The new millennium has marked a new era in the development of treatment strategies for peripheral arterial disease (PAD). The general belief that this is a benign condition is no longer held, having been replaced by the realization that PAD is a manifestation of systemic atherosclerosis and is associated with a two to three-fold increase in both cardiovascular and cerebrovascular events. Critical limb ischemia (CLI), the most severe form of PAD, is a particularly potent risk marker, being associated with a 20-25% risk of major amputation and a mortality rate approaching 50% at 5 years, which is worse than that of many cancers. This contributes to an overall societal burden from PAD that is ever increasing as the population ages. To confront this, there was a strong impetus to improve the management of PAD, with cardiovascular societies from the USA and Europe advocating for maximal medical therapy as the primary mode of treatment for intermittent claudication and CLI.
Understanding Peripheral Arterial Disease
Symptoms of PAD result from ischemia of the leg muscles and can present in many ways, with intermittent claudication being the most classic presentation in the past. The Fontaine classification can be used to stage the severity of PAD based on symptoms. In stage I, there are no symptoms; stage II is intermittent claudication; stage III is pain at rest, and stage IV is the development of ulcers or gangrene. Intermittent claudication is currently defined as pain, aching, or cramping in the muscles of the lower extremities that occurs during exercise and is relieved by rest. However, it is not a very sensitive marker, and many patients may complain of leg fatigue or weakness and difficulty walking, without necessarily having classic claudication.
Smoking has an especially strong association with PAD; the risk of claudication or developing an abnormal ABI is 2-3 times higher in current smokers than non-smokers. Diabetes carries a 2-4 fold increase in risk of symptomatic PAD, with the disease often presenting at an earlier age and being more severe. High blood pressure is also a significant risk factor for PAD, as it can lead to accelerated atherosclerosis and increased risk of developing stenosis. High cholesterol, specifically LDL, had a clear linear association with the risk of developing PAD.
There are numerous risk factors for the development of PAD. A strong association exists between PAD and other cardiovascular and cerebrovascular diseases. Risk factors for developing PAD can be divided into non-modifiable and modifiable. Age is the strongest known risk factor; while PAD can occur at any age, it is most common in those over 50, with prevalence increasing with each subsequent decade. Gender is a significant factor, as men are at higher risk; data from the Framingham study showed nearly 6% prevalence in men aged 60-69 as opposed to 3.6% in women of the same age group. Ankle brachial index less than 0.90 had the same sensitivity and specificity for predicting silent CAD as it did for predicting CAD in the general population.
Peripheral artery disease is one of the most prevalent, chronic, limb-threatening ailments. It is defined as atherosclerotic occlusive disease of the lower extremities which reduces blood flow to the leg muscles, especially during exercise. The atherosclerotic process occurs over many years. The actual stenosis is often a result of a complicated lesion containing plaque, scar tissue, calcification, and/or thrombus. More than 10 million people are affected in the United States alone, with increasing incidence and prevalence noted among older age groups. While PAD has many presentations and affects patients differently, one thing holds true: PAD patients are at increased risk for cardiovascular events and death.
Risk Factors
In assessing the severity of the disease and the best treatment options for the patient, it is important to consider the overall functional status and the health-related quality of life in addition to the symptoms of the disease. This can be achieved using the treadmill walking performance tests. Measures of claudication, such as the treadmill test, are reproducible and have been used to evaluate changes in symptoms with medical therapy. Invasive methods, such as measuring the patient’s walking impairment, muscle oxygen extraction, limb blood flow, and hemodynamic changes before and after treatment, are useful in assessing the severity of critical limb ischemia.
Once the diagnosis of PAD has been made, healthcare providers should identify the stage of the disease and the severity of the symptoms. This is done with an array of non-invasive and invasive tests. In the past, the ankle-brachial index (ABI) has been used as a reliable tool to diagnose and assess the severity of PAD. Due to advances in technology, the ABI has been replaced by Duplex Ultrasound Imaging, which is reliable and more cost-effective. Magnetic Resonance Angiography (MRA) and Computed Tomographic Angiography (CTA) are also useful to diagnose PAD and provide detailed information about the location and nature of the arterial lesions. With recent advances in technology, more physicians are utilizing invasive tests such as angiogram with the intention of proceeding directly to angioplasty or stent placement if a treatable lesion is found. This approach has its positives and negatives and is dependent largely upon the patient and the overall clinical situation. A consultation with a vascular surgeon may be warranted in cases where the anatomy of the arterial lesions is unfavorable for an endovascular approach.
