Peripheral arterial disease overview

# Overview
The term peripheral arterial disease refers to a group of disorders characterized by progressive stenosis and altered structure and function of non coronary arteries that supply the brain, visceral organs and limbs. Peripheral arterial disease (PAD) are most commonly of atherosclerotic type and hence this term is generally used to refer to the atherosclerotic peripheral arterial lesions in lower extremities. However, PAD also includes aneurysmal and thromboembolic lesions of arteries.
In contrast, peripheral vascular disease (PVD) refers to all vascular disorders affecting not only arteries but also veins and lymphatics. Peripheral arterial occlusive diseases (PAOD) are part of the peripheral arterial diseases but they exclude aneurysmal disorders, and hence only include atherosclerotic and and thromboembolic arterial lesions. PAD is a systemic disease most commonly caused by atherosclerosis. It is usually present with other atherosclerosis related diseases like coronary artery disease and cerebrovascular disease. PAD is associated with decrease quality of life and increase risk of mortality.

# Classification
Peripheral arterial disease is commonly divided in the Fontaine stages, introduced by Dr. Rene Fontaine in 1954. A more recent classification by Rutherford consists of three grades and six categories. In addition, the American College of Cardiology/American Heart Assocommon iliac arterytion (ACC/AHA) uses a symptoms-based classification (absence of symptoms, claudication, critical limb ischemia and acute limb ischemia) in their guidelines. TASC (Trans Atlantic Inter-Society Consensus) morphological consensus is used to guide the choice between endovascular and surgical revarscularization in the management of patients with peripheral artery disease.

# Pathophysiology
Peripheral arterial disease is characterized by a narrowing of the peripheral blood vessels leading to decreased blood flow to the limbs. The most common underlying cause of PAD is atherosclerosis. As the atherosclerosis progresses with time beyond the ability of the vessels to compensate for it, mainly upon increased blood demand in exercise, symptoms of claudication start.

# Causes
Peripheral arterial disease (PAD) is most commonly a manifestation of atherosclerosis resulting from vascular inflammation. Other uncommon causes should be suspected when the PAD occurs occurs at a young age and in the context of a positive history. Uncommon causes include degenerative diseases (marfan's syndrome and ehlers-danlos syndrome), dysplastic disorders (fibromuscular dysplasia), inflammatory diseases (arteritis) and hypercoagulable states.

# Differentiating Peripheral Artery Disease from other Disorders
The most important disorder that peripheral arterial disease and the associated symptom of claudication must be distinguished from is pseudoclaudication caused by lumbar spinal stenosis. Intermittent claudication (IC) must also be differentiated from lower extremity pain caused by non-vascular etiologies that may include neurologic, musculoskeletal and venous pathologies.  Given the diversity in and the severity of symptoms among patients with peripheral arterial disease, there is a long list of disorders that peripheral arterial disease must be distinguished from.  In fact, the false-positive diagnosis rates of peripheral arterial disease are estimated to be around 44% and the false-negative rates are estimated to be around 19%.

# Epidemiology and Demographics
The prevalence of peripheral arterial disease varies considerably depending on how PAD is defined, and the age of the population being studied. The prevalence of peripheral arterial disease in the general population is 1214%.  Peripheral arterial disease is even more common among the elderly and affects up to 20% of patients over  the age of 70 years. Peripheral vascular disease affects 1 in 3 diabetics over the age of 50.  Approximately 10 million Americans have peripheral arterial disease.

# Risk Factors
The risk factors associated with peripheral artery disease are similar to those associated with coronary artery disease. They can be classified as traditional and non traditional. Another way to classify the risk factors is depending on their level of risk: high risk factors (tobacco and diabetes), moderate risk factors (hypertension and hyperhomocysteinemia) and low risk factors (hypercholesterolemia). Some risk factors are modifiable, like hypertension, whereas others are not.

# Screening
A resting ankle brachial index is the screening study of choice in a patient who has suspected lower extremity peripheral arterial disease.  The ankle brachial index is defined as the ratio of the ankle blood pressure divided by the highest brachial blood pressure.  An ankle branchial index should be obtained if a patient has one or more of the following characteristics: 1) exertional claudication; 2) the presence of nonhealing wounds; 3) age over 50 with a history of smoking or diabetes or 4) age over 65.

# Natural History, Complications and Prognosis
Most patients with peripheral arterial disease (PAD) have a benign course, with the majority of patients being asymptomatic. However, clinical manifestations may progress rapidly in smokers, patients with diabetes and patients with chronic renal failure. Peripheral arterial disease is associated with complications that include ischemic leg pain at rest, ulceration and gangrene. In addition, the mortality rate among patients with peripheral arterial disease is higher than that of the general population. Mortality is mainly due to concomitant coronary artery disease and cerebrovascular disease rather than to the peripheral arterial disease itself.

