Peripheral Artery Disease Clinical Trials

Peripheral Artery Occlusive Disease

In medicine Peripheral Artery Occlusive Disease (PAOD), also known as peripheral vascular disease (PVD) and peripheral artery disease (PAD) is a collator for all diseases caused by the obstruction of large peripheral arteries, which can result from atherosclerosis, inflammatory processes leading to stenosis, an embolism or thrombus formation. It causes either acute or chronic ischemia.

Current Research

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Classification

Peripheral artery occlusive disease is commonly divided in the Fontaine stages:

I: mild pain on walking ("claudication")

II: severe pain on walking relatively shorter distances (intermittent claudication)

III: pain while resting

IV: loss of sensation to the lower part of the extremity

V: tissue loss (gangrene)

Symptoms

Claudication - pain, weakness, 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

Diminished hair and nail growth on affected limb and digits.

Causes

Smoking - tobacco use in any form is the single most important modifiable cause of PAD internationally. Smokers have up to a tenfold increase in relative risk for PAOD 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 - increased risk of PAOD 2-4X 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 - elevation of total cholesterol, LDL cholesterol, and triglyceride levels each have been correlated with accelerated PAOD. 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).

Other risk factors which are being studied include levels of various inflammatory mediators such as C-reactive protein, homocysteine, and fibrinogen.

Risk of PAOD also increases if the patient is: over the age of 50, African American, male, obese, or has a personal history of vascular disease, heart attack, or stroke.

Diagnosis

Upon suspicion of PAOD, the first-line test is the ankle brachial pressure index (ABPI/ABI) which is a measure of the fall in blood pressure in the arteries supplying the legs. A reduced ABPI (less than 0.9) is consistent with PAOD. Values of ABPI below 0.8 indicate moderate disease and below 0.5 severe disease.

If ABI's are abnormal the next step is generally a lower limb doppler ultrasound examination to look at site and extent of atherosclerosis at the femoral artery. Other imaging can be performed by angiography, where a catheter is inserted into the femoral artery and selectively guided to the artery in question and then used to inject radiodense contrast agent whilst an X-ray is taken. Any stenosis of the arteries can be identified and treated at the same time by balloon angioplasty if the stenosis is over a short segment (<3cm). However if the artery is occluded or there is diffuse disease present, then arterial bypass surgery may be required.

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.

Therapy

Dependent on the severity of the disease, the following steps can be taken:

Conservative measures include Smoking cessation (cigarettes promote PAOD 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. 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.

Angioplasty (PTA or percutaneous transluminal angioplasty) can be done on solitary lesions in large arteries, such as the femoral artery.

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.

Associations

Many PAOD patients also have angina pectoris or have had myocardial infarction. There is also an increased risk for stroke.

(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Peripheral_artery_occlusive_disease)

Findings From Current Research

Pharmacological Interventions for Peripheral Artery Disease

Authors: Duprez DA.

University of Minnesota, Cardiovascular Division, Medical School, VCRC-Room 270, Minneapolis, MN 55455, USA. dupre007@umn.edu

Peripheral Artery Tonometry Demonstrates Altered Endothelial Function in Children with Type 1 Diabetes

Authors: Haller MJ, Stein J, Shuster J, Theriaque D, Silverstein J, Schatz DA, Earing MG, Lerman A, Mahmud FH.

Division of Pediatric Endocrinology, Department of Pediatrics, University of Florida, Gainesville, FL, USA.

Genetic Susceptibility to Peripheral Arterial Disease: A Dark Corner in Vascular Biology

Authors: Knowles JW, Assimes TL, Li J, Quertermous T, Cooke JP.

Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, Calif; Stanford Human Genome Center, Department of Genetics, Stanford University School of Medicine, Palo Alto, Calif.

The Effect of the Introduction of MR and CT Angiography on the Utilization of Catheter Angiography for Peripheral Arterial Disease

Authors: Levin DC, Rao VM, Parker L, Frangos AJ, Sunshine JH.

Department of Radiology, Thomas Jefferson University Hospital and Jefferson Medical College, Philadelphia, Penn, USA. david.levin@mail.tju.edu

Sildenafil Promotes Ischemia-Induced Angiogenesis Through a PKG-Dependent Pathway

Authors: Senthilkumar A, Smith RD, Khitha J, Arora N, Veerareddy S, Langston W, Chidlow Jr JH, Barlow SC, Teng X, Patel RP, Lefer DJ, Kevil CG.

Departments of Cardiology, Pathology, and Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport; the Department of Molecular and Cellular Pathology and Center for Free Radical Biology, University of Alabama at Birmingham; and the Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, New York.

Prognostic Value of Ankle-Brachial Index and Dobutamine Stress Echocardiography for Cardiovascular Morbidity and All-Cause Mortality in Patients with Peripheral Arterial Disease

Authors: Thatipelli MR, Pellikka PA, McBane RD, Rooke TW, Rosales GA, Hodge D, Herges RM, Wysokinski WE.

Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Results from Clinical Connection:

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