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Peripheral vascular disease

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BACKGROUND

Peripheral vascular disease (PVD), also known as peripheral artery disease (PAD), is a slow and progressive circulation disorder. It may involve disease in any of the blood vessels outside of the heart and diseases of the lymph vessels - the arteries, veins, or lymphatic vessels. Organs supplied by these vessels such as the brain, heart, and legs, may not receive adequate blood flow for ordinary function. However, the legs and feet are most commonly affected, thus the name peripheral vascular disease.

Conditions associated with PVD that affect the veins include deep vein thrombosis (DVT), varicose veins, and chronic venous insufficiency. Lymphedema is an example of PVD that affects the lymphatic vessels.

An individual with PVD also has an increased risk of heart attack, stroke, and transient ischemic attack (TIA).

PVD affects eight to 12 million people in the United States. An estimated 5% of adults in the United States over age 50 have PVD. Among adults age 65 and older, 12-20% may have PVD.

CAUSES

Atherosclerosis: The most common cause of peripheral vascular disease is atherosclerosis. Atherosclerosis is a gradual process in which a fatty material (called plaque) builds up inside the arteries. The fat may then mix with calcium, scar tissue, and other substances and harden slightly, forming plaques. These plaques block, narrow, or weaken the vessel walls. Blood flow through the arteries can be restricted or blocked totally.

Other causes of peripheral vascular disease include blood clots, diabetes, inflammation of the arteries, infection, structural defects, and injury.

Blood clots: A blood clot can form and block a blood vessel, which is then called a thrombus or emboli. This process can lead to a stroke or heart attack. The cause of blood clots is often related to medications, trauma, and lifestyle (such as smoking or sedentary). Genetic factors can contribute to blood clot formation.

Diabetes: Chronic (long-term) high blood sugar levels in diabetics may damage blood vessels. This makes the blood vessels more likely to become narrowed or weakened. Additionally, those with diabetes frequently have high blood pressure and high cholesterol levels in the blood, which accelerates the development of atherosclerosis. In individuals with diabetes, sugar (glucose) accumulates in the blood to very high levels. The excess glucose can attach to proteins in the blood vessels and alter their normal structure and function. One effect of this is that the vessels become thicker and less elastic, making it hard for blood to squeeze through.

Inflammation of the arteries: Inflammation of the arteries, or arteritis, can cause narrowing or weakening of the arteries. Arteritis usually occurs due to autoimmune conditions (such as rheumatoid arthritis) or infection.

Infection: The inflammation and scarring caused by an infection may block, narrow, or weaken blood vessels. Both infection with Salmonella bacteria and syphilis may result in damage to the blood vessels.

Structural defects: Defects in the structure of a blood vessel can cause narrowing. Most of these cases are acquired at birth, and the cause remains unknown.

Injury: Blood vessels can be injured in an accident, such as a car wreck or a bad fall.

RISK FACTORS

Smoking: Smoking is more closely related to developing peripheral vascular disease (PVD) than any other risk factor. Smoking increases the risk of developing PVD three to five times. On average, smokers who develop PVD experience symptoms 10 years earlier than nonsmokers who develop PVD. Nicotine constricts blood vessels and forces the heart to pump harder. A buildup of carbon monoxide (CO) reduces oxygen in the blood and damages the lining of the blood vessels. Stopping smoking will slow the progress of PVD. Smoking even one or two cigarettes daily can interfere with the treatment for PVD. Smokers who have diabetes have the greatest risk of complications from PVD, including gangrene in the leg from decreased blood flow.

Chronic or serious illnesses: Chronic illnesses, such as diabetes, can increase the risk of developing PVD. One in three people over age 50 with diabetes is likely to have PVD. Anyone over age 50 with diabetes should be screened for PVD. Other conditions may also increase the risks of developing PVD, including kidney disease, high blood pressure, a high cholesterol level, heart disease, a family history of stroke, heart disease and high blood pressure, and age. Men who are older than age 50 and women who are older than age 55 are at higher risk for PVD.

High blood pressure: High blood pressure is a common and important risk factor for vascular disorders, including PVD. About 2-5% of individuals with hypertension have symptoms of PVD, with the prevalence increasing with age. Similarly, 35-55% of patients with PVD at presentation also have hypertension. Individuals who suffer from hypertension with PVD have a greatly increased risk of myocardial infarction and stroke.

High cholesterol: High cholesterol levels are present in 40% of individuals with PVD. The relative risk of PVD is 1.2-1.4 for each 40-50 milligrams per deciliter (mg/dl) increase in total cholesterol. High levels of triglycerides and an elevated plasma concentration of lipoprotein(a) each increase the risk of developing PVD.

Obesity: Being overweight contributes to other risk factors for stroke, such as high blood pressure, PVD, cardiovascular disease, and diabetes. Weight loss of as little as 10 pounds may lower blood pressure and improve cholesterol levels.

Sedentary lifestyle: People who do not exercise regularly have an increased risk of developing PVD. Exercise is important because it can lower blood pressure, increase the level of HDL cholesterol (good cholesterol), and improve the overall health of blood vessels and the heart. It also helps control weight, control diabetes, and reduce stress. Thirty minutes daily of moderate exercise is normally recommended. Patients should talk to their doctors before starting a new exercise program.

