Grade: I The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Read the clinical considerations section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for peripheral artery disease (PAD) and cardiovascular disease (CVD) risk with the ankle-brachial index (ABI) in asymptomatic adults. See the Clinical Considerations section for suggestions for practice regarding the I statement.
Frequency of Service
No information available.
Risk Factor Information
In addition to older age, major risk factors for PAD include diabetes, current smoking, high blood pressure, high cholesterol levels, obesity, and physical inactivity, with current smoking and diabetes showing the strongest association.6
Patient Population Under Consideration
This recommendation applies to asymptomatic adults without a known diagnosis of PAD, CVD, or severe chronic kidney disease.
Suggestions for Practice Regarding the I Statement
In deciding whether to screen for PAD with the ABI in asymptomatic adults, clinicians should consider the following factors.
Potential Preventable Burden
The true prevalence of PAD in the general population is not known. Data from the 1999-2004 National Health and Nutrition Examination Survey show that 5.9% of the US population 40 years or older (7.1 million adults) has a low ABI (≤0.9), which may indicate the presence of PAD.1 The most recent prevalence data available are from a screening trial of Danish men aged 65 to 74 years, which identified a prevalence of 11% when PAD was defined as an ABI less than 0.9 or greater than 1.4. Two-thirds of identified patients reported no intermittent claudication, which is considered to be the classic symptom of PAD.2
A 2016 systematic review3 found that over 5 years of follow-up, approximately 7% of patients with asymptomatic PAD developed intermittent claudication and approximately 21% of patients with intermittent claudication progressed to critical limb ischemia. In addition to the risk of worsening symptoms in the lower limbs, a low ABI is associated with increased risk of CVD events. Studies suggest that the 5-year cumulative incidence of cardiovascular mortality is 9% (95% CI, 7%-12%) in asymptomatic patients with a low ABI and 13% (95% CI, 9%-17%) in symptomatic patients with a low ABI; patients with a normal ABI had an average incidence of 5% (95% CI, 4%-6%).3
Although minimal harms are associated with the ABI test, subsequent harms are possible. False-positive test results, false-negative test results, anxiety, labeling, and exposure to gadolinium or contrast dye from confirmatory MRA or CTA may occur, while further evaluation of CVD risk may involve stress testing or angiography. If the ABI is used to determine the need for pharmacologic treatment to reduce CVD risk, patients could receive additional treatment with resulting adverse effects or be reclassified to a lower risk category and potentially discontinue treatment that may be beneficial.4
An older study of US primary care practices found that 12% to 13% reported using the ABI for CVD screening weekly or monthly, 6% to 8% reported using it annually, and 68% reported never using it. However, the study was conducted more than a decade ago and may not reflect current practice.5
Assessment of Risk
In addition to older age, major risk factors for PAD include diabetes, current smoking, high blood pressure, high cholesterol levels, obesity, and physical inactivity, with current smoking and diabetes showing the strongest association.6 Although women have a slightly lower ABI compared with men, the prevalence of low ABI does not appear to vary significantly by sex after adjusting for age.4 Among healthy US men aged 40 to 75 years without a history of CVD, the risk for PAD over 25 years in the absence of 4 conventional cardiovascular risk factors (current smoking, high blood pressure, high cholesterol levels, or type 2 diabetes) is rare (9 cases per 100,000 men per year). These 4 risk factors account for 75% of all cases of PAD, and at least 1 of these risk factors is present at the time of PAD diagnosis in 96% of men.7
Resting ABI is the most commonly used measurement for detection of PAD in clinical settings, although variation in measurement protocols may lead to differences in the ABI values obtained. Ankle-brachial index is calculated as the systolic blood pressure obtained at the ankle divided by the systolic blood pressure obtained at the brachial artery while the patient is lying down. A ratio of less than 1 (typically defined as <0.9) is considered abnormal and is commonly used to define PAD. Data on the accuracy of the ABI in asymptomatic populations are limited. One study of men and women older than 70 years reported that an ABI of less than 0.9 had a sensitivity of 15% to 20% and a specificity of 99% compared with whole-body MRA.8, 9 Physical examination has low sensitivity for detecting mild PAD in asymptomatic persons.4 Although femoral bruit (vascular murmur at the femoral artery), pulse abnormalities, or ischemic skin changes significantly increase the likelihood ratio for low ABI (≤0.9), these signs indicate moderate to severe obstruction of blood flow or clinical disease.10 The clinical benefits and harms of screening for PAD with a physical examination have not been well evaluated, although such screening is often performed.4
Treatment and Interventions
Because PAD is a manifestation of systemic atherosclerosis in the lower limbs, treatment of PAD has 2 potential targets: reducing morbidity and mortality from lower limb ischemia and preventing CVD events due to systemic atherosclerosis. Treatment of PAD focuses on improving outcomes in symptomatic patients (eg, increasing walking distance and quality of life by improving symptoms of intermittent claudication and leg function, preventing or reducing limb complications, and preserving limb viability). Interventions to prevent CVD events include smoking cessation, lowering cholesterol levels, managing high blood pressure, and antiplatelet therapy. However, because the major risk factors for PAD are also used to calculate CVD risk, patients with a low ABI may already be recommended for these treatments.
