Peripheral Arterial Disease

SACHIN KUMAR AMRUTHLAL JAIN

ARTHUR TARRICONE

BHASKAR PURUSHOTTAM

PRAKASH KRISHNAN

Peripheral artery disease (PAD) most commonly results from atherosclerosis (plaque) of the arteries that carries blood to the upper and lower extremities, kidneys, and the splanchnic circulation. However, in this chapter, we focus on lower extremity arterial disease. Atherosclerotic plaque is primarily made up of cholesterol, inflammatory tissue, calcium, and fibrous tissue. Over time, they harden and narrow the arteries, thereby limiting the flow of blood. Impaired blood flow to your legs can cause pain and numbness. This can increase the risk of infection, especially in diabetic patients, and also prevent healing after foot surgeries. In addition, prolonged, persistent ischemia of the lower extremity can lead to gangrene (tissue death), nonhealing ulcers, and eventually amputation.

PAD is a very common condition affecting 12% to 20% of Americans who are 65 years and older. It is a leading cause of disability among patients who are 50 years and older and those who have diabetes. PAD affects men and women equally and is more prevalent in African Americans.¹ The Framingham Heart Study and the National Health and Nutrition Examination Survey (NHANES) have revealed that traditional coronary and cerebrovascular risk factors such as age, diabetes, hypertension, hypercholesterolemia, metabolic syndrome, and smoking increase the risk of PAD.² Importantly, patients with PAD have high cardiac and cerebrovascular event rates. Interestingly, though, only 10% to 35% of patients with PAD present with typical features. Most of the patients are either asymptomatic or present with atypical symptoms, which is associated with functional limitation. One to two percent of PAD patients present with critical limb ischemia (CLI) without any warning signs or symptoms. Given the fact that CLI has been associated with a high rate of morbidity and mortality, it makes it the most concerning category among PAD. Hence, it becomes of utmost importance to recognize CLI at the earliest.

The appropriate treatment may slow disease progression to some extent and reduce the burden of morbidity associated with PAD. Treatment can be broadly categorized into lifestyle changes, medical management, endovascular therapy, and surgery. The significant morbidity and mortality associated with PAD along with its adverse impact on economics makes it an important public health problem. The overlap of PAD with coronary artery disease (CAD) has led interventional cardiologists to be more involved in the care of these patients. Finally, in the last few years, there has been a tremendous growth in endovascular techniques and devices, which has led to the preference of endovascular therapy over surgery when it comes to revascularization.

Risk Factors

Several risk factors as mentioned earlier have been associated with PAD. Smoking and diabetes remain the most important ones. Smoking is the main risk factor for PAD, which can increase the risk up to fourfold. Smokers with PAD become symptomatic 10 years earlier than their nonsmoking counterparts. Abstinence of smoking halts the progression of the disease. Diabetic patients who are also smokers are at the highest risk for developing PAD and its associated complications, such as gangrene. About one in three people older than 50 who have diabetes have PAD. PAD is twice as common in diabetics.¹ Diabetic PAD patients often have extensive involvement of infrapopliteal arteries. PAD increases the risk of CAD, myocardial infarction (MI), stroke, and transient ischemic attack. Of the people who have CAD, there is a one in three chance of having PAD. The prevalence of foot ulcers ranges from 4% to 10% among diabetic patients.³ Annual incidence of ulcers in diabetics ranges from 1% to 4.1%, with a lifetime incidence being as high as 25%. Diabetic foot ulcers frequently become infected and are a major cause of hospital admissions. In a recent two-center study, PAD partially contributed to 30% of all foot ulcers.⁴

History and Physical

A thorough history and physical examination is absolutely critical in the diagnosis of PAD and also for planning further management. PAD patients may present with typical claudication or with atypical symptoms on most occasions. Intermittent claudication is defined as a reproducible discomfort of a group of lower extremity muscles, which is brought on with exertion and typically relieved with rest. Claudication is derived from the Latin word, “Claudicato,” which means limp. Atypical symptoms may vary from nonspecific pain, numbness, aching, or heaviness in the lower extremities. When the arteries of lower extremities start to develop obstruction and result in reduced blood flow, the respective muscle group accumulates lactic acid with exertion. This accumulation of lactic acid
and other metabolites causes pain. With rest, lactic acid and other metabolites are washed away and the patient becomes free of pain. The longer the time needed for the pain to be relieved with rest, the worse is the obstruction. The presence of lower extremity resting pain, which improves when the lower extremities are dependent, herald CLI. The presence of gangrene and ulcers signifies CLI and needs urgent attention. Patients with a history of amputation or foot surgeries should undergo comprehensive evaluation with regard to the details of the amputation/foot surgery, such as the cause for it and the recovery or healing phase of the stump (Table 9-1).

