Peripheral vascular disease

Peripheral vascular disease (PVD), commonly referred to as peripheral arterial disease (PAD) or peripheral artery occlusive disease (PAOD), refers to the obstruction of large arteries not within the coronary, aortic arch vasculature, or brain. PVD can result from atherosclerosis, inflammatory processes leading to stenosis, an embolism, or thrombus formation. It causes either acute or chronic ischemia (lack of blood supply). Often PAD is a term used to refer to atherosclerotic blockages found in the lower extremity.

PVD also includes a subset of diseases classified as microvascular diseases resulting from episodal narrowing of the arteries (Raynaud's phenomenon), or widening thereof (erythromelalgia), i.e. vascular spasms.

Classification
Peripheral artery occlusive disease is commonly divided in the Fontaine stages, introduced by René Fontaine in 1954 for ischemia:


 * 1) mild pain when walking (claudication), incomplete blood vessel obstruction;
 * 2) severe pain when walking relatively short distances (intermittent claudication), pain triggered by walking "after a distance of >150 m in stage IIa and after <150 m in stage II-b";
 * 3) pain while resting (rest pain), mostly in the feet, increasing when the limb is raised;
 * 4) biological tissue loss (gangrene) and difficulty walking.

A more recent classification by Rutherford consists of three grades and six categories:
 * 1) Mild claudication
 * 2) Moderate claudication
 * 3) Severe claudication
 * 4) Ischemic pain at rest
 * 5) Minor tissue loss
 * 6) Major tissue loss

Symptoms
About 20% of patients with mild PAD may be asymptomatic; other symptoms include:
 * Claudication - pain, weakness, numbness, or cramping in muscles due to decreased blood flow
 * Sores, wounds, or ulcers that heal slowly or not at all
 * Noticeable change in color (blueness or paleness) or temperature (coolness) when compared to the other limb (termed unilateral dependent rubor; when both limbs are affected this is termed bilateral dependent rubor)
 * Diminished hair and nail growth on affected limb and digits.

Causes
Risk factors contributing to PAD are the same as those for atherosclerosis:


 * Smoking - tobacco use in any form is the single most important modifiable cause of PVD internationally. Smokers have up to a tenfold increase in relative risk for PVD in a dose-related effect. Exposure to second-hand smoke from environmental exposure has also been shown to promote changes in blood vessel lining (endothelium) which is a precursor to atherosclerosis.
 * Diabetes mellitus - causes between two and four times increased risk of PVD by causing endothelial and smooth muscle cell dysfunction in peripheral arteries. Diabetics account for up to 70% of nontraumatic amputations performed, and a known diabetic who smokes runs an approximately 30% risk of amputation within 5 years.
 * Dyslipidemia (high low density lipoprotein [LDL] cholesterol, low high density lipoprotein [HDL] cholesterol) - elevation of total cholesterol, LDL cholesterol, and triglyceride levels each have been correlated with accelerated PAD. Correction of dyslipidemia by diet and/or medication is associated with a major improvement in short-term rates of heart attack and stroke. This benefit is gained even though current evidence does not demonstrate a major reversal of peripheral and/or coronary atherosclerosis.
 * Hypertension - elevated blood pressure is correlated with an increase in the risk of developing PAD, as well as in associated coronary and cerebrovascular events (heart attack and stroke).
 * Risk of PAD also increases in individuals who are over the age of 50, male, obese, or with a family history of vascular disease, heart attack, or stroke.
 * Other risk factors which are being studied include levels of various inflammatory mediators such as C-reactive protein, homocysteine.

Diagnosis
Upon suspicion of PVD, the first-line study is the ankle brachial pressure index (ABPI/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. An ABI ratio less than 0.9 is consistent with PVD; values of ABI below 0.8 indicate moderate disease and below 0.4 imply severe ischemic disease.

It is possible for conditions which stiffen the vessel walls (such as calcifications that occur in the setting of chronic diabetes) to produce false negatives usually, but not always, indicated by abnormally high ABIs (> 1.3). Such results and suspicions merit further investigation and higher level studies.

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, 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. Modern multislice computerized tomography (CT) scanners provide direct imaging of the arterial system as an alternative to angiography. CT provides complete evaluation of the aorta and lower limb arteries without the need for an angiogram's arterial injection of contrast agent.

Treatment
Dependent on the severity of the disease, the following steps can be taken: Treatment with other drugs or vitamins are unsupported by clinical evidence, "but trials evaluating the effect of folate and vitamin B-12 on hyperhomocysteinaemia, a putative vascular risk factor, are near completion".
 * Smoking cessation (cigarettes promote PVD and are a risk factor for cardiovascular disease).
 * Management of diabetes.
 * Management of hypertension.
 * Management of cholesterol, and medication with antiplatelet drugs. Medication with aspirin, clopidogrel and statins, which reduce clot formation and cholesterol levels, respectively, can help with disease progression and address the other cardiovascular risks that the patient is likely to have.
 * 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, 3 to 4 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.
 * Cilostazol or pentoxifylline treatment to relieve symptoms of claudication.

After a trial of the best medical treatment outline above, if symptoms remain unnacceptable, patients may be referred to a vascular or endovascular surgeon; however, "No convincing evidence supports the use of percutaneous balloon angioplasty or stenting in patients with intermittent claudication".


 * Angioplasty (PTA or percutaneous transluminal angioplasty) can be done on solitary lesions in large arteries, such as the femoral artery, but angioplasty may not have sustained benefits.
 * Plaque excision, in which the plaque is scraped off of the inside of the vessel wall.
 * Occasionally, bypass grafting is needed to circumvent a seriously stenosed area of the arterial vasculature. Generally, the saphenous vein is used, although artificial (Gore-Tex) material is often used for large tracts when the veins are of lesser quality.
 * Rarely, sympathectomy is used - removing the nerves that make arteries contract, effectively leading to vasodilatation.
 * When gangrene of toes has set in, amputation is often a last resort to stop infected dying tissues from causing septicemia.
 * Arterial thrombosis or embolism has a dismal prognosis, but is occasionally treated successfully with thrombolysis.

Guidelines
Several different guideline standards have been developed, including:


 * TASC II Guidelines


 * ACC/AHA Guidelines

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 the Ankle brachial pressure index (ABPI). Large-vessel PAD increases mortality from cardiovascular disease significantly. PAD carries a greater than "20% risk of a coronary event in 10 years".

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. 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 peripheral vascular disease in the general population is 12–14%, affecting up to 20% of those over 70; 70%–80% of affected individuals are asymptomatic; only a minority ever require revascularisation or amputation. Peripheral vascular 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 PVD. Despite its prevalence and cardiovascular risk implications, only 25 percent of PAD patients are undergoing treatment.

The incidence of symptomatic PVD 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 PVD 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 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.