Peripheral artery disease (PAD) is a vascular disorder that causes abnormal narrowing of arteries other than those that supply the heart or brain. PAD may happen in any blood vessel, but it is more common in the legs than the arms.
When narrowing occurs in the heart, it is called coronary artery disease (CAD), and in the brain, it is called cerebrovascular disease. Peripheral artery disease in humans most commonly affects the legs, but other arteries also may be involved, such as those of the arms, neck, or kidneys.
Peripheral artery disease (PAD) is a form of peripheral vascular disease. Vascular refers to the arteries and veins within the body. PAD differs from peripheral veinous disease. PAD means the arteries are narrowed or blocked—the vessels that carry oxygen-rich blood as it moves from the heart to other parts of the body. Peripheral veinous disease, on the other hand, refers to problems with veins—the vessels that bring the blood back to the heart.
The classic symptom is leg pain when walking that resolves with rest and is known as intermittent claudication. Other symptoms include skin ulcers, bluish skin, cold skin, or abnormal nail and hair growth in the affected leg. Complications may include an infection or tissue death that may require amputation, coronary artery disease, or stroke. As many as 50% of people with PAD do not have symptoms.
The greatest risk factor for PAD is cigarette smoking. Other risk factors include diabetes, high blood pressure, kidney problems, and high blood cholesterol. PAD is primarily caused by the buildup of fatty plaque in the arteries that is called atherosclerosis, especially in individuals greater than 40 years of age. Additional risk factors include artery spasm, blood clots, trauma, fibromuscular dysplasia, and vasculitis. PAD is typically diagnosed by finding an ankle-brachial index (ABI) less than 0.90, which is the systolic blood pressure at the ankle divided by the systolic blood pressure of the arm. Duplex ultrasonography and angiography also may be used to make a diagnosis. Angiography is more accurate and allows for treatment at the same time, however, it is associated with greater risks.
It is unclear whether screening for peripheral artery disease in people without symptoms is useful, as it has not been properly studied. For those with intermittent claudication from PAD, stopping smoking and supervised exercise therapy may improve outcomes. Medications, including statins, ACE inhibitors, and cilostazol, may also help. Aspirin, which helps with thinning the blood and thus improving blood flow, does not appear to help those with mild disease, but is usually recommended for those with more significant disease due to the increased risk of heart attacks. Anticoagulants (blood thinners) such as warfarin show no definitive scientific evidence of benefit in PAD. Surgical procedures used to treat PAD include bypass grafting, angioplasty, and atherectomy.
In 2015, approximately 155 million people had PAD worldwide. It becomes more common with age. In the developed world, it affects about 5.3% of 45- to 50-year-olds and 18.6% of 85- to 90-year-olds. In the developing world, it affects 4.6% of people between the ages of 45 and 50 and 15% of people between the ages of 85 and 90. PAD in the developed world is equally common among men and women, although in the developing world, women are affected more commonly. In 2015, PAD resulted in about 52,500 deaths, which is an increase from the 16,000 deaths in 1990.
Signs and symptoms
The signs and symptoms of peripheral artery disease are based on the affected body part. Approximately 66% of patients affected by PAD either do not have symptoms or have atypical symptoms. The most common presenting symptom is intermittent claudication (IC), which typically refers to lower extremity skeletal muscle pain that occurs during exercise. IC presents when there is insufficient oxygen delivery to meet the metabolic requirements of the skeletal muscles. IC is a common manifestation of peripheral arterial disease (PAD). The pain is usually located in the calf muscles of the affected leg and is relieved by rest. This occurs because during exercise, the muscles require more oxygen. Normally, the arteries would be able to increase the amount of blood flow and therefore increase the amount of oxygen going to the exercised muscle. However, in PAD, the artery cannot respond appropriately to the increased muscular demand for oxygen. Therefore, the muscles are deprived of oxygen, leading to muscle pain that subsides with rest.
Other symptoms may include: Pain, aches, and/or cramps in the buttocks, hip, or thigh Muscle atrophy (muscle loss) of the affected limb Hair loss of the affected limb Skin that is smooth, shiny, or cool to the touch in the affected area Decreased or absent pulse in the feet Cold and/or numbness in the toes Sores or ulcers on the affected limb that do not heal
In individuals with severe PAD, complications may arise, including critical limb ischemia and gangrene. Critical limb ischemia occurs when the obstruction of blood flow in the artery is compromised to the point where the blood cannot maintain oxygenation of the tissue at rest. This may lead to pain at rest, a feeling of coldness, or numbness in the affected foot and toes. Other complications of severe PAD include lower limb tissue loss (amputation), arterial insufficiency ulcers, erectile dysfunction, and gangrene. People with diabetes are affected by gangrene of the feet at a rate that is 30 times higher than the unaffected population. Many of these severe complications, such as those leading to amputation, are irreversible.
