Vascular disease as a consequence of atherosclerosis results in a wide range of conditions making up the cardiovascular and peripheral vascular diseases. Vascular disease is, without question, the current leading cause of morbidity and premature deaths of modern era medicine. Likewise, it is one of the primary causes of disability.
Approximately 14 million people in the United States have a history of myocardial infarction (MI) and/or angina pectoris, while the annual incidence is reported at 1.5 million cases. Many of the risk factors for coronary artery disease are applicable to patients with peripheral vascular disease (PVD), because both are manifestations of atherosclerotic disease.
Patients with PVD can be assured that less than one third of such patients need surgical or radiologic intervention. Although approximately 4-8% of patients with PVD require amputation, this fact should not minimize the statistical data showing that patients with symptomatic PVD have at least a 30% risk of death from MI or cerebrovascular disease within 5 years and a risk of approximately 50% in 10 years. PVD is an independent risk factor for cardiovascular death. Approximately 50% of patients presenting with PVD have additional symptoms related to coronary artery disease (CAD), with 90% likely to have abnormalities on coronary angiography and 40% demonstrating carotid artery disease on duplex ultrasonograms.  Progressive, symptomatic PVD requiring surgical intervention more than doubles a patient's risk for cardiovascular events.
As many as two thirds of patients with a clinically significant vascular event have an incomplete recovery, and it is in this patient population that physical, psychosocial, and vocational rehabilitation can have a positive bearing on morbidity and mortality.  Conversely, it is crucial to recognize that patients with chronic physical disability have a higher incidence of vascular disease development, due to a greater incidence of obesity and metabolic syndrome (which herald diabetes, hypercholesterolemia, and hypertriglyceridemia).
It is a well-known fact that individuals with disability caused by deficits in motor and sensory function are less mobile and active than their age-matched counterparts. Therefore, it is prudent to say that physical disability, by severely compromising the ability to exercise, is a risk factor for developing vascular disease. In people with chronic disability, vascular disease is known to be a leading cause of morbidity and mortality.
For excellent patient education resources, see eMedicineHealth's patient education article Peripheral Vascular Disease.
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The systemic manifestation of arteriosclerosis commonly manifests as peripheral arterial occlusive disease (PAOD); most common in older individuals, it also disproportionately affects African Americans. PAOD develops earlier in men than in women. Rates of PAOD increase with age, with estimates of 1-2.5% in individuals aged 50-60 years and of 5-9% in persons older than 65 years. Causes of arterial occlusive disease include thrombosis, embolism, dissection, atherosclerosis obliterans, vasculitis, vasospastic disorders, fibromuscular dysplasia, and thromboangiitis obliterans.
Peripheral arterial occlusion of the extremities often results from atherosclerotic plaques (atheromas), thrombi, or emboli. Such occlusions manifest as acute or chronic ischemia. Intermittent claudication is the most common initial symptom. Most patients present with occlusive disease in the femoropopliteal vessels, and 40% of patients have stenosis in the distribution of the tibioperoneal artery. Nearly one third of these individuals have disease in the aorta or the iliac arteries. Further division occurs in patients with diabetes mellitus (DM). The vessels most commonly affected in patients with DM are the femoral and tibial arteries; in contrast, the abdominal aorta and the iliac and femoral arteries are most often affected in patients without DM.
Acute ischemia is often a consequence of a ruptured proximal atherosclerotic plaque, a dissecting aneurysm, or an embolism from the heart, aorta, or other large vessel. In contrast, chronic ischemia is typically due to the gradual circumferential enlargement of an atheromatous plaque. Life-threatening ischemia occurs in 2-5% of patients with intermittent claudication. The mortality rate in this patient population is 20-30% at 5 years after diagnosis, 40-70% after 10 years, and 74% after 15 years. Cardiovascular events cause 75% of deaths in these patients.
