A Brief Evidence Update for the U.S. Preventive Services Task Force (USPSTF)
Address correspondence to: Managing Editor USPSTF; 540 Gaither Road; Rockville, MD 20850; E-mail: info@ahrq.gov. Select for Copyright Information. The USPSTF recommendation based on this update is available online.
Contents
Introduction
Epidemiology and Background
Methodology
Key Questions and Results
Summary
Recommendations of Professional Organizations
References
Copyright, Reprinting, and Linking Information
Introduction
Systematic reviews of the literature serve as the basis for the U.S. Preventive Services Task
Force (USPSTF) recommendations on clinical prevention topics. In 1996, the USPSTF
addressed the utility of routine screening for peripheral arterial disease (PAD):
Routine screening for peripheral arterial disease in asymptomatic persons is not
recommended ("D" recommendation). Clinicians should be alert to symptoms of
PAD in persons at increased risk (persons over age 50, smokers, diabetics) and
evaluate patients who have clinical evidence of vascular disease.1
The USPSTF tailors the scope of these reviews to each topic. The USPSTF determined that
a brief, focused evidence review was needed to update its 1996 recommendation on screening for
PAD. AHRQ staff and the Lewin Group reviewed the literature published on this topic between
1994 and 2005, and AHRQ staff wrote this evidence update. The review was focused to search
for direct evidence of decreased PAD-specific morbidity (improved health outcomes) from
routine PAD screening, incremental benefit for patients (and subgroups) who received early
treatment secondary to screen-detected PAD, and harms from PAD screening. The USPSTF
reviewed and graded the evidence to draft its updated recommendations.
This brief update and
the updated USPSTF recommendations are available through the AHRQ Web site
(http://www.preventiveservices.ahrq.gov). The recommendations are also available at the
National Guideline Clearinghouse™ (http://www.guideline.gov).
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Epidemiology and Background
PAD refers to atherosclerotic occlusive disease of the arterial system distal to the aortic
bifurcation, and is a relatively common disorder in the elderly.2 The American Heart Association
estimates that as many as 8 to 12 million Americans have PAD and that nearly 75 percent of those with
PAD are asymptomatic.3 The prevalence of lower-extremity PAD based on ankle-brachial blood
pressure ratios is approximately 10 to 20 percent of community-dwelling individuals aged 65 and
older and 18 to 29 percent of patients aged 50 and older in general medicine practices.4-8
The prevalence of symptomatic claudication is less than half that of PAD. The disease
spectrum ranges from mild, intermittent claudication resulting in calf pain, to severe, chronic leg
ischemia requiring arterial bypass or amputation. Severe critical leg ischemia affects fewer than
1 million adults in the United States.5 Risk factors associated with PAD include older age,
cigarette smoking, diabetes mellitus, hypercholesterolemia, hypertension, and (possibly) genetic
factors.2
Screening for PAD may be conducted by instruments, such as history-taking or
questionnaires, or by ankle-brachial index (ABI). Results from one study found that the
sensitivity and positive predictive value of a classic history of claudication were only 54 percent and
9 percent, respectively, when compared with the results of formal noninvasive testing, such as the
ankle-brachial index.9 In general, less than 20 percent of persons with PAD are symptomatic,7,10
exacerbating the unreliability of history in the diagnosis of PAD.
Aside from history-taking, a common screening measure is the Edinburgh Claudication
Questionnaire (ECQ), which is a modification of the World Health Organization/Rose
Questionnaire. The ECQ has been validated in a study of approximately 300 patients aged 55 and
older who saw their physician for any complaint. When compared with the independent
assessment of two blinded clinicians, the ECQ showed a sensitivity of 91 percent and a specificity of
99 percent for the diagnosis of intermittent claudication.11
The ABI is another common screening tool in determining the presence of PAD, and it has
demonstrated better accuracy than other instruments. Hummel, et al. found that an ABI
measurement of less than 0.9 (the accepted cut-off for the presence of PAD) is 95 percent sensitive and
specific for detecting angiographic arterial disease.12 The accuracy of this screening tool
increases as the severity of lower extremity stenosis increases.
