The principal risk factors are those of atherosclerotic disease (see Chapter 18), with cigarette smoking and diabetes mellitus making the greatest contributions along with hyperlipidemia. Homocysteinemia has attracted considerable attention as a risk factor in persons with premature peripheral vascular disease in the absence of better-established atherosclerotic risk factors (see Chapters 18 and 27). Because these risk factors are the same as those for coronary artery disease and cerebrovascular disease, it is not surprising to find increased prevalence of these conditions in persons with peripheral artery disease. The probability of encountering symptomatic cardiovascular disease in patients with peripheral artery insufficiency is about 30%; more than 60% prove to have underlying cardiovascular disease when subjected to diagnostic testing. Peripheral artery disease is an independent risk factor for the development of atherosclerotic disease elsewhere.

Occlusive disease generally becomes symptomatic by the gradual reduction of blood flow to the involved extremity or organ. Symptoms finally occur when a critical arterial stenosis is reached. Pressure and blood flow are not significantly diminished until at least 75% of the cross-sectional area of the vessel lumen is obliterated by the disease process. This is approximately equivalent to a 50% reduction in lumen diameter. More-severe stenoses or even total occlusions may remain essentially asymptomatic as long as collateral circulation maintains sufficient blood flow around a lesion to satisfy the metabolic demands of the distal limb at rest and during exercise. Development of ischemic symptoms in the leg implies either inadequate collateral circulation or additional occlusive disease distal to the particular collateral bed. Thus, lesions in the aortoiliac segment may cause little difficulty unless, as is commonly the case, there is an associated disease in the femoropopliteal arterial territory.

Atherosclerotic plaques producing stenosis or occlusion of the arterial lumen are often segmentally distributed, with a predilection for arterial bifurcations. The infrarenal abdominal aorta and aortic bifurcation are common sites of disease, as are the iliac and femoral artery bifurcations. Diabetic patients seem prone to the onset of arteriosclerosis at an earlier age and often have a more distal distribution of occlusive arterial lesions involving the infrapopliteal, tibial, and small runoff vessels.

The first sign of impaired arterial circulation is usually intermittent claudication (from the Latin claudicare, to limp), a manifestation of reduced arterial blood flow that remains adequate at rest but inadequate during exercise. During exercise, the metabolic demands of skeletal muscle in the legs require a 5- to 10-fold increase in blood flow and oxygen delivery. In patients with occlusive disease of major conduit vessels, the requisite increase in blood flow cannot be achieved, and a supply-and-demand mismatch occurs, resulting in muscle ischemia and pain. With the cessation of activity, metabolic demand quickly returns to baseline and symptoms abate.

Patients report pain or discomfort in the lower extremity brought on by walking and relieved by stopping. Discomfort is usually described as a cramping or aching that steadily increases in severity as the distance or speed of walking increases and is frequently worse when walking up an incline. Most characteristically, it involves the calf muscles as a result of disease in the superficial femoral artery, the most common location of lower extremity obliterative disease. However, claudication may also be noted in more-proximal muscle groups of the hip, thigh, and buttock area when there is aortoiliac involvement.

As the severity of the occlusive process worsens, blood flow becomes inadequate for tissue needs even at rest, resulting in the manifestations of more-severe arterial insufficiency: ischemic rest pain and tissue necrosis (ischemic ulceration or gangrene). Rest pain typically occurs at night from leg elevation associated with lying in bed. Patients classically describe ischemic rest pain as an “ache,” “pain,” “numbness,” or “squeezing,” most often in the toes and arch of the foot. It may awaken them from
sleep and ease when the leg is placed in a dependent position (e.g., dangling the leg over the bedside or standing and walking about). Simple gravitational effects improve arteriolar flow and lessen ischemia.

Ischemic ulcers are painful and appear as punched-out lesions on the dorsum or lateral aspect of the foot. A hallmark of ischemic ulceration is intense pain associated with the lesion.

Peripheral arterial insufficiency has three basic anatomic variations, although any number may be present in a given patient. Aortoiliac disease is most common in patients who smoke or have hypercholesterolemia. Claudication in the buttock or thigh is characteristic. The femoral pulses are absent or diminished, but pedal pulses may be intact. Femoropopliteal disease accounts for two thirds of cases and presents as calf pain with exertion. Femoral pulses may be preserved, but popliteal and pedal pulses are absent or diminished. Tibioperoneal occlusion is a disease of diabetics and older patients. Skin ulcers and atrophic skin changes are common.

The natural history and associated clinical course of peripheral arterial disease are quite variable and often favorable. In the Framingham Study population, only one third of those developing claudication went on to have persistent symptoms; the remainder experienced remission or transient symptoms. However, 15% of those presenting with severe disease required amputation over the ensuing 2 years. Persistent smokers and diabetics have the worst prognoses.

Any consideration of prognosis for this atherosclerotic disease has to include the substantial risks of cardiovascular morbidity and mortality, which are increased fivefold compared with persons without peripheral arterial disease.