Depending on the severity of motor and sensory loss, people with physical disability become less physically active or completely inactive. With this disadvantage, caloric intake does not equal energy expenditure, leading to weight gain and obesity. The body undergoes various compositional changes—including atrophy of skeletal muscle and an increase in adipose tissue—as the disability becomes chronic, resulting in hypercholesterolemia, hypertriglyceridemia, and insulin resistance and diabetes. As a consequence of this metabolic syndrome, people with disability are at very high risk of developing cardiovascular and peripheral vascular disease at a younger age, with the risk increasing with every year of survival following the occurrence of the initial disability. [3, 4]
Most research on vascular disease in people with disability has been done on people with spinal cord injury. Current studies on vascular function in people with spinal cord injury demonstrate the following [5, 6] :
Physical inactivity does not strongly affect conduit artery resting blood flow
Arteries in people who are inactive are not able to maintain basal shear levels
Reactive hyperemic blood flow after a period of inactivity is reduced when deconditioning occurs
Arterial remodeling with a decrease in vessel diameter occurs in the femoral arteries of paralyzed limbs
Flow-mediated dilatation response is enhanced in deconditioned arteries
These data suggest that in people who are inactive, there is a deterioration of arterial function in the lower extremities.
For the above-mentioned reasons, stricter and earlier surveillance is necessary in the disabled population. There should be a greater emphasis on the importance of modifying risk factors, such as diet, smoking, and alcohol intake, in this population.
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Major risk factors for the development of atherosclerotic vascular disease include the following:
Elevated levels of low-density lipoprotein (LDL) cholesterol
Reduced levels of high-density lipoprotein (HDL) cholesterol
Physical inactivity, deconditioning, lack of exercise
Sex - Peripheral arterial occlusive disease (PAOD) develops earlier in males than in females
Elevated levels of homocysteine
Family history of premature atherosclerotic disease
Motor weakness, paralysis
As mentioned, PAOD develops earlier in men than in women, with peak incidence during the sixth and seventh decades of life. Rates of PAOD increase with age, with estimates of 1-2.5% in individuals aged 50-60 years, and of 5-9% in persons older than 65 years.
Cigarette smoking is a more potent risk factor for PAOD than for coronary artery disease, increasing a patient's risk of developing peripheral atherosclerosis 3- to 4-fold. Nicotine use affects patient outcomes and is associated with an increased risk of progressing from claudication to ischemic rest pain, as well as with an increased risk of amputation. Patients with arteriosclerosis in its advanced stage are also likely to have systemic disorders involving the coronary, cerebral, pulmonary, renal, and peripheral vessels. Diabetes mellitus is also a risk factor for PAOD. An individual with diabetes is twice as likely to develop claudication as is a nondiabetic counterpart. Hypertension is also a risk factor for PAOD. Among individuals with hypertension, 2-5% have intermittent claudication, while 35-55% of patients with PAOD have hypertension. In a review of literature, differences in systolic blood pressure (SBP) of 10 mm Hg or more, or 15 mm Hg or more between arms, have been associatedwithperipheralvascular disease and attributed to subclavian stenosis.  The combination of hypertension and PAOD markedly increases the risk for myocardial infarction, stroke, and death.
An inability to exercise and be physically active plays a huge role in the development of obesity and contributes to harmful changes in body composition. Increases in adipose tissue and insulin resistance produce diabetes, an elevation in LDL cholesterol, and a reduction in HDL cholesterol, all of which contribute to the development of atherosclerosis and vascular disease.
A study by Hamur et al indicated that increased red cell distribution width and uric acid levels and decreased total bilirubin levels have an independent relation to the development of chronic total occlusion in persons with peripheral arterial disease. 
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Type 1 Diabetes Mellitus [Endocrinology]
Type 2 Diabetes Mellitus [Endocrinology]
Pediatric Type 1 Diabetes Mellitus [Pediatrics: General Medicine]
Pediatric Type 2 Diabetes Mellitus [Pediatrics: General Medicine]
Clinical Presentation and Symptoms
Patients may present with various symptoms depending on the vessels involved, the degree of compromise to the vascular lumen, the rate of progression, and the presence of collateral flow. In general, a history of sudden onset of severe pain, numbness, coldness, and pallor in an extremity at presentation is consistent with acute occlusion. Physical examination may reveal absent distal pulses, sensory or motor loss, or muscular tenderness on palpation.