Symptoms
Pain in the muscles of the legs, thighs, or buttocks when you exercise is called intermittent claudication. It’s the most common symptom of peripheral arterial disease. The pain usually eases within a few minutes after you stop exercising. In the early stages of peripheral arterial disease, you may only feel muscle pain in one of your legs, but the pain is usually in both legs as the disease progresses. The location of the pain depends on where the narrowed or blocked arteries are. For example, if you have a blockage in the arteries supplying your shins and feet, you may feel pain in your calves. Your thighs or buttocks may ache if the arteries supplying these areas are narrowed. Pain in your legs and feet at rest is usually a sign of more advanced peripheral arterial disease. The pain of intermittent claudication and rest pain are due to the poor blood flow to your legs.
Diagnosis
An ankle brachial pressure index (ABPI) of less than 0.9 is abnormal and consistent with the diagnosis of PAD. An ABPI of less than 0.8 is 95% sensitive and 99% specific for detecting angiographic stenosis greater than 50%. The test measures the systolic blood pressure in each arm and each ankle using a hand-held Doppler probe and an appropriate width blood pressure cuff. Ankle pressures are divided by the higher of the two brachial readings. This gives the ABPI value for each leg. It is simple, non-invasive, cheap, and carries no risk to the patient. Repeat measurements have a standard error of ±0.05, which is considered acceptable variance in research trials. The ABPI can be falsely high in patients with calcified, non-compressible leg arteries, such as those with diabetes. This leads to overestimation of the ABPI and should alert the physician to consider other methods of diagnosis. Repeat assessment of the ABPI to detect worsening of the condition is a sensitive method of follow-up for the patient with PAD.
The most important aspect in the diagnosis of peripheral arterial disease (PAD) is an appropriate suspicion of the condition by the physician. The limitations of the traditional method of diagnosis, the taking of a careful history and a thorough physical examination of the patient, are that the physician may not ask the right questions or examine the appropriate parts of the body when dealing with a patient who has atypical leg pain or is in the early stages of the disease.
Conventional Treatment Methods
Cilostazol is the only medication approved by the FDA specifically for the treatment of claudication. It is a phosphodiesterase inhibitor with vasodilatory and anti-platelet properties. Patients with intermittent claudication and a positive exercise test for PAD demonstrate improvement in walking performance with cilostazol treatment. Two recent studies have demonstrated that cilostazol is effective in improving symptoms and functional status in patients with intermittent claudication due to PAD. These results may be influenced by the significant placebo effect often observed in trials treating intermittent claudication, but despite this, it is clear that cilostazol has a treatment effect beyond that of placebo. It is currently unknown if cilostazol therapy improves cardiovascular outcomes or limb outcomes such as amputation or revascularization. A second-line treatment for symptomatic PAD is pentoxifylline, which is a xanthine derivative with complex pharmacological properties. This medication has been shown in some, but not all, trials to have a modest effect in improving walking distance in patients with intermittent claudication.
Patients with PAD should do aerobic exercises to the point of maximal claudication for as long and as often as tolerated. Walking is the best exercise in most patients with PAD. In patients with claudication, supervision of exercise in a formal rehabilitation program may be more effective than a home-based program. In addition, the use of lower extremity resistance training in patients with PAD improves strength and functional capacity. He suggested that it be considered as a primary therapy for symptomatic PAD. In more severely affected patients with limb-threatening ischemia, supervised exercise therapy may have no role or can be harmful. In such patients, exercise therapy is often pursued in the hope of avoiding amputation, but it is almost always an ineffective therapy for relief of ischemic symptoms. Overall, however, exercise therapy is a very cost-effective way of improving cardiovascular and limb health in patients with PAD, and its adoption should be encouraged both for patients with claudication and those with limb-threatening ischemia.
Medications
Drugs that lower blood pressure and/or cholesterol levels are sometimes used to slow or stop the progression of atherosclerosis. Some of these drugs may improve how blood flows through your limbs, reduce symptoms, and lower the risk of heart attack, stroke, and death. High blood pressure is an important risk factor for atherosclerosis. Research studies have shown that people with high blood pressure who were treated with anti-hypertensive drugs had lower rates of heart attacks and strokes. High blood pressure and cholesterol are key risk factors in the progression of the atherosclerotic disease process in the body’s arteries. Medicines that reduce blood “stickiness” and the formation of blood clots, such as acetylsalicylic acid or clopidogrel, may be prescribed to reduce symptoms and lower the risk of heart attack, stroke, or limb loss in people with PAD.
