In the event of chronic obstruction of major arterial vessels, collateral pathways exist that allow preservation of sufficient distal blood flow to maintain viability of the tissues distally. The degree of adequacy of these pathways determines what degree of functional disability results.

With obstruction at the level of the distal aorta and common iliac arteries, a variety of pathways for collateral circulation exist (Fig. 21.2). Communications may exist between the lumbar and circumflex iliac or hypogastric arteries. Other communications may exist between the gluteal branches of the hypogastric arteries and recurrent branches of the common femoral or profunda femoris arteries. Visceral–parietal communications may also exist at this level between the inferior mesenteric and internal iliac vessels via hemorrhoidal branches at the level of the rectum.

More distally, with obstruction of the common femoral artery, collateral circulation around the hip is provided via communication of the inferior epigastric and deep circumflex branches of the external iliac arteries with the internal pudendal and obturator branches of the internal iliac arteries (Fig. 21.2b).

With chronic obstruction of the superficial femoral artery, collateral circulation to the popliteal artery is provided by communications with the profunda femoris artery via the geniculate arteries, as well as descending branches of the lateral femoral circumflex arteries. With popliteal occlusion, it is these geniculate arteries that are responsible for the filling of the more distal tibial vessels as well (Fig. 21.2). More distally, branches of the peroneal, anterior tibial, and posterior tibial arteries all provide collateral supply to the plantar arch vessels [1, 2].

The intima, the innermost layer, consists of a layer of endothelium that lines the luminal surface and overlies one or more layers of smooth muscle. These are then covered by a layer of connective tissue known as the internal elastic lamina.

Just beyond the internal elastic lamina begins the media, which is bounded by the internal and external elastic lamina. The media is composed of smooth muscle cells arranged in layers and lying in a matrix of proteoglycan substance. Collagen and elastin fibers are also present within this layer.

The adventitia is the outermost layer of the arterial wall and the layer responsible for the majority of the vessel’s strength. It is composed of connective tissue, fibroblasts, capillaries, neural fibers, and occasional leukocytes. In large vessels a microvasculature known as the vasa vasorum is present within the adventitial layer, serving to nourish the adventitia and outermost layers of the media [3].

The overall prevalence of peripheral arterial disease (PAD) based on objective data has been evaluated in several epidemiological studies [4–6] and has been demonstrated to be a global problem with the number of people with PAD increased by 23.5% from the year 2000 to 2010 [6]. The prevalence of PAD increases with age in the range of 3–10%, in the general population which increases to 10–20% in people over the age of 70 years [4–6]. Peripheral arterial disease affects up to one in six individuals older than 80 years old [6]. The prevalence of asymptomatic PAD of the lower extremity can only be estimated using noninvasive vascular testing in the general population with the ankle-brachial index (ABI) being the most widely used testing. A resting ABI of ≤0.9 is generally caused by hemodynamically significant arterial stenosis and most often is used as a hemodynamic definition of PAD. This definition in symptomatic individuals (ABI ≤0.9) is 95% sensitive in detecting PAD confirmed by angiography and 100% specific in identifying healthy individuals [4]. The PARTNERS (PAD Awareness, Risk, and Treatment: New Resources for Survival) study, which screened 6979 patients for PAD who were aged 70 years or older or aged 50 through 69 years with history of cigarette smoking or diabetes using an ABI of ≤0.9 or a prior history of lower extremity revascularization, reported the presence of PAD in 29% of the total population [7]. Classic vascular claudication was present in 5.5% of the newly diagnosed patients with PAD versus 12.6% of patients with a prior diagnosis of PAD [7].