In contrast, patients with chronic occlusion initially present with intermittent claudication. This most commonly affects the gastrocnemius muscle, but it can also involve the foot, thigh, hip, or buttocks. The usual relationships between the site of pain and the presence of arterial occlusive disease are summarized as follows:
Buttock and hip involvement - Aortoiliac disease
Thigh - Common femoral artery or aortoiliac disease
Upper two thirds of the calf - Disease of the superficial femoral artery
Lower one third of the calf - Disease of the popliteal artery
Foot claudication - Disease of the tibial or peroneal artery
Claudication is consistently reproducible and worsens with exertion, although it usually resolves within minutes after the person stops exercising. It is important to differentiate this from neurogenic claudication due to spinal arthropathy. When relatively old individuals with peripheral arterial occlusive disease were compared with healthy counterparts, individuals with claudication had 50% less peak exercise capacity. Symptomatic claudication affected patients' quality-of-life (QOL) scores in comparison with those of asymptomatic individuals. The reduction was related to concomitant disease rather than to domains of social functioning or mental health.
The site of claudication can help to provide a gross estimate of the level of occlusion. The progression of peripheral vascular disease (PVD) corresponds with reductions in the distance that a patient can walk without symptoms. Ischemic pain eventually occurs at rest, often in the most distal extremity, particularly with the limb elevated, and it often disrupts sleep. Patients with such pain are forced to sleep with their feet over the side of their bed or in a chair with their legs in a dependent position. Decreased arterial flow and perfusion, edema, and further ischemia are likely consequences of persistent dependency of the involved extremity.
Signs on physical examination that can help the physician to confirm arterial insufficiency include diminished or absent pulses, delayed venous filling time on dependency after elevation (>20 s), and marked pallor of the involved extremity after elevation within 60 seconds or less. With gradual progression of ischemia, patients may develop trophic changes in the skin, which can appear dry and scaly, with poor hair and nail growth. As ischemia worsens, ulcerations may develop, especially after local trauma. Severe ischemia leads to atrophy, necrosis, or gangrene with rubor, pain, and edema that can mimic cellulitis or venous insufficiency.
An important concept to keep in mind is that many patients who have PVD may also have concomitant cardiovascular, pulmonary, or renal problems. For these patients, in-depth history taking and clinical evaluation are warranted, especially if surgery is being considered. As mentioned earlier, risk factors for PVD overlap those for coronary artery disease (CAD). The prevalence of serious CAD in patients undergoing peripheral vascular surgery is 37-78%. In these individuals, the risk of perioperative mortality is 4 times that for patients without CAD.
People with disability who have motor and sensory deficits may present differently than do able-bodied individuals. In persons with motor and sensory deficits, frequent examination of the extremities for pallor or erythema is imperative, because pain from occlusion or claudication is not experienced. Pain from occlusion or claudication, however, can present as an increase in neuropathic pain or spasticity; in people with spinal cord injury, it can present as autonomic dysreflexia.
Although arterial disease can be diagnosed clinically, noninvasive and invasive tests can help the physician to confirm and delineate the extent of disease. Noninvasive tests frequently used to diagnose arterial insufficiency include calculation of the ankle-brachial index (ABI), ultrasonography, and magnetic resonance angiography (MRA). The systolic blood pressure in the ankle at rest normally is more than 90% of the brachial pressure, with mild arterial insufficiency occurring at 70-90% of brachial pressure; moderate insufficiency, at 50-70%; and severe insufficiency, at under 50%.
It is notable from a rehabilitation perspective that when systolic blood pressure in the ankle is less than 55 mm Hg in a nondiabetic patient or less than 70 mm Hg in a diabetic patient, ischemic lesions tend not to heal spontaneously. An ankle systolic blood pressure of over 70 mm Hg is more affirmative for healing after below-knee amputation. An ankle–brachial systolic pressure ratio of 0.9 or less supports the diagnosis of arterial occlusive disease.
The segmental-pressure technique is used to obtain systolic pressures in the upper and lower thigh and calf in addition to ankle measurements. An abnormal pressure gradient between measurement sites indicates the presence and location of disease. This technique is problematic in persons with diabetes, who can present with falsely elevated pressure due to incompressible, calcified arteries. Moderate areas of stenosis can also be missed, because little or no pressure gradient may be created at rest.
With continuous-wave Doppler ultrasonography, normal peripheral arteries have flow waveforms that are typically triphasic, a feature that reflects forward flow during systole, reversed flow in early diastole, and forward flow again before a subsequent heartbeat. Waveforms recorded just distal to the stenosis are monophasic in the absence of reversed component. Directly over the stenotic segment, a high-frequency signal is revealed during systole and diastole, because the narrowed segment increases the velocity of flow. By comparison, duplex ultrasonography combines pulsed Doppler with real-time B-mode scanning that allows for the exact localization of stenosis and helps in defining the hemodynamic significance of the lesion. Although safer than arteriography, Doppler ultrasonography and duplex imaging are operator dependent in terms of accuracy.
