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Legs for Life Leg Pain and Peripheral Arterial Disease

Risk Factors
Taking Preventative Steps
Treatment to Reduce Vascular Events
Treatment to Improve Symptoms

Atherosclerosis with severe, occlusive disease limited to the aorta and common iliac arteries.

The development of atherosclerosis- commonly referred to as “hardening of the arteries”- has reached epidemic proportions in the United States.  A manifestation of this disease is well known as coronary artery disease and is the leading cause of death in our country. 

What is not well known by the general public, however, is that atherosclerosis is never confined to one area of the body- if you have it in your heart, you can rest assured that you have it everywhere in your body. 

And conversely, if you have it elsewhere in your body, you have it in your heart.  The degree to which it has progressed may be variable and the symptoms attributable to atherosclerosis may be subtle, or even non-existent, early in the disease process.

However, there is little doubt that atherosclerosis spares no vascular bed.  One particularly under appreciated presentation of atherosclerosis occurs in the form of peripheral arterial disease. Peripheral arterial disease, or PAD, refers to the condition of progressive atherosclerosis in the arteries of lower extremities, which prevents oxygen-rich blood from reaching the muscles and other tissues. 

This chronic atherosclerotic syndrome affects eight to twelve million people in the United States and approximately 20 percent of people over the age of 70 have PAD.  The most common symptom of patients with hemodynamically significant artery narrowing is claudication. The word claudication stems from the Latin word claudicatio, to limp. The symptom complex of claudication is defined as muscle cramps in the leg(s) that occur following exercise and are relieved by resting. This may also include fatigue, discomfort or vague leg pain.  The exercise distance at which claudication occurs is quite constant. Claudication usually occurs first in the calf muscles, although thigh, hip, and buttocks muscles also can be affected when more extensive proximal artery narrowings are present.

Major physical findings, such as arterial bruits, decreased or absent pulses, decreased skin temperature, dependent rubor, dystrophic nails and shiny, hairless skin, support the diagnosis of peripheral arterial occlusive disease (PAD).

Risk Factors
Many of the risk factors for coronary artery disease also are associated with the development of PAD. Although advancing age and family history cannot be controlled, some simple changes in lifestyle may help reduce the chance of developing PAD.  Several risk factors exist for the development of arterial lesions, and recognition of these factors enables physicians to prescribe nonoperative treatment that may alleviate symptoms as well as prolong life.

Atherosclerosis is an extraordinarily complex degenerative disease with no known single cause.  However, many variables are known to contribute to the development of atherosclerotic lesions. One popular theory emphasizes that atherosclerosis occurs as a response to arterial injury. Factors that are known to be injurious to the arterial wall include mechanical factors such as hypertension and wall shear stress, as well as chemical factors such as nicotine (tobacco), hyperglycemia (diabetes), hyperlipidemia (elevated cholesterol), and homocysteine.

Tobacco use is the most significant risk factor for the development and progression of PAD.  Stopping smoking can improve symptoms of intermittent claudication in up to 85 percent of PAD patients and improve walking distance by 300 percent.

People with diabetes develop symptoms of PAD a decade earlier than average and have a seven-fold higher rate of limb amputation than non-diabetics.  This is probably because the claudication is more often associated with calcification in the artery walls, which is not amenable to other surgical or pharmacological options.

Hyperlipidemia leads to lipid accumulation  within the smooth muscle cells of artery walls.  Macrophages become involved and this leads to an inflammatory response with endothelial injury, and a "fatty streak" begins to form in the artery wall.  This atheroma consists of differing compositions of cholesterol, cholesterol esters, and triglycerides. Some plaques are unstable, and fissures occur on the surface of the plaque that can expose the circulating platelets to the inner elements of the atheroma.  This leads to platelet aggregation and possibly thrombus (clots) or emboli within a vessel.

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Because many patients with peripheral vascular disease (PAD) also have coronary artery disease or carotid stenosis, aggressive risk factor modification is necessary to reduce overall morbidity and mortality

The diagnosis of patients with PAD is often made following a careful history with the tell-tale story of difficulty with walking.  Unfortunately, however, a PAD diagnosis can be missed since nearly 50% of patients are asymptomatic or have atypical symptoms.  Thus, a high index of suspicion is necessary in patients presenting with potential risk factors.

As alluded to above, the mere presence of PAD signals the overlap of other atherosclerotic diseases such as coronary artery disease and/or cerebrovascular disease which often leads to stroke.  It is well known that at five years from the time of presentation 32 percent of those with PAD will die from coronary artery disease and/or stroke and at 10 years roughly 50 percent will no longer be alive. 

In other words, a 50-year-old with PAD has a 50-50 chance of seeing age sixty because he or she will likely die from a heart attack or stroke-  this is serious business.  Furthermore, since PAD symptoms can dramatically impair walking comfort, overall physical conditioning is reduced and life quality suffers to the point that PAD can be even more disabling than heart disease

In those patients with intermittent claudication, if risk factors are modified, the symptoms usually remain stable for years.  Unfortunately, approximately 15 percent of patients eventually progress to develop lifestyle-limiting ischemia requiring arterial surgical bypass or other limb- salvage procedures, and five percent of people eventually require an amputation.