# Diagnosis

## History and Symptoms
Patients with peripheral arterial disease can be asymptomatic in 70% of cases, can have symptoms of intermittent claudication or can sometimes have critical symptoms that include ulceration and gangrene. The hallmark of peripheral arterial disease is the symptom of claudication which is an intermittent cramping pain in the leg that is induced by exercise and relieved by rest. The clinical presentation of peripheral arterial disease depends on the location and severity of stenosis of the vessel; in fact, calf cramping in the upper 2/3 of the calf is usually due to superficial femoral disease, while cramping in the lower 1/3 of the calf is due to popliteal disease. Buttock, thigh, calf or foot claudication, can occur either singly or in combination. The most frequently affected artery in intermittent claudication is the popliteal artery. Leg pain occurs in one leg in 40% of patients and in both legs in 60% of patients. Patients may also experience fatigue or pain in the thighs and buttocks.

## Physical Examination
The patient's lower legs and feet should be examined with shoes and socks off, with attention to pulses, hair loss, skin color, and trophic skin changes. Patients with PAD might have cyanosis, atrophic changes like loss of hair, shiny skin, decreased temperature, decreased pulse or redness when limb is returned to a dependent position. The location of the symptoms depends on the nature of the involved arteries.

## CT
When symptoms suggestive of peripheral artery disease are present, clinical evaluation along with non invasive testing are enough to establish the diagnosis. CT angiography, one of invasive diagnostic studies, provides anatomic evaluation of the vessels. Invasive diagnostic studies are anatomic studies that are not used for diagnosis but rather for preoperative evaluation of the structural details of the vessels.

## MRI
When symptoms suggestive of peripheral artery disease are present, clinical evaluation along with non invasive testing are enough to establish the diagnosis. Invasive diagnostic studies are anatomic studies that are not used for diagnosis but rather for preoperative evaluation of the anatomy of the vessels. The invasive diagnostic studies, which are basically anatomic studies that rely on imaging, include the following: conventional angiography, CT angiography, MRA and duplex ultrasound.

## Ultrasound
Ultrasound is somewhat insensitive in making the diagnosis of PVD.

## Other Imaging findings
When symptoms suggestive of peripheral artery disease are present, clinical evaluation along with non invasive testing are enough to establish the diagnosis. Invasive diagnostic studies are anatomic studies that are not used for diagnosis but rather for preoperative evaluation of the anatomy of the vessels.
The invasive diagnostic studies, which are basically anatomic studies that rely on imaging, include conventional angiography, CT angiography, MRA and duplex ultrasound.

## Other Diagnostic Findings
When symptoms suggestive of peripheral artery disease are present, clinical evaluation along with non invasive testing are enough to establish the diagnosis. Invasive diagnostic studies are anatomic studies that are not used for diagnosis but rather for preoperative evaluation of the anatomy of the vessels.The non invasive modality mostly used in the diagnosis of peripheral artery disease is the measurement of the ankle brachial index (ABI) at rest and after exercise testing. The non invasive diagnostic studies are functional studies and they include the following: measurement of ABI at rest and after exercise, pulse volume recording, transcutaneous oxygen pressure measurement and laser doppler fluximetry. The invasive diagnostic studies are anatomic studies and they include the following: conventional angiography, CT angiography, MRA and duplex ultrasound.

# Treatment

## Medical Therapy
Despite its prevalence and cardiovascular risk implications, only 25 percent of patients with peripheral arterial disease are actively being treated. The medical therapy aims to reduce the atherosclerotic risk factors which include diabetes mellitus, hypertension, dyslipidemia and smoking, to improve walking time and distance and to prevent the progression of the peripheral arterial disease and the need of invasive surgical procedures. All patients with peripheral arterial disease should be prescribed an antiplatelet agent.

## Surgery
Revascularization, whether endovascular or surgical, is reserved for patients with intermittent claudication symptoms refractory to medical therapy, critical limb ischemia and acute limb ischemia. The choice between endovascular and surgical intervention is done on case-to-case basis; however, endovascular intervention is usually chosen first and surgery is done when the non surgical intervention fails. In addition, the anatomic characteristics of the PAD lesions guides the management plan. Amputation might be required in severe cases of critical limb ischemia.

## Primary Prevention
As atherosclerosis is the major cause of peripheral artery disease, its risk factors are the same as those of other atherosclerotic diseases. Diabetes mellitus, hypertension, dyslipidemia and smoking are considered as some of the most important modifiable risk factors. Hence, the primary prevention of PAD can be mainly achieved by smoking cessation as well as by the appropriate control of diabetes, blood pressure and lipid profile.