Peripheral Artery Occlusive Disease
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Peripheral artery disease (PAD) is a vascular disorder that causes abnormal narrowing of
arteries An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...
other than those that supply the
heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...
or
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
. PAD can 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 Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
(CAD), and in the brain, it is called
cerebrovascular disease Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. Th ...
. 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 Vascular can refer to: * blood vessels, the vascular system in animals * vascular tissue Vascular tissue is a complex transporting tissue, formed of more than one cell type, found in vascular plants. The primary components of vascular tissue ...
disease.
Vascular Vascular can refer to: * blood vessels, the vascular system in animals * vascular tissue Vascular tissue is a complex transporting tissue, formed of more than one cell type, found in vascular plants. The primary components of vascular tissue ...
refers to the arteries and veins within the body. PAD differs from peripheral
vein Veins () are blood vessels in the circulatory system of humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are those of the pulmonary and feta ...
ous 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
vein Veins () are blood vessels in the circulatory system of humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are those of the pulmonary and feta ...
ous 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 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, which may require
amputation Amputation is the removal of a Limb (anatomy), limb or other body part by Physical trauma, trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as cancer, malign ...
;
coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
; or
stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
. Up to 50% of people with PAD do not have symptoms. The greatest risk factor for PAD is
cigarette smoking Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or released from the mouth, as is generally done with pipes and cigars. The practice is believed to hav ...
. Other risk factors include
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
,
high blood pressure Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major ri ...
, kidney problems, and high blood cholesterol. PAD is primarily caused by the buildup of fatty plaque in the arteries, which is called
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
, especially in individuals over 40 years old. Other mechanisms include artery spasm,
blood clots A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulati ...
, trauma, fibromuscular dysplasia, and
vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both artery, arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily c ...
. PAD is typically diagnosed by finding an ankle-brachial index (ABI) less than 0.90, which is the
systolic blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
at the ankle divided by the systolic blood pressure of the arm.
Duplex ultrasonography Doppler ultrasonography is medical ultrasonography that employs the Doppler effect to perform medical imaging, imaging of the movement of tissue (biology), tissues and body fluids (usually blood), and their relative velocity to the ultrasound pro ...
and
angiography Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perfo ...
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. For those with intermittent claudication from PAD, stopping smoking and supervised exercise therapy may improve outcomes. Medications, including
statins Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...
,
ACE inhibitors Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as ...
, and cilostazol, may also help.
Aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...
, 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.
Anticoagulant An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which ...
s (blood thinners) such as
warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...
show no definitive scientific evidence of benefit in PAD. Surgical procedures used to treat PAD include bypass grafting,
angioplasty Angioplasty, also known as balloon angioplasty and percutaneous transluminal angioplasty, is a minimally invasive procedure, minimally invasive endovascular surgery, endovascular Medical procedure, procedure used to widen narrowed or obstructe ...
, and
atherectomy Atherectomy is a minimally invasive technique for removing atherosclerosis from blood vessels within the body. It is an alternative to angioplasty for the treatment of peripheral artery disease, but the studies that exist are not adequate to deter ...
. 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

