Peripheral Vascular Disease: Introduction
Background
Peripheral vascular disease (PVD) is a nearly pandemic
condition that has the potential to cause loss of limb or even
loss of life. Peripheral vascular disease manifests as
insufficient tissue perfusion
caused by existing
atherosclerosis that may be acutely compounded by either
emboli or thrombi. Many people live daily with peripheral
vascular disease; however, in settings such as acute limb
ischemia, this pandemic disease can be life threatening and
can require emergency intervention to minimize morbidity
and mortality.
Pathophysiology
PVD, also known as arteriosclerosis obliterans, is primarily
the result of atherosclerosis. The atheroma consists of a core
of cholesterol joined to proteins with a fibrous intravascular
covering. The atherosclerotic process may gradually progress
to complete occlusion of medium and large arteries. The
disease typically is segmental, with significant variation from
patient to patient.
Vascular disease may manifest acutely when thrombi,
emboli, or acute trauma compromises perfusion.
Thromboses are often of an atheromatous nature and occur
in the lower extremities more frequently than in the upper
extremities. Multiple factors predispose patients for
thrombosis. These factors include sepsis, hypotension, low
cardiac output, aneurysms, aortic dissection, bypass grafts,
and underlying atherosclerotic narrowing of the arterial
lumen.
Emboli, the most common cause of sudden ischemia, usually
are of cardiac origin (80%); they also can originate from
proximal atheroma, tumor, or foreign objects. Emboli tend to
lodge at artery bifurcations or in areas where vessels
abruptly narrow. The femoral artery bifurcation is the most
common site (43%), followed by the iliac arteries (18%), the
aorta (15%), and the popliteal arteries (15%).
The site of occlusion, presence of collateral circulation, and
nature of the occlusion (thrombus or embolus) determine the
severity of the acute manifestation. Emboli tend to carry
higher morbidity because the extremity has not had time to
develop collateral circulation. Whether caused by embolus or
thrombus, occlusion results in both proximal and distal
thrombus formation due to flow stagnation.
Clinical
History
The primary factor for developing peripheral vascular disease
(PVD) is atherosclerosis.
1. Other maladies that often coexist with PVD are coronary
artery disease (CAD), myocardial infarction (MI), atrial
fibrillation, transient ischemic attack, stroke, and renal
disease. Studies have suggested that even asymptomatic
peripheral arterial disease (PAD) is associated with
increased CAD mortality.1
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Risk factors for PVD include smoking, hyperlipidemia,
diabetes mellitus, and hyperviscosity.
Other etiologies for developing PVD may include
phlebitis, injury or surgery, and autoimmune disease,
including vasculitides, arthritis, or coagulopathy.
PVD rarely exhibits an acute onset; it instead manifests a
more chronic progression of symptoms.
Patients with acute emboli causing limb ischemia may
have new or chronic atrial fibrillation, valvular disease, or
recent MI, whereas a history of claudication, rest pain, or
ulceration suggests thrombosis of existing PVD.
Radiation-induced PAD is becoming more common,
perhaps due to the efficacy of current antineoplastic
treatment and increased survival.2
Intermittent claudication may be the sole manifestation
of early symptomatic PVD. The level of arterial
compromise and the location of the claudication are
closely related as follows:
Aortoiliac disease manifests as pain in the thigh and
buttock, whereas femoral-popliteal disease manifests as
pain in the calf.
Symptoms are precipitated by walking a predictable
distance and are relieved by rest.
Collateral circulation may develop, reducing the
symptoms of intermittent claudication, but failure to
control precipitant factors and risk factors often causes
its reemergence.
Claudication may also present as the hip or leg "giving
out" after a certain period of exertion and may not
demonstrate the typical symptom of pain on exertion.
The pain of claudication usually does not occur with
sitting or standing.
Ischemic rest pain is more worrisome; it refers to pain in
the extremity due to a combination of PVD and
inadequate perfusion.
Ischemic rest pain often is exacerbated by poor cardiac
output.
The condition is often partially or fully relieved by placing
the extremity in a dependent position, so that perfusion
is enhanced by the effects of gravity.
Leriche syndrome is a clinical syndrome described by
intermittent claudication, impotence, and significantly
decreased or absent femoral pulses. This syndrome
indicates chronic peripheral arterial insufficiency due to
narrowing of the distal aorta.
The patient's medications may provide a clue to the
existence of PVD.
Pentoxifylline is a commonly used medication specifically
prescribed for PVD.
