html xmlns=”http://www.w3.org/1999/xhtml” xmlns:mml=”http://www.w3.org/1998/Math/MathML” xmlns:epub=”http://www.idpf.org/2007/ops”>
Introduction
“Peripheral arterial disease” (PAD) is a term that encompasses atherosclerotic, aneurysmal and thromboembolic diseases of the peripheral arteries. As the term generally refers to a range of arterial disorders, for the purpose of this chapter, the authors have chosen to focus on atherosclerotic diseases of the abdominal aorta, trunk, and lower extremity arteries. Lower extremity PAD is caused by atherosclerosis of the underlying arteries (excluding coronary and cerebral), resulting in a narrowing or complete occlusion of these vessels and consequent reduction in blood flow to the extremities. In most people PAD is asymptomatic, and thus commonly remains undetected; however, others may experience pain with activity (known as intermittent claudication), thereby limiting walking ability and physical activity levels. Therefore, the clinical sequelae of symptomatic disease can be devastating. PAD is associated with reduced cardiorespiratory fitness, sarcopenia,[1, 2] impaired lower extremity functioning,[2, 4] and reduced quality of life (QOL),[5] as well as increased risk of morbidity and mortality.[6] In addition to the morbidity directly associated with PAD, persons with PAD have an increased risk of coexisting coronary and cerebrovascular disease due to reduced activity levels. In fact, a diagnosis of PAD is critical evidence of more widespread cardiovascular disease (CVD) with substantially increased risk of subsequent CVD events and mortality.[6]
Being an atherosclerotic disease, PAD shares similar risk factors to cerebrovascular and coronary artery disease. Traditional risk factors include increasing age, cigarette smoking,[7, 8] hypertension,[9] dyslipidaemia,[9] diabetes,[9] and physical inactivity,[10] with emerging risk factors including elevated homocysteine, lipoprotein A, fibrinogen, and c-reactive protein levels.[11] Cigarette smoking, however, is still one of the strongest contributing risk factors with some epidemiological studies reporting that smoking increases the risk of developing PAD up to six times.[12] Recent research has shown that both men and women with PAD have greater long-term risks of cardiovascular and all-cause mortality when compared to those with a history of myocardial infarction alone, with recommendations that PAD should be considered a coronary artery disease equivalent.[13] However, even though the incidence and prevalence of PAD is rising, it largely remains underdiagnosed and undertreated.[14] With its presence being linked to a number of other significant health conditions and due to the asymptomatic nature of the disease, recent recommendations have been made of screening for and early detection of PAD in adults with the use of the ankle brachial pressure index (ABI).[15] The ABI is a PAD specific diagnostic tool that compares ankle pressures to brachial pressures and is explained in more detail later in this chapter. It has been recently recommended to be used as a screening tool in patients at increased risk of the disease, which includes all adults over the age of 65 years.[16] For prevention of disease progression, early identification is vital and may in fact improve the health, quality of life, morbidity, and mortality of elderly populations.
Epidemiology
Atherosclerotic PAD affects up to 8.5 million (one in sixteen, or 7.2%) Americans aged ≥40 years.[17] Prevalence increases exponentially across age groups,[17] with approximately 12%–20% of individuals older than 60 years having PAD.[18] PAD is associated with significant morbidity and mortality, with prevalence higher in older individuals and black race/ethnicity.[17] Historically, PAD has been known to affect men, more so than women. However, while most studies suggest that the prevalence of PAD is now similar in men and women,[19, 20] a recent epidemiological study reported a higher prevalence of PAD among women.[20] Non-Hispanic whites contributed the most individuals to the total prevalence, however, among older ages, the prevalence rate for African Americans was two to three times higher.[17] This same study concluded that people of Hispanic origin may have similar to slightly higher rates of PAD compared to non-Hispanic whites.[17]
Among the general population, approximately 10% of people with PAD have the classic symptom of intermittent claudication. Approximately 40% are asymptomatic, and the remaining 50% experience a variety of leg symptoms different from the classic intermittent claudication.[4, 21] Data from NHANES 1999–2002 suggests that up to one-quarter of adults have severe PAD (ABI ≤0.7).[22] Data from a 2006 systematic review found that PAD (defined by ABI ≤0.9) is a marker for systemic atherosclerosis,[23] further supporting the notion that a diagnosis of PAD is critical evidence of more widespread cardiovascular disease (CVD) with substantially increased risk of subsequent CVD events and mortality.[6] A further meta-analysis conducted in 2008 on up to 49,000 people reported an association between ABI and mortality where persons with an ABI of between 1.11 and 1.40 are at lowest risk of mortality. A low ABI of ≤0.9 carried a threefold risk of all-cause death compared to persons with a normal ABI of between 1.11 and 1.40.[24]
In addition, further studies identified that a decline in ABI of >0.15 within a 10-year period was associated with a subsequent 2.4-fold increased risk in all-cause mortality and 2.8-fold increased risk of CVD mortality.[25]