The signs and symptoms of peripheral artery disease are based on the affected body part. 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 of the affected leg and is relieved by rest. This occurs because during exercise, the muscles require more
oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
. 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/ulcers on the affected limb that do not heal In individuals with severe PAD, complications may arise, including critical limb ischemia and
gangrene Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the ga ...
. 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 can lead to pain at rest, a feeling of coldness, or
numbness Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to Sensory receptor, sensory stimuli. In everyday speech this is generally r ...
in the affected foot and toes. Other complications of severe PAD include lower limb tissue loss (amputation),
arterial insufficiency ulcer Arterial insufficiency ulcers (also known as ischemic ulcers, or ischemic wounds) are ulcers mostly located on the lateral surface of the ankle or the distal digits. They are commonly caused by peripheral artery disease (PAD). Characteristics ...
s,
erectile dysfunction Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...
, and
gangrene Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the ga ...
. 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, sex, and ethnicity. PAD is twice as common in males as in 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 associations are hyperlipidemia, hypertension, diabetes mellitus, chronic kidney disease, and smoking. Presenting three of these factors or more 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 has also been shown to promote changes in the lining of blood vessels (
endothelium The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the r ...
), 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 Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...
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 Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of ...
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 Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density ...
(LDL
cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...
), low levels of
high-density lipoprotein High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...
(HDL cholesterol), elevation of total cholesterol, and/or high
triglyceride A triglyceride (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other vertebrates ...
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 Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
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 aneurysm Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta such that the diameter is greater than 3 cm or more than 50% larger than normal. An AAA usually causes no symptoms, except during rupture. Occasionally, abdo ...
s. 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 over, regardless of
risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...
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 The renal arteries are paired arteries that supply the kidneys with blood. Each is directed across the crus of the diaphragm, so as to form nearly a right angle. The renal arteries carry a large portion of total blood flow to the kidneys. Up to ...
disease * All people with a Framingham risk score of 10%–20% * All people who have previously 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, which causes inadequate blood flow to the limbs. As previously mentioned, the most common
etiology Etiology (; alternatively spelled aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek word ''()'', meaning "giving a reason for" (). More completely, etiology is the study of the causes, origins ...
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 buildup 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 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 Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...
) to 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 is a clear risk of limb loss if adequate blood flow is not re-established, either by surgery or endovascular therapy. Differentiating between the two concepts 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 can 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 Thrombosis () is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fib ...
, or the formation of a blood clot, usually occurs due to stasis or trauma.