Daily aspirin commonly is used for prevention of cardiac
disease (CAD), but PVD often coexists, to some degree,
in patients with CAD.
Physical
A systematic examination of the peripheral vasculature is
critical for proper evaluation.
1. Peripheral signs of peripheral vascular disease are the
classic "5 P's":
o Pulselessness
o Paralysis
o Paraesthesia
o Pain
o Pallor
2. Paralysis and paraesthesia suggest limb-threatening
ischemia and mandate prompt evaluation and
consultation.
3. Assess the heart for murmurs or other abnormalities.
Investigate all peripheral vessels, including carotid,
abdominal, and femoral, for pulse quality and bruit. Note
that the dorsalis pedis artery is absent in 5-8% of normal
subjects, but the posterior tibial artery usually is present.
Both pulses are absent in only about 0.5% of patients.
Exercise may cause the obliteration of these pulses.
4. The Allen test may provide information on the radial and
ulnar arteries.
5. The skin may have an atrophic, shiny appearance and
may demonstrate trophic changes, including alopecia;
dry, scaly, or erythematous skin; chronic pigmentation
changes; and brittle nails.
6. Advanced PVD may manifest as mottling in a "fishnet
pattern" (livedo reticularis), pulselessness, numbness, or
cyanosis. Paralysis may follow, and the extremity may
become cold; gangrene eventually may be seen. Poorly
healing injuries or ulcers in the extremities help provide
evidence of preexisting PVD.
7. The ankle-brachial index (ABI) can be measured at
bedside. Using Doppler ultrasonography, the pressure at
the brachial artery and at the posterior tibialis artery is
measured. The ankle systolic pressure is divided by the
brachial pressure, both measured in the supine position.
Normally, the ratio is more than 1. In severe disease, it is
less than 0.5.
8. A semiquantitative assessment of the degree of pallor
also may be helpful. While supine, the degree of pallor is
assessed.
 If pallor manifests when the extremity is level, the pallor
is classified as level 4.
 If not, the extremity is raised 60°. If pallor occurs within
30 seconds, it is a level 3; in less than 60 seconds, level 2;
in 60 seconds, level 1; and no pallor within 60 seconds,
level 0.
Differential Diagnoses
Aneurysm, Abdominal
Lumbar
(Intervertebral)
Disorders
Ankle Injury, Soft Tissue
Thrombophlebitis, Septic
Back Pain, Mechanical
Thrombophlebitis, Superficial
Disk
Deep
Venous Trauma,
Thrombosis
and Injuries
Thrombophlebitis
Peripheral
Vascular
Workup
Laboratory Studies
1. Routine blood tests generally are indicated in the
evaluation of patients with suspected serious
compromise of vascular flow to an extremity. CBC, BUN,
creatinine, and electrolytes studies help evaluate factors
that might lead to worsening of peripheral perfusion.
Risk factors for the development of vascular disease
(lipid profile, coagulation tests) can also be evaluated,
although not necessarily in the ED setting.
2. An ECG may be obtained to look for evidence of
dysrhythmia, chamber enlargement, or MI.
3. Elevated levels of inflammatory blood markers such as D
dimer, C-reactive protein, interleukin 6, and
homocysteine have been linked to decreased lower
extremity tolerance of exercise. Higher levels of activity
in daily life have been shown to decrease these
levels. The applicability to practice in Emergency
Medicine is unknown.
Imaging Studies
1. Plain films are of little use in the setting of PVD. Doppler
ultrasonographic studies are useful as primary
noninvasive studies to determine flow status. Upper
extremities are evaluated over the axillary, brachial,
ulnar, and radial arteries. Lower extremities are
evaluated over the femoral, popliteal, dorsalis pedis, and
posterior tibial arteries. Note the presence of Doppler
signal and the quality of the signal (ie, monophasic,
biphasic, triphasic). The presence of distal flow does not
exclude emboli or thrombi because collateral circulation
may provide these findings.
2. Magnetic resonance imaging (MRI) may be of some
clinical benefit due to its high visual detail. Plaques are
imaged easily, as is the difference between vessel wall
and flowing blood. MRI also has the benefits of
angiography to provide even higher detail and can
replace traditional arteriography. The utility of MRI is
limited in the emergency setting, often due to location of
the device and the technical skill required to interpret
the highly detailed images.
3. Computerized tomography (CT) can be of use to the
emergency physician since it does not have the time and
availability constraints of MRI. Although noncontrast
studies can be useful to image calcification and
arteriosclerosis, contrast studies are most useful to
image arterial insufficiency. Renal function should be
confirmed before contrast administration, since PVD
often coexists with risk factors for contrast-induced renal
failure.