Peripheral arterial disease (PAD) is a disease in which plaque builds up in the arteries that carry blood to your head, organs, and limbs. Plaque is made up of fat, cholesterol, calcium, fibrous tissue, and sometimes blood components. When plaque builds up in the body’s arteries, the condition is called atherosclerosis. Over time, plaque can harden and narrow the arteries. This limits the flow of oxygen-rich blood to your organs and other parts of your body. PAD usually affects the arteries in the legs, but it also can affect the arteries that carry blood from your aorta to your head, arms, and kidneys.
Surgical Procedures
Diagnosis and indications Patients appropriate for revascularization are those who suffer from ischemic rest pain, ulcers, or gangrene as a result of P.A.D. The choice to operate depends largely on the anatomical location and extent of arterial disease. Revascularization is appropriate for a patient with life or limb-threatening ischemia, who is likely to improve functional status with relief of symptoms. Because of the implications and potential risks of surgery, the decision to operate should always be preceded by an adequate trial of best medical therapy.
An overview of lower extremity revascularization Lower extremity revascularization is a series of surgical procedures utilized to re-establish blood flow in patients with P.A.D., when the stenosis or occlusion is likely to produce tissue loss or gangrene, or to provide relief from ischemic pain. It is a technique which has been developed in the past 50 years and been subject to many changes in indications for surgery, methods for practice, and more recently has been an area of much debate.
Lifestyle Modifications
Hypertension affects approximately three-fourths of patients with PAD. Those suffering from PAD and high blood pressure have a significantly higher incidence of heart attack and stroke. Many patients do not understand the need to aggressively treat high blood pressure because they cannot feel the direct effects. It is important to educate the patient on the cardiovascular risk and get them motivated to control this risk factor. With the implementation of lifestyle changes and often pharmacological treatment, one can expect a decrease in cardiovascular events and slowed progression of the disease.
Lifestyle modification is a critical and often overlooked part of the treatment plan for patients with peripheral arterial disease. It is very important that patients be involved with all aspects of their treatment. Everything a patient can do to decrease cardiovascular risk factors will help in the overall management of their PAD. This is also an area where the physician can help the patient gain momentum because the recommendations not only benefit the PAD but contribute to an overall healthier life. There are several significant health issues that require attention in the care of a PAD patient. High blood pressure, elevated blood sugar and cholesterol levels, obesity, and tobacco use all have detrimental effects on the progression of the disease and increase the risk of heart attack, stroke, and amputation. Often times the treatment for PAD can be the cornerstone in a patient’s understanding of the severity of their other health issues.
Holistic Approaches to Treatment
The Mediterranean Diet is one alternative that inherently includes a larger intake of fish, through this replaced the one step further: fish oil supplements. This possesses large clinical evidence of a dependable favorable effect on atherosclerotic sickness. Over every other variety of diet modification, the Dietary Approaches to Stop Hypertension (DASH) weight loss program has proven most effective for PAD patients looking to lower high blood pressure. This weight loss plan comprises herbal remedies reminiscent of garlic and onions, which might also be believed to impact atherosclerosis. In all modified diet cases or specific recommendations, it is often infinitely helpful to refer patients to a dietitian in order to assist create a food plan tailored to the personal tastes and food choices of the individual patient. This varies greatly from person to person, and simplified recommendations will not always help in compliance with a garden variety patient.
This chapter addresses the higher-than-noted need to give you dietary and lifestyle modifications and other conservative treatment methods for PAD. There is a vast quantity of scientific evidence exhibiting that lifestyle adjustments and risk factor managements can lead to significant improvement in walking distance, less pain, and perhaps a slowing or even regression of atherosclerotic disorder. The cause most often advisable by guideline-writers is to change from a meat-based Western diet, high in saturated and trans-fats, to a low-fat eating regimen built around fruits, veggies, and whole grains. Because vegetarian diets are already tremendously consumed by populations in the world regarding lower rates of PAD, such as in India, that is another potential choice to suggest to patients.
Diet and Nutrition
Patients with PAD should avoid food and drugs that constrict blood vessels or elevate blood pressure. Diabetics must strictly monitor and control their blood sugar. High cholesterol has long been associated with PAD and other cardiovascular disease. Most of the cholesterol found in the body comes from food, as the liver, which makes most of the cholesterol our bodies need, has the ability to adjust and produce less if we consume sufficient amounts. It is for this reason that lowering dietary cholesterol is recommended for patients with PAD. Saturated fat and trans fatty acids increase blood cholesterol and LDL levels more so than dietary cholesterol itself. High cholesterol is associated with an increased intake of saturated fats and/or trans fatty acids, thus reducing intake of these will help lower cholesterol.
