Peripheral artery disease (PAD) is an abnormal narrowing of
arteries
An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...
other than those that supply the
heart
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
or
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
.
When narrowing occurs in the heart, it is called
coronary artery disease, 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
A leg is a weight-bearing and locomotive anatomical structure, usually having a columnar shape. During locomotion, legs function as "extensible struts". The combination of movements at all joints can be modeled as a single, linear element ...
, but other arteries may also be involved – such as those of the arms, neck, or kidneys.
The classic symptom is leg pain when walking which resolves with rest, known as
intermittent claudication
Intermittent claudication, also known as vascular claudication, is a symptom that describes muscle pain on mild exertion (ache, cramp, numbness or sense of fatigue), classically in the calf muscle, which occurs during exercise, such as walking, an ...
.
Other symptoms include
skin ulcers
An ulcer is a sore on the skin or a mucous membrane, accompanied by the disintegration of tissue. Ulcers can result in complete loss of the epidermis and often portions of the dermis and even subcutaneous fat. Ulcers are most common on the skin ...
,
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
Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
.
[ Other risk factors include ]diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, high blood pressure, kidney problems, and high blood cholesterol.[ The most common underlying mechanism of peripheral artery disease is ]atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...
, especially in individuals over 40 years old.[ Other mechanisms include artery spasm, blood clots, trauma, ]fibromuscular dysplasia
Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory disease of the blood vessels that causes abnormal growth within the wall of an artery. FMD has been found in nearly every arterial bed in the body although the most common ...
, and vasculitis
Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused ...
. 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 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 ...
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 perfor ...
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
Screening may refer to:
* Screening cultures, a type a medical test that is done to find an infection
* Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees)
* Screening (environmental), a ...
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
Physical therapy (PT), also known as physiotherapy, is one of the allied health professions. It is provided by physical therapists who promote, maintain, or restore health through physical examination, diagnosis, management, prognosis, patient ...
improve outcomes.[ Medications, including statins, ]ACE inhibitors
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volume ...
, and cilostazol
Cilostazol, sold under the brand name Pletal among others, is a medication used to help the symptoms of intermittent claudication in peripheral vascular disease. If no improvement is seen after 3 months, stopping the medication is reasonable. It ...
may also help. Aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
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 such as ]warfarin
Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent st ...
are not typically of benefit. Procedures used to treat the disease include bypass grafting
Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage") is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest p ...
, angioplasty
Angioplasty, is also known as balloon angioplasty and percutaneous transluminal angioplasty (PTA), is a minimally invasive endovascular procedure used to widen narrowed or obstructed arteries or veins, typically to treat arterial atheroscle ...
, 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 determ ...
.
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 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
Intermittent claudication, also known as vascular claudication, is a symptom that describes muscle pain on mild exertion (ache, cramp, numbness or sense of fatigue), classically in the calf muscle, which occurs during exercise, such as walking, an ...
, which causes pain and severe cramping when walking or exercising. The pain is usually located in the calf muscles of the affected leg and relieved by rest. This occurs because during exercise the muscles of the leg need more oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
. Normally, the arteries would be able to increase the amount of blood flow and therefore increase the amount of oxygen going to the exercised leg. However, in PAD, the artery is unable to respond appropriately to the increased demand for oxygen by the muscles, as a result, the leg muscles are overly saturated with lactic acid
Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as nat ...
, resulting in pain of the muscle that only goes away 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
Chronic limb threatening ischemia (CLTI), also known as critical limb ischemia (CLI), is an advanced stage of peripheral artery disease (PAD). It is defined as ischemic rest pain, arterial insufficiency ulcers, and gangrene. The latter two cond ...
and gangrene. Critical limb ischemia occurs when the obstruction to 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
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 stimuli. In everyday speech this is generally referred to as num ...
in the affected foot and toes. Other complications of severe PAD include lower limb tissue loss, arterial insufficiency ulcer
Arterial insufficiency ulcers (also known as ischemic ulcers, or ischemic wounds) are mostly located on the lateral surface of the ankle or the distal digits. They are commonly caused by peripheral artery disease (PAD).
Characteristics
The ulcer ...
s, 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 are irreversible.
Causes
Risk factor
Factors contributing to increased risk of PAD are the same as those for atherosclerosis.[. Retrieved August 9, 2010.] 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
The endothelium 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 rest of the vesse ...
), 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, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
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
Dyslipidemia is an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease ( ASCVD). ASCVD includes coronary ar ...
, 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
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 dens ...
(LDL cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
), 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 (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''wikt:tri-#Prefix, tri-'' and ''glyceride'').
Triglycerides are the main constituents of body fat in humans and other ...
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 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. They usually cause no symptoms, except during rupture. Occasionally, abdominal, ...
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 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:[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 ...