Other Tests
1. The ankle-brachial index (ABI) is a useful test to compare
pressures in the lower extremity to the upper extremity.
Blood pressure normally is slightly higher in the lower
extremities than in the upper extremities. Comparison to
the contralateral side may suggest the degree of
ischemia.
2. The ABI is obtained by applying blood pressure cuffs to
the calf and the upper arm. The blood pressure is
measured, and the systolic ankle pressure is divided by
the systolic brachial pressure. Normal ABI is more than 1;
a value less than 0.95 is considered abnormal. This test
can be influenced by arteriosclerosis and small vessel
disease (eg, diabetes), reducing reliability. Progressive
PAD, indicated by ABI decline of greater than 0.15, has
been associated with increased cardiovascular disease
risk.5
3. Transcutaneous oximetry affords assessment of impaired
flow secondary to both microvascular and macrovascular
disruption. Its use is increasing, especially in the realm of
wound care and patients with diabetes. Transcutaneous
oximetry has not been studied extensively in emergent
occlusion.
Procedures
The criterion standard for intraluminal obstruction has
always been arteriography, although this is both potentially
risky and often unobtainable in the emergency setting. The
delay associated with obtaining arteriography in the setting
of obvious limb ischemia can delay definitive treatment to
deleterious effect. If time allows, arteriography can prove
useful in discriminating thrombotic disease from embolic
disease.
Treatment
Prehospital Care
Prehospital care for peripheral vascular disease (PVD)
involves the basics: control ABCs, obtain intravenous access,
and administer oxygen. Generally, do not elevate the
extremity. Note and record distal pulses and skin condition.
Perform and document a neurological examination of the
affected extremities.
Emergency Department Care
Attention to the ABCs, intravenous access, and obtaining
baseline laboratory studies should occur early in the ED visit.
Obtain an ECG and chest radiograph.
Treatment of either thrombi or emboli in the setting of
peripheral vascular disease is similar. Empirically, initiate a
heparin infusion with the goal of increasing activated partial
thromboplastin time to 1.5 times normal levels. Acute leg
pain correlated with a cool distal extremity, diminished or
absent distal pulses, and an ankle blood pressure less than 50
mm Hg should prompt consideration of emergent surgical
referral.
In some cases of emboli, intra-arterial thrombolytic agents
may be useful. The exact technique of administration varies,
in both dosage and time of administration. Remember that
intra-arterial thrombolysis remains investigational. Obviously,
such thrombolytic therapy is contraindicated in the presence
of active internal bleeding, intracranial bleeding, or bleeding
at noncompressible sites.
Consultations
Early surgical consultation in patients with acute limb
ischemia is prudent. Depending on the case, the surgeon may
involve interventional radiology or proceed operatively.
Emboli may be treated successfully by Fogarty catheter (ie,
an intravascular catheter with a balloon at the tip). The
balloon is passed distal to the lesion; the balloon is inflated,
and the catheter is withdrawn along with the embolus. This
technique most commonly is used for iliac, femoral, or
popliteal emboli.
Definitive treatment of hemodynamically significant
aortoiliac disease is usually by aortobifemoral bypass. Its 5year patency rate is approximately 90%. Those patients in
whom PVD becomes significant, however, often have a
plethora of comorbid medical conditions, such as
cardiovascular disease, diabetes, and chronic obstructive
pulmonary disease, which increase procedural morbidity and
mortality. Axillobifemoral bypass and femoral-femoral bypass
are alternatives, both of which have lower 5-year patencies
but have lower procedural mortality.
Some areas of arteriostenosis can be revascularized with
percutaneous transluminal coronary angioplasty (PTCA). If
the occlusion is complete, a laser may be useful in making a
small hole through which to pass the balloon. Restenosis is a
concern with PTCA, particularly for larger lesions. Stents and
lasers are still considered experimental.
An initial study shows promise in relieving the pain of PAD
with topically applied lidocaine spray. Suzuki and colleagues
studied 24 subjects with PAD and noted a significant drop in
pain associated with PAD by applying an 8% lidocaine
metered dose spray to the affected areas. Blood levels of
lidocaine were minimal, and this technique may show
promise for those affected with focal PAD pain.6
Medication
The goal of pharmacotherapy is to reduce morbidity and to
prevent complications.
Anticoagulants
Anticoagulants reduce thrombin generation and fibrin
formation and minimize clot propagation.
