Pain at rest
Minor tissue loss
Major tissue loss
They constitute the largest group. The diagnosis is made by the ankle-brachial index . Despite the absence of symptoms, individuals with peripheral arterial disease (ankle-brachial index <0.9) have higher morbidity rates than patients with normal index. The risks are inversely proportional to the daily physical activity. This group of patients should be conducted medically in the same manner as the symptomatic .
Intermittent claudication patients have fatigue or muscle pain while walking. It is most common in the calf but may be present in the buttock or thigh, according to the site of arterial obstruction. Symptoms cease with rest and restart with the next effort .
The pain results from ischemic neuropathy and local intramuscular acidosis . The pain intensity depends on physical activity degree. Therefore, some patients may be asymptomatic due to poor clinical conditions and/or low functional capacity. Elderly patients usually walk indoors, not completing the necessary distance to elicit symptoms. At the same time, a workman that needs to walk more than 1000 m to perform their labor activities will complain of limiting symptoms .
The intermittent claudication causes functional disability. It is marked by slow progression, rarely leading to critical limb ischemia . In 75 % of cases, it stabilizes or alleviates symptoms. Only 25 % deteriorate, most commonly in the first year (6–9 % in the first year and 2–3 % per year) .
A low ankle-brachial index (<0.5) is a predictor of clinical worsening. The best single predictor, however, is a reduced ankle absolute pressure, between 40 and 60 mmHg. Amputation is rare, with rates as low as 2 % in 5 years . Mortality, on the other hand, is high, reaching 42 % at 5 years and 65 % at 10 years .
Critical Limb Ischemia
Critical limb ischemia is the most severe presentation of peripheral arterial disease. It affects 1 % of all symptomatic cases. It is divided into two groups: rest pain and ischemic trophic lesion .
Rest pain is described as burning sensation or uncomfortable cold or numbness, sufficiently intense to interfere with sleep. The discomfort is aggravated by leg elevation, relieving in standing position or dangling the leg over the edge of the bed [21, 22]. Pain always affects the limb most distal segment, the forefoot or at the amputation stump. Rest pain does not affect the calf or thigh, except for patients with acute limb ischemia .
The degree of sleep interference informs about its intensity. The patient is woken up by the pain, returning to sleep soon after. With the progression of the ischemia, they only can sleep dangling the leg over the edge of the bed leading to leg edema [21, 22].
Ulcers and gangrenes occur when blood flow to the limb is insufficient to maintain cell viability at rest. They predominate in the toes but also can be present in the ankle and heel. The pain can be increased by ischemic neuropathy, skin loss, exposure of subcutaneous sensory nerves, osteomyelitis, and ascending infection. Diabetes is an important risk factor for gangrene, present in 40 % versus 9 % in nondiabetic patients with critical limb ischemia .
Patients with critical limb ischemia have a poor prognosis. About 25 % will undergo amputation immediately; 25 % will have medical treatment and 50 % will be revascularized. After 1 year, only 25 % will have the critical limb ischemia resolved; 20 % will remain with symptoms, 25 % will be dead, and 30 % will be amputees. Critical limb ischemia can be the first peripheral arterial disease presentation in most patients, which hinders therapies for prevention .
Due to atherosclerosis’s systemic involvement, a severe peripheral arterial disease is often associated with advanced coronary artery and cerebrovascular diseases. Thus, all patients with this disease require strict control of the modifiable risk factors, to slow atherosclerosis progression, besides improvement of the benefits, duration, and safety of vascular intervention .
It is based on medical history and physical examination. Peripheral arterial disease must be confirmed by noninvasive tests since its prevalence is underestimated when based solely on symptoms, and overestimated if based exclusively on pulses palpation. The diagnosis is confirmed by hemodynamic measurements with a handheld Doppler (ankle-brachial index <0.9) .
On physical examination, one should search for the absence of pulses, changes on foot color and temperature, muscular atrophy (by disuse), reduction of the amount of hair, slow toe’s nail growth, and nail hypertrophy .
