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


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.


   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

   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

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.

   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

             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.


   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;
   3. Mohler, ER. Medical management of claudication. UpToDate 2004
   4. Mohler, E.R. et al. Noninvasive diagnosis of peripheral vascular disease.
      UpToDate 2004

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