Heparin
Augments activity of antithrombin III and prevents
conversion of fibrinogen to fibrin. Does not actively lyse but
is able to inhibit further thrombogenesis. Prevents
reaccumulation of clot after spontaneous fibrinolysis.
Adult
80 U/kg IV bolus, followed by infusion of 18 U/kg/h
Follow-up
Further Outpatient Care
1. Patients who have significant peripheral vascular disease
but whose illness is not so severe or acute that it
requires inpatient treatment may be discharged with
appropriate follow-up. However, counsel these patients
regarding the potential effects of various activities and
medications on the course of their illness. Advise
patients to stop smoking and to avoid cold exposures
and medications that can lead to vasoconstriction,
including medications used for migraines and over-thecounter medications.
2. Some recreational drugs (eg, cocaine) may have a
deleterious effect on peripheral arterial tone, and betablockers may exacerbate the condition.
3. Consultation with providers who will be following the
patient after ED discharge is advised when making
decisions regarding the discontinuation of medications
used for chronic medical conditions.
Peripheral Arterial Occlusive Disease
Introduction
Background
Claudication, which is defined as reproducible ischemic
muscle pain, is one of the most common manifestations of
peripheral vascular disease caused by atherosclerosis.
Claudication occurs during physical activity and is relieved
after a short rest. Pain develops because of inadequate blood
flow.
Pathophysiology
Single or multiple arterial stenoses produce impaired
hemodynamics at the tissue level in patients with peripheral
arterial occlusive disease (PAOD), shown below. Arterial
stenoses lead to alterations in the distal pressures available
to affected muscle groups and to blood flow.
Peripheral arterial occlusive
disease. This angiogram shows
a superficial femoral artery
occlusion on one side (with
reconstitution of the
suprageniculate popliteal
artery) and superficial femoral
artery stenosis on the other
side. This is the most common
area for peripheral vascular
disease.
Under resting conditions, normal blood flow to extremity
muscle groups averages 300-400 mm/min. Once exercise
begins, blood flow increases up to 10-fold owing to the
increase in cardiac output and compensatory vasodilation at
the tissue level. When exercise ceases, blood flow returns to
normal within minutes.
In patients with PAOD, resting blood flow is similar to that of
a healthy person. However, during exercise, blood flow
cannot maximally increase in muscle tissue because of
proximal arterial stenoses. When the metabolic demands of
the muscle exceed blood flow, claudication symptoms ensue.
At the same time, a longer recovery period is required for
blood flow to return to baseline once exercise is terminated.
Similar abnormal alterations occur in distal perfusion
pressure in affected extremities. In normal extremities, the
mean blood pressure drop from the heart to the ankles is no
more than a few millimeters of mercury. In fact, as pressure
travels distally, the measured systolic pressure actually
increases because of the higher resistance encountered in
smaller-diameter vessels.
At baseline, a healthy person may have a higher measured
ankle pressure than arm pressure. When exercise begins, no
change in measured blood pressure occurs in the healthy
extremity.
In the atherosclerotic limb, each stenotic segment acts to
reduce the pressure head experienced by distal muscle
groups. Correspondingly, at rest, the measured blood
pressure at the ankle is less than that of a healthy person.
Once physical activity starts, the reduction in pressure
produced by the atherosclerotic lesion becomes more
significant and the distal pressure is greatly diminished.
The phenomenon of increased blood flow causing decreased
pressure distally to an area of stenosis is a matter of physics.
Poiseuille calculated energy losses across areas of resistance
with varying flow rates by using the following equation, in
which Q is flow, v is viscosity, L is the length of the stenotic
area, r is the radius of the open area within the stenosis, and
k is constant:
Resistance = pressure = Q8vL/kr4
Applying this equation, the pressure gradient is directly
proportional to the flow and length of stenosis and inversely
proportional to the fourth power of the radius.
Therefore, while increasing the rate of flow directly increases
the pressure gradient at any given radius, these effects are
much less marked than those due to changes in the radius of
the stenosis.
As the radius is raised to the fourth power, it has the most
dramatic impact on a pressure gradient across a lesion. This
impact is additive when 2 or more occlusive lesions are
located sequentially within the same artery.
Frequency
United States
Atherosclerosis affects up to 10% of the Western population
older than 65 years. With the elderly population expected to
increase 22% by the year 2040, atherosclerosis is expected to
have a huge financial impact on medicine. When claudication
is used as an indicator, estimates are that 2% of the
population aged 40-60 years and 6% older than 70 years are
affected.