Additional Approaches to Prevention
The National Heart, Lung, and Blood Institute provides resources on assessing cardiovascular risk, including a link to an online version of the Pooled Cohort Equations,11 as well as resources on preventing PAD.12 Healthy People 2020 provides a database of evidence-based resources for achieving Healthy People 2020 goals, including interventions to prevent CVD.13
The USPSTF has made recommendations on many factors related to CVD prevention, including screening for high blood pressure,14 statin use,15 screening for diabetes,16 counseling on smoking cessation,17 counseling on healthful diet and physical activity,18 and CVD risk assessment with nontraditional risk factors.19 In addition, the USPSTF recommends use of low-dose aspirin by certain adults at increased risk for CVD.20
Peripheral artery disease is a manifestation of atherosclerosis in the lower limbs. It can impair walking and, in severe cases, can lead to tissue loss, infection, and amputation. In addition to morbidity directly caused by PAD, patients with PAD are at increased risk for CVD events, because atherosclerosis is a systemic disease that also causes coronary and cerebrovascular events. The most recent data from the National Health and Nutrition Examination Survey (1999-2004) show that 5.9% of the US population 40 years or older has a low ABI (≤0.9), which indicates the presence of PAD. The true prevalence of PAD is difficult to establish, because more than half of persons with a low ABI are asymptomatic or have atypical symptoms and because population screening studies that use a gold standard diagnostic test are lacking.
The USPSTF found inadequate evidence on the accuracy of the ABI for identifying asymptomatic persons with PAD who can benefit from treatment.
Benefits of Early Detection and Intervention or Treatment
The USPSTF found inadequate evidence to assess whether screening for and treatment of PAD in asymptomatic patients leads to clinically important benefits in either preventing the progression of PAD or preventing CVD events.
Harms of Early Detection and Intervention or Treatment
The USPSTF found adequate evidence that the direct harms of screening, beyond the time needed for testing, are minimal. Other harms may include false-positive test results, exposure to gadolinium or contrast dye if magnetic resonance angiography (MRA) or computed tomography angiography (CTA) is used to confirm a diagnosis of PAD, anxiety, labeling, and opportunity costs. If a low ABI finding prompts further evaluation for CVD, harms could include those attributable to stress testing and angiography. The harms of preventive treatment for PAD or CVD include bleeding (with aspirin use) and possibly diabetes (with statin use).
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for PAD and CVD risk with the ABI in asymptomatic adults.
Other Considerations Research Needs and Gaps Large, population-based, randomized trials of screening vs no screening are needed to determine whether screening for PAD with the ABI improves clinical outcomes. One ongoing study in Denmark has published preliminary results; however, that study limited enrollment to men aged 65 to 74 years and included screening for abdominal aortic aneurysm and high blood pressure, making it difficult to evaluate the benefit of screening with the ABI alone.2 Two other ongoing trials that include the ABI as part of a screening bundle may have the same limitation.21, 22 Future studies, in addition to isolating the effect of individual tests, should address the population of persons at potentially increased risk for PAD who are not already receiving interventions to reduce cardiovascular risk, because this is the population most likely to benefit from an additional screening intervention. Studies of screening with the ABI and interventions to stop disease progression in the lower limbs in more diverse populations (eg, women, racial/ethnic minorities, or persons with a lower socioeconomic status) and populations at high risk (ie, persons with diabetes) would also be valuable. Update of Previous TF Recommendations This recommendation replaces the 2013 USPSTF recommendation. Although the USPSTF expanded its evidence review to include a broader population and range of interventions, the USPSTF’s recommendation remains an I statement. Recommendations of Others The American College of Cardiology and the American Heart Association released joint practice guidelines recommending screening with the ABI in patients at increased risk, including adults 65 years or older, adults 50 years or older with risk factors for atherosclerosis or a family history of PAD, and adults younger than 50 years with diabetes and 1 other risk factor for atherosclerosis.31 In 2015, the Society for Vascular Surgery recommended against screening with the ABI in adults in the absence of risk factors, history, signs, or symptoms of PAD; however, screening is considered reasonable in adults at higher risk (defined as age older than 70 years, current smoking, or diabetes; abnormal pulse examination; or other established CVD).32 In 2013, the American Academy of Family Physicians concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for PAD and CVD risk with the ABI in asymptomatic adults.33