Peripheral Arterial Disease

Key points

• Peripheral arterial disease (PAD) is the extracoronary manifestation of atherosclerosis 
• In PAD, the ankle-brachial index (ABI) is an important tool for initial diagnosis, as the disease is often difficult to detect
• Co-existent coronary artery disease and/or carotid disease is very common in patients with PAD
• Medical management of PAD includes aspirin (or clopidogrel), exercise, cholesterol lowering, blood pressure control, and smoking cessation. In patients with diabetes improved control of the blood sugar levels also improves prognosis
• Revascularization is important treatment for severe symptoms or critical limb ischemia
• The prognosis and complications of PAD are similar to those of atherosclerosis elsewhere in the body
• Acute ischemia, characterized by the 'five Ps' (pain, pallor, pulselessness, paresthesias, and paralysis), is a surgical emergency

Background

Description

• Chronic extracoronary manifestation of atherosclerosis may affect the extremities, carotid/vertebral vessels, or mesenteric/renal vasculature in addition to the aorta. Unless otherwise noted, this article focuses on lower extremity PAD
• Most often occurs in elderly patients and smokers
• Progressive atherosclerosis is associated with decreasing blood flow to distal tissues, particularly during time of increased metabolic demand such as exercise or injury. The decreased blood flow results in the classic signs and symptoms of PAD
• PAD is associated with the history or presence of claudication. Intermittent claudication is leg pain that occurs with activity (walking) and is relieved by rest (standing or sitting). Claudication may remain stable or progress to pain during rest and limb ischemia
• Limb-threatening ischemia may have a variable time course. Acute limb ischemia is most commonly due to sudden occlusion of the artery by an embolism or trauma, but up to 20% of acute limb ischemia is due to in situ arterial thrombosis associated with PAD. Key findings include resting pain, hair loss, thickened brittle nails, shiny and smooth skin, changes in skin color (especially in the digits), muscular atrophy, gangrenous ulcers, numbness, and/or paralysis
• Chronic limb ischemia presents with similar findings to acute limb ischemia, but develops more slowly, over at least 2 weeks, and often longer. It is almost always a manifestation of PAD. Chronic, critical limb ischemia is a more common form of limb-threatening PAD
• The ABI is the ratio of blood pressure in the arms to the legs. Normally the pressures are equal in all four extremities. PAD is strongly linked to an ABI lower than 0.90 (or a toe systolic pressure index lower than 0.60 in diabetic patients), even in the absence of symptoms and signs. As PAD progresses, the ABI decreases. Other features include decreases or absent pulses distal to the diseases segment and audible bruits over the affected artery
• PAD is important clinically because affected patients are at an increased risk of stroke, myocardial infarction, renal failure, intestinal angina, lower leg ulcers, limb loss, and death

Epidemiology

Incidence and prevalence

Incidence:

• Annual incidence of symptomatic PAD: 2.6/1000 in men; 1.2/1000 in women
• Incidence increases in individuals older than 75 years

Prevalence:

• Prevalence in men aged 45 to 70 years is 1% to 5% and in women prevalence is 1% to 2%, although women have more asymptomatic disease
• The overall prevalence in both symptomatic and asymptomatic men and women is similar
• Prevalence increases with age. In those aged 55 to 74 years, 50/1000 have intermittent claudication and a further 100/1000 have asymptomatic PAD

Demographics

Age:

• Risk increases with age: PAD occurs most often in patients from 60 to 80 years
• Elderly patients with PAD, even those who are asymptomatic, have a high risk of mortality and vascular adverse outcomes. The risk of adverse cardiovascular outcomes is significantly higher compared to patients without PAD

Gender:

• Traditionally, men were thought to be generally affected twice as often as women
• Recent data suggest that the overall prevalence of PAD as assessed by ABI, not symptoms, is similar in women and men

Race:

• Atherosclerotic disease is less prevalent in Indo-Asians and African-Americans; however, Indo-Asians have a higher prevalence of thromboangiitis obliterans
• In one Veterans Administration Medical Center population, black patients had almost double the incidence of PAD of white or Hispanic patients as assessed by ABI

Genetics:

• Incidence is increased in those with a familial history of PAD, myocardial infarction, coronary heart disease, or stroke

Socioeconomic status:

• Socioeconomic factors may cause increased incidence of PAD in less educated, lower income and unemployed populations

Causes and risk factors

Common cause:

• Atherosclerosis

Risk factors:

• Patients with diabetes are three to four times more likely to develop PAD than those with normal glucose tolerance
• Smokers are two and half to three times more likely to develop PAD than nonsmokers
• Patients with hypertension have a relative risk of 1.5 to 2.5 of developing PAD
• For patients with hyperlipidemia, there is an increased relative risk of 1.1 for every 10 mg/dL increase in total cholesterol
• Individuals with hyperhomocysteinemia have a relative risk of 1.7 to 2.6 of developing PAD
• Intermittent claudication affects 1% to 2% of men aged younger than 50 years, but affects 5% of men over this age. A similar trend is seen in women
• The prevalence of intermittent claudication is twice as great in men as in women
• Obesity is a recognized risk factor for atherosclerosis
• PAD is more likely in those with a family history of PAD or other manifestations of atherosclerosis
• Sedentary lifestyle is a recognized risk factor for atherosclerosis; regular exercise is effective in reducing the symptoms of PAD

Associated disorders

• Generalized or systemic atherosclerosis
• Myocardial infarction
• Coronary heart disease
• Stroke
• Renal artery stenosis
• Leriche syndrome
• Cardiac arrhythmias, including atrial fibrillation, with emboli to the extremities
• Hypercoagulable states due to elevation of several coagulation factors

Screening

The U.S. Preventive Services Task Force (USPSTF) 2005 evidence update on screening for PAD recommends against any routine screening for PAD 'because the prevalence of PAD in [the general population] is low, and because there is little evidence that treatment of PAD at this asymptomatic stage of disease, beyond treatment based on standard cardiovascular risk assessment, improves health outcomes.' However, the USPSTF found that the ABI is an accurate screening and diagnostic test and more accurate than history-taking, questionnaires, and palpation of peripheral pulses.

Primary prevention

Summary approach

Primary prevention is critical to stave off cardiovascular complication. Patients at high risk for atherosclerosis are also at high risk for developing PAD

Population at risk

• Patients with diabetes mellitus or glucose intolerance should be managed aggressively and educated about the risks of their condition
• Those with hypertension should be managed with drugs and lifestyle changes appropriate to their condition
• Although hyperhomocysteinemia is a risk factor for atherosclerotic disease, there is no clear evidence that treatment with oral folate and pyridoxine influence important cardiovascular outcomes
• Hyperlipidemia should be managed with diet and usually also with lipid-lowering agents

Preventive measures

• All patients should be encouraged not to smoke
• Obese patients should be encouraged to attain a healthy weight, and all patients should eat a nutritious diet that is low in saturated fat
• Patients should be encouraged to exercise regularly
• Patients who have a family history of PAD or other manifestations of atherosclerosis should be questioned about symptoms at consultations

Cholesterol screening:

• Dyslipidemia is a well documented risk factor for the development of atherosclerosis, and therefore, indirectly, PAD. Fasting lipid panel screening plays a critical role in the primary prevention of vascular disease in high-risk patients

Ankle-brachial index (ABI):

• ABI or toe systolic pressure index should be performed in any patient with clinical evidence (by history or physical examination) of PAD