Careful and meticulous examination should be performed in these patients. Blood pressure (BP) should be recorded from both the upper extremities as a difference (in systolic blood pressure [SBP]) exceeding 20 mm Hg indicates potential innominate, subclavian, or axillary occlusive arterial disease. Auscultation over the carotid, subclavian, and renal arteries is important, as the presence of bruit can be a clue to underlying stenosis and is also associated with higher cardiovascular mortality (especially with carotid bruit).⁵ The presence of a pulsatile abdominal mass should raise the suspicion for an abdominal aortic aneurysm. It is absolutely imperative to make every effort possible to palpate all the peripheral pulses (radial, brachial, femoral, popliteal, dorsalis pedis, and posterior tibial). If the pulses are not palpable, the use of a handheld Doppler should be strongly considered. The dorsalis pedis pulse can be absent in 8% to 12% of healthy individuals, but the posterior tibial pulse is absent in only 2%. The lack of palpable pedal pulses strongly suggests the presence of PAD. However, the presence of a palpable pulse does not exclude PAD as collateral blood flow can give rise to a palpable distal pulse.⁶ If pedal pulses are nonpalpable, there would be a need for further workup with noninvasive or invasive assessment based on the clinical presentation. Expansile and palpable masses in the femoral and popliteal arterial regions should raise the suspicion for aneurysms. Capillary filling time is assessed by squeezing the great toe to cause the skin to blanch and then letting go to see how long it takes for the skin to regain its original color. A capillary filling time of greater than 5 seconds is considered prolonged. Feet and nails should be examined thoroughly for any calluses, discoloration, gangrenous changes, ulceration, and infections. The presence of the above should warrant an immediate assessment of the arterial circulation to the lower extremity. Consultation with a vascular specialist is recommended. It is important to understand that a large proportion of PAD patients are asymptomatic. Strict foot care is very important, especially so in diabetics, as they are prone to develop gangrene and eventually amputation.

Screening recommended per American Heart Association (AHA) as a screening initiative⁷ recommends ankle-brachial index (ABI) in asymptomatic individuals who are:

Table 9-1. Site of Pain to Presumed Level of Obstruction

Site of pain	Presumed level of obstruction
Buttock and hip	Aortoiliac artery disease
Impotence	Bilateral aortoiliac artery disease (Leriche)
Thigh	Common femoral or aortoiliac artery disease
Upper two-thirds of calf	Superficial femoral artery
Lower one-third of calf	Popliteal artery disease
Foot claudication	Tibial or Peroneal artery disease

Older than 50 years of age with a history of diabetes mellitus or smoking
Anyone older than 65 years of age

Classification of Pad Patients

There are two types of classification that are accepted internationally to clinically categorize the PAD patients.

The Fontaine classification, introduced by René Fontaine in 1954 for chronic limb ischemia,⁸ is based on symptoms and walking distance:

Stage I: Asymptomatic

Stage II: Mild claudication

Stage IIA: Claudication distance of greater than 200 meters

Stage IIB: Claudication distance of less than 200 meters

Stage III: Rest pain, mostly in the feet

Stage IV: Necrosis and/or gangrene of the limb

The more recent classification by Rutherford consists of four grades and seven categories⁹ based on symptom alone:

Grade 0, Category 0: Asymptomatic

Grade I,

Category 1: Mild claudication

Category 2: Moderate claudication

Category 3: Severe claudication

Grade II, Category 4: Rest pain

Grade III, Category 5: Minor tissue loss, ischemic ulceration not exceeding ulcer of the digits of the foot

Grade IV, Category 6: Major tissue loss, severe ischemic ulcers or frank gangrene

Other Pad Disorders

Two diseases need special mention because of their unique presentation and characteristics. Leriche syndrome is an atherosclerotic occlusive disease involving the abdominal aortic bifurcation and may extend into both the common iliacs. It is recognized with intermittent thigh claudication and impotence from hypogastric artery occlusion with decreased flow to the pudendal artery. Distal pulses are usually diminished. Any tissue loss implies distal disease, except in case of
“blue toe” syndrome where multiple toes are involved from embolization of the iliac plaque. Blue toe is also associated with aortic aneurysms. Angioplasty is the treatment of choice.

The other one is Berger syndrome, which is also known as thromboangiitis obliterans. This inflammatory disease involves the small and medium arteries as well as the veins. The histopathology is characterized by inflammatory tissue, thrombus, and microabscess. It is distinctively seen in male smokers. Typically, the pedal pulses are not palpable.