The prevalence of symptomatic PAD, i.e., intermittent claudication, would appear to increase from about 3% in patients aged 40 to 6% in patients aged 60 years. Several large population studies have analyzed the prevalence of intermittent claudication as noted in Fig. 21.3. As noted in this figure, the prevalence in patients between 30 and 34 years is less than 1%, which increases to approximately 7% for patients between 70 and 74 years. It has also been reported that in relatively younger age groups, claudication is more common in men, but at an older age, there is little difference between men and women. It has also been reported that black ethnicity increases the risk of PAD by over twofold, which cannot be explained by a higher level of other risk factors for PAD [4].

Through epidemiologic data, a number of risk factors for the development of atherosclerosis have been reasonably well established. These factors include hypertension, hypercholesterolemia, cigarette smoking, obesity, diabetes mellitus, stress, sedentary lifestyle, and family history.

Pooling evidence from available studies, the Transatlantic Intersociety Consensus (TASC) concluded that approximately 60% of patients with peripheral arterial disease have significant coronary artery disease , cerebrovascular disease , or both, whereas about 40% of those with coronary artery or cerebrovascular disease also have peripheral arterial disease [21]. Murabito et al. [22] reported that the diagnosis of concomitant coronary artery disease can be established with a clinical history, physical examination, and EKG in 40–60% of all patients with intermittent claudication. The 4-year risk of myocardial infarction for a patient with intermittent claudication is 6.6% and ranges from 9.4–10.9% for a patient with critical limb ischemia [23]. Also concerning is that the 4-year risk of ischemic stroke in a patient with PAD is 5.4% for a patient with intermittent claudication and ranges from 7.4%–9.1% for a patient with critical limb ischemia [23].

Vascular hemodynamics are described in Chap. 5. Atherosclerotic occlusive disease primarily affects circulatory flow through energy losses at fixed arterial stenoses . The reasons for this arise from knowledge of the physical properties of blood as a fluid. As blood flow enters an area of stenosis, its velocity increases across the stenosis to maintain constant flow. Energy is then lost with the change in velocity at both the entry to and exit from the stenotic area. The greater the degree of stenosis, the more severe the change in velocity and thus the greater the energy loss will be. In general, flow studies have demonstrated that significant changes in flow and velocity do not occur until the degree of stenosis approaches 50%, which in turn corresponds to an area reduction of approximately 75%. This is termed critical stenosis.

It is important to remember, however, that resistances in series are additive; thus multiple subcritical stenoses in series can produce significant hemodynamic changes and result in marked impairment of distal flow [40, 41].

The clinical manifestations of lower extremity atherosclerotic occlusive disease occur along a well-defined spectrum of severity, ranging from asymptomatic to intermittent claudication to the observation of trophic changes in critical limb ischemia suggesting impending limb loss.

Claudication is defined as pain (or discomfort) produced with brisk use of an extremity and relieved with rest. We have also observed that the location of the discomfort is typically experienced one joint distal to the stenotic area. For example, disease involving the superficial femoral artery manifests itself via calf claudication. Blood flow is adequate in the resting state; thus pain occurs only when the increased metabolic demand created by exercising muscle exceeds the supply available due to the degree of fixed arterial obstruction [42]. Aside from diminished distal pulses, significant physical findings are usually absent at this stage.

The differential diagnosis of intermittent claudication should include other conditions, which may be neurologic or musculoskeletal in origin. Calf pseudoclaudication can be caused by venous claudication, chronic compartment syndrome, Baker’s cyst, and nerve root compression. The tight bursting pain of compartment syndrome is generally typical, and venous claudication is relieved by leg elevation. Hip or buttock claudication should be differentiated from pain related to hip arthritis and spinal cord compression. The persistent aching pain caused by variable amounts of exercise and associated symptoms in other joints may distinguish arthritis from claudication. Patients with spinal cord compression frequently present with a history of back pain and have symptoms on standing, but require a change in position as well as rest to obtain relief. Foot claudication should be distinguished from other causes and can be related to arthritis or inflammatory processes.