Uncontrolled diabetes: Managing diabetes with diet, exercise, weight control, and medication is essential. Strict control of blood sugar may reduce damage to the heart and blood vessels.

Inflammation: Elevations in markers of inflammation, including levels of C-reactive protein, may also be risk factors for the development of PVD.

SIGNS AND SYMPTOMS

General: Only about half of people with peripheral vascular disease (PVD) have symptoms. Almost always, symptoms are caused by the leg muscles not getting enough blood. Whether the individual has symptoms depends partly on which artery is affected and to what extent blood flow is restricted.

Pain: The most common symptom of peripheral vascular disease in the legs is pain in one or both calves, thighs, or hips. The pain usually occurs while walking or climbing stairs and stops when at rest. The muscles' demand for blood and oxygen increases during walking and other exercise. In PVD, the narrowed or blocked arteries cannot supply more blood, so the muscles are deprived of oxygen and other nutrients. This pain is called intermittent (comes and goes) claudication. Intermittent claudication is usually a dull, cramping pain. It may also feel like a heaviness, tightness, or tiredness in the muscles of the legs.

Muscle cramps: Cramps in the legs have several causes, but cramps that start with exercise and stop with rest most likely are due to intermittent claudication. When the blood vessels in the legs are completely blocked, leg pain at night is very typical, and the individual almost always hangs his or her feet down to ease the pain. Hanging the legs down allows for blood to passively flow into the distal part of the legs. Other symptoms of peripheral vascular disease include buttock pain, numbness, tingling, or weakness in the legs, burning or aching pain in the feet or toes while resting, a sore on a leg or a foot that will not heal, one or both legs or feet feel cold or change color (pale, bluish, dark reddish), loss of hair on the legs, and impotence. Having symptoms while at rest is a sign of more severe disease.

COMPLICATIONS

Open sores: Peripheral vascular disease (PVD) can lead to open sores that do not heal properly, injury, or infection of the feet and legs, especially if the individual also has diabetes. Diabetes damages small capillaries, so oxygen and nutrients cannot be carried to the cells, causing tissue death. Also, diabetes may damage nerve endings and decrease sensitivity in areas such as the feet. Trauma to the feet or other areas of the body may not be felt and may result in open sores that are difficult to heal (diabetic sores). Critical limb ischemia (CLI) is the extreme of this condition and can cause tissue death (gangrene), sometimes requiring amputation of the affected limb.

Stroke and heart attack: Stroke (neurological damage caused by a lack of blood flow to the brain) and heart attack are among the more serious and most common complications that accompany peripheral arterial disease. Fat deposits also build up in arteries supplying the heart and brain. As a result, individuals have a greater risk of heart disease and stroke.

DIAGNOSIS

A medical and family history is important in diagnosing peripheral vascular disease (PVD). A doctor may ask about family history of heart disease and review medical history, including medications and the presence of health conditions, such as high blood pressure or diabetes. The doctor may also ask if the individual smokes or has any symptoms in the legs when sitting, standing, walking, or exercising. The physical exam may involve: checking blood flow in the leg or foot to see if the pulse is either weak or absent; checking pulses in the leg arteries for an abnormal whooshing sound called a bruit (a bruit can be heard with a stethoscope and may be a warning of a narrow or blocked section of an artery); checking for poor wound healing; comparing blood pressure between the limbs to see if blood pressure is lower in the affected limb; and checking hair, skin, and nails for any changes that may indicate PVD.

Ankle-brachial index (ABI): The ankle-brachial index (ABI) test compares the blood pressure in the ankle with the blood pressure in the arm to determine how well the blood is flowing and if further tests are needed. To get a blood pressure reading, a doctor uses a regular blood pressure cuff and a special ultrasound device to evaluate blood pressure and flow. The individual may walk on a treadmill and have readings taken before and immediately after exercising to capture the severity of the narrowed arteries during walking. ABI blood pressure readings will appear higher than a blood pressure reading in the arm.

Angiography: An angiography is a form of imaging that allows a doctor to view blood flow through the arteries. A contrast material (dye) is injected into the blood vessels. This allows the doctor to see the flow of the contrast material with the use of imaging machines. Blood flow in individuals with PVD may be slow or blocked completely. Angiography can be done using X-ray imaging or procedures called magnetic resonance angiography (MRA) or computed tomography angiography (CTA).

Electrocardiogram (ECG): An electrocardiogram (ECG) is a diagnostic test in which electrode patches are attached to the skin to measure electrical impulses in the heart. A doctor may monitor an ECG during and after the treadmill test. If PVD is causing blocked arteries in the individual, changes in the ECG may be seen.

Blood tests: Doctors can check the individual's blood to measure cholesterol and check the level of C-reactive protein, which is a marker for heart disease.

TREATMENT

General:

The goals of treatment for peripheral vascular disease (PVD) are to manage symptoms, such as leg pain, and to stop the progression throughout the body, in order to reduce the risk of heart attack and stroke.

Some individuals may be able to treat PVD appropriately with lifestyles changes. Lifestyle changes include quitting smoking, losing weight, exercising, and changing the diet (see "Prevention"). Smoking cessation is the single most important thing an individual can do to reduce the progression of the blockage and to reduce the risk of complications of PVD.

If lifestyle changes are not enough, additional medical treatment may be needed. A doctor may prescribe medicine to prevent blood clots, lower blood pressure and cholesterol, and control pain and other symptoms.