As mentioned earlier, most of the PAD population do not have any signs or symptoms. Thus, screening and having a low threshold to perform noninvasive testing are of critical importance.

Vasculitis of the Lower Extremities

Vasculitis is inflammatory systemic or local syndromes, which is the result of autoimmune-mediated inflammation of the blood vessels. There are several types, and a significant proportion of the syndromes involve the lower extremity arteries. They are known to present with systemic symptoms such as fever, weight loss, fatigue, malaise, and constellation of symptoms, depending on which organs are involved. On physical examination, rash, nodules, ulcers, and gangrenous changes of upper and lower extremities can be identified. When there is a concern for vasculitis, an immediate consultation to a vascular specialist is warranted.

Diagnostic Tools

In this current era, there are multiple noninvasive tools and techniques available to diagnose PAD. They can be as simple as the ABI to a sophisticated magnetic resonance arteriography. It is important to understand the pros and cons of these tests, as a combination of these investigations may be used in the PAD population. Essentially, the testing is individualized to the patients. Nevertheless, ABI remains the first choice of investigation in screening as well as in diagnosing PAD.

Ankle-brachial Index

ABI = Highest SBP in ankle (dorsalis pedis and posterior tibial arteries)/highest SBP in upper arm (brachial artery)

This test has 95% sensitivity and 99% specificity to detect PAD. An ABI ≤ 0.90 is diagnostic of PAD. Depending on the ABI values, we can assess the severity of PAD. It is also used to follow patients subsequent to their endovascular or surgical intervention. Finally, ABI is an independent multivariate predictor of cardiovascular and cerebrovascular mortality (Table 9-2).

Alternate ABI is a variant of the standard ABI, which is derived by dividing the lowest SBP of the ankle (either dorsalis pedis or posterior tibial) by the highest SBP of the upper arm. An abnormal ABI by this method implies that there is an isolated tibial artery disease, which is not identified by the standard ABI as it uses the higher SBP of the two tibial vessels. It is important to acknowledge that both these forms of ABIs can impact on your cardiovascular morbidity and mortality.¹⁰ Segmental BP and pulse volume recordings (PVRs) may be useful for localizing the vascular lesions in the lower extremities, and are most useful in patients who have abnormal ABI scores at rest. Thus, they help in determining the level and extent of disease. The patient is placed in a supine position and standard size BP cuffs are placed at several segments of the lower extremity. The reference BP cuff is placed at the arm level. In the three-cuff technique, there is one cuff above and below the knee and at the ankle level. In the four-cuff technique, two narrower BP cuffs are placed at the thigh level (this helps in the differentiation between aortoiliac and superficial femoral artery [SFA] disease). A 20 mm Hg or greater reduction in SBP between two segments is indicative of a flow-limiting lesion. It is important to note that well-developed collaterals can diminish the gradients. In hypertensive patients, the gradients may falsely increase, and in low cardiac output states, the gradients may falsely decrease.

Table 9-2. Interpretation of ABIs

≥0.9-1.4	Normal
>1.4	Calcified vessels, which prompts further studies
≤0.9	Diagnostic for occlusive arterial disease
0.4-0.9	Suggests arterial obstruction associated with claudication (mild to moderate)
<0.4	Multilevel disease (any combination of iliac, femoral, or tibial vessel disease), associated with nonhealing ulcers, ischemic rest pain, pedal gangrene

