PERIPHERAL ARTERIAL DISEASE Henry Green, MD, FACC, FACP June 24, 2009 Etiology Atherosclerosis This is the commonest cause of PAD. Ischemia is mainly the result of progressive narrowing of the arterial bed, most commonly in the lower extremities. Buerger’s Disease This is also known as thromboangiitis obliterans. It is rare, and can occur in the upper extremities as well. There are also reports of involvement of other vascular beds. Venous involvement may be present. It is due to inflammation and thrombosis. While the exact mechanism is unknown, it is strongly linked to tobacco use. It is usually but not exclusively found in men aged 20 to 40. Its complications include ulcerations and gangrene of the fingers and toes, which often require amputation. Smoking cessation and wound care are the treatment. It usually does not involve the large arteries. Venous disease may present as thrombophlebitis, which is often migratory. Other causes are rare These include the congenital or acquired hypercoagulable states, radiation therapy, primary tumors, and the iliac syndrome of cyclists.7 Embolism Sudden occurrence of arterial occlusion usually results from embolism. This can be the result of atrial fibrillation or a ventricular thrombus. Significance Incidence It is estimated that 5% of adults over 50 and 12-20% over 65 have PAD. The incidence is the same in men and postmenopausal women. Associated conditions PAD is a coronary risk equivalent. 30% of these patients have symptomatic coronary artery disease and most others have silent coronary disease. Some patients are “protected” from experiencing angina because the claudication stops them from walking far enough to get it. It is strongly associated with disease of other arterial beds as well. Cerebrovascular disease occurs in 40-50% of patients with PAD. These patients have a 5-year death rate that is higher than that of breast cancer. They are several times more likely to experience a myocardial infarction, stroke or death than those without PAD.3 Risk factors The risk factors for PAD are the same as for atherosclerosis in general. These include smoking, hypertension, diabetes and dyslipidemia.

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Clinical features Screening Whether to screen routinely for PAD is uncertain. It is probably more fruitful to screen for the risk factors in asymptomatic individuals. Symptoms More than half of patients with PAD are asymptomatic. The commonest symptom is intermittent claudication. This is experienced as a disagreeable sensation in the legs that occurs with walking and subsides with rest. It is often described as a cramp. Other terms applied include fatigue, numbness, heaviness or weakness. The site of the discomfort depends on the location of the arterial stenosis. Commonly it is felt in the calf muscles. Patient often find they are able to walk a defined distance, and are then forced to stop for a few minutes. They can then resume walking, only to be halted at about the same distance. Aortoiliac disease may be associated with claudication that is experienced in the buttocks. Thigh claudication occurs with femoral or iliac stenosis. Erectile dysfunction is a common accompaniment of PAD. When the disease becomes more critical, night pain can occur. This is a very disagreeable sensation that keeps the patient awake. It is often relieved by hanging the leg over the side of the bed. Physical findings The pedal pulses are diminished or absent. Depending on the level of occlusion, the popliteal and femoral pulses may also be affected. The lower extremities are often cool, and there may be an appreciable temperature demarcation on careful palpation. Trophic changes develop, such as loss of hair and ulcerations. Capillary filling becomes impaired. This can be assessed by pressing one’s finger against the sole of the foot. Upon removing the finger, the skin is blanched for a few seconds. In PAD, the color returns slowly. With severe PAD, there is elevation pallor and sometimes dependent rubor of the legs. Gangrene may ultimately develop. Differential diagnosis4 Spinal stenosis The pain may be similar in quality and location to that of intermittent claudication. However it differs in that it is generally worse with standing and relieved by changing position. Usually it is associated with an identifiable back problem. Arthritis If the pain is in the lower extremity, it is felt in a major joint rather than in the muscles. It is generally related to specific movements rather than walking as such.

