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Peripheral Arterial Disease: Tips on Diagnosis and Management


Signs and symptoms that strongly suggest peripheral arterial occlusive disease include diminished or absent pedal pulses, a unilaterally cool limb, and atrophic skin that is shiny and hairless. An ankle-brachial index of less than 0.5 suggests multisegment disease. Management goals are to decrease functional impairment, treat underlying atherosclerosis, and control risk factors. Smoking cessation is imperative. A graduated walking program is a mainstay of treatment and is associated with greater improvement in pain-free walking than is drug therapy. Surgery and percutaneous intervention are generally reserved for patients with lifestyle-limiting claudication, ischemic pain at rest, tissue loss, or gangrene.

Chronic peripheral arterial occlusive disease (PAOD) is a problem seen increasingly often in office practice, as the population of older Americans grows. This condition affects 7% of those aged 35 to 44 years and 20% of those older than 65 years.1 The prevalence ranges from 3% to 18% for men older than 55 years and women older than 60 years.1,2 It is twice as common in men as in women. Most patients with PAOD have underlying atherosclerosis and are at risk for acute or chronic ischemia.

Since many persons who have symptoms of peripheral arterial disease attribute them to "normal aging" and may not report them, the diagnosis may be missed if a comprehensive history and vascular examination are not a routine part of the assessment.3 A high index of suspicion is warranted in patients with hypertension, hyperlipidemia, or a personal or family history of cardiovascular disease. In this article, I offer guidelines on the diagnosis of PAOD and discuss key treatment strategies.


PAOD has no definite genetic component. The principal risk factors include smoking, hyperlipidemia, diabetes, hypertension, obesity, elevated homocysteine levels, and a family history of premature atherosclerosis. The hallmark of chronic occlusion-intermittent claudication of sudden or gradual onset-manifests as pain or fatigue with exercise that is relieved by rest. As the disease progresses, the distance that the patient can walk without symptoms is reduced.

Intermittent claudication occurs when blood flow is restricted through partially or completely occluded peripheral arteries, which sets up small areas of anaerobic metabolism in affected muscles. With rest, adequate blood flow and aerobic metabolism are restored. If intermittent claudication is the patient's only symptom, the extremity may look normal.

The site of arterial occlusion determines the site of pain or fatigue. Occlusion in the aorta or iliac arteries leads to claudication in thebuttocks and hips. In femoropopliteal disease, claudication typically occurs in the calf. The degree of stenosis determines exercise tolerance. A severely stenotic vessel can cause pain at rest.


The hallmark of chronic PAOD in the physical examination is evidence of decreased blood flow in the lower extremities.The findings include diminished or absent pulses, and a limb that is cooland/or pale and that has dependent ruborand atrophic skin that is shiny and hairless. Findings that point to severe PAOD include femoral bruits, unilateral reduced measured skin temperatures, abnormal foot pulses, an absent femoral pulse, and ulcers on the toes or feet. (Unlike neuropathic diabetic ulcers, those associated with PAOD are painful.) The combination of abnormal pedal pulses and a femoral artery bruit, prolonged venous filling time (more than 3 to 5 seconds), and a unilateral cool limb strongly suggest PAOD in a patient older than 60 years who has symptoms of claudication and atrophic skin changes.3


Although laboratory testing is not necessary for the initial diagnosis, it can help confirm the diagnosis and quantify the extent of disease.

The ankle-brachial index (ABI) is used to compare the systolic blood pressure in the upper and lower limbs for evidence of arterial occlusion. The systolic blood pressure is measured at the ankle and at the brachial artery with a Doppler probe. The ankle systolic blood pressure is divided by the brachial artery systolic blood pressure. A normal result is greater than 1. An ABI of 0.5 to 1.0 is evidence of involvement of a single arterial segment. An ABI of less than 0.5 is evidence of multisegment disease, and an ABI of less than 0.3 can be evidence of stenosissevere enough to result in tissue damage and/or pain at rest.4

Another method for comparing the systolic blood pressure between the arm and the ankle when Doppler ultrasonography is not available is the visual flush test (Box), which is similar to the Allen test in the wrist.5I have found that the results with this meth-od correlate with the ABI calculated with use of a Doppler probe 85% of the time.

Other options for testing include conventional angiography, photoplethysmography, Doppler and duplex ultrasonography, and CT and magnetic resonance (MR) angiography. Conventional angiography and duplex arterial ultrasonography are not necessary for the initial diagnosis of PAOD. They are used mainly in patients who may be candidates for surgery or other interventional treatment. Photoplethysmography is useful in patients who have calcified arteries. CT and MR angiography have excellent sensitivity and specificity (98% and 96%, respectively) compared with conventional angiography.6 Their role in the management of PAOD remains to be determined, principally because of concerns about cost and lack of consensus about whether they are essential for making the diagnosis. Doppler ultrasonographic measurement of vascular flow has a sensitivity of 88% and a specificity of 95%.7