Lifestyle changes:

Experts recommend eating healthy foods. A brain-healthy diet should include five or more daily servings of fruits and vegetables, foods rich in soluble fiber (such as oatmeal and beans), foods rich in calcium (dairy products, spinach), soy products (such as tempeh, miso, tofu, and soy milk), and foods rich in omega-3 fatty acids, including cold-water fish, such as salmon, mackerel, and tuna. Pregnant women and women who plan to become pregnant in the next several years should limit their weekly intake of cold-water fish because of the potential for mercury contamination.

Eating less cholesterol and fat, especially saturated fat, may reduce the amount of plaque in the arteries. Weight loss of as little as 10 pounds may lower blood pressure and improve cholesterol levels.

People with PVD are encouraged to quit smoking because it may worsen symptoms. Quitting smoking will slow the progress of PVD.

People with diabetes should stay in close contact with their doctors to ensure that their condition is well controlled. Managing diabetes with diet, exercise, weight control, and medication is essential because strict control of blood sugar may reduce damage to the heart and blood vessels.

Exercise can lower blood pressure, increase the level of HDL cholesterol (good cholesterol), and improve the overall health of blood vessels and the heart. It also helps control weight, control diabetes, and reduce stress. Thirty minutes daily of exercise is normally recommended. Patients should talk to their doctors before starting a new exercise program.

Managing stress can be vital to keeping the heart and blood vessels healthy. This is because stress can cause an increase in blood pressure along with increasing the blood's tendency to clot.

Medications:

Medications for claudication: Medications used to treat PVD and intermittent claudication include those that aim to lower the risk and progression of atherosclerosis throughout the body, such as those that help quit smoking, lower blood pressure, lower cholesterol, and optimize the blood sugar in people with diabetes.

Two prescription medications have been approved by the U.S. Food and Drug Administration (FDA) for the direct treatment of the symptom of intermittent claudication. Pentoxifylline (Trental©) is believed to improve blood flow by decreasing the viscosity (thickness) of blood and making red blood cells more flexible. With these alterations, the blood can move more easily past obstructions in the blood vessel. Cilostazol (Pletal©) keeps platelets from clumping together. This clumping promotes formation of clots and slows down blood flow. The drug also helps dilate, or expand, the blood vessels, encouraging the flow of blood.

Other prescription medications used to treat symptoms of PVD include antiplatelet agents, anticoagulants, and "clot-busters" (thrombolytics). Antiplatelet agents include aspirin, ticlopidine (Ticlid©), and clopidogrel (Plavix©). These drugs do not get rid of an existing clot, but they prevent further clots from forming by keeping blood cells and platelets from clumping together. Anticoagulant agents include heparin, warfarin (Coumadin©), enoxaparin (Lovenox©), and low-molecular-weight heparin. These drugs also do not remove an existing clot, but they interfere with the sequence of blood clotting factors that causes a clot to form. Thrombolytics are drugs that can actually dissolve an existing clot. Thrombolytics can be used only under certain circumstances and are given only in the hospital. Thrombolytics can be injected directly into the blocked artery under angiographic guidance. To be effective, they have to be administered intravenously within the first four to eight hours after an individual develops symptoms. All of these medications may increase the chances of bleeding. Individuals should inform their healthcare providers about over-the-counter (OTC) medicines and integrative therapies (such as herbs and vitamins) they may be taking.

Cholesterol-lowering medications: Cholesterol-lowering drugs called statins, such as lovastatin (Mevacor©) or atorvastatin (Lipitor©), may be prescribed by a doctor to reduce the risk for heart attack and stroke. The goal for individuals who have PVD is to reduce low-density lipoprotein (LDL) cholesterol, the "bad" cholesterol, to less than 100 milligrams per deciliter (mg/dL). The goal is even lower if there are additional major risk factors for heart attack and stroke, especially diabetes, or continued smoking. Statin drugs may deplete Coenzyme Q10 from the body, leading to muscle weakness and pain. Coenzyme Q10 is important in cellular energy production.

Blood pressure-lowering medications: If high blood pressure exists, a doctor may prescribe medications to lower it, such as beta-blockers or ACE inhibitors. The goal of these medications is to reduce the systolic blood pressure (the top number of the two numbers) to 140 millimeters of mercury (mmHg) and the diastolic blood pressure (the bottom number) to 90 mmHg or lower. If diabetes is present, the blood pressure goals are even lower.

Medications to control blood sugar: If the individual also has diabetes, blood sugar (glucose) control is even more important. Taking prescribed medications, such as metformin (Glucophage©), appropriately and following a proper diet is necessary.

Medications to prevent blood clots: Because peripheral arterial disease is related to reduced blood flow to the limbs, it is important to reduce the risk of blood clots. A blood clot can completely block an already narrowed blood vessel and cause tissue death. A doctor may prescribe daily aspirin therapy or another medication that helps prevent blood clots, such as clopidogrel (Plavix©) or warfarin (Coumadin©).

Surgery:

Balloon angioplasty: In a balloon angioplasty, a small hollow tube (called a catheter) is threaded through a blood vessel to the affected artery. Then, a small balloon on the tip of the catheter is inflated to reopen the artery and flatten the blockage into the artery wall, while at the same time stretching the artery open to increase blood flow. In some cases, a mesh framework called a stent is deployed and left in the artery to help keep it open. This is the same procedure doctors use to open heart arteries. Stents can also contain drugs that decrease blood clotting. Risks of angioplasty include: bleeding in area where the catheter was inserted, blockage of blood flow to an area of the heart (very rare), damage to a heart valve or blood vessel, kidney failure (higher risk in those with existing kidney problems), irregular heartbeats (arrhythmias), stroke (rare), and death.