PAD is associated with increased risk of cardiovascular morbidity and mortality.6,13,14 Early
PAD is associated with several intermediate indicators for which the frequencies are higher and,
therefore, lend themselves for further study. These include intermittent claudication (a clinical
manifestation of atherosclerosis in the lower extremities), the maximum walking distance before
onset of intermittent claudication, and the ankle-brachial index.15
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Methodology
The literature search was guided by an analytical framework developed specifically for PAD
by the USPSTF. Specifically, this review focused on PAD outcomes and did not examine PAD
as a risk factor for coronary heart disease.
Five Key Questions were identified from this
framework:
- Does screening for PAD lead to reduced morbidity from PAD (including claudication, amputation, impaired ambulation)?
- What is the yield of screening (e.g., prevalence, sensitivity, specificity) for PAD in primary care practice?
- What are the harms of screening (e.g., labeling, over-diagnosis, over-treatment)?
- Does treatment of people with screening-detected PAD lead to improvement in the outcomes specified in Question #1 beyond the benefits of treatment at the time of symptoms?
- a. Is there a subgroup of screening-detected PAD patients in whom detection of PAD results in more effective treatment of claudication beyond identification of conventional risk factors alone (e.g., through earlier or more aggressive use of treatments, such as aspirin or other anti-platelet agents, lipid-lowering therapy, blood pressure treatment, or lifestyle intervention)?
- What are the harms of earlier treatment for PAD (i.e., side effects of treatment)?
The search strategy included a review of English language articles identified from PubMed®,
the Cochrane Library, and the National Guideline Clearinghouse™ published between 1994 and
2003. The search excluded letters, editorials, and narrative reviews. Studies of symptomatic (i.e.,
PAD or intermittent claudication) populations were also excluded from this search. Table 1 summarizes the results:
Search Criteria | Number |
---|
Peripheral Vascular Diseases [mh] OR Intermittent Claudication
[mh] | 3,500 |
Limits | Number |
---|
AND Mass Screening [mh] | 28 |
AND (Clinical Trial [pt] OR Randomized Controlled Trial [pt]) | 459 |
AND Practice Guideline [pt] | 4 |
AND Meta-analysis [pt] | 29 |
AND (Review [pt] AND systematic*[tw]) | 13 |
Total | 533 |
Abstracts were reviewed to determine which articles addressed the Key Questions. One
reviewer examined the abstracts with the instruction to retain all that were clearly in-scope and
those with potential or ambiguous relevance. These abstracts were then reviewed by a senior
staff member for relevance.
Upon finalizing this report, a subsequent bridge search was conducted of literature published
between January 2004 and June 2005. No relevant studies were identified.
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Key Questions and Results
Key Question 1: Does screening for PAD lead to reduced morbidity from PAD (including
claudication, amputation, impaired ambulation)?
One fair-quality randomized controlled trial (RCT) addressed this overarching question.
Fowler, et al. investigated the impact of increased physical activity and cessation of smoking on
the natural history of early PAD identified through population-based screening.15 Participants
were identified through either the ECQ or the ABI. The study involved 882 men divided equally
into a control group that received "usual care" from their general practitioner and an intervention group that received a "stop smoking and keep walking" regime. Followup occurred at 2 and 12
months via self-reported physical activity questionnaires. Maximum walking distance was the
outcome of interest. At 12 months, significantly more men allocated to the intervention group
had improved their maximum walking distance and reported walking more than 3 times per
week. More smokers in the intervention group had stopped smoking than had smokers in the
control group, but this difference was not statistically significant.
The study results indicated that
a combination of simple and safe interventions that are readily available in the community has
the potential to improve outcomes in early PAD. The study determined that ambulation did
improve as a result of the interventions applied. These interventions (smoking cessation and
increased physical activity) are recommended to most patients with or without health concerns,
regardless of the presence of PAD, as counseling measures to encourage healthy lifestyles.
Key Question 2: What is the yield of screening (e.g., prevalence, sensitivity, specificity) for PAD
in primary care practice?
No new evidence meeting search criteria was identified.
Key Question 3: What are the harms of screening (e.g., labeling, over-diagnosis, overtreatment)?
No new evidence meeting search criteria was identified.
Key Question 4: Does treatment of people with screening-detected PAD lead to improvement
in the outcomes specified in Question #1 beyond the benefits of treatment at the time of
symptoms?
