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The goals of therapy include reductions in cardiovascular morbidity and mortality. improvement in quality of life by decreasing symptoms of claudication and eliminating rest pain, and preservation of limb viability.

The first step in managing patients with PAD is risk factor modification. Because of the likelihood of coexisting atherosclerotic vascular disease such as coronary artery disease, patients with symptomatic PAD have an estimated mortality rate of 50% in 10 years, most often as a consequence of cardiovascular events. Smoking cessation is. by far, the single most important risk factor impacting both claudication symptoms and overall cardiovascular mortality. Besides slowing the progression to critical leg ischemia, tobacco cessation reduces the risk of fatal or nonfatal myocardial infarction by as much as 50%, more than any other medical or surgical intervention. In addition, treatment of hypercholesterolemia, control of hypertension and diabetes, and use of antiplatelet agents such as aspirin or clopidogrel all have been shown to improve cardiovascular health and may have an effect on peripheral arterial circulation. Carefully supervised exercise programs can improve muscle strength and prolong walking distance.

Specific medications for improving claudication symptoms have been used, with some benefit. Pentoxifylline, a substituted xanthine derivative that increases erythrocyte elasticity, has been reported to decrease blood viscosity, thus allowing improved blood flow to the microcirculation; however, results from clinical trials are conflicting, and the benefit of pentoxifylline, if present, appears small. A newer agent, cilostazol. a phosphodiesterase inhibitor with vasodilatory and antiplatelet properties, has been approved by the Food and Drag Administration (FDA) for treatment of claudication. It has been shown in randomized controlled trials to improve maximal walking distance. Figure 8-1 shows a management algorithm.

Patients with critical leg ischemia, defined as ABI <0.40, severe or disabling claudication, rest pain, or nonhealing ulcers, should be evaluated for a revascularization procedure. This can be accomplished by percutaneous angioplasty, with or without placement of intraarterial stents, or surgical bypass grafting. Angiography (either conventional or magnetic resonance arteriography) should be performed to define the flow-limiting lesions prior to any vascular procedure. Ideal candidates for arterial revascularization are those with discrete stenosis of large vessels: diffuse atherosclerotic and small-vessel disease respond poorly.

Less common causes of chronic peripheral arterial insufficiency include thromboangiitis obliterans, or Buerger disease, which is an inflammatory

Thromboangiitis Obliterans
Figure 8-1. Management algorithm of peripheral arterial disease. (Data from: Hiatt W. Medical treatment of peripheral arterial disease and claudication. N Engl J Med 2001:344:1608-1621.)

condition of small- and medium-size arteries that may affect the upper or lower extremities and is found almost exclusively in smokers, especially males younger than 40 years. Fibromuscular dysplasia is a hyperplastic disorder affecting medium and small arteries that usually occurs in women. Generally, the renal or carotid arteries are involved, but when the arteries to the limbs are affected, the clinical symptoms are identical to those of atherosclerotic PAD. Takayasu arteritis is an inflammatory condition, seen primarily in younger women, that usually affects branches of the aorta, most commonly the subclavian arteries, and causes arm claudication and Raynaud phenomenon. along with constitutional symptoms such as fever and weight loss.

Patients with chronic peripheral arterial insufficiency who present with sudden unremitting pain may have an acute arterial occlusion, most commonly the result of embolism or in situ thrombosis. The heart is the most common source of emboli: conditions that may cause cardiogenic emboli include atrial fibrillation, dilated cardiomyopathy, and endocarditis. Artery-to-artery embolization of atherosclerotic debris from the aorta or large vessels may occur spontaneously or, more often, after an intravascular procedure, such as arterial catheterization. Emboli tend to lodge at the bifurcation of two vessels, most often in the femoral, iliac, popliteal, or tibioperoneal arteries. Arterial thrombosis may occur in atherosclerotic vessels at the site of stenosis or in an area of aneurysmal dilation, which may also complicate atherosclerotic disease.

Patients with acute arterial occlusion may present with a number of signs, which can be remembered as "six Ps:" pain, pallor, pulselessness, paresthesias, poikilothermia (coolness), and paralysis. The first five signs occur fairly quickly with acute ischemia: paralysis will develop if the arterial occlusion is severe and persistent.

Rapid restoration of arterial supply is mandatory in patients with an acute arterial occlusion that threatens limb viability. Initial management includes anticoagulation with heparin to prevent propagation of the thrombus. The affected limb should be placed below the horizontal plane without any pressure applied to it. Conventional arteriography usually is indicated to identify the location of the occlusion and to evaluate potential methods of revascularization. Surgical removal of an embolus or arterial bypass may be performed, particularly if a large proximal artery is occluded. A balloon catheter may also be attempted to remove the clot Alternatively, a catheter can be used to deliver intraarterial thrombolytic therapy directly into the thrombus. In comparison with systemic fibrinolytic therapy, localized infusion is associated with fewer bleeding complications.

Comprehension Questions f8.1] A 49-year-old smoker with hypertension, diabetes, and hypercholesterolemia comes to the office complaining of pain in his calves when he walks 2-3 blocks. What therapy might offer him the greatest benefit in symptom reduction and in overall mortality?

A. Aspirin

B. Limb revascularization procedure

C. Cilostazol

D. Smoking cessation

E. Pravastatin

For Questions 8.2-8.4, match the most likely cause (A-E) of arterial insufficiency to the patient described:

A. Cholesterol embolism

B. Fibromuscular dysplasia

C. Thromboangiitis obliterans (Buerger disease)

D. Takayasu aortitis

E. Psychogenic pain

18.2] A 31-year-old male smoker with resting pain in his legs and a nonhealing foot ulcer.

[8.3] A 21-year-old woman with fever, fatigue, and unequal pulses and blood pressures in her arms.

[8.4[ A 62-year-old man with livido reticularis and three blue toes, including one with gangrene following cardiac catheterization.

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