Bypass surgery: Bypass surgery can be done on arteries to improve circulation. Bypass surgery involves using one of the individual's own veins or a synthetic graft to re-route blood around a segment of a narrow or blocked artery. Blood flow then goes from the artery, through the bypassed graft, and out to the rest of the body.

INTEGRATIVE THERAPIES

Strong scientific evidence:

Ginkgo: Ginkgo (Ginkgo biloba) has been used medicinally for thousands of years. Today, it is one of the top-selling herbs in the United States. Numerous studies suggest that Ginkgo biloba taken by mouth causes small improvements in symptoms of claudication (leg pain with exercise or at rest due to clogged arteries). However, ginkgo may not be as helpful for this condition as exercise therapy or prescription drugs. Additional evidence is needed.

Ginkgo may increase bleeding in sensitive individuals, including those taking blood-thinning medications such warfarin (Coumadin©) and aspirin, and should be stopped two weeks before surgical procedures. Avoid if allergic or hypersensitive to members of the Ginkgoaceae family. If allergic to mango rind, sumac, poison ivy or oak or cashews, then allergy to ginkgo is possible. Ginkgo seeds are dangerous and should be avoided. Skin irritation and itching may also occur due to ginkgo allergies. Avoid supplemental doses if pregnant or breastfeeding.

Grape seed: Human studies report that extracts from grape seed may reduce symptoms of chronic venous insufficiency. Symptoms of poor circulation in leg veins that showed significant improvements include itching, swelling, heaviness, nighttime cramps, tingling, burning, numbness and nerve pain. Several small human studies show that grape seed ingredients may speed the reduction of edema and swelling after many types of injury, including surgery. Further research is needed in this area.

Avoid if allergic or hypersensitive to grapes or other grape compounds. Use cautiously if taking blood thinners such as warfarin, aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), or anti-platelet agents. Use cautiously with bleeding disorders or if taking drugs that may increase the risk of bleeding. Use cautiously with drugs processed using the liver's "cytochrome P450" enzyme system. Use cautiously with blood pressure disorders or if taking ACE inhibitors. Avoid with disorders that increase the risk of bleeding or with active bleeding disorders (stomach ulcers, bleeding into the brain, etc.). Avoid if pregnant or breastfeeding.

Horse chestnut: Laboratory, animal, and human research suggests that horse chestnut seed extract (HCSE) may be beneficial to patients with chronic venous insufficiency. Studies report significant decreases in leg size, leg pain, itchiness, fatigue, and "tenseness." There is preliminary evidence that HCSE may be as effective as compression stockings.

Avoid if allergic to horse chestnut, esculin, or any of its ingredients (e.g. flavonoids, biosides, trisides of quertins, and oligosacharides including 1-ketose and 2-ketose). Avoid horse chestnut products other than HCSE due to known toxicity. Use cautiously with diabetes, glucose intolerance, or in those taking antidiabetic agents. Use parenteral (not by mouth) horse chestnut seed preparations cautiously with kidney insufficiency. Avoid if pregnant or breastfeeding.

Good scientific evidence:

Aortic acid: Aortic acid comes from the hearts of animals, usually sheep, cows, or pigs. Aortic acid is a broad term encompassing several constituents. Mesoglycan, a preparation of glycosaminoglycans, is the most studied of these constituents. Intermittent claudication is part of late stage atherosclerosis, and mesoglycan has shown some therapeutic ability in preliminary atherosclerosis studies in humans. In addition, mesoglycan is a heparin-like substance that has shown anticoagulation ("blood thinning") properties in clinical studies. Additional study is needed regarding use of aortic acid for intermittent claudication and chronic venous ulcers.

Allergic reactions have not been reported in the available literature. Due to the heparan sulfate content of mesoglycan, patients with an allergy to heparin or heparinoid derivatives should use caution. Use cautiously with coagulation (blood) disorders or in patients taking anticoagulation therapy. Use cautiously with hypertension (high blood pressure) or in patients taking antihypertensive drugs. Avoid if pregnant or breastfeeding.

Arginine: L-arginine, or arginine, is considered a semi-essential amino acid, because although it is normally synthesized in sufficient amounts by the body, supplementation is sometimes required. Intermittent claudication causes leg pain and tiredness because cholesterol plaques or clots develop in leg arteries and block blood flow. A small number of studies report that arginine therapy may improve walking distance in patients with claudication or peripheral vascular disease. Further research is needed.

Avoid if allergic to arginine, or with a history of stroke, or liver or kidney disease. Avoid if pregnant or breastfeeding. Use caution if taking blood-thinning drugs (like warfarin or Coumadin©) and blood pressure drugs or herbs or supplements with similar effects. Blood potassium levels should be monitored. L-arginine may worsen symptoms of sickle cell disease. Caution is advised in patients taking prescription drugs to control sugar levels.

Gotu kola: Multiple small trials suggest that the total triterpenoid fraction of Centella asiatica (TTFCA) (from gotu kola) may have small to moderate benefits on objective and subjective parameters associated with chronic venous insufficiency and varicose veins. However, further research is necessary before a conclusion can be made.