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Venous congestion Venous congestion produces more of a tight or bursting pain that is felt in the groin or thigh. It tends to occur after walking, and not necessarily at a fixed distance. It is slowly relieved by leg elevation. These patients have a history of deep vein thrombosis and exhibit signs of venous congestion. Acute onset of pain Sudden occurrence of leg pain may result from an arterial embolus or deep venous thrombosis. Evaluation Ankle-brachial index (ABI) This simple test consists of comparing the systolic pressure in the leg with that in the arm. Measuring the leg pressure requires a large blood pressure cuff placed on the calf. A doppler stethoscope is used. Normally the leg pressure is greater. PAD is defined by an ABI of less than 0.90. A normal ABI does not always exclude PAD. An exercise ABI may then be helpful. With exercise, there is normally vasodilatation. PAD is diagnosed if the ABI diminishes by 20% after exercise. Details of the technique are given in reference 2. The ABI is unreliable if there is arterial calcification (commonly in diabetics or those with kidney disease). In such cases, the toe-brachial index may be more accurate. The toe pressure is measured using plethysmography and a small blood pressure cuff. A toebrachial index of less than 0.5 indicates PAD. Imaging When indications for surgery are found, detailed imaging of the affected vessels is required. This can be done noninvasively using magnetic resonance angiography. Computed tomographic angiography is also useful. More detailed evaluation requires digital subtraction arteriography. Management Medical Risk factor modification can slow the progression and sometimes reverse PAD. Smoking cessation is extremely important. This is even true of patients who have undergone revascularization. Lipid management should be carried out. PAD is a coronary risk equivalent. Statins are indicated even if the LDL cholesterol is not elevated, primarily for the prevention of cardiovascular events. There is also evidence that angiotensin converting enzyme inhibitors are beneficial. Beta-blockers are not contraindicated in PAD, and may be prescribed if indications are present. Optimal glucose control is important. Exercise can be an effective means of improving symptoms. This works best under supervision, but even unsupervised exercise is beneficial. Patients are instructed to walk 30-40 minutes, stopping when necessary, 4-5 times a week.2,4,6 Specific recommendations are given in reference 6. All patients with PAD should receive aspirin 81 mg daily unless contraindicated. This is done to prevent cardiovascular events. Clopidogrel is a reasonable alternative. Cilostazol 3

(Pletal) can provide relief of claudication. It is contraindicated in heart failure. Another agent, pentoxifylline (Trental), is less well established, but may be used instead. Surgical Revascularization procedures are used in patients with lifestyle limiting disability and who do not respond to medical therapy. Other indications are nonhealing ulcers, or rest pain. Stenting is preferred for patients age 50 or less who have discrete stenoses. Surgical bypass has long been standard therapy. Autologous grafts are preferred over synthetic material. Currently it is mainly used for lesions that are not amenable to endovascular stenting, such as long stenoses. It is also favored for occlusions of the popliteal or tibial-peroneal vessels. Amputation is necessary when other alternatives have been exhausted. Some patients can be managed with a transmetatarsal or other conservative limb-sparing surgery. A belowknee amputation is better tolerated than one above the knee, and such patients are obviously much easier to rehabilitate. Investigational Both stem cell therapy and gene therapy are being tested and may hold some promise. Acute limb ischemia This is manifested by pain and a cold, pulseless, pale limb. Such patients should be hospitalized and heparinized. Emergent revascularization may salvage the extremity. Catheter-directed thrombolytic therapy is an option. Irreversible acute limb ischemia requires amputation. When possible, a below-knee amputation affords greater rehabilitation potential than an above-knee operation. Mesenteric arterial disease1 Arterial insufficiency of the mesenteric vessels can result from atherosclerosis, thrombosis, embolism, extrinsic compression, or vasculitis. Acute occlusion, such as might occur with embolism, can be devastating. A large segment of intestine may be infarcted. Chronic narrowing is often asymptomatic, but may result in postprandial pain (“intestinal angina”) and weight loss. Renal artery stenosis1 While renal artery stenosis may lead to refractory hypertension as well as renal insufficiency, its presence does not establish a causal relationship. Renal artery stenting is useful in carefully selected patients with hypertension that does not respond adequately to drug therapy. One serious complication is atheroembolism, which results in further worsening of renal function. References 1. Creager MA et al. Atherosclerotic peripheral vascular disease symposium II: Executive summary. Circulation 2008;118:2811-2835 2. Laine C and Goldmann D. Peripheral arterial disease. Ann Intern Med 2007; ITC3-1ITC3-16

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3. Almahameed A. Peripheral arterial disease: recognition and management. Cleveland Clin J Med 2006; 73:621-638 4. White C. Intermittent claudication. N Engl J Med 2007; 356: 1241-1250 5. McDermott MM et al. Treadmill exercise and resistance training in patients with peripheral arterial disease with and without intermittent claudication. JAMA 2009; 301:165-174 6. Stewart et al. Exercise training for claudication. N Engl J Med 2002; 347:1941-1951 7. Feugier P and Chevalier JM. Endofibrosis of the iliac arteries” and underestimated problem. Acta chir belg 2004; 104:635-640

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