and rubor, when associated with pain at rest, are grim signs. Skin ulceration or frank gangrene, particularly of the toes, heels, and lateral malleoli, suggests extensive disease.

A full lipid profile, including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride levels, should be obtained after the patient has fasted. Measuring the homocysteine level is also advisable. If the homocysteine level is borderline, a methionine loading test (ingestion of methionine followed by serial homocysteine measurements) can be performed. If the homocysteine level is high, vitamin B₁₂ levels should be measured.

Peripheral atherosclerosis must be differentiated from other disorders that cause similar symptoms. Lumbar and spinal stenosis, very common among the elderly, may produce symptoms similar to claudication. However, the symptoms of stenosis occur at rest as well as during walking and are often worse when the patient is sitting, and the pain tends to radiate down the entire extremity. The pain of diabetic neuropathy may be similar to that of atherosclerosis but is generally bilateral and extends above the feet. Diabetic neuropathy, which may coexist with peripheral atherosclerosis, can also cause numbness and paresthesias.

Treatment

Asymptomatic patients: Therapy consists primarily of preventive measures involving foot care (including walking regularly) (see Table 56-2) and control of risk factors (eg, smoking cessation, weight loss). Patients should be advised to avoid positions that may impair circulation (eg, crossing the legs while sitting). In general, all patients with clinical evidence of atherosclerosis should take folic acid, vitamin B₆ (pyridoxine), and vitamin B₁₂ (cyanocobalamin) supplements.

Patients with intermittent claudication: Patients should be taught about foot care (see Table 56-2) and advised to walk as much as possible; risk factors should be controlled. As soon as claudication occurs, patients should rest and then continue walking. For a small but significant number of patients who follow these instructions, symptoms abate within the first 3 months. Most patients can adjust to walking long distances with frequent rest stops.

The results of drug therapy for claudication (including vasodilators, pentoxifylline, and cilostazol) are mixed. Pentoxifylline, the first of a new class of drugs approved for treating claudication, decreases blood viscosity and improves red blood cell flexibility, leading to improved blood flow through arterioles and capillaries. In one study, the mean walking distance of patients taking the drug increased by 165 feet (50 meters). Adverse effects are few. However, clinical results have been disappointing, and follow-up studies have not shown increases in muscle blood flow sufficient to prevent claudication. Thus, many experts do not recommend the use of pentoxifylline for claudication.

Early studies suggest that cilostazol produces a mild to moderate increase in walking distance comparable to that produced by pentoxifylline. Because cilostazol is a phosphodiesterase inhibitor, it is contraindicated in patients with heart failure. Cardiovascular toxicity in other patients is also a concern, and the drug should be used with extreme caution.

Because -blockers increase the longevity of patients with atherosclerotic coronary artery disease and only rarely aggravate intermittent claudication, they should not be withheld from patients who have heart disease and claudication.

The most effective treatment for intermittent claudication is arterial bypass surgery or, for less severe cases, percutaneous transluminal angioplasty. However, bypass surgery and angioplasty are generally reserved for patients who have claudication due to isolated aortoiliac disease and severe symptoms.

Risks of bypass surgery or angioplasty must be weighed against potential benefits. A failed bypass may worsen circulatory impairment if collateral vessels are transected during surgery. Factors such as the patient's general health, lifestyle, and age; the presence of heart disease; and location of the lesions must be considered. Significant coronary artery disease is a contraindication to peripheral artery surgery because heart disease increases the operative mortality rate and because angina, unmasked after a successful bypass, may prevent or mitigate improvement in walking distance.

Angiography to determine the feasibility of surgery should be performed only if surgery is being seriously considered. For surgery to be successful, a major vessel beyond the obstruction must be patent, and distal flow beyond the patent vessel must be good.

The more proximal the lesion, the better the clinical results of bypass surgery and the longer the graft remains patent. In patients with localized aortoiliac disease, the 5-year graft patency rate is > 90%. In patients with femoropopliteal disease, the 5-year patency rate is probably 60 to 70% for bypasses above the knee. Bypasses across the knee into the distal popliteal or proximal tibial arteries have a somewhat lower patency rate. The 5-year patency rate for distal femorotibial grafts is well below 50%, and patency rates are even lower when patients have generalized disease.

When arterial occlusion is bilateral, a femoropopliteal bypass may unmask claudication in the contralateral limb, resulting in only slight clinical improvement. A second operation is necessary to significantly increase claudication-free walking distance.

For aortoiliac and aortofemoral bypass grafts, prosthetic material (Teflon) is used, but for a femoropopliteal bypass, an autologous saphenous vein is preferable because long-term patency rates are higher.

Percutaneous transluminal angioplasty is an alternative to bypass surgery for short stenoses in the aortoiliac and proximal femoral areas. Although it is a relatively simple procedure that can be performed using a local anesthetic, complications (eg, arterial rupture, distal embolization of ruptured atherosclerotic plaques) may require emergency surgery. Therefore, a patient undergoing percutaneous transluminal angioplasty must be able to undergo a full surgical procedure.

Patients with significant foot ischemia: Severe cutaneous ischemia (eg, causing pain at rest, dependent rubor, and tissue loss) is a strong indication for arterial bypass surgery, which may relieve disabling pain and prevent amputation. Patches of dry gangrene, particularly on the toes, should be allowed to demarcate because autoamputation of toes may result in proximal healing. Ischemic ulcers can heal if the surrounding blood flow is adequate; they may respond to pressure relief, debriding agents (eg, collagenase, fibrinolysin with desoxyribonuclease, becaplermin gel), and local antiseptic solutions (eg, povidone-iodine applied bid). Soaking the foot in body-temperature water helps infected lesions heal. Pentoxifylline is of uncertain benefit, but it has few adverse effects and can be tried. -Blockers should be avoided.

Elderly patients who do not have tissue loss or pain at rest should not undergo surgery, even if they have florid dependent rubor. For patients with severe heart disease, amputation is sometimes preferable to the risk of bypass surgery.

Lower-risk procedures may be used. A subcutaneous femorofemoral bypass across the lower pelvic area may help save a limb if the disease is unilateral. The graft patency rate with this procedure is almost as high as that with aortofemoral bypass. A subcutaneous bypass from an axillary to a femoral artery may help if the disease is bilateral. These grafts often become thrombosed but may be reopened by performing a local thrombectomy within a few days of closure. The 5-year graft patency rate is about 50%.

When a limb is threatened, the presence of stenoses in many areas is not a contraindication to surgery. Bypass of the most proximal occlusion often increases collateral flow around more distal occlusions sufficiently to salvage the limb. For a short iliac stenosis, angioplasty may be tried before femoropopliteal or femorotibial bypass surgery.

In patients with gangrene, limb salvage after injection of vascular endothelial growth factor into the calf muscle--an experimental approach--has been reported.