Mortality/Morbidity
The most feared consequence is severe limb-threatening
ischemia leading to amputation. However, studies of large
patient groups with claudication reveal that amputation is
uncommon. Boyd prospectively followed 1440 patients with
intermittent claudication for as long as 10 years and reported
that only 12.2% required amputation.1 In the Framingham
study, only 1.6% of patients with claudication reached the
amputation stage after 8.3 years of follow-up.
1. Limb amputation largely depends on the number and
severity of cardiovascular risk factors (ie, smoking,
hypertension, diabetes). Continued smoking has been
identified as the most consistent adverse risk factor
associated with the progression of peripheral arterial
occlusive disease (PAOD). Other factors are the severity
of disease at the time of the initial patient encounter
and, in some studies, the presence of diabetes.
2. As with most patients with vascular disease, survival is
less than that of age-matched control groups. Coronary
artery disease with a subsequent myocardial event is the
major contributor to outcome. Predicted mortality rates
for patients with claudication at 5, 10, and 15 years of
follow-up are approximately 30%, 50%, and 70%,
respectively.
Race
Peripheral arterial occlusive disease (PAOD) has no racial
predilection.
Sex
1. Intermittent claudication most commonly manifests in
men older than 50 years.
2. Although younger patients may present with symptoms
consistent with intermittent claudication, other
etiologies of leg pain and claudication (eg, popliteal
entrapment syndrome) must be strongly considered.
Clinical
History
Intermittent claudication typically causes pain that occurs
with physical activity. Determining how much physical
activity is needed before the onset of pain is crucial.
1. Typically, vascular surgeons relate the onset of pain to a
particular walking distance in terms of street blocks (eg,
2-block claudication). This helps to quantify patients with
some standard measure of walking distance before and
after therapy.
2. Other important aspects of claudication pain are that the
pain is reproducible within the same muscle groups and
that it ceases with a resting period of 2-5 minutes.
3. Location of the pain is determined by the anatomical
location of the arterial lesions. Peripheral arterial
occlusive disease (PAOD) is most common with the distal
superficial femoral artery (located just above the knee
joint), which corresponds to claudication in the calf
muscle area (the muscle group just distal to the arterial
disease).
4. When atherosclerosis is distributed throughout the
aortoiliac area, thigh and buttock muscle claudication
predominates.
5.
The perceived significance of claudication is variable.
Most patients appear to accept a decrease in walking
distance as a normal part of aging. Investigators report
that 50-90% of patients with definite intermittent
claudication do not report this symptom to their
clinician.
6. Atherosclerosis is a systemic disease process. Patients
who present with claudication due to PAOD can be
expected to have atherosclerosis elsewhere. A full
assessment of the patient's risk factors for vascular
disease should be performed.
7. The risk factors for PAOD are the same as those for
coronary artery disease or cerebrovascular disease and
include diabetes, hypertension, hyperlipidemia, family
history, sedentary lifestyle, and tobacco use.
8. Smoking is the greatest of all the cardiovascular risk
factors. The mechanism by which smoking causes or
accentuates atherosclerosis is unknown. What is known
is that the degree of damage is directly related to the
amount of tobacco used. Counseling patients on the
importance of smoking cessation is paramount in PAOD
management.
Physical
Essential to the physical examination of a patient with
claudication is a complete lower extremity evaluation and
pulse examination, including measuring segmental pressures,
as depicted in the image below. Atrophy of calf muscles, loss
of extremity hair, and thickened toenails are clues to
underlying peripheral arterial occlusive disease (PAOD).
Peripheral arterial
occlusive
disease.
Measuring
segmental pressures.
1.
2.
3.
Palpation of pulses should be attempted from the
abdominal aorta to the foot, with auscultation for bruits
in the abdominal and pelvic regions. This can be difficult
in a patient who is obese, in whom palpable pulses may
be hidden under a deep subcutaneous layer.
Except in the rare case of a congenital absence of a pulse
(eg, persistent sciatic artery), the absence of a pulse
signifies arterial obstruction proximal to the area
palpated. For example, if no femoral artery pulse is
palpated, significant PAOD is present in the aortoiliac
distribution. The same can be said if no palpable
popliteal artery pulse is present because of existing
superficial femoral artery occlusive disease.
Patients who report intermittent claudication and have
palpable pulses can present a clinical dilemma.

