Peripheral artery disease

Peripheral artery disease
Synonyms Peripheral vascular disease (PVD), peripheral artery occlusive disease, peripheral obliterative arteriopathy
An arterial insufficiency ulcer in a person with severe peripheral artery disease
Specialty Vascular surgery
Symptoms Leg pain when walking which resolves with rest, skin ulcers, bluish skin, cold skin[1][2]
Complications Infection, amputation[3]
Causes Atherosclerosis, artery spasm[4][5]
Risk factors Cigarette smoking, diabetes, high blood pressure, high blood cholesterol.[3][6]
Diagnostic method Ankle-brachial index < 0.90, duplex ultrasonography, angiography[7][8]
Treatment Stopping smoking, supervised exercise therapy, surgery[9][10][11]
Medication Statins, ACE inhibitors, cilostazol[11]
Frequency 155 million (2015)[12]
Deaths 52,500 (2015)[13]

Peripheral artery disease (PAD) is a narrowing of the arteries other than those that supply the heart or the brain.[4] When narrowing occurs in the heart, it is called coronary artery disease, while, in the brain, it is called cerebrovascular disease. Peripheral artery disease most commonly affects the legs, but other arteries may also be involved.[3] The classic symptom is leg pain when walking which resolves with rest, known as intermittent claudication.[1] Other symptoms including skin ulcers, bluish skin, cold skin, or poor nail and hair growth may occur in the affected leg.[2] Complications may include an infection or tissue death which may require amputation; coronary artery disease, or stroke.[3] Up to 50% of cases of PAD are without symptoms.[1]

The main risk factor is cigarette smoking.[3] Other risk factors include diabetes, high blood pressure, and high blood cholesterol.[6] The underlying mechanism is usually atherosclerosis.[5] Other causes include artery spasm.[4] PAD is typically diagnosed by finding an ankle-brachial index (ABI) less than 0.90, which is the systolic blood pressure at the ankle divided by the systolic blood pressure of the arm.[8] Duplex ultrasonography and angiography may also be used.[7] Angiography is more accurate and allows for treatment at the same time; however, it is associated with greater risks.[8]

It is unclear if screening for disease is useful as it has not been properly studied.[14][15] In those with intermittent claudication from PAD, stopping smoking and supervised exercise therapy improves outcomes.[10][11] Medications, including statins, ACE inhibitors, and cilostazol also may help.[11][16] Aspirin does not appear to help those with mild disease but is usually recommended in those with more significant disease.[17][18] Anticoagulants such as warfarin are not typically of benefit.[19] Procedures used to treat the disease include bypass grafting, angioplasty, and atherectomy.[9]

In 2015 about 155 million people had PAD worldwide.[12] In the developed world it affects about 5.3% of 45 to 50 years olds and 18.6% of 85- to 90-year-olds.[6] In the developing world it affects 4.6% of people between the ages of 45 to 50 and 15% of people between the ages of 85 to 90.[6] In the developed world PAD is equally common among men and women while in the developing world women are more commonly affected.[6] In 2015 PAD resulted in about 52,500 deaths up from 16,000 deaths in 1990.[13][20]

Signs and symptoms

Up to 50% of people with PAD may have no symptoms.[1] Symptoms of PAD in the legs and feet are generally divided into 2 categories:

  1. Intermittent claudication—pain in muscles when walking or using the affected muscles that is relieved by resting those muscles. This is due to the unmet oxygen demand in muscles with use in the setting of inadequate blood flow.
  2. Critical limb ischemia, consisting of:

Medical signs of PAD in the legs, due to inadequate perfusion, include:

PAD in other parts of the body depends on the organ affected. Renal artery stenosis can cause renovascular hypertension. Carotid artery disease can cause strokes and transient ischemic attacks.

Causes

The illustration shows how PAD can affect arteries in the legs. Figure A shows a normal artery with normal blood flow. The inset image shows a cross-section of the normal artery. Figure B shows an artery with plaque buildup that's partially blocking blood flow. The inset image shows a cross-section of the narrowed artery.

Risk factors contributing to PAD are the same as those for atherosclerosis:[21][22]

Risk factors

Peripheral arterial disease is more common in the following populations of people:[26][38]

Diagnosis

Measuring the ankle-brachial index

Upon suspicion of PAD, the first-line study is the ankle–brachial index (ABI). When the blood pressure readings in the ankles is lower than that in the arms, blockages in the arteries which provide blood from the heart to the ankle are suspected. Normal ABI range of 1.00 to 1.40.The patient is diagnosed with PAD when the ABI is ≤ 0.90 . ABI values of 0.91 to 0.99 are considered ‘‘borderline’’ and values >1.40 indicate noncompressible arteries. PAD is graded as mild to moderate if the ABI is between 0.41 and 0.90, and an ABI less than 0.40 is suggestive of severe PAD. These relative categories have prognostic value.[26]

In people with suspected PAD but normal resting ABIs, exercise testing of ABI can be done. A base line 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 (or a maximum of 5 minutes), following which the ankle pressure is again measured. A decrease in ABI of 15%-20% would be diagnostic of PAD.[26][38]

It is possible for conditions which stiffen the vessel walls (such as calcifications that occur in the setting of long term diabetes) to produce false negatives usually, but not always, indicated by abnormally high ABIs (> 1.40). Such results and suspicions merit further investigation and higher level studies.[39]

If ABIs are abnormal the next step is generally a lower limb doppler ultrasound examination to look at site and extent of atherosclerosis. Other imaging can be performed by angiography,[21] where a catheter is inserted into the common femoral artery and selectively guided to the artery in question. While injecting a radiodense contrast agent an X-ray is taken. Any flow limiting stenoses found in the x-ray can be identified and treated by atherectomy, angioplasty or stenting. Contrast angiography is the most readily available and widely used imaging technique.