Diagnosis

Diagnosing or identifying peripheral artery disease requires a history of symptoms and a physical exam, followed by confirmatory testing. These tests could include CT scans (Computed Tomographic Angiography), MRA scans (Magnetic Resonance Angiography), or ultrasounds for imaging. A physician will examine an individual for specific exam findings if symptoms are consistent with peripheral artery disease. Abnormal physical exam findings can lead a healthcare provider to consider the diagnosis. However, to confirm a diagnosis, confirmatory testing is required. These findings are associated with peripheral artery disease: * Decreased or absent pulses * Muscle atrophy or wasting * Noticeable blueness of the affected limb * Decreased temperature (coolness) in the affected limb when compared to the other * Thickened nails * Smooth or shiny skin and hair loss *
Buerger's test Buerger's test is performed in an assessment of arterial sufficiency. It is named after Leo Buerger. The ''vascular angle'', which is also called ''Buerger's angle'', is the angle to which the leg has to be raised before it becomes pale, whilst ...
can check for
pallor Pallor is a pale color of the skin that can be caused by illness, emotional shock or stress, stimulant use, or anemia, and is the result of a reduced amount of oxyhaemoglobin and may also be visible as pallor of the conjunctivae of the eye ...
when the affected limb is in an elevated position. The limb is then moved from an elevated to a sitting position and checked for redness, which is called reactive hyperemia. Buerger's test is an assessment of arterial sufficiency, which is the ability of the artery to supply oxygenated blood to the tissue that it goes to. * Nonhealing lower extremity wound If peripheral artery disease is suspected, the initial study is the ankle–brachial index (ABI). The ABI is a simple, non-invasive test that measures the ratio of systolic blood pressure in the ankle to the systolic blood pressure in the upper arm. This is based on the idea that if blood pressure readings in the ankle are lower than those in the arm, a blockage in the arteries that provide blood from the heart to the ankle is suspected. An ABI range of 0.90 to 1.40 is considered normal. A person is considered to have PAD when the ABI is ≤ 0.90. However, PAD can be further graded as mild to moderate if the ABI is between 0.41 and 0.90, and severe if the ABI is less than 0.40. These categories can provide insight into the disease course. Furthermore, ABI values of 0.91 to 0.99 are considered borderline, and values >1.40 indicate noncompressible arteries. If an ABI >1.40 is calculated, this could indicate vessel wall stiffness caused by calcification, which can occur in people with uncontrolled diabetes. Abnormally high ABIs (>1.40) are usually considered
false negatives A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resu ...
, and thus, such results merit further investigation and higher-level studies. – Describes ABI procedure, interpretation of results, and notes the somewhat arbitrary selection of "ABI of 0.8 has become the accepted endpoint for high-compression therapy, the trigger for referral for a vascular surgical opinion and the defining upper marker for an ulcer of mixed etiology. Individuals with noncompressible arteries have an increased risk of cardiovascular mortality within two years. Individuals with suspected PAD with normal ABIs can undergo exercise testing for ABI. A baseline ABI is obtained before exercise. The patient is then asked to exercise (usually patients are made to walk on a treadmill at a constant speed) until claudication pain occurs (for a maximum of 5 minutes), after which the ankle pressure is again measured. A decrease in ABI of 15%–20% would be diagnostic of PAD. If ABIs are abnormal, the next step is generally a lower limb
Doppler ultrasound Doppler ultrasonography is medical ultrasonography that employs the Doppler effect to perform imaging of the movement of tissues and body fluids (usually blood), and their relative velocity to the probe. By calculating the frequency shift of a ...
to look at the site of obstruction and the extent of atherosclerosis. Other imaging can be performed by
angiography Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perfo ...
, where a catheter is inserted into the common
femoral artery The femoral artery is a large artery in the thigh and the main arterial supply to the thigh and leg. The femoral artery gives off the deep femoral artery and descends along the anteromedial part of the thigh in the femoral triangle. It enters ...
and selectively guided to the artery in question. While injecting a radio-dense contrast agent, an
X-ray An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...
is taken. Any blood flow-limiting blockage found in the X-ray can be identified and treated by procedures including
atherectomy Atherectomy is a minimally invasive technique for removing atherosclerosis from blood vessels within the body. It is an alternative to angioplasty for the treatment of peripheral artery disease, but the studies that exist are not adequate to deter ...
, angioplasty, or
stent In medicine, a stent is a tube usually constructed of a metallic alloy or a polymer. It is inserted into the Lumen (anatomy), lumen (hollow space) of an anatomic vessel or duct to keep the passageway open. Stenting refers to the placement of ...
ing. Contrast angiography is the most readily available and widely used imaging technique. Modern
computerized tomography A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
(CT) scanners provide direct imaging of the arterial system. Studies have shown the sensitivity and specificity of CT in identifying lesions with >50% stenosis to be 95% and 96%, respectively. As such, CT may be considered as an alternative to invasive angiography. An important distinction between the two is that, unlike invasive angiography, assessment of the arterial system with CT does not allow for vascular intervention.
Magnetic resonance angiography Magnetic resonance angiography (MRA) is a group of techniques based on magnetic resonance imaging (MRI) to image blood vessels. Magnetic resonance angiography is used to generate images of arteries (and less commonly veins) in order to evaluate ...
(MRA) is a noninvasive diagnostic procedure that uses a combination of a large magnet, radio frequencies, and a computer to produce detailed images of blood vessels inside the body. The advantages of MRA include its safety and ability to provide high-resolution, three-dimensional imaging of the entire abdomen, pelvis, and lower extremities in one sitting.


