BMN Blog

SEP 28
Peripheral Arterial Disease

Most people are aware that atherosclerosis can cause blockages in the coronary arteries, resulting in chest pain or heart attack, or in the carotid arteries, precipitating a stroke. But atherosclerosis can lead to another serious but often under-diagnosed condition: peripheral arterial disease (PAD). Defined as atherosclerotic obstruction of the arteries to the lower extremities, PAD causes leg pain and is associated with other cardiovascular disease. Although lower extremity PAD affects an estimated 12 to 20 million people in the United States, only four to five million of them are experiencing symptoms.




Atherosclerosis is the major cause of lower extremity PAD, and its risk factors are the same as for atherosclerosis of the coronary or carotid arteries.


CIGARETTE SMOKING-More than 80 percent of patients with lower extremity PAD are current or former smokers. Studies have found that smoking increases the risk of lower extremity PAD two- to six-fold and the risk of intermittent claudication (leg pain during walking) three- to ten-fold. Smoking is two to three times more likely to cause lower extremity PAD than coronary artery disease.1


DIABETES MELLITUS-12 percent to 20 percent of patients with lower extremity PAD also suffer from diabetes, which increases the risk of lower extremity PAD two- to four-fold. That risk is proportional to the severity and duration of diabetes.2


HIGH CHOLESTEROL-Elevated lipid levels (cholesterol and triglyceride) are associated with the development of lower extremity PAD, as are elevated total and low-density lipoproteinema (LDL) cholesterol, decreased high-density lipoproteinema (HD) cholesterol, and hypertriglyceridemia.


HIGH BLOOD PRESSURE-Hypertension is associated with lower extremity PAD, although not as strongly as it is with cerebral vascular and coronary artery disease. Patients with hypertension are two-and-a-half to four times more likely to experience intermittent claudication.


HYPERHOMOCYSTEINEMIA-Elevated levels of homocysteine in the blood (homocysteine is an amino acid) and C-reactive protein (inflammation) are also associated with lower extremity PAD.


AGE -The incidence of PAD increases with age. PAD is present in 2.5 percent of individuals 60 years and under, 8.3 percent of those aged 60 to 69, and 18.8 percent of those 70 years and older.3 As the population ages, we’re likely to see an increase in the prevalence of lower extremity PAD. By the year 2030, 45 percent more men and 14 percent more women are expected to suffer from lower extremity PAD.


The prognosis of patients with lower extremity PAD depends on whether or not they also have coronary artery disease and cerebrovascular disease—conditions that are two to four times more likely in patients with lower extremity PAD. Among patients presenting with lower extremity PAD, approximately half to two-thirds show evidence of coronary artery disease, and approximately 12 to 25 percent have significant carotid artery disease. Approximately one-third of men and one-quarter of women with known coronary artery or cerebrovascular disease also have lower extremity PAD.


Heart attack, stroke, and cardiovascular death are also more frequent in patients with lower extremity PAD. For example, the risk of heart attack is increased 20 percent to 60 percent. The risk of death due to coronary artery disease is two to six times higher, and the risk of stroke is increased approximately 40 percent.




CLAUDICATION—Intermittent claudication (leg pain during walking) is the most common symptom in patients with lower extremity PAD. Claudication is defined as fatigue, discomfort, or pain that occurs in the leg muscles during exertion caused by exercise-induced ischemia (lack of adequate blood flow). When claudication occurs during exercise only, with adequate blood flow restored after several minutes of rest, the diagnosis is “intermittent claudication.”


Symptoms of intermittent claudication include fatigue, aching, numbness or pain while walking, and these symptoms can be aggravated if the individual is walking uphill or at a rapid pace. Specific leg symptoms often depend on the anatomic site of the arterial blockage. For example, blockage of the iliac arteries can produce pain in the hip or buttocks in addition to the thigh and calf. Blockage in the femoral and popliteal (knee) arteries is usually associated with calf pain, while blockage in the tibial arteries (below the knee) can produce calf pain, foot pain, and numbness.


Claudication is considered mild if individuals experience little or no lifestyle limitations. Patients with mild claudication usually can walk more than 200 yards before suffering any significant symptoms. Moderate to severe claudication, however, is lifestyle-limiting. These individuals cannot walk 200 yards before experiencing symptoms.


CRITICAL LIMB ISCHEMIA—More severe than claudication, critical limb ischemia is limb pain that occurs at rest, or impending limb loss that is caused by severely restricted blood flow to the leg. Patients with critical limb ischemia have inadequate blood flow to sustain the leg, resulting in chronic rest pain, ulcers, and gangrene. The discomfort is often worse when the patient is in bed with the leg elevated and can lessen when the limb is lowered. The pain can awaken patients from sleep and can render them severely disabled, often unable to walk. If untreated, these individuals usually require a major amputation within six months. The quality of life for patients with critical limb ischemia can be worse than that of patients with terminal cancer.


Factors that can contribute to or exacerbate critical limb ischemia include diabetes, severe congestive heart failure, infection, skin breakdown, and traumatic injury.


The majority of people with lower extremity PAD, however, do not experience symptoms. In a study of lower extremity PAD, 11.7 percent of symptomatic patients showed large-vessel lower extremity PAD on noninvasive testing. The prevalence of intermittent claudication was 2.2 percent in men and 1.7 percent in women.4 Thus, the fraction of individuals with intermittent claudication (classic symptoms) dramatically underestimates the true prevalence of lower extremity PAD. Overall, symptoms were present in approximately one-fifth of the population with evidence of lower extremity PAD.