Imaging exams such as duplex scan, computed angiography, magnet resonance angiography, and digital subtraction angiography are not required for diagnosis. They are necessary for anatomical details and revascularization planning and may be useful on atypical presentation or doubtful situations . The differential diagnosis is made with peripheral neuropathy conditions (burning or tingling sensations especially in hands and feet); nerve root compression (pain, weakness, and loss of sensation in the posterior aspect of the lower limb); night cramps (muscle pain located in the calf and foot); Buerger’s disease (ischemia of the distal part of extremities in young smokers); gout (severe pain in the joints of the feet, ankles, hands, and wrists); plantar fasciitis (pain, stiffness, and burning in the sole of the foot); neuroma (numbness and pain in the forefoot); and rheumatoid arthritis (pain and swelling in small joints, particularly in hands) . Such groups of disease simulating peripheral arterial disease are called pseudoclaudication.
Treatment of peripheral arterial disease is aimed at pain relief, healing of ulcerations, prevention of limb loss, independent walking maintenance, risk factors control, and survival increasing.
Risk Factors Control
It is recommended smoking cessation [27, 28]; lipid control (Low-density lipoprotein [LDL] <100 mg/dL, or, in case of patients at high risk of ischemic events, <70 mg/dL) ; rigorous glycemic control and blood pressure control (<140/90 or 130/80 mmHg for diabetic or chronic renal failure patients) .
Drugs aimed at modifying risk factors, such as statins and antiplatelet agents, are used in all stages of peripheral arterial disease, aiming at slowing atherosclerosis progression .
Treatment ofIntermittent Claudication
Intermittent claudication therapy targets pain relief and better daily physical performance. The patient has to be advised to walk to the limit of pain’s tolerance, followed by a short rest period. Then, must return to walking, redoing all this cycle for at least 30 min, three times a week .
Some patients are able to accomplish this training by themselves. Most, however, require support, being referred to a supervised exercise program. This consists of performing physical activities monitored and guided by a physiotherapist, to increase patient’s adherence and intervention’s effectiveness .
Cilostazol is a phosphodiesterase III inhibitor drug with vasodilatory, metabolic, and antiplatelet activity. It is the only drug with proven efficacy for intermittent claudication symptoms’ relief [33–36]. That said, it should be prescribed for all these individuals, for about 3–6 months [13, 33].
The lack of response to exercise and/or drug therapy leads to limb’s revascularization evaluation. However, patients who present with proximal lesions, i.e., aortoiliac obstruction manifested by buttocks’ claudication and femoral pulse reduction, revascularization can be considered earlier .
Treatment of Critical Limb Ischemia
Critical limb ischemia implies the imminent risk of limb loss. This risk is only reduced by limb’s blood supply reestablishment. Thus, patients with this condition should be promptly referred to a vascular surgery team for a proper approach .
Bypass surgery consists on the diversion of blood flow from an area of normal blood flow to an area with low flow, distal to the arterial obstructed segment, with the aid of tubular grafts. These can be autologous, such as the great saphenous vein, or synthetic, such as polytetrafluoroethylene, commonly shortened as PTFE, or polyester grafts .
The endovascular surgery is a minimally invasive image-guided approach, used for restoring the patency of the arteries. First, an arterial puncture is made, usually on the femoral or brachial artery, through which catheters, guidewires, and other endovascular devices are introduced. After crossing the vascular obstruction with a guidewire, the angioplasty with a balloon catheter is performed. Angioplasty is the compression of the atherosclerosis plaque against the artery wall to reopen the vessel lumen. According to the lesion type and location and the angioplasty results, a stent, which is a tubular metal cylinder, is delivered. Its function is to maintain the plaque compacted and fixed against the artery wall, allowing the free blood circulation.
The choice between one method and the other is made according to the extension of the lesion, the comorbidities of the patient, operative risk, the patient life span, availability of local resources and surgeon preference . The BASIL (Bypass versus angioplasty in severe ischemia of the leg ) trial compared results of surgery and angioplasty in patients presenting with severe limb ischemia due to infrainguinal disease and observed that patients with expected survival of less than 2 years, whenever possible, should be treated with angioplasty . On the other hand, patients with expected survival of more than two years are better treated with surgery, particularly if performed with autologous vein . A recent good systematic review showed that primary patency for vein bypass grafts is significantly improved compared with PTFE grafts in the above-knee setting .