PERIPHERAL VASCULAR DISEASE
Paul B. Tabereaux, M.D., M.P.H.
WEEK 13
Learning Objectives:
1. To understand the risk factors, clinical presentation, and evaluation of peripheral
vascular disease
2. Recognize different modalities of testing for peripheral vascular disease
3. Evaluate the options of medical therapy for this disorder
CASE ONE:
Ms. A.K. Leggs is a 66-year-old female that presents to your office with complaints
of left lower extremity pain. She states that while walking on the golf course she
gets pain in her lower calf, primarily on her left side. She states that when she stops
and rests on a bench at the next tee, the pain slowly resolves. She does not have the
pain when she uses a golf cart.
Her past history is significant for HTN, hyperlipidemia (Recent: LDL 160,
Triglycerides of 210). She takes HCTZ, and was recently started on atorvastatin
10mg after her recent lab work.
Examination of her legs shows that her left leg is slightly cooler to the touch than
her right. There is paucity of hair on her lower leg and on exam you note a
diminished posterior tibial pulsation.
Questions:
1. What risk factors does this patient have for peripheral vascular disease?
Atherosclerosis is the leading cause of occlusive arterial disease of the
extremities in patients over 40 years old; the highest incidence occurs in the sixth
and seventh decades of life. As in patients with atherosclerosis of the coronary
and cerebral vasculature, there is an increased prevalence of peripheral
atherosclerotic disease in individuals with diabetes mellitus,
hypercholesterolemia, hypertension, or hyperhomocysteinemia and in cigarette
smokers.
2. What clues for PVD should be ascertained in the history and physical?
Fewer than 50% of patients with peripheral arterial disease (PAD) are
symptomatic, though many have a slow or impaired gait. The most common
symptom is intermittent claudication, which is defined as a pain, ache, cramp,
numbness, or a sense of fatigue in the muscles; it occurs during exercise and is
relieved by rest. The site of claudication is distal to the location of the occlusive
lesion. For example, buttock, hip, and thigh discomfort occur in patients with
aortoiliac disease (Leriche syndrome), whereas calf claudication develops in
patients with femoral-popliteal disease. Symptoms are far more common in the
lower than in the upper extremities because of the higher incidence of obstructive
lesions in the former region. In patients with severe arterial occlusive disease,
critical limb ischemia may develop. Patients will complain of rest pain or a
feeling of cold or numbness in the foot and toes. Frequently, these symptoms
occur at night when the legs are horizontal and improve when the legs are in a
dependent position. With severe ischemia, rest pain may be persistent.
Important physical findings of PAD include decreased or absent pulses distal to
the obstruction, the presence of bruits over the narrowed artery, and muscle
atrophy. With more severe disease, hair loss, thickened nails, smooth and shiny
skin, reduced skin temperature, and pallor or cyanosis are frequent physical
signs. In addition, ulcers or gangrene may occur. Elevation of the legs and
repeated flexing of the calf muscles produce pallor of the soles of the feet,
whereas rubor, secondary to reactive hyperemia, may develop when the legs are
dependent. The time required for rubor to develop, or for the veins in the foot to
fill when the patient's legs are transferred from an elevated to a dependent
position, is related to the severity of the ischemia and the presence of collateral
vessels. Patients with severe ischemia may develop peripheral edema because
they keep their legs in a dependent position much of the time. Ischemic neuritis
can result in numbness and hyporeflexia.
3. How would you begin your workup for PVD?
ABI’s – please see Figure 1 of the NEJM article.
A relatively simple and inexpensive method to confirm the clinical suspicion of
arterial occlusive disease is to measure the resting and post-exercise systolic
blood pressures in the ankle and arm. This measurement is referred to as the
ankle-brachial (or ankle-arm) index or ratio and provides a measure of the
severity of peripheral vascular disease.
Calculation of the ankle-brachial index (ABI) is performed by measuring the
systolic blood pressure (by Doppler probe) in the brachial, posterior tibial, and
dorsalis pedis arteries. The highest of the four measurements in the ankles and
feet is divided by the higher of the two brachial measurements:

Normal ABI is 1.0 to as high as 1.3, since the pressure is higher in the
ankle than in the arm.

An ABI below 0.9 has 95 percent sensitivity (and 100 percent
specificity) for detecting angiogram-positive peripheral vascular
disease and is associated with 50 percent stenosis in one or more
major vessels.

An ABI of 0.40 to 0.90 suggests a degree of arterial obstruction often
associated with claudication.