One cross-sectional study addresses this question. McDermott, et al. investigated the
association of statin use with improved lower-extremity function in a population of persons with
and without PAD.16 Three hundred ninety-two men and women with PAD (defined as ABI<0.9)
and 249 without PAD (defined as 0.9<ABI<1.5) participated in the study. Participants were
recruited from noninvasive vascular laboratories and general medicine clinics. Names of
prescription drugs and over-the-counter medicines (but not their doses or duration of use) were
recorded. Outcome measures included 6-minute walking distance and 4-meter walking velocity.
The summary performance score—an accepted summary metric that indicates lower-extremity
functioning and predicts mobility loss, nursing home placement, and mortality among
community-dwelling older men and women—was calculated.
The study concluded that statin use, independent of cholesterol level and other confounding
variables, is significantly associated with superior lower-extremity leg functioning in patients
with and without PAD. There was no association between the outcome measures and aspirin,
angiotensin-converting enzyme (ACE) inhibitors, vasodilators, or beta-blockers. The authors
postulated that statin use favorably influenced functioning in patients with and without PAD due
to the medication's non-cholesterol-lowering properties.
Key Question 4a: Is there a subgroup of screening-detected PAD patients in whom detection of
PAD results in more effective treatment of claudication beyond identification of conventional risk factors alone (e.g., through earlier or more aggressive use of treatments, such as aspirin or
other anti-platelet agents, lipid-lowering therapy, blood pressure treatment, or lifestyle
intervention)?
One fair-quality study addressed this question for a subgroup of smokers. The outcome of
interest was first occurrence of intermittent claudication, which is an intermediate outcome of
interest in the Key Question. Tornwall, et al. performed a subgroup analysis of an RCT that
involved 26,289 male smokers aged 50 to 69 with no history or symptoms of intermittent
claudication.17 The Rose Questionnaire was administered annually to identify incident cases of
typical intermittent claudication. Subjects were randomly assigned to receive long-term
supplementation with vitamin E, beta-carotene, both, or placebo. There were 2,704 cases of first
occurrence of typical intermittent claudication during a median followup time of 4 years. The
adjusted relative risk (RR) for development of intermittent claudication among those who
received vitamin E only was 1.11 (95% confidence interval, 1.00-1.24); for those who received
both vitamin E and beta-carotene, adjusted RR was 1.02 (0.91-1.13); and among those who
received beta-carotene only, it was 1.02 (0.92-1.14). When compared with those who received no
vitamin E, the adjusted RR was 1.05 (0.98-1.14). Therefore, the analysis found that vitamin E
and beta-carotene have no primary preventive effects on intermittent claudication among middle-aged
males.
Key Question 5: What are the harms of earlier treatment for PAD (i.e., side effects of
treatment)?
No new evidence meeting the search criteria was identified.
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Summary
Although there is substantial literature on PAD, most recent evidence pertains to
symptomatic patients, including use of diagnostic tests (e.g., magnetic resonance angiography) or
treatments for intermittent claudication (e.g., exercise therapy, naftidrofuryl) or leg ischemia (e.g.,
revascularization via bypass surgery or angioplasty), and is therefore outside the scope of this
analysis.
Evidence does exist to support the use of increased physical activity and smoking cessation
to improve the outcomes from early PAD. These interventions, however, are already offered to
all patients to encourage healthy lifestyles and do not necessarily offer additional benefit for
persons with screen-identified PAD.
A cross-sectional study found that statin use was associated with superior lower-extremity
functioning in patients with and without PAD. No conclusions could be made regarding statin
dose or duration of use and the outcome of asymptomatic versus symptomatic PAD.
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Recommendations of Professional Organizations
The American Diabetes Association currently recommends annual screening for PAD in people
with diabetes that includes a history of claudication and palpation of pedal pulses.18 The
American Academy of Family Physicians recommends against the use of Doppler or duplex
ultrasound or other vascular laboratory tests in asymptomatic persons for PAD.19 A few
organizations, such as the American Heart Association and the Society of Interventional
Radiology, support the use of the ankle brachial index in the evaluation of suspected PAD.
For
further information, please refer to the following Web sites:
- American Heart Association, http://www.americanheart.org.
- American College of Surgeons, http://www.facs.org/index.html.
- Society of Interventional Radiology, http://www.sirweb.org/.