If the history is consistent with typical claudication
symptoms, the clinician can have the patient walk
around the office (or perform toe raises) until the
symptoms are reproduced and then palpate for pulses.
 The exercise should cause the atherosclerotic lesion to
become significant and should diminish the strength of
the pulses distal to the lesion.
4. When palpable pulses are not present, further
assessment of the circulation can be made with a
handheld Doppler device.
 An audible Doppler signal assures the clinician that some
blood flow is perfusing the extremity.
 If no Doppler signals can be heard, a vascular surgeon
should be immediately consulted.
5. Pressure measurements can be performed to gain
objective data on the circulatory status.
 To obtain an accurate pressure reading, (1) place the
pneumatic cuff around the ankle, (2) position the
Doppler probe over the dorsalis pedis or posterior tibial
artery, and (3) inflate the cuff to a reading above the
systolic pressure and deflate. The systolic tone at the
ankle vessel is the pressure recorded.
 A healthy person has no pressure drop from the heart to
the ankle. In fact, the pressure at the ankle may be 10-20
mm Hg higher due to the augmentation of the pressure
wave with travel distally.
 In patients with claudication, the measured pressure is
diminished to some extent, depending on the severity of
PAOD.
6. A useful tool in assessing a patient with claudication is
the ankle-brachial index (ABI), which is calculated as the
ratio of systolic blood pressure at the ankle to the arm.
 Determining the ABI provides an assessment of the
impact that the PAOD is having on the patient. A normal
ABI is 0.9-1.1. However, any patient with an ABI less than
0.9, by definition, has some degree of PAOD. The ABI
decreases with worsening PAOD.
 One area of inaccuracy with the ABI is in patients with
diabetes who have PAOD. Peripheral vessels in patients
with diabetes may have extensive medial layer calcinosis,
rendering the vessel resistant to compression by the
pneumatic cuff. These patients should be referred to a
vascular laboratory for further evaluation.
Other Problems to Be Considered
Some disease processes mimic claudication symptoms and
must be excluded. They include the following:
1. Osteoarthritis: This is associated with arthritic pain that
is variable from day to day and may be aggravated by
certain weather patterns or movements. Rest does not
relieve pain.
2. Venous disease: Described as a dull, aching pain that
typically occurs at the end of the day or after prolonged
standing, venous disease is not exacerbated by exercise.
3.
Neurospinal disease: Pain occurs in the morning and is
not relieved by short resting periods. Neurospinal pain is
frequently relieved by leaning forward against a solid
surface or by sitting.
4. Chronic compartment syndrome: This is rare. It is usually
observed in runners and other athletes with large,
developed calf muscles. Muscles swell during activity,
leading to increased compartment pressure and
decreased venous return. Consistent with claudication
pain, this pain occurs with exercise and is relieved with
rest. However, the type of exercise is at a more
strenuous level and the recovery period is prolonged.
5. Popliteal entrapment syndrome: This syndrome is similar
to intermittent claudication but is usually observed in
active young people. The syndrome is caused by various
abnormal anatomical configurations of the insertion of
the medial gastrocnemius muscle head, which causes
compression of the popliteal artery. Upon physical
examination, tibial pulses may disappear when the knee
is at full extension. Pain is aggravated with walking but
not with running because knee extension is not as severe
with running.
6. Reflex sympathetic dystrophy or minor causalgia: This is
characteristically described as a burning pain. The
superficial pain is often distributed along a somatic nerve
and is often related to a past trauma in the extremity.
7. Diabetic neuropathy: Pain is due to a peripheral neuritis.
Differentiation from intermittent claudication can be
difficult because of accompanying skin discoloration and
diminished pulses. An extensive neurologic evaluation is
essential.
8. Venous thrombosis: Swelling and leg pain occur with
walking. Pain is relieved by extremity elevation, which
distinguishes this entity from arterial insufficiency.
Workup
Laboratory Studies
A laboratory workup is only helpful for identifying
accompanying silent alterations in renal function and
elevated lipid profiles.
Imaging Studies
1. Angiography still remains the criterion standard arterial
imaging study used in the diagnosis of PAOD, as depicted
in the image below. However, this test is usually
reserved for when an intervention (either endovascular
or traditional open surgery) is planned.
2. Monaco et al examined the effects of systematic
(routine) coronary angiography, as shown below, on
patients undergoing surgical treatment of peripheral
arterial disease.2 Patients undergoing vascular surgery
have a high-risk for cardiovascular complications and
mortality. The authors found that routine coronary
angiography had a positive impact compared with
selectively determining if coronary angiography was
needed. The routine coronary angiography improved
survival (P=0.01) and no reports of death or
cardiovascular events (P=0.003) occurred compared with
those patients who were selectively chosen to have
coronary angiography prior to vascular surgery. The
authors recommend that multicenter trials confirm this
finding in a larger population.