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
Hyperhomocysteinemia is a medical condition characterized by an abnormally high level of homocysteine in the blood, conventionally described as above 15 μmol/L.
As a consequence of the biochemical reactions in which homocysteine is involved ...
)
* Individuals with an abnormal lower extremity pulse examination
In medicine, a pulse represents the tactile arterial palpation of the cardiac cycle (heartbeat) by trained fingertips. The pulse may be palpated in any place that allows an artery to be compressed near the surface of the body, such as at the nec ...
* 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
The Framingham Risk Score is a sex-specific algorithm used to estimate the 10-year cardiovascular risk of an individual. The Framingham Risk Score was first developed based on data obtained from the Framingham Heart Study, to estimate the 10-year r ...
of 10%–20%
* All people who have previously experienced chest pain
Mechanism
As previously mentioned, the most common cause 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 most commonly affected site occurs at arterial branch points, because there is an increase in turbulence
In fluid dynamics, turbulence or turbulent flow is fluid motion characterized by chaotic changes in pressure and flow velocity. It is in contrast to a laminar flow, which occurs when a fluid flows in parallel layers, with no disruption between ...
and stress on the artery at these areas where the artery branches to supply distant structures. Disease of distant structures, including feet and toes, are usually caused by diabetes and seen in the elderly population.
Additional mechanisms of peripheral artery disease including arterial spasm, thrombosis, and fibromuscular dysplasia. The mechanism of arterial spasm is still being studied, but it 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
Thrombosis (from Ancient Greek "clotting") 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 (t ...
, or the formation of a blood clot, occurs usually due stasis or trauma. Damage to the lining of the blood vessel begins the process of clot formation. The blood clot ultimately creates a narrowing in the artery preventing adequate blood flow and oxygen to the tissue further down.
Diagnosis
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 Angiography), MRA scans (Magnetic Resonance Angiography), or ultrasounds for imaging. In the setting of symptoms consistent with peripheral artery disease a physician will then examine an individual for specific exam findings. Abnormal physical exam findings can lead a health care provider to consider a specific diagnosis. However, in order 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 affected limb when compared to the other
* Thickened nails
* Smooth or shiny skin and hair loss
* Buerger's test
Buerger's test is used 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 lying d ...
can check for pallor when the affected limb is in an elevated position. The limb is then moved from elevated to sitting position and is 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, which 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 an 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 result ...
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 aetiology.] Individuals with noncompressible arteries have an increased risk of cardiovascular mortality within a two-year period.
In individuals with suspected PAD with normal ABIs can undergo exercise testing of ABI. A baseline ABI is obtained prior to 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 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 perfor ...
, 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 or profunda femoris artery and descends along the anteromedial part of the thigh in the f ...
and selectively guided to the artery in question. While injecting a radio-dense contrast agent, an X-ray
An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...
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 determ ...
, angioplasty, or stent
In medicine, a stent is a metal or plastic tube inserted into the lumen of an anatomic vessel or duct to keep the passageway open, and stenting is the placement of a stent. A wide variety of stents are used for different purposes, from expandab ...
ing. Contrast angiography is the most readily available and widely used imaging technique. Modern computerized tomography (CT) scanners provide direct imaging of the arterial system as an alternative to angiography.
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 the Rutherford systems of classification. The Fontaine stages, were introduced by René Fontaine in 1954 to define severity of chronic limb ischemia:
* 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 o ...
or gangrene of the limb
The Rutherford classification was created by the Society for Vascular Surgery
The Society for Vascular Surgery (SVS) is the major national academic society for vascular surgery in the United States. Its mission includes education, research, career development and advocacy. The SVS is the national advocate for more than 6, ...
and 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
Robert B. Rutherford, MD, (1931 – November 22, 2013) was an American vascular surgeon, scientific journal editor, and medical textbook author. He established the definitive textbook in vascular surgery and was a Senior Editor of the '' Journal ...
). 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 limb threat (risk of limb loss) in the form of critical limb ischemia
Chronic limb threatening ischemia (CLTI), also known as critical limb ischemia (CLI), is an advanced stage of peripheral artery disease (PAD). It is defined as ischemic rest pain, arterial insufficiency ulcers, and gangrene. The latter two cond ...
.
Recently, the Society for Vascular Surgery
The Society for Vascular Surgery (SVS) is the major national academic society for vascular surgery in the United States. Its mission includes education, research, career development and advocacy. The SVS is the national advocate for more than 6, ...
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 increased incidence of high blood sugar and evolving techniques and ability 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 rev ...
. This system was created on the basis of ischemia and angiographic disease patterns not being 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 on the presence of ulceration and/or 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 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 suggested PAD treatment is based on the severity of disease seen on 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 performe ...
.
Screening
It is not clear if screening for disease in the general population is useful as it has not been properly studied. This includes screening with the ankle-brachial index.