A physical examination may reveal arterial bruits (whooshing sound heard with the stethoscope over the artery), decreased or absent pulse in the extremities, or decreased blood pressure in the affected extremity.  Blood pressure measurements taken on the lower extremities are a relatively easy test that reveals physiologic information on the quality of arterial blood flow in the legs. This test, along with other comprehensive artery studies, is considered an extension of the physical exam and is performed at the Martha Jefferson Vascular Center in the Peripheral Vascular Laboratory.  This test generally takes less than 1 hour and is non-invasive using a sound-wave probe (duplex ultrasound).  These non-invasive tests determine the degree of PAD, and helps plan a clinical pathway for the best treatment option- either medical or interventional/surgical.

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Common PAD Risk Factors

  • Diabetes
  • Smoking
  • Hyperlipidemia
  • Hypertension
  • Over age of 70
  • Hyperhomocystinemia
Taking Preventive Steps
The treatment goals in patients with PAD are the same as those in patients with coronary artery disease. Treatment of patients with PAD has two goals. The first and foremost goal is to reduce the risk of vascular events (myocardial infarction, stroke, vascular death) that occur at an alarmingly high rate in patients with PAD.  The second goal of treatment is to improve symptoms in those patients with claudication and prevent amputation in patients with critical limb ischemia. Critical limb ischemia is present when patients have symptoms of ischemic rest pain, nonhealing foot ulcers, or gangrene, and its presence mandates a more invasive evaluation with angiography and endovascular and/or surgical revascularization to prevent limb loss.

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Shiny, hairless skin, dystrophic nail changes and
dependent rubor associated with peripheral arterial
occlusive disease of the patient's right foot.
Treatment to Reduce Vascular Events
Hypertension is a major risk factor for PAD, but it is not completely clear whether treatment alters PAD progression or symptoms. However, controlling high blood pressure through diet, exercise and medication is well established for reducing overall atherosclerotic risk. All classes of antihypertensive agents are suitable in the treatment of PAD; the type of therapy is influenced by coexisting disease.

Tobacco is directly toxic to the vascular endothelium and is implicated in initiating and perpetuating atherosclerosis.  All patients must be strongly encouraged to abstain from tobacco use.

In diabetics, monitoring blood glucose carefully, taking medications as prescribed, exercising regularly, maintaining a moderate body weight and eating a healthy diet should be the primary goal even with or without PAD

Lipid abnormalities must be recognized and treated. High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol and high levels of triglycerides are associated with the development and progression of atherosclerosis. Patients should be treated in accordance with the guidelines of the National Cholesterol Education Program, which recommends a target LDL cholesterol level of less than 100 mg per dL in patients with symptomatic vascular disease.  Managing high cholesterol levels with medication can be helpful in reducing symptoms and in some cases, reverse disease progression.

Two major antiplatelet agents are readily available for use in patients with vascular disease. Aspirin should be considered for use in any patient with coronary artery disease, cerebrovascular disease or PAD. The Antiplatelet Trialists' Collaboration Study demonstrated that patients with intermittent claudication who were treated with antiplatelet therapy had an 18 percent relative reduction in the incidence of myocardial infarction, stroke and vascular death.

Treatment with clopidogrel (Plavix) should be considered in patients who are intolerant of aspirin therapy.  The mechanism of action of clopidogrel is different than that of aspirin. In the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial, patients with recent ischemic stroke, recent myocardial infarction or symptomatic PAD were evaluated. Patients who were treated with Plavix for the combined end points of stroke, myocardial infarction and vascular death demonstrated an overall relative risk reduction of nine percent compared with patients who were treated with aspirin without a significant reduction in overall mortality. In the subgroup analysis, patients with PAD had a relative risk reduction of 24 percent for the combined end points.

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Treament to Improve Symptoms
improves the symptoms of claudication in several ways. The muscle can better adapt to anaerobic metabolism with repeated exposure to an ischemic environment. Oxidative metabolism and the overall number of available mitochondria increase.  Many studies have shown significant increases in claudication distances in patients who followed a walking program. Five components of a successful program have been identified. Walking is the preferred mode of exercise. Patients should walk at least three times per week for at least 30 minutes at each session. Near-maximal claudication pain (absolute claudication distance) should be the resting point, and the patients should follow the program for at least six months.  A supervised program is superior to a home-based exercise program.  A walking program can increase the objective distance that the patient with claudication can ambulate. This may result in subjective improvement and lead to an enhanced quality of life.

Historically many medications have been evaluated in an effort to treat symptoms of PAD and many more medications are presently being studied for their efficacy.  However, at this time the majority of vascular specialists feel the most effective agent for treating intermittent claudication is cilostazol (Pletal). Pletal is a phosphodiesterase inhibitor that suppresses platelet aggregation and acts as a direct arterial vasodilator (expander).  In one study, the patients who received cilostazol had a 35 percent increase in the distance they could walk before claudication and a 41 percent increase in absolute claudication distance when compared with the subjects who received placebo. One half of the patients treated with Pletal judged their walking to be "better" or "much better"; 84 percent of patients taking placebo felt that their symptoms were unchanged or worse.  Other patients taking Pletal documented improvement in the absolute claudication distance, along with similar subjective improvements in quality of life and walking ability.

If you think you may have symptoms of PAD, or are at risk for PAD, you should check with your doctor about getting a complete leg and vascular examination.  There are often national screening events at local hospitals specializing in vascular disease.  Martha Jefferson Vascular Center sponsers a free yearly program that screens patients with leg pain conditions for PAD - Legs for Life.

For further information, click here.

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