Lower limb atherosclerosis usually manifests at different levels, however, may also be restricted to a particular region. Typically it is classified as either “proximal” or “distal.” Proximal usually refers to the aortoiliac arteries,[26] with distal involving only the femoropopliteal and/or tibial vessels.[27] One further classification known as multilevel disease includes atherosclerotic lesions of both proximal and distal arteries.[27] One study found that among 440 patients with PAD, male sex and smoking were associated more with proximal rather than distal disease and proximal disease was associated with a threefold increased risk of mortality.[28]
Pathophysiology
PAD is characterized by stenosis or occlusion of the lower limb arteries, leading to a reduction in blood flow capacity. Although arterial obstruction may occasionally result from conditions such as fibromuscular dysplasia, Buerger’s disease, or arteritis, PAD is most commonly a manifestation of atherosclerosis – the same underlying disease process that is responsible for coronary and cerebrovascular disease. Atherosclerosis is initiated by injury or irritation of the vessel walls, which results in a chronic, systemic inflammatory process leading to the development of arterial wall lesions, the accumulation of lipid deposits and the gradual formation of fibrous atherosclerotic plaques.[29] These plaques protrude into the lumen of the vessel causing a chronic impairment in blood flow capacity. Furthermore, unstable plaques may ulcerate and cause thrombotic occlusion or embolization.[30] Arterial lesions most commonly develop in regions of low shear stress and turbulent flow, including the proximal regions of the aorto-iliac and femoro-popliteal segments, and there is some evidence that distal lesions are more common in older patients.[31] Atherosclerosis and the presence of PAD is associated with vascular endothelial dysfunction and a limited capacity for arterial vasodilation, which may further exacerbate the blood flow impairment to the lower limbs and contribute to the elevated cardiovascular risk of PAD patients.[32]
Risk factors
PAD has a risk factor profile similar to those associated with coronary artery disease. Traditional risk factors include age, diabetes, smoking, hypertension, and hyperlipidemia.[19] Past studies have shown chronic kidney disease,[33] hyperhomocystinemia,[34] elevated fibrinogen concentration,[35] and certain ethnic backgrounds [17] as also contributing to the development of PAD. A more recent study has highlighted more nontraditional biomarkers of elevated risk including soluble intercellular adhesion molecule-1, high sensitivity C-reactive protein, high-density lipoprotein cholesterol (HDL-C) and the ratio of total cholesterol to HDL-C being significantly associated with incident symptomatic PAD in women.[11] Cigarette smoking, both tobacco and marijuana, is the most modifiable risk factor for the development of PAD, whereas age is the most significant nonmodifiable risk factor, with prevalence increasing exponentially across the age groups reaching approximately 20% of persons older than 60 years.[18] Many studies have shown that the distribution, extent and progression of PAD are influenced by CVD risk factors but the findings are inconsistent among certain risk factors.[31] However, most studies tend to suggest that smoking related PAD predominantly affects the proximal arteries, with diabetes predominantly affecting the distal arteries.[31] A recent “call to action” from the AHA association highlighted the increasing prevalence of PAD among women, with data from the 2010 US census showing that there were more women than men with PAD among US adults ≥40 years of age.[36]
Clinical presentation
PAD is associated with a wide range of symptoms and presentations. Symptoms will depend on the size and location of the affected artery (Table 14.1). PAD is typically asymptomatic in its early stages; however, as the disease develops the most commonly recognized/reported symptom is intermittent claudication, meaning “to limp,” which has historically been described as a cramplike pain in the muscles of the calf. This pain is “intermittent” in nature in that it reproducibly appears with exertion (e.g., during walking), dissipates quickly with rest, and does not dissipate if exertion continues.[37] It is now recognized that exertional symptoms may be more varied and include tingling, numbness, burning, throbbing or shooting-pain; and symptoms may present in other regions of the limb such as the buttocks, thighs, and feet.[38] With proximal aortoiliac disease, thigh, hip, or buttock claudication may develop with activity and will usually precede calf pain. More distal disease may cause calf, ankle or foot pain while walking. Intermittent claudication tends to be more frequently reported in those with distal lesions.[28] Buttock and thigh pain seem to be more commonly present with proximal lesions, whereas calf pain is more common with distal lesions; however, patients may still report pain at a variety of levels throughout their legs, regardless of the location of the lesion.[28] Many older patients with PAD may present as being asymptomatic because their lower physical activity levels are below the threshold that induces symptoms.[39]
| Location of lesion | Frequency of involvement | Common location of symptoms |
|---|---|---|