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References
1. U.S. Preventive Services Task Force. Guide to
Clinical Preventive Services, 2nd ed. Washington,
DC: Office of Disease Prevention and Health
Promotion; 1996.
2. Meijer WT, Grobee DE, Hunink MGM, Hofman A,
Hoes AW. Determinants of peripheral arterial disease
in the elderly: the Rotterdam Study. Arch Int Med 2000;160(19):2934-8.
3. American Heart Association. PAD Quick Facts.
Diseases and Conditions. Available at:
http://www.americanheart.org/presenter.jhtml?identifier=3020248. Accessed July 9, 2004.
4. Fowkes FG. Edinburgh Artery Study: prevalence of
asymptomatic and symptomatic peripheral arterial
disease in the general population. International
Journal of Epidemiology 1991;20:384-92.
5. Goldman L, Bennett JC, editors. Cecil's Textbook of
Medicine, 21st ed. Philadelphia: W.B. Saunders
Company, 2000.
6. McDermott MM. Peripheral arterial disease:
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7. Schroll M, Munck O. Estimation of peripheral
arteriosclerotic disease by ankle blood pressure
measurements in a population study of 60 year-old
men and women. J Chronic Dis 1981;34:261-9.
8. Meijer WT, Hoes AW, Rutgers D, Bots ML, Hofman
A, Grobbee DE. Peripheral arterial disease in the
elderly: the Rotterdam Study. Arterioscler Thromb
Vasc Biol 1998;18(2):185-92.
9. Criqui MH, Fronek A, Klauber MR, Barrett-Connor E,
Gabriel S. The sensitivity, specificity, and predictive
value of traditional clinical evaluation of peripheral
arterial disease: results from noninvasive testing in a
defined population. Circulation 1985;71(3):516-22.
10. Leng GC, Papacosta O, Whincup P, et al. Femoral
atherosclerosis in an older British population:
prevalence and risk factors. Atherosclerosis
2000;152(1):167-74.
11. Leng GC, Fowkes FG. The Edinburgh Claudication
Questionnaire: an improved version of the WHO/Rose
Questionnaire for use in epidemiological surveys. J
Clin Epidemiol 1992;45(10):1101-9.
12. Hummel BW, Hummel BA, Mowbry A, Maixner W,
Barnes RW. Reactive hyperemia vs treadmill exercise
testing in arterial disease. Arch Surg 1978;113(1):95-8.
13. Weitz JI, Byrne J, Clagett GP, et al. Diagnosis and
treatment of chronic arterial insufficiency of the lower
extremities: a critical review. Circulation 1996;94(11):3026-49.
14. Criqui MH, Langer RD, Fronek A, et al. Mortality
over a period of 10 years in patients with peripheral
arterial disease. N Engl J Med 1992;326(6):381-6.
15. Fowler B, Jamrozik K, Norman P, Allen Y, Wilkinson
E. Improving maximum walking distance in early
peripheral arterial disease: randomised controlled trial.
Aust J Physiother 2002;48(4):269-75.
16. 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(5):757-61.
17. Tornwall ME, Virtamo J, Haukka JK, et al. Effect of
alpha-tocopherol (vitamin E) and beta-carotene
supplementation on the incidence of intermittent
claudication in male smokers. Arterioscler Thromb
Vasc Biol 1997;17(12):3475-80.
18. Mayfield JA, Reiber GE, Sanders LJ, Janisse D,
Pogach LM. Preventive foot care in diabetes. Diabetes
Care 2004;27 Suppl 1:S63-S64.
19. American Academy of Family Physicians.
Recommendations for periodic health examinations.
Clinical Care and Research. Available at:
http://www.aafp.org/x24973.xml. Accessed July 13,
2004.
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Copyright, Reprinting, and Linking Information
This document is in the public domain within the United States. For information on reprinting, contact Randie Siegel, Director, Division of Printing and Electronic Publishing, Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850. Requests for linking or to incorporate content in electronic resources should be sent to: info@ahrq.gov.
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AHRQ Publication No. 05-0583-B-EF
Current as of August 2005
Internet Citation:
Screening for Peripheral Arterial Disease: A Brief Evidence Update for the U.S. Preventive Services Task Force (USPSTF). AHRQ Publication No. 05-0583-B-EF, August 2005. Agency for Healthcare
Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/uspstf05/pad/padup.htm