Laboratory blood testing is not necessary in the initial diagnosis of PAOD. However, a fasting lipid panel and serum glucose test are recommended to check for hyperlipidemia and diabetes mellitus. New information on the role of inflammation in vascular disease is emerging. C-reactive protein and homocysteine levels are elevated in patients with PAOD; however, their role in the diagnosis of this disease remains to be determined.8,9


Aggressive management is essential to decrease functional impairment, improve quality of life, and reduce the risk of critical limb ischemia and underlying systemic atherothrombosis (Table). These measures will lower the incidence of cardiovascular ischemic events, especially myocardial infarction and stroke.10

Smoking cessation is a cornerstone of treatment.1 Other measures include exercise, antiplatelet therapy, lipid-lowering therapy, and correction of other modifiable vascular risk factors.11,12 Recent data indicate that many patients with PAOD are not treated comprehensively.11 Management of pain and any comorbid conditions, such as diabetes, is important as well.

Educate patients about the warning signs and symptoms of a potentially limb-threatening arterial thrombus so that they will know when to seek urgent medical care. Meticulous prophylactic foot and limb care is critical-especially for diabetic patients-to avoid complications (such as ulcerations)that may result from vascular insufficiency. Instruct patients to avoid heat application or prolonged elevation of the affected extremity. Elevation decreases arterial blood flow in partially occluded arteries. Heat can cause tissue damage in skin that has altered heat-dissipating mechanisms as a result of diminished blood flow.

Exercise. Physical activity is essential.10 A meta-analysis of randomized, controlled trials concluded that exercise increased the duration of walking time by an average of 150%.13 For optimum benefit, patients should walk every day-increasing the distance in small increments-until they experience claudication. The distance of each walk should be noted.

In a meta-analysis that compared drug treatments with smoking cessation or a graduated exercise program, exercise was associated with the greatest improvement in pain-free walking.13 The review was updated in 2001 and included patients who had undergone angioplasty and bypass surgery. Graduated exercise continued to provide excellent improvement in walking time and distance; the results were comparable to those obtained with surgery or angioplasty. As challenging as it is to motivate patients to start and continue an exercise program, the benefits of exercise cannot be overstated.

Pharmacologic therapy. Although some agents were associated with modest statistically significant increases in walking time and distance, none approached the improvements shown with a graduated exercise program.

Statins have recently been studied to assess their effect on walking time and distance in patients with PAOD. One randomized, controlled trial demonstrated an increase in pain-free walking time of 50 seconds that was associated with decreased serum cholesterol levels.14 This effect was similar to that obtained with cilostazol. A second study demonstrated improved walking distance with statins independent of serum cholesterol levels.15 Regardless of whether statins increase walking distances as a result of their cholesterol-lowering or anti- inflammatory effects, the improvement is much less significant than that achieved with a graduated walking program.

Pentoxifylline has been the most intensively studied medication for PAOD. One meta-analysis demonstrated a modest increase in functional status.13 A pooled randomized, controlled trial demonstrated improved walking capacity.16 However, most studies of this agent have been of poor quality; the results are thus questionable.

In a small study with a rather brief follow-up period, verapamil was associated with a slight increase in walking distances for patients with the most severe disease.17 Cilostazol was associated with a greater walking distance than pentoxifylline, but the improvement was far less than that seen with graduated walking.18,19

Other medications and supplements-including gingko biloba, buflomedil, garlic, propionyl-L-carnitine, and vitamin E-have not been associated with a significant increase in walking distances compared with placebo.20-26 Trials of heparin showed that this agent was associated with an increase in bleeding complications; it is therefore not recommended.27

Surgery. Surgery or percutaneous intervention is generally reserved for patients with lifestyle-limiting claudication, ischemic pain at rest, or tissue loss/gangrene.The options for surgical intervention include endarterectomy, bypass surgery, angioplasty, and amputation. Surgery for aortoiliac disease is associated with better outcomes than surgery for disease in other distributions.1 In patients with femoropopliteal disease, surgery is reserved for those with severe or disabling symptoms. Promising procedures include laser angioplasty and stent placement. Amputation is indicated for patients who have unsuccessful arterial reconstructive surgery, gangrene, persistent infection that does not respond to conservative treatment, or intractable pain.

A recent meta-analysis compared bypass surgery with percutaneous angioplasty and thromboendarterectomy.28 There was no significant difference in mortality or amputation rates among the 3 groups. The surgical group did show improved patency at 1 year; however, the significance for long-term outcome is unclear. Larger and longer trials were recommended.


Screening the general population for PAOD has not been recommended. A recent study noted that patients at risk are often asymptomatic, but there is no evidence that early detection improves outcomes.29 In 1996, the US Preventive Services Task Force gave routine screening for PAOD by history, palpation of pulses, and Doppler ultrasound evaluation a "D" recommendation, indicating that it may actually harm patients by potentially subjecting them to invasive testing, such as angiography, and to adverse effects from medical therapy.



1. Brass EP, Hiatt WR, Nehler MR. Peripheral arterial disease. In: Wachter RM, Goldman L, Hollander H, eds. Hospital Medicine. Philadelphia: Lippincott, Williams and Wilkins; 2000.

