peripheral artery disease peripheral artery disease peripheral artery disease (pad) is an abnormal narrowing of arteries other than those that supply the heart or brain. pad can happen in any blood vessel, but it is more common in the legs than the arms. peripheral artery diseaseother namesperipheral vascular disease (pvd), peripheral artery occlusive disease, peripheral obliterative arteriopathyan arterial insufficiency ulcer in a person with severe peripheral artery diseasespecialtyinterventional radiology, vascular surgerysymptomsleg pain when walking that resolves with rest, skin ulcers, bluish skin, cold skincomplicationsinfection, amputationcausesatherosclerosis, artery spasmrisk factorscigarette smoking, diabetes, high blood pressure, high blood cholesterol.diagnostic methodankle-brachial index < 0.90, duplex ultrasonography, angiographytreatmentstopping smoking, supervised exercise therapy, surgerymedicationstatins, ace inhibitors, cilostazolfrequency155 million (2015)deaths52,500 (2015) 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 most commonly affects the legs, but other arteries may also 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 both 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 away 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 which resolves with rest, 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 which may require amputation; coronary artery disease, or stroke. up to 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, which is called atherosclerosis, especially in individuals over 40 years old. other mechanisms 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 may also be used. angiography is more accurate and allows for treatment at the same time; however, it is associated with greater risks. it is unclear if screening for peripheral artery disease in people without symptoms is useful as it has not been properly studied. in 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 blow, does not appear to help those with mild disease but is usually recommended in 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, about 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, though in the developing world, women are more commonly affected. in 2015 pad resulted in about 52,500 deaths, which is an increase from the 16,000 deaths in 1990. signs and symptoms peripheral arterial disease resulting in necrosis of multiple toes the signs and symptoms of peripheral artery disease are based on the part of the body that is affected. about 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 in the affected leg and 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 is unable to respond appropriately to the increased demand for oxygen of the muscles and as a result the muscles are deprived of oxygen leading to pain of the muscle 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 feet cold and/or numbness in the toes sores/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 is unable to maintain oxygenation of tissue at rest. this can lead to pain at rest, feeling of cold, 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 the illustration shows how pad can affect arteries in the legs. figure a shows a normal artery with normal blood flow. the inset image shows a cross-section of the normal artery. figure b shows an artery with plaque buildup that is partially blocking blood flow. the inset image shows a cross-section of the narrowed artery. factors contributing to increased risk of pad are the same as those for atherosclerosis. these include age, sex, and ethnicity. pad is two times as common in males as females. in terms of ethnicity, pad is more common in people of color compared to the white population in a 2:1 ratio. the factors with the greatest risk association are hyperlipidemia, hypertension, diabetes mellitus, chronic kidney disease, and smoking. presenting three of these factors or more increases the risk of developing pad ten-fold. smoking – tobacco use in any form is the single greatest risk factor of peripheral artery disease internationally. smokers have up to a 10-fold increase in risk of pad in a dose-response relationship. exposure to second-hand smoke has also been shown to promote changes in the lining of blood vessels (endothelium), which can 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 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, which is an abnormally high level of cholesterol or fat in the blood. dyslipidemia is caused 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 have 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 can 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 which 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 peripheral artery disease. while there are genetics 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: all people who have leg symptoms with exertion (suggestive of claudication) or ischemic rest pain all people aged 65 years and over regardless of risk factor status all people between 50 and 69 and 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 have previously experienced chest pain etiology and pathophysiology illustration of how the buildup of lipids cause a blockage of blood flow to the portion of the artery below the narrowing. peripheral arterial disease is considered to be a set of chronic or acute syndromes, generally derived from the presence of occlusive arterial disease, which cause inadequate blood flow to the limbs. as previously mentioned, the most common etiology of peripheral artery disease, especially in patients over 40 years old, is atherosclerosis. atherosclerosis is a narrowing of the arteries caused by lipid or fat build up and 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 the plaque buildup by dilating to preserve flow through the vessel. eventually, the artery cannot dilate any further, and the atherosclerotic plaque starts to narrow the arterial flow lumen. when there is an imbalance between the needs of the peripheral tissues and the blood supply, we are faced with a situation of ischemia. from the pathophysiologic point of view, a restriction of blood supply (ischemia) of the lower limbs can 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 fundamental, as there exists a clear risk of loss of the limb if adequate blood flow is not re-established, either by surgery or by endovascular therapy. differentiating between the 2 concepts is important in order 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 including arterial spasm and fibromuscular dysplasia. the cause and pathophysiology of arterial spasm is not fully understood, but it is hypothesised that can occur secondary to trauma. the symptoms of claudication ensue when the artery spasms, or clamps down on itself, creating an obstruction. similar to atherosclerosis, this leads to decreased blood flow to the tissue downstream of the obstruction. thrombosis, or the formation of a blood clot, occurs usually due stasis or trauma. diagnosis measuring the ankle-brachial index diagnosing or identifying peripheral artery disease requires history of symptoms and a physical exam followed by confirmatory testing. these tests could include ct scans (computed tomagraphic