Classification

The two most commonly used methods to classify peripheral artery disease are the Fontaine and Rutherford classification systems. The Fontaine stages were introduced by René Fontaine in 1954 to define the severity of chronic limb
ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...
: * Stage I: asymptomatic * Stage IIa: intermittent claudication after walking a distance of more than 200 meters * Stage IIb: intermittent claudication after walking a distance of less than 200 meters * Stage III: rest pain * Stage IV:
ulcers An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing ...
or
gangrene Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the ga ...
of the limb The Rutherford classification was created by the
Society for Vascular Surgery A society () is a group of individuals involved in persistent social interaction or a large social group sharing the same spatial or social territory, typically subject to the same political authority and dominant cultural expectations. ...
and the International Society of Cardiovascular Surgery, introduced in 1986 and revised in 1997 (and known as the Rutherford classification after the lead author, Robert B. Rutherford). This classification system consists of four grades and seven categories (categories 0–6): * Grade 0, Category 0: asymptomatic * Grade I, Category 1: mild claudication * Grade I, Category 2: moderate claudication * Grade I, Category 3: severe claudication * Grade II, Category 4: rest pain * Grade III, Category 5: minor tissue loss; ischemic ulceration not exceeding ulcer of the digits of the foot * Grade IV, Category 6: major tissue loss; severe ischemic ulcers or frank gangrene Moderate to severe PAD, classified by Fontaine's stages III to IV or Rutherford's categories 4 to 5, presents a limb threat (risk of limb loss) in the form of critical limb ischemia. Recently, the
Society for Vascular Surgery A society () is a group of individuals involved in persistent social interaction or a large social group sharing the same spatial or social territory, typically subject to the same political authority and dominant cultural expectations. ...
came out with a classification system based on "wound, ischemia and foot infection" (WIfI). This classification system, published in 2013, was created to account for the demographic changes that have occurred over the past forty years, including the increased incidence of high blood sugar and evolving techniques and abilities for
revascularization In medical and surgical therapy, revascularization is the restoration of perfusion to a body part or organ that has had ischemia. It is typically accomplished by surgical means. Vascular bypass and angioplasty are the two primary means of r ...
. This system was created on the basis that ischemia and angiographic disease patterns are not the sole determinants of amputation risk. The WIfI classification system is broken up into two parts: wounds and ischemia. Wounds are graded 0 through 3 based on the presence of ulceration, gangrene, and ischemia. * Grade 0: no ulcer, no gangrene * Grade 1: small, shallow ulcer; no gangrene * Grade 2: deep ulcer with exposed tendon or bone, gangrene limited to toes * Grade 3: extensive, full-thickness ulcer; gangrene extending to the forefoot or midfoot Ischemia is graded 0 through 3 based on ABI, ankle systolic pressure, and toe pressure. * Grade 0: ABI ≥0.80, ankle systolic pressure ≥100 mm Hg, toe pressure ≥60 mm Hg * Grade 1: arterial brachial index 0.6 to 0.79, ankle systolic pressure 70 to 100 mm Hg, toe pressure 40 to 59 mm Hg * Grade 2: ABI 0.4–0.59, ankle systolic pressure 50 to 70 mm Hg, toe pressure 30 to 39 mm Hg * Grade 3: ABI ≤0.39, ankle systolic pressure <50 mm Hg, toe pressure <30 mm Hg The TASC (and TASC II) classification suggests PAD treatment is based on the severity of the disease seen on an
angiogram Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perform ...
.


Screening

It is unclear if screening for disease in the general population is useful, as it has not been extensively studied. This includes screening with the ankle-brachial index (ABI), although a systematic review of the literature did not support the use of routine ABI screening in asymptomatic patients. Testing for coronary artery disease or carotid artery disease is of unclear benefit. While PAD is a risk factor for
abdominal aortic aneurysm Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta such that the diameter is greater than 3 cm or more than 50% larger than normal. An AAA usually causes no symptoms, except during rupture. Occasionally, abdo ...
s (AAA), there is no data on screening individuals with asymptomatic PAD for abdominal aortic aneurysms. For people with symptomatic PAD, screening by ultrasound for AAA is not unreasonable.