Ischemic rest pain develops when the degree of circulatory impairment progresses to the point at which the blood supply is inadequate to meet the metabolic demand of the muscle even in the resting state. Frequently, the pain increases during periods of lower extremity elevation (lying in a bed) and is relieved with dependency. Physical findings at this stage typically include decreased skin temperature and delayed capillary refill, as well as Buerger’s signs (dependent rubor and pallor on elevation). Often patients can have neuropathic pain from diabetic neuropathy, and this too needs to be distinguished from ischemic rest pain with some patients having a combination of both.

Trophic changes represent the most severe manifestations of chronically impaired lower extremity circulation. In this stage of the disease, the lower extremity displays actual changes related to ischemia that are visible to the naked eye. These changes range from subtle signs such as dependent rubor, atrophy of skin and muscle, and loss of hair or nail substance to frank ulceration, cyanosis, and gangrene. The presence of trophic changes is suggestive of impending limb loss and necessitates urgent intervention for limb salvage to be possible [43].

Several studies over the past 40 years have concluded that approximately 75% of all patients with claudication experience symptom stabilization or improvement over their lifetime without the need for any intervention [43, 44]. This clinical improvement or stabilization holds true, despite arteriographic evidence for disease progression in most of these patients. In 25% of claudicant patients, symptoms worsen, particularly during the first year, in approximately 8%, and subsequently at the rate of 2–3% per year. It has been estimated that around 5% of these patients will undergo an intervention within 5 years of their initial diagnosis. Several large studies estimate that 2–4% of these patients will require a major amputation [45, 46]. Diabetes and smoking are the most significant primary risk factors for disease progression and higher intervention and amputation rates. Dormandy and Murray [47] concluded that an ABI of 0.5 on initial diagnosis was the most significant predictor for peripheral arterial disease deterioration requiring intervention. They also observed that men were at higher risk for disease progression than women. Other studies have confirmed that the presence of peripheral arterial disease significantly increased the risk of myocardial infarction, stroke, ischemia of splanchnic organs, and the risk of cardiovascular death. Criqui et al. [48] noted a relative risk of 3.3 for total mortality and a relative risk of 5.8 for coronary artery disease mortality in men with peripheral arterial disease over a 10-year study. They also noted a twofold higher relative risk of a total, coronary, and cardiovascular mortality in symptomatic versus asymptomatic peripheral artery disease patients. It has been estimated that the average life expectancy of patients with intermittent claudication was decreased by about 10 years [44]. A review of over 20 studies by TASC places the 5-, 10-, and 15-year mortality rate for patients with intermittent claudication at 30%, 50%, and 70%, respectively [21].

Determination of the ABI has proven to be a powerful clinical tool. An ABI of <0.5 has been associated with more severe coronary artery disease and increased mortality [49]. It has been demonstrated that patients with an ABI of <0.3 had a significantly lower survival rate than those with a range of 0.31–0.9 [49].

Sheikh et al. reported on the usefulness of post-exercise ABI to predict all-cause mortality. They conducted an observational study of consecutive patients referred for ABI measurement before and after fixed-grade treadmill or symptom-limited exercise component to a noninvasive vascular laboratory during a 10-year period. The patients were classified into two groups: Group 1 included patients with an ABI of ≥0.85 before and after exercise, and Group 2 included patients with a normal ABI at rest, but <0.85 after exercise. A total of 6292 patients were analyzed. The 10-year mortality rate for Groups 1 and 2 was 33% and 41%, respectively. An abnormal post-exercise ABI result independently predicted mortality (a hazard ratio of 1.3, p = 0.008). Additional independent predictors of mortality were age, male gender, hypertension, and diabetes. After the exclusion of patients with a history of cardiovascular events, the predictive value of an abnormal post-exercise ABI remained statistically significant (a hazard ratio of 1.67, p < 0.0001). They concluded that the post-exercise ABI was a powerful independent predictor of all-cause mortality and provides additional risk stratification beyond resting ABI [50].