PVR may be especially useful in diabetic patients with noncompressible arteries as it is less affected by medial calcinosis than segmental BP recording. PVR detects changes in blood volume in the lower extremities and not the pressures. A normal PVR waveform is composed of a systolic upstroke with a sharp systolic peak followed by a downstroke that contains a prominent dicrotic notch. In calcified arteries, BPs are falsely elevated (as they are not compressible by the BP cuff) and thus can have normal ABIs and segmental pressures. Thus, the PVR becomes a valuable tool in detecting obstructive PAD in such calcified arteries. Mild to moderate disease is characterized by loss of the dicrotic notch and an outward “bowing” of the downstroke of the waveform. In severe disease, the amplitude of waveform is blunted (Fig. 9-1). As previously mentioned, calcification of the arteries can result in a falsely normal ankle-brachial pressure index. In addition to PVR, toe-brachial index (TBI) can be used to assess significant obstructive PAD as the smaller pedal arteries are relatively free from calcinosis. This is done by placing a pneumatic cuff on one toe (usually the great toe) and a photoelectrode on the tip of the toe to obtain a photoplethysmographic (PPG)
signal using infrared light (an arterial waveform is created from these signals). The signal is proportional to the quantity of red blood cells in the cutaneous circulation. The toe cuff is inflated until the PPG waveform flattens and then the cuff is deflated. The systolic pressure is recorded when the waveform reestablishes. Pressure gradient of 20 to 30 mm Hg normally exists between the ankle and toe. Normal TBI values are 0.7 to 0.8. A toe pressure of >30 mm Hg is required for general wound healing. In diabetics, toe pressures >50 mm Hg are needed for better wound healing (as they have capillary dysfunction and thus need greater perfusion pressures to overcome this dysfunction). Patients with aortoiliac disease can have normal resting ABIs, but with exercise their ABIs fall to abnormal levels. Hence, exercise stress testing can increase the sensitivity of detecting obstructive PAD. In fact, every ambulatory patient should undergo rest and exercise ABIs. Normally, with exercise the perfusion pressures increase to the lower extremities. The two most commonly used exercise protocols are as follows: one involves walking on a treadmill at a constant speed with no change in incline and the other protocol involves walking on a treadmill at 2 mph at 12% incline for at least 5 minutes or until the symptoms are reproduced. The walking distance and time of onset of pain or symptoms are recorded. The ABIs are done at rest, 1 minute after exercise, and every minute thereafter (up to 5 minutes). The normal response is a slight increase or no change in ABI. The fall in ankle systolic pressure by more than 20% from baseline or below absolute 60 mm Hg that requires more than 3 minutes to recover is abnormal. Those patients whose postexercise systolic ankle pressure drops below 50 mm Hg have severe claudication and potentially multivessel or inflow disease. Also, with exercise, the gradients across stenotic lesions worsen. Patients with occlusive internal iliac disease present with typical buttock claudication and can have normal resting and exercise ABIs. Such patients should undergo computed tomography angiography (CTA) or invasive angiography to delineate the disease and undergo treatment if warranted. Transcutaneous oxygen tension measurement (TcPO₂) is a noninvasive diagnostic study, which measures the partial pressure of oxygen at the skin surface. The electrode element has a heating element that raises the temperature of the underlying tissue and results in an increase in capillary flow and partial pressure of oxygen. This then results in diffusion of oxygen through the skin, which can be measured by the electrode. It is important to remember that this device measures the underlying oxygen tension in the tissue and not the arterial oxygen tension. As long as hemodynamic conditions are stable, transcutaneous measurements can be used as a surrogate of arterial oxygen tension. In simple words, this test quantifies the oxygen delivered to the microvascular tissue. Importantly, they have a prognostic value in predicting wound healing.¹¹

FIGURE 9-1. Pulse volume recording.

Ultrasonography

Ultrasonography comprises B-mode imaging, pulse wave Doppler, continuous wave Doppler, and color Doppler. They are helpful in understanding the underlying anatomy, hemodynamics, and lesion morphology. It is cost-effective and can be done in an office setting. They are extremely useful in diagnosing obstructive PAD, localizing the stenosis, quantifying the severity of the disease, and assessing the patency of stents, grafts, and other interventions.¹² Hence, they are recommended in the surveillance period postendovascular and surgical interventions. B-mode ultrasonography with the help of color Doppler provides information on the anatomy of the lesion and also the morphology of the atherosclerotic plaque. Duplex ultrasonography helps in the accurate assessment of the severity of stenosis using pulsed and continuous Doppler techniques. Therefore, Duplex ultrasonography is a very important tool in following up patients who have undergone endovascular and surgical interventions. They help in the early recognition of restenosis.¹³

Computed Tomography Angiography and Magnetic Resonance Angiography

In recent years, the use of CT and magnetic resonance angiography (MRA) in the evaluation of PAD has increased. However, this varies from institution to institution, as it is highly dependent on the resources and the expertise available to perform these tests and interpret them. CTA has a sensitivity and specificity greater than 95% for identifying significant stenotic lesions.¹⁴,¹⁵ MRA acquired with contrast (gadolinium) produces high-resolution images of the infrapopliteal vessels. MRA has a sensitivity of 90% and a specificity of 97% for identifying significant stenotic lesions.¹⁶ CTA is associated with the risks seen with contrast and radiation exposure. The MRA test done with gadolinium contrast carries the risk of nephrogenic systemic fibrosis (especially so in patients with chronic kidney disease). It is important to note that the presence of metallic implants, calcified lesions, and total occlusions results in distorted images and artifacts with CT and MRI.

Only gold members can continue reading. Log In or Register to continue