Modern multislice computerized tomography (CT) scanners provide direct imaging of the arterial system as an alternative to angiography.

Magnetic resonance angiography (MRA) is a noninvasive diagnostic procedure that uses a combination of a large magnet, radio frequencies, and a computer to produce detailed images to provide pictures of blood vessels inside the body. The advantages of MRA include its safety and ability to provide high-resolution three-dimensional (3D) imaging of the entire abdomen, pelvis and lower extremities in one sitting.[40][41]

Classification

Peripheral artery occlusive disease is commonly divided in the Fontaine stages, introduced by René Fontaine in 1954 for chronic limb ischemia:[38][42]

  • Stage IIA: Claudication when walking a distance of greater than 200 meters
  • Stage IIB: Claudication when walking a distance of less than 200 meters

A classification by the Society for Vascular Surgery and International Society of Cardiovascular Surgery (SVS/ISCVS), introduced in 1986 and revised in 1997 (and known as the Rutherford classification after the lead author, Robert B. Rutherford), consists of four grades and seven categories:[38][43]

The TASC (and TASC II) classification suggested PAD treatment by severity of disease seen on angiogram.[38] More recently classifications, such as the Society for Vascular Surgery "Wound, Ischemia and Foot Infection" (WIFI) classification, take into account that ischemia and angiographic disease patterns are not the only determinants of amputation risk.[44]

Moderate to severe PAD in the area of Fontaine's stage III to IV, or Rutherford's category 4 to 5, presents limb threat (risk of limb loss) in the form of critical limb ischemia.[45]

Screening

It is not clear if screening for disease is useful as it has not been properly studied.[14]

Treatment

Depending on the severity of the disease, the following steps can be taken, according to the following guidelines:[46]

Lifestyle changes

Medication

Cilostazol or pentoxifylline can improve symptoms in some.[16][47] Cilostazol may improve walking distance for people who experience claudication due to peripheral artery disease, but there is no strong evidence to suggest that it improves the quality of life, decreases mortality, or decreases the risk of cardiovascular events.[16]

Treatment with other drugs or vitamins are unsupported by clinical evidence, "but trials evaluating the effect of folate and vitamin B-12 on hyperhomocysteinemia, a putative vascular risk factor, are near completion".[46]

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 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.[44]

Guidelines

An updated consensus guideline from the American College of Cardiology 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.[26]

Prognosis

Individuals with PAD have an "exceptionally elevated risk for cardiovascular events and the majority will eventually die of a cardiac or cerebrovascular etiology";[53] prognosis is correlated with the severity of the PAD as measured by the ankle–brachial index.[53] Large-vessel PAD increases mortality from cardiovascular disease significantly. PAD carries a greater than "20% risk of a coronary event in 10 years".[53]

There is a low risk 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.[46] 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)".[53]

Epidemiology

The prevalence of peripheral artery disease in the general population is 12–14%, affecting up to 20% of those over 70;[53] 70%–80% of affected individuals are asymptomatic; only a minority ever require revascularisation or amputation. Peripheral artery disease affects 1 in 3 diabetics over the age of 50.

In the USA peripheral arterial disease affects 12–20 percent of Americans age 65 and older. Approximately 10 million Americans have PAD. Despite its prevalence and cardiovascular risk implications, only 25 percent of PAD patients are undergoing treatment.

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 times higher risk of heart attack 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. It may be that pathologic changes occurring in small vessels are more sensitive to chronically elevated glucose levels than is atherosclerosis occurring in larger arteries.[54]

Research

In those who have developed critically poor blood flow to the legs, it is unclear if autotransplantation of autologous mononuclear cells is useful or not.[55]

Only one randomized controlled trial has been conducted comparing vascular bypass to angioplasty for the treatment of severe PAD.[56] The trial found no difference in amputation-free survival between vascular bypass and angioplasty at the planned clinical endpoint, however the trial has been criticized as being underpowered, limiting endovascular options, and comparing inappropriate endpoints.[57] 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 Angio plasty in Severe Ischaemia of the Leg – 2 )Trial. [58][59]

In 2011, pCMV-vegf165 was registered in Russia as the first-in-class gene therapy drug for treatment of peripheral artery disease, including the advanced stage of critical limb ischemia.[60][61]

See also

References

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  56. ↑ Adam DJ, Beard JD, Cleveland T, Bell J, Bradbury AW, Forbes JF, Fowkes FG, Gillepsie I, Ruckley CV, Raab G, Storkey H (Dec 2005). "Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial.". Lancet. 366: 1925–34. PMID 16325694. doi:10.1016/S0140-6736(05)67704-5.
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