Even without classic symptoms, patients with lower extremity PAD still have systemic (generalized) atherosclerotic disease and often experience leg dysfunction, diminished functional status, and increased cardiovascular risk. In other words, even without symptoms, people with lower extremity PAD still have measurable limb dysfunction and adverse cardiovascular outcomes, and they bear the same risk factors of patients with symptomatic lower extremity PAD. (Patients with asymptomatic lower extremity PAD can also have other causes of leg pain—lumbar disc disease, spinal stenosis, sciatica, radiculopathy, muscle strain, and neuropathy.) Thus, regardless of symptom status, patients with lower extremity PAD should take steps to reduce their risk factors and seek treatment as they would for coronary artery disease.






To reduce the risk of heart attack or stroke associated with lower extremity PAD, lifelong treatment should include modification or elimination of the atherosclerotic risk factors.


STOP SMOKING—Studies have found that the risk of death, heart attack, and amputation is substantially greater in these individuals with PAD who continue to smoke compared with those who stop smoking.


MANAGE DIABETES—Patients with both lower extremity PAD and diabetes should receive proper foot care, including an evaluation by a podiatrist. Skin lesions and ulcerations should be addressed urgently. Diabetic patients with lower extremity PAD should be treated with glucose-control therapies that reduce the hemoglobin A1C to less than seven percent. Home care should include the use of appropriate footwear, daily foot inspection, and skin cleansing.


LOWER BLOOD PRESSURE—Treatment of high blood pressure reduces the risk of cardiovascular events such as stroke, heart failure, and death. In the “Heart Outcome Prevention Evaluation Study,” patients with coronary disease, cerebrovascular disease and PAD were randomly treated with ramipril (Altace®) or placebo. Ramipril (Altace®) reduced the risk of heart attack, stroke, or vascular death in patients with PAD by 25 percent.6 Therefore, ace-inhibitors should be considered as treatment for patients with lower extremity PAD.


LOWER CHOLESTEROL—Treatment of elevated lipids reduces the risk of adverse cardiac events in patients with atherosclerosis. The “Heart Protection Study” treated patients with coronary artery disease, cerebrovascular disease and peripheral arterial disease randomly with simvastatin (Zocor®) or placebo. This study included 6,748 patients with PAD and demonstrated a 25 percent risk reduction over five years.5 On the basis of these findings, it is now recommended that patients with PAD and LDL cholesterol of greater than 100 mg per dl be treated with a statin (lipid lowering drug).


BLOOD THINNERS—Patients with lower extremity PAD should be treated with antiplatelet therapy to reduce the risk of heart attack, stroke, or vascular death. Aspirin, in daily doses of 75 to 325 mg, is recommended as safe and effective antiplatelet therapy.




A supervised exercise program is the initial treatment for patients with lower extremity PAD and claudication. Patients who walk regularly will, over time, increase the speed and duration of the walk and experience decreased claudication symptoms. Structured exercises are also likely to benefit patients who are treated with the other therapies listed below.


Drug therapy is another option for lower extremity PAD. Cilostazol (Pletal®) has been found to improve symptoms and increase walking distance in patients with lower extremity PAD and intermittent claudication in the absence of congestive heart failure.


Endovascular procedures are indicated for individuals with lifestyle-limiting lower extremity PAD with claudication. Endovascular techniques to treat peripheral arterial occlusive disease include balloon angioplasty, stents, laser, cutting balloons, thermal angioplasty, and plaque excision. Endovascular therapy for individuals with lower extremity PAD and claudication offers a high success rate, a low incidence of complications or death, and in the majority of patients, it can be performed as an outpatient procedure.


In general, surgery should only be considered after nonsurgical therapies have failed. Surgical intervention is typically reserved for patients whose impairment significantly threatens their employment or requires significant alteration in lifestyle.




More than 20 percent of patients with critical limb ischemia (CLI) will die within one year, and nearly half of CLI patients require revascularization to save the limb. An estimated 220,000 to 240,000 major and minor lower extremity amputations are performed in the United States in Europe each year because of critical limb ischemia.7


This naturally mandates a more aggressive treatment approach, which should be determined on a case-by-case basis. Issues to consider include the severity of the patient’s condition, the presence of additional complications, and the arterial anatomy.


If the individual is a candidate for endovascular therapy, this strategy should be attempted first. If the patient is not a candidate for endovascular therapy, surgical revascularization can be required. Regardless of the initial treatment strategy, patients must be monitored closely.


You should discuss your individual treatment options with your personal physician.




  1. Price JF, Mowbray PI, Lee AJ, et al. Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study. Eur Heart Jour 1999; 20:344-353.


  1. Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study. Circulation 1995; 91:1472-1479.


  1. Kannel WB. The demographics of claudication and the aging of the American population. Vasc Med 1996; 1:60-64.


  1. Criqui MH, Fronek A, Barrett-Connor E. The prevalence of peripheral arterial disease in the defined population. Circulation 1985; 75:510-515.


  1. Heart Protection Study Collaborative Group MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-rick individuals: a randomized placebo-controlled trial. Lancet 2002; 360:7-22.


  1. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 200; 342-145-53. Errata in: N Engl J Med 2000; 342-1376; N Engl J Med 2000; 342:748.


  1. Allie DE, Hebert CJ, Lirtzman MD, et al. Critical limb ischemia: a global epidemic. A critical analysis of current treatment, unmasks clinical and economic costs of CLI. Eurointervention 2005: 1:60-69
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