MRA can further assist in visualizing the quality of peripheral vascular disease (PVD). MRA is often used when ultrasonography is not feasible, such as when the pelvic or intra-abdominal vasculature must be visualized. This is a new approach to the diagnosis of peripheral arterial disease. MRA is safer than angiography, and in studies, MRA was found to be sensitive and specific in comparison with the criterion standard of angiography.  However, MRA might not aid in distinguishing complete tight or complete stenotic lesions, and it is institution dependent with regard to accuracy. As MRA is further developed, the need for angiography may be reduced in many instances.
The benefit of invasive tests, such as contrast angiography or percutaneous catheterization, is that they can be used to accurately document the location and extent of disease should angioplasty, fibrinolytic therapy, or surgical bypass be pursued. In patients with renal insufficiency, cautious use of contrast material should be emphasized because these patients are at high risk for renal failure.
Arteriography should be obtained only if intervention is planned. It enables visualization of the extent and type of peripheral arterial occlusion and defines the rest of the arterial circulation. Iodinated contrast agent is injected. Arteriography is not without risk in patients with renal disease or other comorbidities. The mortality risk is approximately 0.15%, with a morbidity risk slightly higher than this.
The development of nonionic contrast material, digital subtraction angiography, and sophisticated imaging technology mitigates some of the risks of arteriography. Partial angiography involving the acquisition of selected views of the arterial tree also reduces the risk. In addition, the risks can be reduced by using CO2 and gadolinium-based contrast agents in patients with renal insufficiency. Arteriography is considered the criterion standard for defining the anatomy of the arterial tree.
Risk modification is fundamental to the treatment of peripheral arterial occlusive disease (PAOD). Management should aggressively address the control of modifiable risk factors, including tobacco use, hypertension, and hyperlipidemia. In addition, patients with PAOD should be screened for diabetes. In the ideal situation, glycohemoglobin levels should be maintained at less than 7.0%.
Glycemic control alone is not enough to halt PAOD progression. Intense glycemic control is still important, however, because it lowers the risk of other complications of diabetes that will worsen PAOD and limit its treatment options. An example is the development of diabetic sensorimotor peripheral neuropathy. With reduced sensation and motor control of the lower limbs, affected individuals are at increased risk for ulceration. Neuropathy, coupled with underlying arterial disease, increases the risk for foot infection and sepsis, as well as for limb amputation.
Smoking increases the risk of arterial disease and worsens disease progression; it is correlated with an increased risk of amputation, stroke, myocardial infarction (MI), and death. Smoking cessation is critical to successful management. Patients should be informed that continued tobacco use accelerates disease progression and increases their mortality risk. Evidence suggests that disease progression slows and that symptom severity improves in patients who stop smoking. 
Hyperlipidemia is a well-recognized risk factor for atherosclerotic disease. Fasting lipid profiles should be evaluated in individuals with PAOD. Elevated low-density lipoprotein (LDL) cholesterol and triglyceride levels, as well as depressed high-density lipoprotein (HDL) cholesterol levels, are associated with atherosclerosis. The target lipid profile includes reduction of the serum LDL cholesterol concentration to less than 100 mg/dL and perhaps to less than 70 mg/dL. Pharmacologic intervention is often required.
Hypertension should be treated similarly to the way it is treated in patients with cardiovascular disease. Reduction of blood pressure is required to lower the risk of the morbidity and mortality associated with MI, stroke, and cardiovascular disease.
Loss or impairment of sensation in disability: neuropathy and skin care
Foot problems are an important cause of morbidity in patients with diabetes or who have suffered the loss or impairment of sensation from conditions such as spinal cord injury or stroke. Vascular and neurologic factors contribute to this problem. Neuropathy is present in more than 80% of patients with foot ulcers. Lower extremity wounds are prevalent as well in people with disabilities in whom there has been loss or impairment of sensation. The lack of sensation promotes ulcer formation by decreasing pain sensation and pressure perception, by causing muscular imbalance that can lead to anatomic deformities, and by impairing microcirculation and skin integrity. After ulcers form, healing may be delayed or difficult to achieve, particularly if infection penetrates to deep tissues and bone and/or if local blood flow is diminished.