Avoid with a known allergy to gotu kola, asiaticoside, asiatic acid, or madecassic acid. Avoid with a history of high cholesterol, cancer or diabetes. Avoid if pregnant or breastfeeding.

Grape seed: Small human studies suggest that ingredients from grape seed may be of benefit for vascular fragility by making small blood vessels less fragile and less likely to leak.

Avoid if allergic or hypersensitive to grapes or other grape compounds. Use cautiously if taking blood thinners such as warfarin, aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), or anti-platelet agents. Use cautiously with bleeding disorders or if taking drugs that may increase the risk of bleeding. Use cautiously with drugs processed using the liver's "cytochrome P450" enzyme system. Use cautiously with blood pressure disorders or if taking ACE inhibitors. Avoid with disorders that increase the risk of bleeding or with active bleeding disorders (stomach ulcers, bleeding into the brain, etc.). Avoid if pregnant or breastfeeding.

Policosanol: Policosanol is a cholesterol-lowering natural mixture of primary alcohols, isolated and purified from sugar cane wax. There is limited study on the effects of policosanol supplementation on walking distance in individuals with intermittent claudication. Additional human trials are necessary before a strong recommendation can be made.

Policosanol is generally considered to be safe and well tolerated. Avoid in individuals with a known allergy or hypersensitivity to policosanol. Use cautiously if taking aspirin or blood pressure medications. Use cautiously with high blood pressure. Use cautiously if pregnant or breastfeeding.

Pycnogenol©: Pycnogenol© is the patented trade name for a water extract of the bark of the French maritime pine (Pinus pinaster ssp. atlantica), which is grown in coastal south-west France. Pycnogenol© used in patients with chronic venous insufficiency is reported to reduce edema and pain. Pycnogenol© may also be used in the management of other symptoms of chronic venous insufficiency. Additional study is needed before a conclusion can be made.

Avoid if allergic/hypersensitive to Pycnogenol©, its components, or members of the Pinaceae family. Use cautiously with diabetes, hypoglycemia, bleeding disorders. Use cautiously if taking hypolipidemics, medications that may increase the risk of bleeding, hypertensive medications, or immune stimulating or inhibiting drugs. Avoid if pregnant or breastfeeding.

Rutin: Rutin is a yellow crystalline flavonol glycoside that occurs in various plants, especially the buckwheat plant, black tea, apple peels, onions, and citrus. Overall, the results suggest a benefit of various rutin compounds for chronic venous insufficiency and edema. Additional study is needed to confirm these findings.

Avoid if allergic or hypersensitive to O-(beta-hydroxyethyl)-rutosides or plants that rutin is commonly found in, such as rue, tobacco, or buckwheat. Use cautiously in elderly patients. Use cautiously with skin conditions. Use cautiously if taking medications for edema, diuretics, or anticoagulation medications (e.g. heparin or warfarin). Use cautiously if pregnant or breastfeeding.

Unclear or conflicting scientific evidence:

Aortic acid: Mesoglycan has shown activity for anticoagulation ("blood thinning") and increasing blood vessel health. Low quality research shows that mesoglycan may be helpful in various venous disorders, including postphlebitic syndrome, venous insufficiency, and varicose syndrome. Additional study is needed.

Allergic reactions have not been reported in the available literature. Due to the heparan sulfate content of mesoglycan, patients with an allergy to heparin or heparinoid derivatives should use caution. Use cautiously with coagulation (blood) disorders or in patients taking anticoagulation therapy. Use cautiously with hypertension (high blood pressure) or in patients taking antihypertensive drugs. Avoid if pregnant or breastfeeding.

Arginine: Early human studies suggest that intravenous arginine may increase blood flow in patients with critical limb ischemia. This condition occurs when blood flow to the arms and/or legs is blocked. Large, well-designed trials are needed.

Avoid if allergic to arginine, or with a history of stroke, or liver or kidney disease. Avoid if pregnant or breastfeeding. Use caution if taking blood-thinning drugs (like warfarin or Coumadin©) and blood pressure drugs or herbs or supplements with similar effects. Blood potassium levels should be monitored. L-arginine may worsen symptoms of sickle cell disease. Caution is advised in patients taking prescription drugs to control sugar levels.

Aromatherapy: In clinical study, massage and skin care with and without aromatherapy improved relief and wellbeing in patients with lymphedema. More study is needed.

Essential oils should be administered in a carrier oil to avoid toxicity. Avoid with a history of allergic dermatitis. Use cautiously if driving or operating heavy machinery. Avoid consuming essential oils. Avoid direct contact of undiluted oils with mucous membranes. Use cautiously if pregnant.

Bilberry: Bilberry is an herb made from the wrinkled, black berries of a small deciduous shrub. The use of bilberry fruit in traditional European medicine dates back to the 12th Century. A standardized extract of bilberry called Vaccinium myrtillius anthocyanoside (VMA) is popular in Europe for the treatment chronic venous insufficiency. However, there is only preliminary research in this area, and more studies are needed before a recommendation can be made.

Avoid if allergic to plants in the Ericaceae family or to anthocyanosides (a component of bilberry). Avoid with a history of low blood pressure, heart disease, bleeding, diabetes, blood clots, or stroke. Avoid if pregnant or breastfeeding. Stop use before surgery or dental or diagnostic procedures involving blood tests.