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. They usually cause no symptoms, except during rupture. Occasionally, abdominal, ...
s (AAA), there is no data on screening individuals with asymptomatic PAD for abdominal aortic aneurysms.[ In people with symptomatic PAD screening by ultrasound for AAA is not unreasonable.][
]
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 a number of positive outcomes, including 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
The term ''diabetes'' includes several different metabolic disorders that all, if left untreated, result in abnormally high concentration of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces ...
* 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 effecti ...
s such as aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
and clopidogrel
Clopidogrel — sold under the brand name Plavix, among others — is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following ...
. Statins reduce clot formation and cholesterol levels, respectively, 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
AMI or Ami may refer to:
Arts, entertainment and media
*AMI-tv, a Canadian TV channel
**AMI-télé, the French-language version
* AMI-audio, a Canadian audio broadcast TV service
*''Ami Magazine'', an Orthodox Jewish news magazine
Businesses ...
("heart attack"), stroke, 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 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 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 prevent blood clots. Specifically it is used to treat deep vein thrombosis and pulmonary emboli and prevent blood clo ...
plus aspirin is effective as a new anti-thrombotic regimen for PAD.
Cilostazol
Cilostazol, sold under the brand name Pletal among others, is a medication used to help the symptoms of intermittent claudication in peripheral vascular disease. If no improvement is seen after 3 months, stopping the medication is reasonable. It ...
can improve symptoms in some. 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 are unsupported by clinical evidence, "but trials evaluating the effect of folate and vitamin B12 on hyperhomocysteinemia
Hyperhomocysteinemia is a medical condition characterized by an abnormally high level of homocysteine in the blood, conventionally described as above 15 μmol/L.
As a consequence of the biochemical reactions in which homocysteine is involved ...
, a putative vascular risk factor, are near completion".[
]
Revascularization
After a trial of the best medical treatment outline 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 rev ...
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, is also known as balloon angioplasty and percutaneous transluminal angioplasty (PTA), is a minimally invasive endovascular procedure used to widen narrowed or obstructed arteries or veins, typically to treat arterial atheroscle ...
(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 or profunda femoris artery and descends along the anteromedial part of the thigh in the f ...
, 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 outcome following revascularization are length of lesion and number of lesions. There does not appear to be long term advantages or sustained benefit to placing a stent following angioplasty in order to hold the narrowing of the subsartorial artery open.
* Atherectomy, in which the plaque is scraped off of 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 nor ...
grafting can be performed to circumvent a diseased area of the arterial vasculature. The great saphenous vein
The great saphenous vein (GSV, alternately "long saphenous vein"; ) is a large, subcutaneous, superficial vein of the leg. It is the longest vein in the body, running along the length of the lower limb, returning blood from the foot, leg and thi ...
is used as a conduit if available, although artificial (Gore-Tex
Gore-Tex is a waterproof, breathable fabric membrane and registered trademark of W. L. Gore & Associates. Invented in 1969, Gore-Tex can repel liquid water while allowing water vapor to pass through and is designed to be a lightweight, waterpr ...
or PTFE) material is often used for long grafts when adequate venous conduit is unavailable.
* When gangrene has set in, amputation may be required to prevent infected tissues from causing sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, a life-threatening illness.
* Thrombolysis
Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massive ...
and thrombectomy
Mechanical thrombectomy, or simply thrombectomy, is the interventional procedure of removing a blood clot (thrombus) from a blood vessel. It is commonly performed in the cerebral arteries (interventional neuroradiology). The effectiveness of throm ...
are used in cases of arterial thrombosis 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 ( gas embolism), amniotic fluid (am ...
.
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 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 revascularisation 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 cardiovascular risk implications, only 25% of PAD patients are undergoing treatment.
In people aged 40 years and older in the United States in 2000, rates of PAD was 4.3%. Rates were 14.5% people aged 70 years or over. Within age groups, rates were generally higher in women than men. Non-Hispanic blacks
Black is a racialized classification of people, usually a political and skin color-based category for specific populations with a mid to dark brown complexion. Not all people considered "black" have dark skin; in certain countries, often in ...
had a rates of 7.9% compared to 4.4% in Non-Hispanic whites and 3.0% (1.4%–4.6%) in Mexican Americans.
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. Diagnosis is critical, as people with PAD have a four- to five-fold higher risk of heart attack
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...
or stroke.
The Diabetes Control and Complications Trial, and the U.K. 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 is atherosclerosis occurring in larger arteries.
Research
Research is being done on therapies to prevent progression of PAD. In those who have developed critically poor blood flow to the legs, the benefit of autotransplantation 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 te ...
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
Clinical endpoints or clinical outcomes are outcome measures referring to occurrence of disease, symptom, sign or laboratory abnormality constituting a target outcome in clinical research trials. The term may also refer to any disease or sign tha ...
, 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 a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
drug for 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
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