Foot amputations, many of which are preventable with early recognition and therapy, are too often the outcome. The mean cost of foot ulcers in diabetic patients is almost $28,000 for the 2 years after the ulcer is diagnosed. The best predictors of future lower limb amputation are a history of foot ulcers, the presence of neuropathy and peripheral arterial disease, and poor glycemic control.
Screening for peripheral neuropathy is recommended in people with diabetes. For such screening, a Semmes-Weinstein 5.07 (10-g) monofilament is applied at specific sites to detect a loss of sensation in the foot and to identify patients at risk.
Routine skin and foot care is extremely important for preventing skin compromise. Patients should inspect their feet daily for cracks, fissures, calluses, corns, and ulcers, and they should seek early intervention from podiatrists. Their feet should be washed daily in lukewarm water with mild soap and dried thoroughly.
Heating pads and hot water should be avoided in order to prevent thermal injuries. A lubricant, such as lanolin, should be applied to dry, scaly skin, whereas moist feet can be remedied with a bland, nonmedicated foot powder. Toenails should not be cut too close to the skin, and patients should change their socks or stockings daily. Constricting garters should be avoided, as should adhesive plasters or tape. Patients should also refrain from using harsh chemicals and corn cures in order to prevent chemical trauma. To prevent mechanical injuries, shoes should fit properly and have a wide toe space, and they should be changed often. If the patient is ambulatory, he/she should always avoid walking barefoot.
Customized footwear or selected foot or lower extremity orthoses should be prescribed for stabilization and protection. The goal is to enhance function of the lower extremity and to reduce pressures. Rocker-sole shoes can diminish the work of the gastrocnemius muscle during ambulation, and ankle-foot orthoses (AFOs) can minimize ankle motion. Improved walking tolerance, distance, and comfort are reported in patients who use orthoses. For patients with pain at rest, particularly at night, the head of the bed should be elevated 4-6 inches, which should improve lower extremity perfusion due to the effects of gravity on blood flow.
In patients with neuropathic ulcers, weight bearing should be avoided in the acute healing process. Then, when appropriate, orthotics should be used to redistribute pressure points and to ensure that shoes fit properly. In patients with diabetes mellitus, aggressive wound care and the tight management of capillary blood glucose levels further augment wound healing. Debridement and the use of antibiotics that have been specifically selected on the basis of wound-culture results greatly contribute to healing, and early drainage of infection may prevent major surgical wound revision. Enzymatic debridement may be irritating and can increase pain.
For people who are nonambulatory and who have a complete loss of sensation in both lower extremities, pressure sores from poor positioning in bed or in a wheelchair should be avoided. Most pressure sores in the lower extremities are located over bony prominences, such as the heels, fibular heads, and greater trochanters. Unnecessary, wound-causing trauma can be avoided with continuous awareness of where the feet and lower extremities are located during transfers and mobility.
Pharmaceutical Intervention and Alternative Options
Drugs, such as vasodilators, are prescribed to manage intermittent claudication, with the general aim of increasing the peripheral delivery of oxygen. However, their efficacy remains questionable. Beta blockers can result in peripheral vasoconstriction, and they are avoided in patients with arterial occlusive disease; the evidence is nonetheless inconclusive as to whether these agents increase claudication. Because platelet aggregation can exacerbate disease by causing mechanical obstruction or by stimulating local vasospasm, drugs that reduce platelet activity are considered beneficial. 
Pentoxifylline (Trental) may be variably effective in patients with intermittent claudication, because they increase RBC deformability, decrease plasma viscosity, and diminish fibrinogen concentrations. One trial comparing pentoxifylline with exercise showed that patients receiving drug therapy achieved significantly greater walking distances after 3 months than did individuals receiving exercise therapy. 
No evidence supports the idea that fibrinolytic agents, anticoagulants, or antiplatelet agents are effective for treating intermittent claudication. However, strong evidence supports the use of aspirin to prevent coronary and vascular-graft thrombosis. Low-dose aspirin has been found to reduce the risk of peripheral arterial surgery by 54% compared with placebo. 