Wearable devices and remote patient monitoring

A 2022 review found that a variety of wearable medical devices measuring different parameters (such as body temperature) were being combined with
remote patient monitoring Remote patient monitoring (RPM) is a technology to enable monitoring of patients outside of conventional clinical settings, such as in the home or in a remote area, which may increase access to care and decrease healthcare delivery costs. RPM invo ...
of PAD patients, to improve health outcomes. Some studies propose the development of devices measuring oxygen continuously during exercise. This is because resting perfusion and metabolic activity are extremely low and differences between non-patients and PAD patients are barely measurable. As such, testing of vascular function and energetics requires a physiological challenge. Pulse oximeters can be inconvenient to wear during exercise and only give oxygen values at discrete time points, nor is there sufficient evidence to support any use in identifying PAD. Some publications and studies therefore discuss the use of wearable sensors measuring oxygen levels continuously in PAD patients, such as through transcutaneous means. However, because transcutaneous measurements are affected by movement (such as during exercise) and body temperature, the use of oxygen sensors that are inserted
subcutaneously The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, or superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and m ...
as opposed to transcutaneously may most effectively help monitor a PAD patient's progress and direct therapy decisions. To date, one oxygen sensing system has been approved for use in Europe to measure tissue perfusion in all PAD patients.


Treatment

Depending on the severity of the disease, these steps can be taken, according to these guidelines:


Lifestyle

* Stopping smoking (cigarettes promote PAD and are a risk factor for cardiovascular disease) * Regular exercise for those with claudication helps open up alternative small vessels (collateral flow), and the limitation in walking often improves. Treadmill exercise (35 to 50 minutes, three or four times per week) has been reviewed as another treatment with several positive outcomes, including a reduction in cardiovascular events and improved quality of life. Supervised exercise programs increase pain-free walking time and the maximum walking distance in people with PAD.


Medication

* Management of diabetes * Management of hypertension * Management of high cholesterol, and
antiplatelet drug An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effectiv ...
s such as
aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...
and
clopidogrel Clopidogrel, sold under the brand name Plavix among others, is an antiplatelet drug, antiplatelet medication used to reduce the risk of Cardiovascular disease, heart disease and stroke in those at high risk. It is also used together with aspi ...
.
Statins Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...
reduce clot formation and cholesterol levels, respectively, and can help with disease progression and address the other cardiovascular risks that the affected person is likely to have. According to guidelines, taking aspirin or clopidogrel is recommended to reduce AMI ("heart attack"),
stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
, and other causes of vascular death in people with symptomatic peripheral artery disease. It is recommended that aspirin and clopidogrel be taken alone and not in conjunction with one another (i.e., not as dual
antiplatelet An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effectiv ...
therapy). The recommended daily dosage of aspirin for treating PAD is between 75 and 325 mg, while the recommended daily dosage for clopidogrel is 75 mg. The effectiveness of both aspirin and clopidogrel to reduce the risk of cardiovascular ischemic events in people with symptomatic PAD is not well established. Research also suggests that low-dose
rivaroxaban Rivaroxaban, sold under the brand name Xarelto among others, is an anticoagulant medication (blood thinner) used to treat and reduce the risk of blood clots. Specifically it is used to treat deep vein thrombosis and pulmonary emboli and prev ...
plus aspirin is effective as a new anti-thrombotic regimen for PAD. Cilostazol can improve symptoms in some people. Pentoxifylline is of unclear benefit. Cilostazol may improve walking distance for people who experience claudication due to peripheral artery disease, but no strong evidence suggests that it improves the quality of life, decreases mortality, or decreases the risk of cardiovascular events. Treatment with other drugs or vitamins is unsupported by clinical evidence, "but trials evaluating the effect of folate and vitamin B12 on hyperhomocysteinemia, a putative vascular risk factor, are near completion".