All practitioners would agree that patients with peripheral arterial disease would benefit from a diet aimed at weight reduction and atherosclerosis prevention. There is evidence to show that elevated plasma homocysteine levels may be a risk factor for developing PAD. Homocysteine is an amino acid produced as a by-product in the body and can be harmful to blood vessels. Certain B vitamins have been shown to be effective in lowering homocysteine levels, and it is logical to try and incorporate these into a patient’s diet. It is very important that patients with PAD regulate any other medical conditions that could be affecting their disease, such as diabetes, high blood pressure, and high cholesterol. A diet aimed at weight reduction would obviously be good for patients with diabetes and/or high blood pressure. It has been recommended that diabetic patients consume fats high in monounsaturated to polyunsaturated content.
Exercise and Physical Activity
Exercise is a low cost and effective means of treating peripheral arterial disease. The flow of blood to the legs can be increased by as much as 300 percent during exercise. This increased flow of blood can often relieve intermittent claudication, the pain felt in the legs from PAD, during exercise. Those who suffer from intermittent claudication often stop doing physical activities because of pain. This only leads to a decreased ability to walk and the muscle pain becomes more severe. Although the initial discomfort is hard to overlook, exercise can help these symptoms improve over time. Going for walks is an easy way to get exercise. The distance walked is slowly increased as the symptoms of intermittent claudication get better. A 6-month supervised treadmill exercise program has been proven to improve walking distance and speed in patients with PAD. Cyclers showed some improvement, but thigh and calf muscle biopsies found no increase in exercise capacity. Studies have looked at pain-free walking distance and focused on an alternative exercise such as strength training. One supervised program focused on 8 weeks of strength training exercises. These exercises were isolated to one leg and were done three times a week. The exercise intensity was increased by raising the number of repetitions and adding resistance. The exercise was well tolerated and there was decreased leg pain and improvement of both physical and mental aspects of quality of life. This showed that strength training can be a suitable alternative for patients who cannot handle prolonged walking exercise. Overall, an at-home walking program combined with supervised exercise therapy is the best approach for improving walking ability and quality of life for patients with PAD.
Herbal Remedies and Supplements
Ginkgo Biloba is probably the most well-known herb for PAD, which has been shown to increase pain-free walking distance as well as increasing the distance one can walk before the onset of severe claudication. This is likely to be due to the haemorrheological properties of Ginkgo, which significantly improve blood flow. Ginkgo also has antioxidant and anti-inflammatory effects, which are also beneficial to those with PAD. The dose of Ginkgo in the above trial was 6-8 tablets daily of Ginkgo 50:1 extract (T.E). Start at a dose of 120mg per day and increase slowly over 6-8 weeks to an optimal dose of 240mg to be taken in 2 divided doses. Although there are no drug interactions with Ginkgo, consult with a doctor first, especially if planning to take high doses. Side effects are rare, although there is an increased risk of bleeding with high doses and should not be taken in those with a history of stroke or peptic ulcer disease.
Various herbal remedies and supplements have been used to treat a multitude of conditions for thousands of years and can be used very effectively in the treatment of peripheral arterial disease.
Mind-Body Practices
Meditation is a practice that promotes relaxation, builds internal energy or life force and develops compassion, love, patience, generosity, and forgiveness. A particularly relevant method of meditation to PVD is the mindfulness meditation taught by Dr. Kabat-Zinn. This method is an adaptation of traditional Buddhist meditation practices into a medical intervention and involves focusing attention on experiences in the present moment in a non-judgmental way. This is done through sitting meditation, body scan, hatha yoga, and mindful yoga. A study of 21 patients with PVD found that those who engaged in an 8-week course of mindfulness meditation had significantly improved endothelial function compared to controls. An interview with the same group of patients also revealed a subjective increase in walking duration before experiencing pain. This change in pain response was also seen in a study of 14 patients using mindfulness meditation and an ischemia-provoking mental stress test.
…are utilized in many patient populations for promoting health and quality of life, and are increasingly being used as a treatment in a complementary way with chronic diseases. Mind-body practices incorporate a spectrum of techniques including biofeedback, meditation, yoga, hypnotherapy, and tai chi. The idea of these interventions stems from the concept that the mind and body are intricately connected, and that by affecting the state of the mind it is possible to promote changes in the body. Biofeedback utilizes electronic monitoring of a bodily function in order to promote awareness and conscious alteration of that function. This is achieved by means of reinforcing desired changes through positive feedback. Biofeedback has shown some potential as a treatment for intermittent claudication by training of skin temperature biofeedback to increase blood flow to affected extremities.