Ticlopidine (Ticlid) is a thienopyridine that selectively inhibits adenosine diphosphate (ADP). It is used less now than it was previously to manage PAOD. Ticlopidine therapy requires monitoring because of serious adverse effects, such as neutropenia and thrombotic thrombocytopenia purpura.
Clopidogrel (Plavix) is also a platelet aggregation inhibitor. Clopidogrel therapy is associated with the decreased progression of atherosclerotic disease. However, it has the adverse effects of minor bleeding, gastrointestinal complaints, and edema. This drug is more beneficial than aspirin for patients at high risk of cardiovascular events.
Cilostazol (Pletal) reportedly has fewer adverse effects than does pentoxifylline. This drug induces vasodilatation and inhibits platelet aggregation and proliferation of the smooth muscle. However, the mechanism of its effect is not fully understood. Cilostazol is contraindicated in patients with congestive heart failure. The most common adverse effect in other populations is headache. Transient diarrhea, dizziness, and palpitations have also been reported.
Preliminary evidence led to postulations that antioxidants, such as beta carotene and vitamins C and E, can retard arteriosclerosis.  However, as additional evidence has emerged, the validity of this claim has been questioned. In theory, chelating agents may potentiate the regression of arteriosclerosis, because they extract calcium from the plaques. However, they have not been proven to be clinically effective, and they are not recommended at the present time. Fibroblast growth factors to stimulate the growth of new blood vessels are currently being studied in clinical trials.
Hyperbaric oxygen treatment and the application of negative pressure to the lower limb have gained popularity. However, the present authors know of no data from randomized, controlled studies to support claims of efficacy.
Chelation therapy with ethylene diamine tetra-acetic acid (EDTA) has undergone randomized trials. No reduction in claudication or improvement in perfusion was documented in the treatment of peripheral disease. 
Sympathectomy to manage pain, increase perfusion, reduce tissue loss, or serve as an adjuvant to revascularization surgery has had disappointing results. Sympathectomy is typically reserved for individuals who have inoperable disease. At present, this procedure is most commonly done with injected chemicals.
In general, conservative management is advocated as the treatment of choice for patients with intermittent claudication. With respect to physical rehabilitation and exercise programs, a substantial reduction of 20-25% in cardiovascular death has been observed. A consistent trend toward survival benefit has been demonstrated, and the risk of mortality decreases as the level of physical activity increases.
Participation in exercise training programs by people with or without disability result in physiologic changes, such as improved peripheral utilization of oxygen and increased glycolytic-oxidative metabolic capacity, which improve functional capacity and decrease cardiac effort. Blood flow increases during and after active exercise. Physical training elevates muscular metabolic demand, and increased collateral circulation is the presumed mechanism of symptomatic improvement. Extended walking distance with exercise was demonstrated in many controlled trials. 
Comparing the long-term results of angioplasty and exercise training, investigators reported minimal differences in walking distance and QOL score at 5 years. Patients with intermittent claudication are encouraged to walk 30-60 minutes per day, 3-5 days per week, at a pace of 2 miles per hour. If discomfort occurs, the patient should stop; he /she can resume when the pain abates.
In people with disability, exercise programs are customized to each individual based on his/her motor and functional abilities, on available resources and assistance, and on the exercise equipment and machines that are most accessible to the patient.
Studies have shown that exercise can have cardiovascular benefits in people with spinal cord injury, producing improvements in blood pressure, heart rate, oxygen uptake, cardiac output, femoral artery compliance, and overall fitness. Therefore, exercise promotes peripheral glucose uptake, as well as decreases in cholesterol and low-density lipoprotein (LDL) levels. Furthermore, exercise has been found to improve vascular blood flow velocity, in flow-mediated vasodilation, basal shear forces, and arterial vessel diameter. [17, 18, 19] Walking and regular physical activity was also linked to better preservation of cognitive function in women 65 years or older with vascular disease.  Middle-aged men also benefit from exercise-based rehabilitation. It has shown to not only lower the risk of dying from heart disease, but may also improve a patient’s quality of life. 
A study by Gardner et al suggested that a home exercise program can be at least as effective as supervised exercise therapy in the rehabilitation of patients with peripheral artery disease (PAD). In the study, 180 patients with symptomatic PAD were randomized into either a supervised exercise program, the new exercise training using a step watch (NEXT Step) home exercise program, or a control group. 