Black currant: Black currant treatment may benefit women with blood flow disorders, such as chronic venous insufficiency. More study is needed in this area.

Avoid if allergic or hypersensitive to black currant, its constituents, or plants in the Saxifragaceae family. Avoid with hemophilia or in patients on blood thinners unless otherwise recommended by a qualified healthcare provider. Use cautiously with venous disorders or gastrointestinal disorders. Use cautiously if taking MAOIs (antidepressants) or vitamin C supplements. Avoid if pregnant or breastfeeding.

Calendula: Calendula, also known as marigold, has been suggested as a possible treatment for venous leg ulcers. Further study is warranted.

Avoid if allergic to plants in the Aster/Compositae family such as ragweed, chrysanthemums, marigolds, and daisies. Use cautiously in patients taking sedatives, blood pressure medications, cholesterol medications, blood sugar-altering agents, and immunomodulators. Use cautiously with diabetes and in children. Avoid if pregnant or breastfeeding.

Garlic: Garlic (Allium sativum) is traditionally used for heart health. Some human studies suggest that garlic may improve circulation in the legs by a small amount, but this issue remains unclear. Better-designed studies are needed to better determine the effects of garlic on peripheral vascular disease.

Garlic may increase bleeding in sensitive individuals, including those taking blood-thinning medications such as warfarin (Coumadin©) and aspirin. People with a known allergy to garlic, any of its ingredients, or to other members of the Liliaceae (lily) family, including hyacinth, tulip, onion, leek, and chives, should avoid garlic. Allergic reactions have been reported with garlic taken by mouth, inhaled, or applied to the skin.

Ginkgo: A multi-ingredient product called Ginkor Fort© may aid in treatment of patients with lower limb chronic venous insufficiency. Further study is needed.

Ginkgo may increase bleeding in sensitive individuals, including those taking blood-thinning medications such warfarin (Coumadin©) and aspirin, and should be stopped two weeks before surgical procedures. Avoid if allergic or hypersensitive to members of the Ginkgoaceae family. If allergic to mango rind, sumac, poison ivy or oak or cashews, then allergy to ginkgo is possible. Ginkgo seeds are dangerous and should be avoided. Skin irritation and itching may also occur due to ginkgo allergies. Avoid supplemental doses if pregnant or breastfeeding.

Glucosamine: Currently, there is not enough reliable scientific evidence to recommend glucosamine in the treatment of chronic venous insufficiency.

Avoid if allergic or hypersensitive to shellfish or iodine. Some reports suggest a link between glucosamine/chondroitin products and asthma. Use caution with diabetes or a history of bleeding disorders. Avoid if pregnant or breastfeeding.

Hydrotherapy: Hydrotherapy is broadly defined as the external application of water in any form or temperature (hot, cold, steam, liquid, ice) for healing purposes. It may include immersion in a bath or body of water (such as the ocean or a pool), use of water jets, douches, application of wet towels to the skin, or water birth. Hydrotherapy is used in Europe for various symptoms of chronic venous insufficiency. Hydrotherapy may help increase blood flow to the legs, temporarily relieving symptoms of claudication. A small number of trials have applied cold water stimulation alone or in combination with warm water, and reported improvements in cramps and itching when compared to no therapy. Preliminary research reports improved symptoms and blood flow in patients with varicose veins undergoing hydrotherapy with intermittent cold and hot water hydrotherapy. Additional research is needed before a clear conclusion can be drawn.

Avoid sudden or prolonged exposure to extreme temperatures in baths, wraps, saunas, or other forms of hydrotherapy, particularly with heart disease, lung disease, or if pregnant. Avoid with implanted medical devices like pacemakers, defibrillators, or hepatic (liver) infusion pumps. Vigorous use of water jets should be avoided with fractures, known blood clots, bleeding disorders, severe osteoporosis, open wounds, or during pregnancy. Use cautiously with Raynaud's disease, chilblains, acrocyanosis, erythrocyanosis, and impaired temperature sensitivity, such as neuropathy. Use cautiously if pregnant or breastfeeding. Hydrotherapy should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses. Patients with known illnesses should consult their physician(s) before starting hydrotherapy.

Hypnotherapy, hypnosis: Preliminary study results suggest a protective role of hypnosis against vascular damage. Further research is needed to confirm these results.

Use cautiously with mental illnesses like psychosis and schizophrenia, manic depression, multiple personality disorder or dissociative disorders. Use cautiously with seizure disorders.

Iodine: Footcare with betadine may help in the management of filarial lymphedema. Additional study is needed in this area.

Reactions can be severe, and deaths have occurred with exposure to iodine. Avoid iodine-based products if allergic or hypersensitive to iodine. Do no use for more than 14 days. Avoid Lugol solution and saturated solution of potassium iodide (SSKI, PIMA) with hyperkalemia (high amounts of potassium in the blood), pulmonary edema (fluid in the lungs), bronchitis, or tuberculosis. Use cautiously when applying to the skin because it may irritate or burn tissues. Use sodium iodide cautiously with kidney failure. Avoid sodium iodide with gastrointestinal obstruction. Iodine is safe in recommended doses for pregnant or breastfeeding women. Avoid povidone-iodine for perianal preparation during delivery or postpartum antisepsis.