3. Magnetic resonance angiography (MRA) is useful for
imaging large and small vessels. Although MRA was
initially felt to provide inadequate images, this is no
longer the case. With improved imaging capabilities,
MRA can be used to not only diagnose but to help plan
the type of indicated intervention.
4. Computerized tomographic angiography is another
modality used to image arterial disease. Unfortunately,
the study still requires a large amount of contrast media
and requires an upgraded CT scanner to reconstruct
helpful images.
5. Duplex ultrasonography is a method of evaluating the
status of a patient’s vascular disease. Duplex scanning
has the advantage of being noninvasive and requiring no
contrast media. Unfortunately, duplex scanning is very
technician dependent.
Treatment
Medical Care
Treatment of claudication is medical, with surgery reserved
for severe cases.
1. The goal of medical management is to impede the
progression of peripheral arterial occlusive disease
(PAOD).
 In patients who smoke, the most expedient way to
impede the progress of PAOD is to stop tobacco use.
 Extensive evidence indicates that smoking cessation
improves the prognosis.
 Improved walking distance and ankle pressure have been
attributed to smoking cessation.
2. Exercise plays a vital role in the treatment of
claudication.
 Patients reduce their daily walking because of
claudication pain and fear of further damage. This leads
to an increasingly sedentary lifestyle that is even more
detrimental.
 Regular walking programs result in substantial
improvement in most patients with claudication.
Improvements have ranged from 80-234% in controlled
studies.
 A daily walking program of 45-60 minutes is
recommended. The patient is instructed to walk until
claudication pain occurs, rest until the pain subsides, and
repeat the cycle.
 While the exact mechanism for improvement in walking
distance with exercise remains unknown, regular
exercise is thought to condition muscles to work more
efficiently (more extraction of blood) and increase
collateral vessel formation.
3.
Additional medical treatment includes control of the
lipid profile, diabetes, and hypertension.
Surgical Care
Patients with limb-threatening ischemia or lifestyle-limiting
claudication are referred to a vascular surgeon. Only then
does evaluation warrant an arteriogram.
Medication
Daily aspirin is recommended for overall cardiovascular care.
While standard dosages range from 81-325 mg/d, no
consensus has been reached on the most effective dose.
Pentoxifylline (Trental) shows promise. Numerous
randomized trials have documented modest improvements
in walking distance when compared with placebo treatment
groups. Treatment can take 2-3 months to produce
noticeable results.
The use of clopidogrel bisulfate (Plavix) and enoxaparin
sodium (Lovenox) in the treatment of this entity is increasing;
however, further research is needed to establish clinical
efficacy.
Cilostazol (Pletal) has recently shown increasing promise in
the treatment of intermittent claudication. Several
randomized studies have shown benefits in increasing
walking distances for both the distance before the onset of
claudication pain and the distance before exercise-limiting
symptoms become intolerable (ie, maximal walking distance).
In a randomized, double-blind, placebo-controlled trial,
O’Donnell et al assessed the vascular and biochemical effects
of cilostazol therapy in individuals (n=80) with peripheral
arterial disease. Arterial compliance, transcutaneous
oxygenation, ankle-brachial index, and treadmill walking
distance were measured. The cilostazol group had significant
reduction in the augmentation index and also showed
reduction in transcutaneous oxygenation levels compared
with the placebo group. Mean percentage change in walking
distance improved more in the cilostazol group from baseline
compared with the placebo group. Lipid profiles were also
improved in the cilostazol group. The results showed that
cilostazol is an efficacious treatment of peripheral arterial
disease. In addition to improving patients’ symptoms and
quality of life, cilostazol also appeared to have beneficial
effects on arterial compliance.3
In 2009, Momsen et al evaluated the efficacy of drug therapy
in
improving
walking
distance
in
intermittent
4
claudication. Their study determined that statins seemed to
be the best in improving maximal walking distance.
Cholesterol-lowering statin agents are beneficial in the
medical therapy for peripheral arterial disease.5 In addition to
effectively lowering blood cholesterol profiles, recent
evidence from the Heart Protection Study showed that
cholesterol-lowering statin agents (simvastatin) reduced the
rate of first major vascular events (myocardial infarction,
stroke, or limb revascularization), with the largest benefits
seen in patients with peripheral vascular disease.6
The benefits were demonstrated regardless of the baseline
cholesterol profile. As such, cholesterol-lowering statin
agents should be considered for medical treatment in
patients with peripheral arterial disease.