The supervised and NEXT Step programs involved 12 weeks of intermittent walking to the point of mild to moderate claudication pain, while the control group program consisted of light resistance training. The investigators found that patients in the supervised and NEXT Step groups significantly increased their peak walking time, claudication onset time, daily average cadence, 6-minute walk distance, and time to minimum calf muscle hemoglobin oxygen saturation. It was also determined that only the NEXT Step patients showed improvement in their large-artery elasticity index and high-sensitivity C-reactive protein level. 
Coexisting cardiac limitations should be considered when an exercise program is planned. Gradual improvement should be seen within 3-6 months. Physical rehabilitation involving dynamic aerobic exercise and resistance training improves cardiovascular endurance and positively affects patient survival. Exercise is a noninvasive and inexpensive activity with minimal complications; it is an invaluable first-line treatment for patients with peripheral vascular disease.
Invasive Treatments and Prevention
Percutaneous endovascular therapy
In the setting of acute thrombosis, early intervention is crucial in preventing neuromuscular damage and optimizing limb salvage. Anticoagulation with intravenous (IV) heparin therapy helps to maintain residual luminal patency and to prevent propagation of thrombus, in this way promoting adequate blood flow to the microvasculature. Further intervention depends on the extent of disease delineated with arteriography.
Percutaneous endovascular therapy includes percutaneous transluminal angioplasty (PTA), stenting, and thrombolytic therapy.  Diffuse disease or lack of restorable patent, adjacent, collateral circulation is not successfully treated with this procedure. The outcome of PTA in isolated iliac occlusive disease is improving, such that it may be preferred over surgery. However, infrainguinal disease is most likely to be diffuse, and surgical bypass is likely to be preferred.  Indications for PTA include rest pain, gangrene, and progressive, limiting intermittent claudication that prevents the patient from functioning.
PTA is associated with a high recurrence rate of obstruction, but it is a useful treatment for localized short (< 10 cm), segmental, and occlusive arterial lesions. Successful PTA obviates or delays surgery and requires a short hospital stay. PTA is an optimal choice for high-risk cardiac patients who are poor surgical candidates. Five-year patency rates are 60-90%, depending on the vessel involved.
Stents are inserted into the vessel at the site of the obstruction, and the recurrence rate reportedly is less than that of PTA. However, stents work best in large arteries with high flow; they do not work as well in small vessels and long occlusions. Synthetic grafts are inserted through small catheters into the site of aneurysm and expand to protect and provide structural support of the weakened vessel wall. Patients with stents return home with additional antiplatelet therapy. Thrombolytic therapy is most effective for acute arterial occlusions of less than 2 weeks, and its use is indicated in severely ischemic limbs.
Therapeutic exercise versus PTA
Creasy and colleagues compared the therapeutic effectiveness of exercise with that of angioplasty.  At 6 months, walking time increased in patients given PTA compared with those participating in walking exercise. However, after 6 months, results in the angioplasty group declined, whereas results in the exercise group improved. At 12 months, the exercise group improved further.
In a prospective, randomized trial of 56 patients, investigators compared the effectiveness of PTA with that of a walking exercise program in the treatment of stable claudication.  Over a 15-month follow-up period, the greatest improvements in claudication and maximum walking distance were found in the exercise group. In general, PTA should not be used for mild claudication; the condition that is best treated with an exercise program.
Surgical intervention is indicated in patients with incapacitating claudication, resting pain, gangrene, and tissue loss. Surgery is an option most likely to be pursued in patients with diffuse disease, extended occlusions, and severe arterial calcifications. Surgical procedures include bypass grafting and resection with graft placement and thromboendarterectomy. Autologous veins are used most often to bypass occlusive lesions of the superficial femoropopliteal or tibial arteries. Revascularization is associated with a mortality rate of 50-70% due to the effects of metabolic products on the pulmonary and renal systems (reperfusion syndrome). Early amputation may be a preferred option in patients with extensive vascular disease.
In refractory cases or in cases of osteomyelitis, surgical amputation is necessary, particularly if revascularization, endarterial therapy, or thrombolytic therapy fails. In this patient population, amputations often result because of thermal, chemical, or mechanical trauma to a limb with preexisting chronic occlusive disease. Amputation to manage uncontrolled infection, unrelenting resting pain, and progressive gangrene should be done as distally as possible, because the level of amputation greatly influences the optimal use of a prosthesis. Of interest, the overall rate of amputation (30 cases per 100,000 population) does not decline despite medical intervention. Hence, conservative management of intermittent claudication is further reemphasized as a mainstay of treatment.