| Aortoiliac arteries | 25%–30% | Hips and buttocks, thigh, calf |
| Superficial femoral artery, deep femoral artery, popliteal artery | 80%–90% | Thigh, calf |
| Tibial artery, peroneal artery | 40%–50% | Calf, shin, ankle/foot |
More severe disease with greater hemodynamic impairment is associated with critical limb ischemia (CLI), which manifests as rest pain, or tissue loss through ulceration or gangrene (tissue necrosis). Rest pain commonly affects the feet or toes, usually when the patient is lying down, and patients may find relief by placing the limb in a dependent position. The term “CLI” is used to describe chronic symptoms that have been present for more than two weeks,[19] which distinguishes it from acute limb ischemia where there is a sudden reduction in limb perfusion. The symptoms of PAD, from asymptomatic through to major tissue loss as a result of gangrene, may be classified according to Fontaine or Rutherford categorization systems.[19]
Screening, diagnosis, and investigation
A number of methods are available to investigate PAD and determining which methods are most appropriate depends on a number of factors including the setting the test is being applied in (screening, diagnosis or investigation), the intention of the investigating physician (medical or interventional management) and the comorbidities of the patients (e.g., renal impairment increases the risk of contrast requiring imaging).[40–42] In elderly subjects comorbidities are common, which may impact in a number of ways. Firstly, the concurrent presence of respiratory, cardiac, joint, or other musculoskeletal problems, common in elderly patients, may complicate the diagnosis since patients may not be able to ambulate adequately to appreciate classical symptoms of PAD. Secondly, patients may be unable to complete or are at increased risk with some investigations, such as treadmill tests or imaging tests requiring contrast. Thirdly, the interpretation of investigations maybe more complex, for example peripheral artery calcification may obscure imaging or provide falsely elevated ankle pressures. The following section describes the more commonly employed investigations in clinical practice although others such as questionnaires (e.g., the Edinburgh Claudication Questionnaire) were previously used in diagnosis or screening but are now thought to be too inaccurate due to the realization that many patients with PAD are asymptomatic or have atypical symptoms.[43]
The main objective diagnostic criteria used for PAD is based on the measurement of ankle brachial pressure index (ABI),[40–43] with cut-offs and classifications presented in Table 14.2. ABI assessment involves insonating the Doppler signals in the dorsalis pedis and posterior tibial arteries in both feet and assessing the calf cuff pressure required to obliterate these signals. The higher of the two pedal pressures in each foot is divided by the similarly measured highest brachial pressure and reported as the ABI separately for each foot.
| Ankle Brachial Index | Classification |
|---|---|
| >1.40 | Noncompressible arteries |
| 1.00–1.40 | Normal range |
| 0.91–0.99 | Borderline PAD |
| 0.71–0.90 | Mild PAD |
| 0.41–0.70 | Moderate PAD |
| <0.41 | Severe PAD |
Updates to the diagnosis criteria used is a resting ABI between 1.00 to 1.40 as normal range;[40–43] with abnormal values defined as those ≤0.90. ABI values of 0.91 to 0.99 are considered “borderline” and values ≥1.40 indicate non compressible arteries.[10,16] Some patients with PAD may have resting ABI of 0.9 or greater either because the lower limb atherothrombosis is not hemodynamically significant or because it only becomes relevant during exercise. In the later instance assessment of ABI after a treadmill test may identify an appreciable (≈15%) fall in ankle pressure. ABI readings can be falsely elevated, typically >1.4 or incompressible, in patients with very calcified tibial arteries, sometimes found in subjects with renal failure or diabetes which are common comorbidities in the elderly. ABI readings have values beyond simple diagnosis of PAD since they provide a guide to the severity of the lower limb ischemia and also are independently associated with mortality and cardiovascular events in PAD patients.[44, 45] ABI should be routinely measured in patients suspected of having PAD; however, there is acknowledged reluctance by physicians in assessing ABI, mainly due to time and equipment limitations.[46] Physicians typically prefer to order anatomical imaging tests such as lower limb arterial duplex imaging, computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) which are readily available from radiology providers in most Western countries, although these investigators are best reserved for patients being considered for interventions in whom the information provided is useful for planning the management. Duplex imaging utilizes B mode ultrasound and Doppler to provide anatomical and hemodynamic information. Typically the peak systolic velocity of the Doppler wave form is elevated at the site of a stenosis, with a twofold elevation being commonly used to define a 50% stenosis and a three- or fourfold elevation being used to define a 75% stenosis.[40, 42] The advantages of duplex imaging include its noninvasive nature and absence of established complications, however, detailed and accurate imaging requires a highly trained and experienced sonographer which are not available at every facility. Both CTA and MRA provide detailed mapping of the lower limb arteries with sufficient detail to plan interventional management.