2. Collins TC, Petersen NJ, Suarez-Almazor M, Ashton CM. The prevalence of peripheral arterial disease in a racially diverse population. Arch Intern Med. 2003;163:1469-1474.

3. Doyle J, Creager MA. Pharmacotherapy and behavioral intervention for peripheral arterial disease. Rev Cardiovasc Med. 2003;4:18-24.

4. McGee SR, Boyko EJ. Physical examination and chronic lower-extremity ischemia. A critical review. Arch Intern Med. 1998;158:1357-1364.

5. Fronek A, Criqui MH, Feigelson HS. A simple screening method for peripheral arterial occlusive disease. J Vasc Surg. 1985;22:122.

6. Visser K, Hunink MG. Peripheral arterial disease: gadolinium-enhanced MR angiography versus color-guided duplex US: a meta-analysis. Radiology. 2000;216:67-77.

7. Koelemay MJ, den Hartog D, Prins MH, et al. Diagnosis of arterial disease of the lower extremities with duplex ultrasonography. Br J Surg. 1996;83: 404-409.

8. Ridker PM, Cushman M, Stampfer MJ, et al. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation. 1998;97:425-428.

9. Graham IM, Daly LE, Refsum HM, et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Report. JAMA. 1997;277:1775-1781.

10. Stewart KJ, Hiatt WR, Regensteiner JG, Hirsch AT. Exercise training for claudication. N Engl J Med. 2002;347:1941-1951.

11. Cassar K, Coull R, Bachoo P, et al. Management of secondary risk factors in patients with intermittent claudication. Eur J Vasc Endovasc Surg. 2003;26: 262-266.

12. Bradbury AW. The role of cilostazol (Pletal) in the management of intermittent claudication. Int J Clin Pract. 2003;57:405-409.

13. Leng GC, Fowler B, Ernst E. Exercise for intermittent claudication. Cochrane Database Syst Rev. 2000;(2):CD000990.

14. Mohler ER 3rd, Hiatt WR, Creager MA. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation. 2003;108:1481-1486.

15. McDermott MM, Guralnik JM, Greenland P, et al. Statin use and leg functioning in patients with and without lower-extremity peripheral arterial disease. Circulation. 2003;107:757-761.

16. Hood SC, Moher D, Barber GG. Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials. Can Med Assoc J. 1996;15:1053-1059.

17. Bagger JP, Helligsoe P, Randsback F, et al. Effect of verapamil in intermittent claudication. A randomized, double-blind, placebo-controlled, cross-over study after individual dose-response assessment. Circulation. 1997;95:411-414.

18. Money SR, Herd JA, Isaacsohn JL, et al. Effect of cilostazol on walking distances in patients with intermittent claudication caused by periph-eral vascular disease. J Vascular Surg. 1998;27: 267-274.

19. Regensteiner JG, Ware JE Jr, McCarthy WJ, et al. Effect of cilostazol on treadmill walking, community-based walking ability, and health-related quality of life in patients with intermittent claudication due to peripheral arterial disease: meta-analysis of six randomized controlled trials. J Am Geriatr Soc. 2002;50:1939-1946.

20. Corsi C, Pollastri M, Marrapodi E. L-propionylcarnitine effect on postexercise and postischemic hyperemia in patients affected by peripheral vascular disease. Angiology. 1995;46:705-713.

21. Ciocon JO, Galindo-Ciocon D, Galindo DJ. A comparison between aspirin and pentoxifylline in relieving claudication due to peripheral vascular disease. Angiology. 1997;48:237-240.

22. Blume J, Kieser M, Holscher U. Placebo- controlled double blind study on the efficacy of gingko biloba extract EGb 761 in trained patients suffering from intermittent claudication [in German]. Vasa. 1996;25:265-274.

23. De Backer TL, Vander Stichele RH, Bogaert MG. Buflomedil for intermittent claudication. Cochrane Database Syst Rev. 2001;(1):CD000988.

24. Jepson RG, Kleijnen J, Leng GC. Garlic for peripheral arterial occlusive disease. Cochrane Data-base Syst Rev. 2000;(2):CD000095.

25. Kleijnen J, Mackerras D. Vitamin E for the treatment of intermittent claudication. In: The Cochrane Library. Issue 1, 1998. Oxford, England: Update Software.

26. Villarruz MV, Dans A, Tan F. Chelation therapy for atherosclerotic cardiovascular disease. Cochrane Database Syst Rev. 2002;(4):CD002785.

27. Cosmi B, Conti E, Coccheri S. Anticoagulants (heparin, low molecular weight heparin and oral anticoagulants) for intermittent claudication. Cochrane Database Syst Rev. 2001;(3):001999.

28. Leng GC, Davis M, Baker D. Bypass surgery for chronic lower limb ischemia. Cochrane Database Syst Rev. 2002;Issue 4.

29. US Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd ed. Alexandria, Va: International Medical Publishing; 1996.

30. Burns P, Gough S, Bradbury AW. Management of peripheral arterial disease in primary care. BMJ. 2003;326:584-588.

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