Causes
Risk factors
Factors contributing to an increased risk of PAD are the same as those for atherosclerosis.. Retrieved August 9, 2010. These include age, gender, and ethnicity. PAD is twice as common in males as in females. In terms of ethnicity, PAD is more common in people identified as non-Caucasian in a 2:1 ratio. The factors with the greatest risk associations are hyperlipidemia, hypertension, diabetes mellitus, chronic kidney disease, and smoking. Presenting three or more of these factors increases the risk of developing PAD tenfold. Smoking – Tobacco use in any form is the single greatest risk factor for peripheral artery disease internationally. Smokers have up to a 10-fold increase in the risk of PAD in a dose-response relationship. Exposure to second-hand smoke also has been shown to promote changes in the lining of blood vessels (endothelium), which may lead to atherosclerosis. Smokers are 2–3 times more likely to have lower extremity PAD than coronary artery disease. Greater than 80%–90% of patients with lower extremity peripheral arterial disease are current or former smokers. The risk of PAD increases with the number of cigarettes smoked per day and the number of years smoked. High blood sugar – Diabetes mellitus is shown to increase the risk of PAD by 2–4 fold. It does this by causing endothelial and smooth-muscle cell dysfunction in peripheral arteries. The risk of developing lower extremity peripheral arterial disease is proportional to the severity and duration of diabetes. High blood cholesterol – Dyslipidemia is an unhealthy pattern of cholesterol or fat in the blood. Dyslipidemia is characterized by a high level of a protein called low-density lipoprotein (LDL cholesterol), low levels of high-density lipoprotein (HDL cholesterol), elevation of total cholesterol, and/or high triglyceride levels. This abnormality in blood cholesterol levels has been correlated with accelerated peripheral artery disease. Management of dyslipidemia by diet, exercise, and/or medication is associated with a major reduction in rates of heart attack and stroke. High blood pressure – Hypertension or elevated blood pressure may increase a person's risk of developing PAD. Similarly to PAD, there is a known association between high blood pressure and heart attacks, strokes, and abdominal aortic aneurysms. High blood pressure increases the risk of intermittent claudication, the most common symptom of PAD, by 2.5- to 4-fold in men and women, respectively. Other risk factors that are being studied include levels of various inflammatory mediators such as C-reactive protein, fibrinogen, homocysteine, and lipoprotein A. Individuals with increased levels of homocysteine in their blood have a 2-fold risk of developing peripheral artery disease. While there are genetic factors leading to risk factors for peripheral artery disease, including diabetes and high blood pressure, there have been no specific genes or gene mutations directly associated with the development of peripheral artery disease.
High risk populations Peripheral arterial disease is more common in these populations:TASC II Guidelines
All people who have leg symptoms with exertion (suggestive of claudication) or ischemic rest pain All people aged 65 years and older, regardless of risk factor status All people between 50 and 69 who have a cardiovascular risk factor (particularly diabetes or smoking) Age less than 50 years, with diabetes and one other atherosclerosis risk factor (smoking, dyslipidemia, hypertension, or hyperhomocysteinemia) Individuals with an abnormal lower extremity pulse examination Those with known atherosclerotic coronary, carotid, or renal artery disease All people with a Framingham risk score of 10%–20% All people who previously have experienced chest pain
Etiology and pathophysiology
Peripheral arterial disease is considered to be a set of chronic or acute syndromes, generally derived from the presence of occlusive arterial disease that causes inadequate blood flow to the limbs.
As previously mentioned, the most common etiology of peripheral artery disease, especially in patients greater than 40 years old, is atherosclerosis. Atherosclerosis is a narrowing of the arteries caused by lipid or fat buildup or by calcium deposition in the wall of the affected arteries.
The pathophysiology of atherosclerosis involves complex interactions between cholesterol and vascular cells. In the early stages of PAD, the arteries compensate for plaque buildup by dilating to preserve flow through the vessel. Eventually, the artery cannot dilate further, and the atherosclerotic plaque narrows the arterial flow lumen.
When there is an imbalance between the needs of the peripheral tissues and the blood supply, the affected person is faced with ischemia.
From the pathophysiologic point of view, a restriction of blood supply (ischemia) to the lower limbs may be classified as either functional or critical. Functional ischemia occurs when the blood flow is normal at rest, but insufficient during exercise, presenting clinically as intermittent claudication. Critical ischemia is produced when the reduction in blood flow results in a perfusion deficit at rest and is defined by the presence of pain at rest or trophic lesions in the legs. In this situation, precise diagnosis is crucial, as there is a clear risk of limb loss if adequate blood flow is not re-established, either by surgery or endovascular therapy. Differentiating between functional and critical ischemia is important to establish the therapeutic indication and the prognosis in patients with PAD.
Other causes include vasculitis and in situ thrombosis related to hypercoagulable states. Additional mechanisms of peripheral artery disease include arterial spasm and fibromuscular dysplasia. The cause and pathophysiology of arterial spasm are not fully understood, but it is hypothesized that they may occur secondary to trauma. The symptoms of claudication ensue when the artery spasms, or clamps down on itself, creating an obstruction. Like atherosclerosis, this leads to decreased blood flow to the tissue downstream of the obstruction. Thrombosis, or the formation of a blood clot, usually occurs due to stasis or trauma.
Diagnosis