An ABI below 0.4 represents advanced ischemia.
If ABIs are normal at rest, but symptoms strongly suggest claudication, ABIs and
segmental pressures should be obtained before and after exercise on a treadmill
or using active pedal plantar flexion, which involves repeatedly standing up on
the toes.
A potential source of error with the ABI is that calcified vessels may not compress
normally, possibly resulting in falsely elevated Doppler signals. An ABI above 1.3
is suspicious for a calcified vessel, especially among patients with diabetes
mellitus. In some patients with arterial calcification, an accurate pressure may be
obtained by measuring the toe pressure. In this setting, one must recognize that a
pressure gradient of 20 to 30 mmHg normally exists between the ankle and the
toe.
4. What further tests may be performed if an abnormal result is found?
The next diagnostic test after ABI is segmental pressures and pulse volume
recording amplitudes, performed in the vascular laboratory. Some laboratories
also perform duplex Doppler ultrasound, evaluating the spectral waveform. After
these tests, magnetic resonance angiography (MRA) is recommended to evaluate
for the extent and level of disease. MRA is usually performed if revascularization
is being considered.
5. Can PVD be asymptomatic?
In one report, 239 men and women ages 55 and older with no history of PVD
were recruited from a general internal medicine practice and evaluated in a
noninvasive vascular laboratory. The ankle-brachial index (ABI) was abnormal
(<0.9) in 14%. While most patients did not report exertional leg symptoms, they
were not able to walk as far in six minutes as a group of patients without PVD
(1,362 versus 1,539 feet).
Detection of asymptomatic PVD has value because it identifies patients at
increased risk of atherosclerosis at other sites. As an example, as many as 50% of
patients with PVD have at least a 50% stenosis in one renal artery. Thus,
patients with asymptomatic PVD, most often detected by ABI, should be
aggressively treated with risk factor reduction.
6. What medical therapy options would you offer to this patient?
The medical management of moderate to severe intermittent claudication
secondary to peripheral vascular disease involves three modalities:

Risk factor modification
All patients with claudication should also be encouraged to modify risk
factors for vascular disease. Lipid- lowering is clearly beneficial in
patients with peripheral vascular disease. The benefits of smoking
cessation, diabetes control, and lowering blood pressure in terms of
improving claudication symptoms are not clear, but can be recommended
on other grounds. Beta-1 selective blockers do not appear to adversely
effect claudication symptoms. ACE inhibitors may protect against
cardiovascular events in patients with peripheral vascular disease.

Exercise training or rehabilitation
A supervised exercise program should be considered in all patients who
are motivated and have the necessary resources.
A meta-analysis of 21 non-randomized and randomized studies found that
exercise training increased the distance to onset of claudication by 179%.
The greatest improvements in walking ability occurred when each exercise
session lasted more than 30 minutes with at least three exercise sessions
per week, when the patient walked until near maximal pain was reached at
each session, and when the program continued for at least six months. A
later meta-analysis that considered only randomized, controlled trials,
found that exercise produced significant improvements in walking time
compared with both angioplasty and antiplatelet therapy.

Pharmacologic therapy
Antiplatelet agents are warranted in all patients with claudication. The
Sixth American College of Chest Physicians Consensus Conference
recommended that aspirin alone (81 to 325 mg/day) or in combination
with dipyridamole should be given indefinitely because it can modify the
natural history of intermittent claudication and because these patients are
at high risk for future cardiovascular events. The guidelines suggest that
clopidogrel may be superior to aspirin and should be considered an
alternative treatment.
Cilostazol is probably the most effective drug therapy; the optimal clinical
therapeutic benefit resulting in improved pain free walking distance is
likely to occur with the combination of exercise and cilostazol. Cilostazol
appears to be more effective than pentoxifylline. This was illustrated in a
trial of 698 patients randomly assigned to pentoxifylline (400 mg TID),
cilostazol (100 mg BID), or placebo for 24 weeks. The increase in mean
maximal walking distance over baseline with pentoxifylline and placebo
was the same (30 and 34 percent, respectively), but the increase with
cilostazol was significantly greater (54 percent). The Sixth ACCP
Consensus Conference recommended a trial of cilostazol in patients
experiencing disabling claudication, particularly when lifestyle
modification alone is ineffective and revascularization cannot be offered
or is declined by the patient. Cilostazol is not recommended for routine
use in all patients because of its cost and modest clinical benefit.
Cilostazol may be taken safely with aspirin and/or clopidogrel without an
additional increase in bleeding time.
BONUS:
7. What are the indications for using a revascularization technique in
individuals with PVD?

Surgery should be limited to low risk patients with disabling symptoms
who can be expected to tolerate the procedure and live long enough to
enjoy the improved quality of life; patients who benefit most from elective
surgical revascularization are generally under 70 years of age,
nondiabetic, and have little evidence of disease distal to the primary
lesion.

Revascularization using percutaneous techniques is indicated when the
patient has lifestyle- limiting claudication that does not respond to
conventional medical therapy; it may also be considered in patients who
have severe disease when there is a focal stenosis or occlusion, in some
cases to augment a surgical procedure, and in patients who have limb
threatening ischemia but are not surgical candidates.
References:
1. Hiatt, WR. Medical treatment of peripheral arterial disease and claudication.
NEJM 2001; 344:1608-1621.
Additional References:
1. Kasper, DL. Harrison's Principles of Internal Medicine, 16th Edition
2. McDermott, M.M. et al. Prevalence and significance of unrecognized lower
extremity peripheral arterial disease in general medicine practice. JGIM 2001;
16:384-90
3. Mohler, ER. Medical management of claudication. UpToDate 2004
4. Mohler, E.R. et al. Noninvasive diagnosis of peripheral vascular disease.
UpToDate 2004