L-carnitine: L-carnitine, or acetyl-L-carnitine, is an amino acid found in the body. There is evidence to support l-carnitine's use in cases when there are severe limitations in circulation due to peripheral vascular disease. It is not clear, however, whether angiopathies caused by atherosclerosis and diabetes are equally sensitive to the drugs. Additionally, it is important to know comparative efficiency of propionyl-L-carnitine and other recognized treatments.

Avoid with known allergy or hypersensitivity to carnitine. Use cautiously with peripheral vascular disease, hypertension (high blood pressure), alcohol-induced liver cirrhosis, and diabetes. Use cautiously in low birth weight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding.

Moxibustion: Moxibustion is the application of heat to various points on the body. Preliminary evidence suggests that moxibustion and acupuncture may reduce symptoms of lymphedema caused by intrapelvic lymph node dissection in gynecological cancer. However, evidence is insufficient for making conclusions at this time.

Use cautiously over large blood vessels and thin or weak skin. Avoid with aneurysms, any kind of "heat syndrome," cardiac disease, convulsions or cramps, diabetic neuropathy, extreme fatigue and/or anemia, fever, inflammatory conditions, over allergic skin conditions or ulcerated sores, or skin adhesions. Avoid if pregnant or breastfeeding. Avoid in patients who have just finished exercising or taking a hot bath or shower.

Physical therapy: There is currently insufficient evidence of physical therapy's effectiveness for chronic venous insufficiency or peripheral artery disease. Various types of supervised and unsupervised physical therapy programs such as compression, cold-temperature stimuli, gymnastics, walking, and sauna have been used to improve circulation in the legs. Early evidence suggests small benefits for circulatory disorders when physical therapy is used in combination with drugs. Different types of physical therapy have been employed in the treatment of lymphedema, such as complex physical therapy (CPT), self home maintenance therapy (bandage/wearing of elastic garment and exercise), and pneumatic compression. However, high-quality trials have not shown benefit of these therapies over other therapies or controls. Additional study is needed.

Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with a qualified healthcare professional before beginning any treatments. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the physical therapy literature although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used in pregnancy and although reports of major adverse effects are lacking the available literature, caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.

Pycnogenol©: Pycnogenol© may be useful for reduction of venous leg ulcers. Further research is needed before a recommendation can be made.

Avoid if allergic/hypersensitive to Pycnogenol©, its components, or members of the Pinaceae family. Use cautiously with diabetes, hypoglycemia, bleeding disorders. Use cautiously if taking hypolipidemics, medications that may increase the risk of bleeding, hypertensive medications, or immune stimulating or inhibiting drugs. Avoid if pregnant or breastfeeding.

Reflexology: Early research reports that reflexology is a preferred therapy in women with leg, ankle and foot edema in late pregnancy. Further research is needed before a conclusion about effectiveness can be made.

Avoid with recent or healing foot fractures, unhealed wounds, or active gout flares affecting the foot. Use cautiously and seek prior medical consultation with osteoarthritis affecting the foot or ankle, or severe vascular disease of the legs or feet. Use cautiously with diabetes, heart disease or the presence of a pacemaker, unstable blood pressure, cancer, active infections, past episodes of fainting (syncope), mental illness, gallstones, or kidney stones. Use cautiously if pregnant or breastfeeding. Reflexology should not delay diagnosis or treatment with more proven techniques or therapies.

Rutin: Rutin, in combination with compression, appears to have benefit over compression alone in the treatment of varicose leg ulcers. However, results are conflicting. Additional study is needed in this area. Overall, the evidence suggests a benefit of troxerutin or O-(beta-hydroxyethyl) rutoside for varicose veins. Well-designed clinical trials are required before a conclusion can be made.

Avoid if allergic or hypersensitive to rutin, rutosides, or plants that rutin is commonly found in, such as rue, tobacco, or buckwheat. Use cautiously in elderly patients. Use cautiously with skin conditions. Use cautiously if taking medications for edema, diuretics, or anticoagulation medications (e.g. heparin or warfarin). Use cautiously if pregnant or breastfeeding.

Thiamin: Thiamin (also spelled "thiamine") is a water-soluble B-complex vitamin. It is also known as vitamin B1 or aneurine. Vitamin B supplements have been used to treat leg cramps during pregnancy. However, additional studies are needed to better determine its effectiveness.

Thiamin is generally considered safe and relatively nontoxic, even at high doses. Avoid if allergic or hypersensitive to thiamin. Thiamin appears safe if pregnant or breastfeeding when taken in the recommended dosages.

Vitamin E: Vitamin E is a fat-soluble vitamin with antioxidant properties. Multiple studies have evaluated the use of vitamin E in patients with peripheral vascular disease to improve exercise tolerance and intermittent claudication (pain in the legs with walking due to cholesterol buildup in blood vessels). Although some results have been promising, most studies have been small and poorly designed. It remains unclear if vitamin E is beneficial in this condition.

Vitamin E may increase bleeding in sensitive individuals, including those taking blood-thinning medications such warfarin (Coumadin©) and aspirin. Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Avoid above the recommended daily level in pregnant and breastfeeding women.

Witch hazel: Witch hazel has been studied for the treatment of varicose veins and for improving venous tone. Additional study is needed in this area.