Aboyans et al. assessed the general prognosis of patients with PAD according to the disease location in 400 patients. Aortoiliac disease (proximal PAD) and infrailiac disease (distal PAD) were noted in 211 (53%) and 344 (86%) cases, respectively. Male sex and smoking were prevalent in proximal PAD, whereas an older age, hypertension, diabetes, and renal failure were more prevalent in distal PAD (p < 0.05). At a mean follow-up of 32 months, the event-free survival curves differed according to the PAD localization (p < 0.03). Adjusted for sex, age, cardiovascular disease history, cardiovascular disease risk factors, critical leg ischemia status, and treatment, proximal PAD was significantly associated with a worse prognosis (primary outcome hazard 3.28; death hazard ratio 3.18; p < 0.002) versus distal PAD. This was the first study to report a poorer general prognosis for patients with proximal aortoiliac disease compared to those with more distal disease [51].

After the initial diagnosis of chronic lower extremity ischemia is made, it is important to stage the severity of the disease process accurately. This is crucial because it is the stage of the disease and the natural history of each stage that ultimately determines which therapy is most appropriate.

The most common staging system used by vascular surgeons today is that devised by the Society of Vascular Surgery and the International Society of Cardiovascular Surgery SVS/ISCVS). Rutherford et al. [52] defined peripheral arterial disease into Grade and Categories defined as asymptomatic (Grade 0 and Category 0); claudication as mild, moderate, and severe (Grade I and Categories 1–3); ischemic rest pain (Grade II and Category 4); and tissue loss (Grade III and Categories 5 and 6). See Table 21.1 for details. Critical limb ischemia encompasses Grades II and III and Categories 4–6. Rutherford’s classification is presently the recommended standard when describing clinical assessment and progress [21]. The other classification that is used by our medical colleagues is the Fontaine classification. In this classification, the stages of the disease are categorized into Stages I–IV (Stage I corresponds to Grade 0 and Category 0 in Rutherford’s classification, and Stage IV corresponds to Grade III and Categories 5 and 6 in Rutherford’s classification).

A variety of noninvasive tests are available for assessment of the lower extremity vascular system. These are discussed in detail in subsequent chapters.

Perhaps the most useful bedside noninvasive test available to the clinician is the ABI. This test may be performed with only a sphygmomanometer and a Doppler probe. To perform the test, Doppler systolic pressure measurements are taken at the level of the ankle (use the higher of posterior tibial or dorsalis pedis artery pressure) and compared with those in the brachial artery (both upper extremity pressures should be measured and the highest used) as follows:

A ratio of less than or equal to 0.9 is abnormal. Generally, patients with claudication have indices of 0.5–0.8, whereas those with rest pain have indices of 0.5 or less. When trophic changes are present, the ABI is frequently less than 0.3 [57].

In general, noninvasive testing should precede the ordering of any more invasive evaluations.

Noninvasive vascular tests help the physician to evaluate the presence or absence of significant arterial occlusive disease, severity of disease, location of disease, and in the presence of multi-segmental disease, which arterial segment is mostly affected.

General indications for obtaining noninvasive assessment of the peripheral arterial system include absence of normal pulses, suboptimal examiner reliability or experience, a clinical history or examination potentially consistent with peripheral arterial occlusive disease, and a planned vascular procedure.

Several noninvasive diagnostic techniques have been used in the diagnosis of peripheral arterial disease: continuous-wave (CW) Doppler ultrasound, pulsed Doppler ultrasound, B-mode ultrasound, various plethysmographic techniques, including pulse volume recording, thermography, electromagnetic flowmeter, radionuclide angiography, and the use of radioisotopes. The most commonly used methods for diagnosis of peripheral arterial disease of the lower extremity at present are segmental Doppler pressures (with or without Doppler wave analysis) using CW Doppler, pulse volume recording, and duplex ultrasonography [58–62]. These three commonly used methods will be described in detail in the next chapters.