Prevention with cardiovascular rehabilitation
The goal of therapy should be the reduction of risk factors and the restoration of the ischemic limb to a functionally pain-free state. The extent of vascular disease and the patient's underlying medical problems often dictate the course of treatment.
One of the primary aims of cardiovascular rehabilitation is the secondary prevention of risk factors. Modified diets and routine exercise programs effectively lower levels of low-density lipoprotein (LDL) cholesterol and elevate levels of high-density lipoprotein (HDL) cholesterol. Exercise substantially reduces systolic and diastolic blood pressures during and after the exercise period. Exercise also contributes to weight loss and improves the regulation of capillary blood glucose concentrations in patients with diabetes mellitus. In people with disability, exercise is strongly encouraged and can be adapted to the each person’s ability.
Modified diet and cyanocobalamin-folate supplementation can reduce levels of homocysteine, preventing damage to endothelial cells (which predisposes arterial vessels to premature arteriosclerosis). Salt restriction should be recommended for patients with hypertension or heart failure.
Smoking is associated with silent ischemia and reinfarction, arrhythmias, elevated plasma fibrinogen levels, sudden death after myocardial infarction, and coronary spasms. Smoking cessation is undoubtedly beneficial in improving cardiovascular disease and its associated morbidity and mortality. [10, 27] Secondary prevention improves symptoms and perceived QOL; it also stabilizes angiographic progression in approximately 50% of patients and induces regression in about 25% of them, leading to strong endorsements from the American Heart Association and the American College of Cardiology.
Comprehensive cardiovascular rehabilitation, although underutilized, has a positive bearing on morbidity and mortality in this patient population. Cardiovascular rehabilitation is more cost-effective for secondary prevention and arresting progression of disease process than thrombolytic therapy, coronary artery bypass surgery, or cholesterol-lowering medication.
Cardiovascular rehabilitation involves a multidisciplinary approach to support the patient's functional capacity and symptoms, QOL, early vocational reentry, and psychological recovery. Early intervention reduces loss of function and productivity from the patient's temporary or permanent disability. The multidisciplinary team typically includes, but is certainly not limited to, a physician, a psychiatrist or psychologist, a nurse, a health educator or counselor, a dietitian or nutritionist, an exercise physiologist, an occupational therapist, a physical therapist, a vocational therapist, a social worker, and a pharmacist. Multifaceted programs include physical, pharmacologic, psychosocial, and occupational and vocational rehabilitation, as well as education, counseling, and behavioral intervention.
Cardiovascular events not only result in physical hindrances but also alter psychosocial adaptation. Patients often do not return to their previous work, leisure, and intimate activities, an outcome that eventually leads to social isolation, depression, poor medical compliance, and negative perceptions by the patient about his/her health. Anxiety and depression are common in patients with cardiovascular problems who are enrolled in outpatient cardiac rehabilitation programs. The goals of physical, psychosocial, and vocational rehabilitation are the maximization of functional capacity and adaptation consistent with the patient's impairments and environmental limitations. In this way, the patient can return to a useful and personally satisfying role in society.
The benefits of cardiovascular rehabilitation in people with and without disability involve the physical, emotional, and psychosocial aspects of a patient's life. The American Heart Association established a specific risk-stratification scheme to define the level of intensity and mode of exercise that are safe and effective for the individual patient. With persistence, patients achieve improvements in exercise tolerance and functional capacity. A reduction in cardiac symptoms, as well as a perceived decrease in stress and anxiety, occurs and leads to improved productivity and psychological well-being. Patients learn to adapt and become self-reliant as they realize that they can influence their hypertension, DM, weight, and smoking activity by means of behavioral and lifestyle modifications. With comprehensive rehabilitation, patients' QOL improves, they return to work faster than they otherwise might, and their hospital readmission rates are reduced.
Cardiovascular rehabilitation promotes the reversal of arteriosclerosis and reduces subsequent mortality. Such rehabilitation should be established as the standard of care, in addition to the use of antiplatelet, cholesterol-lowering, and thrombolytic agents, as well as possible revascularization.