Antiplatelet Agents
Decrease overall risk of cardiovascular disease from
myocardial infarction and stroke. Also improve walking
distance by enhancing circulation.
Aspirin (Anacin, Ascriptin, Bayer aspirin)
Inhibits prostaglandin synthesis, which prevents formation of
platelet-aggregating thromboxane A2.
Adult
81-325 mg PO qd
Clopidogrel (Plavix)
Selectively inhibits ADP binding to platelet receptor and
subsequent ADP-mediated activation of glycoprotein
GPIIb/IIIa complex, thereby inhibiting platelet aggregation.
Indicated for reduction of atherosclerotic events.
Adult
75 mg PO qd
Cilostazol (Pletal)
Mechanism of effects on symptoms of intermittent
claudication not fully understood. Cilostazol and several of its
metabolites
are
PDE
III
inhibitors,
inhibiting
phosphodiesterase activity and suppressing cAMP
degradation, with a resultant increase in cAMP in platelets
and blood vessels, leading to inhibition of platelet
aggregation and vasodilation, respectively. Reversibly inhibits
platelet aggregation induced by various stimuli, including
thrombin, ADP, collagen, arachidonic acid, epinephrine, and
shear stress.
Adult
100 mg PO bid at least 30 min before or 2 h after breakfast
and dinner; consider 50 mg bid if coadministered with
inhibitors of CYP3A4 (eg, ketoconazole, itraconazole,
erythromycin, diltiazem) or with inhibitors of CYP2C19 (eg,
omeprazole)
Pentoxifylline (Trental)
Indicated for treatment of patients with intermittent
claudication due to atherosclerosis or other obstructive
arteriopathies. Improves blood flow by increasing red blood
cell deformability, which decreases viscosity of blood.
Adult
400 mg PO tid
Antilipemic Agents
These agents are beneficial in lowering blood cholesterol
profiles, which may reduce the rate of first major vascular
events.
Simvastatin (Zocor)
Reduces cardiovascular heart disease mortality and morbidity
(nonfatal myocardial infarction or stroke, revascularization
procedures) in high-risk patients (ie, existing coronary heart
disease, diabetes, peripheral vessel disease, history of stroke
or other cerebrovascular disease). Competitively inhibits
HMG-CoA, which catalyzes the rate-limiting step in
cholesterol synthesis. Patients should be placed on a
cholesterol-lowering diet; the diet should be continued
indefinitely.
Adult
40 mg PO hs if renal insufficiency not severe
5 mg PO hs in patients with severe renal insufficiency; not to
exceed 10 mg/d when coadministered with fibrates (eg,
gemfibrozil), niacin (>1 g/d), or cyclosporine; not to exceed
20 mg/d when coadministered with verapamil or amiodarone
Follow-up
Further Outpatient Care
1. Patients should be seen every 4-6 months to assess the
effects of medical therapy. Review changes in walking
distance, smoking habits, eating habits, and exercise
performance.
2. Control hypertension and diabetes if necessary. A repeat
pulse examination and ABI complete the follow-up
evaluation.
3. Patients with worsening symptoms may require
intervention and referral to a vascular surgeon.
Complications
1. The most feared consequence is severe limb-threatening
ischemia leading to amputation. However, studies of
large patient groups with claudication reveal that
amputation is uncommon.
 Boyd prospectively followed 1440 patients with
intermittent claudication for as long as 10 years and
reported that only 12.2% required amputation.
 In the Framingham study, only 1.6% of patients with
claudication reached the amputation stage after 8.3
years of follow-up.
Prognosis
1. Whether a patient progresses to limb amputation largely
depends on the number and severity of cardiovascular
risk factors (ie, smoking, hypertension, diabetes).
2. Continued smoking has been identified as the most
consistent adverse risk factor associated with the
progression of the disease.
3. Other factors are the severity of disease at the time of
the initial patient encounter and, in some studies, the
presence of diabetes.
4. As with most patients with vascular disease, survival is
less than that of age-matched control groups. Coronary
artery disease, with a subsequent myocardial event, is
the major contributor to outcome.
5. Predicted mortality rates for patients with claudication
at 5, 10, and 15 years of follow-up are approximately
30%, 50%, and 70%, respectively.