Revascularization

After a trial of the best medical treatment outlined above, if symptoms persist, patients may be referred to a vascular or endovascular surgeon. The benefit of
revascularization In medical and surgical therapy, revascularization is the restoration of perfusion to a body part or organ that has had ischemia. It is typically accomplished by surgical means. Vascular bypass and angioplasty are the two primary means of r ...
is thought to correspond to the severity of ischemia and the presence of other risk factors for limb loss, such as wound and infection severity. *
Angioplasty Angioplasty, also known as balloon angioplasty and percutaneous transluminal angioplasty, is a minimally invasive procedure, minimally invasive endovascular surgery, endovascular Medical procedure, procedure used to widen narrowed or obstructe ...
(or percutaneous transluminal angioplasty) can be done on solitary lesions in large arteries, such as the
femoral artery The femoral artery is a large artery in the thigh and the main arterial supply to the thigh and leg. The femoral artery gives off the deep femoral artery and descends along the anteromedial part of the thigh in the femoral triangle. It enters ...
, but may not have sustained benefits. Patency rates following angioplasty are highest for iliac arteries and decrease with arteries towards the toes. Other criteria that affect the outcome following revascularization are the length of the lesion and the number of lesions. There do not appear to be any long-term advantages or sustained benefits to placing a stent following angioplasty in order to hold the narrowing of the subsartorial artery open. *
Atherectomy Atherectomy is a minimally invasive technique for removing atherosclerosis from blood vessels within the body. It is an alternative to angioplasty for the treatment of peripheral artery disease, but the studies that exist are not adequate to deter ...
, in which the plaque is scraped off the inside of the vessel wall (albeit with no better results than angioplasty). *
Vascular bypass A vascular bypass is a surgical procedure performed to redirect blood flow from one area to another by reconnecting blood vessels. Often, this is done to bypass around a diseased artery, from an area of normal blood flow to another relatively norm ...
grafting can be performed to circumvent a diseased area of the arterial vasculature. The
great saphenous vein The great saphenous vein (GSV; ) or long saphenous vein is a large, subcutaneous, superficial vein of the human leg, leg. It is the longest vein in the body, running along the length of the lower limb, returning blood from the foot, human leg, le ...
is used as a conduit if available, although artificial ( Gore-Tex or
PTFE Polytetrafluoroethylene (PTFE) is a synthetic fluoropolymer of tetrafluoroethylene, and has numerous applications because it is chemically inert. The commonly known brand name of PTFE-based composition is Teflon by Chemours, a spin-off fro ...
) material is often used for long grafts when adequate venous conduit is unavailable. * When
gangrene Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the ga ...
has set in,
amputation Amputation is the removal of a Limb (anatomy), limb or other body part by Physical trauma, trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as cancer, malign ...
may be required to prevent infected tissues from causing
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
, a life-threatening illness. *
Thrombolysis Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of thrombus, blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism ( ...
and
thrombectomy Mechanical thrombectomy, or simply thrombectomy, is the removal of a blood clot (thrombus) from a blood vessel, often and especially endovascularly as an interventional radiology procedure called endovascular thrombectomy (EVT). It thus contr ...
are used in cases of
arterial thrombosis Thrombosis () is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fibrin to for ...
or
embolism An embolism is the lodging of an embolus, a blockage-causing piece of material, inside a blood vessel. The embolus may be a blood clot (thrombus), a fat globule (fat embolism), a bubble of air or other gas (air embolism, gas embolism), amniotic ...
. * shockwave intravascular lithotripsy, a minimally invasive method that uses ultrasound waves to break up plaque within the artery without the need for penetration. The method was first approved by the US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
in February 2021, and has been used as a complement to more widely-used methods of atherectomy.


Guidelines

A guideline from the
American College of Cardiology The American College of Cardiology (ACC), based in Washington, D.C., is a nonprofit medical association established in 1949. It bestows credentials upon cardiovascular specialists who meet its qualifications. Education is a core component of the ...
and
American Heart Association The American Heart Association (AHA) is a nonprofit organization in the United States that funds cardiovascular medical research, educates consumers on healthy living and fosters appropriate Heart, cardiac care in an effort to reduce disability ...
for the diagnosis and treatment of lower extremity, renal, mesenteric, and abdominal aortic PAD was compiled in 2013, combining the 2005 and 2011 guidelines. For chronic limb-threatening ischemia, the ACCF/AHA guidelines recommend balloon angioplasty only for people with a life expectancy of 2 years or less or those who do not have an autogenous vein available. For those with a life expectancy greater than 2 years or who have an autogenous vein, bypass surgery is recommended.