Avoid if allergic or sensitive to witch hazel. Avoid if pregnant or breastfeeding. Use cautiously in people with liver or kidney disorders, diabetes, and in children.

Fair negative scientific evidence:

Chelation therapy: Chelation therapy is the administration of chelating agents, such as EDTA, to remove heavy metals from the body. Chelation is sometimes suggested as a treatment for claudication or peripheral vascular disease, but some studies suggest that it may not be helpful.

Chelation may be dangerous in people with heart, kidney, or liver disease or with conditions affecting blood cells or the immune system. Use during pregnancy, breastfeeding, or in children may also be dangerous due to potential toxic effects. Chelation therapy may cause serious side effects, such as dangerously low calcium levels in the blood, bone marrow damage that leads to low levels of blood cells, kidney damage (with elevated creatinine levels), very low blood pressure, fast heart rate, increased risk of bleeding or blood clots (including interference with the effects of the blood thinning drug warfarin [Coumadin©]), bacterial blood infections, seizures, allergic or immune system reactions, heart rhythm abnormalities, and unstable blood sugar levels. Other side effects may include fever, nausea, vomiting, gastrointestinal upset, excessive thirst, increased sweating, headache, decreased thyroid function, fatigue, low white blood cell count (leukopenia), low blood platelet count (thrombocytopenia), or inflammation of the uvea (uveitis). Severe reactions have occurred causing people to stop breathing. Although deaths have been reported in people receiving chelation, it is unclear if chelation therapy was the direct cause. One possible cause may be due to the loss of calcium.

PREVENTION

High blood pressure (hypertension) control: One of the most important things that can be done for the prevention of peripheral vascular disease (PVD) is to reduce high blood pressure. Blood pressure for a healthy individual should be a systolic reading of 120 and a diastolic reading of 80 (120/80 millimeters of mercury or mmg Hg). Exercising, managing stress, maintaining a healthy weight, and limiting sodium and alcohol intake are all ways to keep blood pressure in check. Medications to treat hypertension, such as diuretics, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers, may be used.

Cholesterol and saturated fat intake reduction: Eating less cholesterol and fat, especially saturated fat, may reduce the amount of plaque arteries. Most people should aim for a low density lipoprotein (LDL) level below 130 milligrams per deciliter. If there are other risk factors for PVD, such as diabetes, the target LDL may be below 100 milligrams per deciliter. Statin drugs (HMG-CoA reductase inhibitors) can be prescribed to help maintain healthy cholesterol levels.

Smoking cessation: Smoking is a major risk factor for PVD. Nicotine constricts blood vessels and forces the heart to pump harder. A buildup of carbon monoxide (CO) reduces oxygen in the blood and damages the lining of the blood vessels.

Diabetes control: Managing diabetes with diet, exercise, weight control, and medication is essential. Strict control of blood sugar may reduce damage to the heart and blood vessels.

Weight control: Being overweight contributes to other risk factors for stroke, such as high blood pressure, PVD, cardiovascular disease, and diabetes. Weight loss of as little as 10 pounds may lower blood pressure and improve cholesterol levels.

Exercise: Exercise can lower blood pressure, increase the level of HDL cholesterol (good cholesterol), and improve the overall health of blood vessels and heart. It also helps control weight, control diabetes, and reduce stress. Thirty minutes of daily of exercise is normally recommended. Patients should talk to their doctors before starting a new exercise program.

Stress management: Stress can cause an increase in blood pressure along with increasing the blood's tendency to clot. Managing stress can be vital to keeping the heart and blood vessels healthy.

Diet modification: Experts recommend eating healthy foods. A healthy diet should include five or more daily servings of fruits and vegetables, foods rich in soluble fiber (such as oatmeal and beans), foods rich in calcium (dairy products, spinach), soy products (such as tempeh, miso, tofu, and soy milk), and foods rich in omega-3 fatty acids, including cold-water fish, such as salmon, mackerel, and tuna. Pregnant women and women who plan to become pregnant in the next several years should limit their weekly intake of cold-water fish because of the potential for mercury contamination.

  • American Academy of Family Physicians (AAFP). http://familydoctor.org. Accessed March 15, 2009.
  • American Heart Association (AHA). www.americanheart.org. Accessed March 15, 2009.
  • Brass EP, Hiatt WR. Review of mortality and cardiovascular event rates in patients enrolled in clinical trials for claudication therapies. Vasc Med. 2006 Nov;11(3):141-5. View abstract
  • Brass EP, Jiao J, Hiatt W. Optimal assessment of baseline treadmill walking performance in claudication clinical trials. Vasc Med. 2007 May;12(2):97-103. View abstract
  • Centers for Disease Control and Prevention (CDC). www.cdc.gov. Accessed March 15, 2009.
  • Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA. 2006 Feb 1;295(5):547-53. View abstract
  • National Heart, Lung, and Blood Institute (NHLBI) www.nhlbi.nih.gov. Accessed March 15, 2009.
  • Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2009. Accessed March 15, 2009.
  • Robless P, Mikhailidis DP, Stansby GP. Cilostazol for peripheral arterial disease. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD003748. View abstract
  • Santilli SM. The Coronary Artery Revascularization Prophylaxis (CARP) Trial: results and remaining controversies. Perspect Vasc Surg Endovasc Ther. 2006 Dec;18(4):282-5. View abstract


Copyright © 2011 Natural Standard (www.naturalstandard.com)
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