[47] CTA does involve ionising radiation and the injection of intravenous contrast with the associated rare but serious risks, such as renal failure (primarily in patients with pre-existing renal impairment), contrast allergy and lactic acidosis (a rare metabolic complication to contrast which may be seen in patients receiving metformin). CTA is also less accurate in patients with marked vascular calcification. MRA is frequently less available than CTA due to the longer time needed to acquire images, the lower number of MR machines established in many cities and the more complex processing needed to reconstruct images. Both CTA and MRA can provide similar accuracy to diagnostic conventional angiography, although typically they are less accurate at assessing tibial arteries than selective angiography.[47] Formal digital subtraction angiography (DSA) typically involves percutaneous placement of a femoral or brachial sheath and selective catheterization of lower limb arteries to provide detailed and high quality assessment of the lumen of the lower limb arteries. It is now unusual to undertake formal angiography for diagnostic purposes alone in patients with PAD, despite the fact that this imaging is still considered the gold standard, owing to its interventional nature and associated but rare risks of serious bleeding, atherothrombotic embolization, renal impairment, and contrast allergy. DSA is usually undertaken as part of directing and quality assessing therapeutic revascularization by angioplasty, stenting, or atherectomy. DSA also does not provide any information about the arterial wall, unlike CTA or MRA, which can limit its ability to identify and assess pathologies such as aneurysms.
Differential diagnosis
Important differential diagnoses to consider in patients presenting with symptoms of intermittent claudication include cauda equina syndrome or spinal claudication, nerve root pathologies such as degenerative lumbo-sacral disc disease, peripheral neuropathy and venous claudication. In patients with classical symptoms and signs, differentiating these diagnoses can be straightforward. Patients with spinal claudication, for example, typically find their symptoms of leg pain are improved on walking up hill whereas those with PAD typically have worse symptoms in this situation. Patients with obstructive venous disease and peripheral neuropathy would typically have signs of leg swelling and sensory loss, respectively. In many elderly patients a number of pathologies coexist. Patients with PAD commonly also have lumbo-sacral disc degeneration, for example. Approximately 30% of patients with PAD have atypical symptoms that can also contribute to difficulty in differentiating diagnoses.[43]
Management
Optimal treatment for the management of PAD is outlined in Table 14.3.
3. Treatment of hypertension (beta blocker or angiotensin-converting enzyme inhibitors) 4. Treatment of diabetes mellitus (foot care and blood glucose control) 6. Treatment of symptoms of claudication with use of vasodilator (pentoxyfilline or cilostazol) |
Smoking cessation
The recently updated American Heart Association (AHA) guidelines recommend the following regarding smoking cessation:[10, 16]
1. Patients who are smokers or former smokers should be asked about status of tobacco use at every visit.
2. Patients should be assisted with counseling and developing a plan for quitting that may include pharmacotherapy and/or referral to a smoking cessation program.
3. Individuals with lower extremity PAD who smoke cigarettes or use other forms of tobacco should be advised by each of their clinicians to stop smoking and offered behavioral and pharmacological treatment.
4. In the absence of contraindication or other compelling clinical indication, one or more of the following pharmacological therapies should be offered: varenicline, bupropion, and nicotine replacement therapy.
Hypercholesterolemia management
The American Heart Association (AHA) guidelines recommend the following for cardiovascular risk factor reduction in the form of lipid lowering drugs for persons with PAD:[45]
1. Treatment with a statin medication is indicated for all patients with PAD to achieve a target LDL cholesterol level of less than 100 mg/dL or 2.6 mmol/L.
2. Treatment with a statin medication is indicated for patients with PAD at high risk of cardiovascular events to achieve a target LDL cholesterol level of less than 70 mg/dL or 1.8 mmol/L.
Furthermore, Gardner et al. recommend that statins should be prescribed to all patients with PAD irrespective of the presence of coronary artery disease, with several studies reporting improvements in walking ability, ABI and symptoms of claudication after treatment with a statin.[48]
Hypertension management
The American Heart Association (AHA) guidelines recommend the following for cardiovascular risk factor reduction in the form of antihypertensive drugs for persons with PAD:[45]
1. Antihypertensive therapy should be administered to hypertensive patients with lower extremity PAD to achieve a goal of less than 140 mmHg systolic over 90 mmHg diastolic in nondiabetics.
2. In persons with diabetes and/or chronic renal disease therapy should aim to reduce blood pressure to less than 130 mmHg systolic over 80 mmHg diastolic to reduce the risk of myocardial infarction, stroke, congestive heart failure, and cardiovascular death.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