Prognosis

Individuals with PAD have an "exceptionally elevated risk for cardiovascular events and the majority will eventually die of a cardiac or cerebrovascular etiology". Prognosis is correlated with the severity of the PAD as measured by an ABI. Large-vessel PAD increases mortality from cardiovascular disease significantly. PAD carries a greater than "20% risk of a coronary event in 10 years". The risk is low that an individual with claudication will develop severe ischemia and require amputation, but the risk of death from coronary events is three to four times higher than matched controls without claudication. Of patients with intermittent claudication, only "7% will undergo lower-extremity bypass surgery, 4% major amputations, and 16% worsening claudication", but stroke and heart attack events are elevated, and the "5-year mortality rate is estimated to be 30% (versus 10% in controls)".


Epidemiology

The prevalence of PAD in the general population is 3–7%, affecting up to 20% of those over 70; 70%–80% of affected individuals are asymptomatic; only a minority ever require revascularization or amputation. Peripheral artery disease affects one in three diabetics over the age of 50. In the US, it affects 12–20 percent of Americans age 65 and older. Around 10 million Americans have PAD. Despite its prevalence and implications for cardiovascular risk, there are still low levels of awareness of risk factors and symptoms, with 26% of the population in the US reported to have knowledge of PAD. In 2000, among people aged 40 years and older in the United States, rates of PAD were 4.3%. Rates were 14.5% for people aged 70 years or over. Within age groups, rates were generally higher for women than men. Non-Hispanic blacks had a rate of 7.9% compared to 4.4% in Non-Hispanic whites and 3.0% (1.4%–4.6%) in
Mexican Americans Mexican Americans are Americans of full or partial Mexican descent. In 2022, Mexican Americans comprised 11.2% of the US population and 58.9% of all Hispanic and Latino Americans. In 2019, 71% of Mexican Americans were born in the United State ...
. The incidence of symptomatic PAD increases with age, from about 0.3% per year for men aged 40–55 years to about 1% per year for men aged over 75 years. The prevalence of PAD varies considerably depending on how PAD is defined and the age of the population being studied. People diagnosed with PAD have a greater risk of a MACE (Major Adverse Cardiac Event) and stroke. Their risk of developing a reinfarction, stroke, or transient ischemic attack within one year following a heart attack increases to 22.9%, compared to 11.4% for those without PAD. The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study trials in people with type 1 and type 2 diabetes, respectively, demonstrated that glycemic control is more strongly associated with microvascular disease than macrovascular disease. Pathologic changes occurring in small vessels may be more sensitive to chronically elevated glucose levels than atherosclerosis occurring in larger arteries.


Research

Research is being done on therapies to prevent the progression of PAD. In those who have developed critically poor blood flow to the legs, the benefit of
autotransplantation Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person ('' auto-'' meaning "self" in Greek). The autologous tissue (also called autogenous, autogenei ...
of autologous mononuclear cells is unclear. Only one
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical ...
has been conducted comparing vascular bypass to angioplasty for the treatment of severe PAD. The trial found no difference in amputation-free survival between vascular bypass and angioplasty at the planned clinical endpoint, but the trial has been criticized as being underpowered, limiting endovascular options, and comparing inappropriate endpoints. As of 2017, two randomized clinical trials are being conducted to better understand the optimal revascularization technique for severe PAD and critical limb ischemia (CLI), the BEST-CLI (Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia) Trial and the BASIL-2 (Bypass Versus Angioplasty in Severe Ischaemia of the Leg – 2 )Trial. In 2011, pCMV-vegf165 was registered in Russia as the first-in-class
gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...
drug for the treatment of PAD, including the advanced stage of critical limb ischemia.


References


External links


"Peripheral Arterial Disease"
at the National Heart, Lung and Blood Institute

at the American College of Foot and Ankle Surgeons * {{DEFAULTSORT:Peripheral Vascular Disease Diseases of arteries, arterioles and capillaries Health effects of tobacco Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate