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Editorials |

Ankle–Brachial Index Screening to Improve Health Outcomes: Where Is the Evidence? FREE

Mary McGrae McDermott, MD
[+] Article and Author Information

From Northwestern University; Chicago, Illinois.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1561.

Requests for Single Reprints: Mary McGrae McDermott, MD, Department of Medicine, Feinberg School of Medicine, Northwestern University, 750 North Lake Shore Drive, 10th Floor, Chicago, IL 60611.


Ann Intern Med. 2013;159(5):362-363. doi:10.7326/0003-4819-159-5-201309030-00012
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Recent estimates indicate that 8 million adults in the United States have peripheral artery disease (PAD) and that its prevalence is increasing worldwide (12). Compared with persons without PAD, those with the disease have a 2- to 4-fold increased rate of cardiovascular events, even when cardiovascular disease (CVD) risk factors are taken into account (3). Statins, antiplatelet therapies, and antihypertensive therapies can reduce cardiovascular events in persons with PAD (4). Peripheral artery disease often presents with no or atypical symptoms but can be diagnosed noninvasively in clinicians’ offices by using the ankle–brachial index (ABI). For these reasons, ABI screening and implementation of cardiovascular preventive therapy for persons with PAD could be expected to reduce cardiovascular morbidity and mortality.

In this issue, Lin and colleagues report the results of a systematic review used to inform the updated U.S. Preventive Services Task Force (USPSTF) recommendation on ABI screening (56). The USPSTF concluded that the current evidence is insufficient to assess the balance of benefits and harms of PAD screening and recommended neither for nor against screening with the ABI (6). In contrast to the previous USPSTF recommendation on ABI screening published in 2005, the updated guidelines considered whether the ABI adds meaningfully to CVD risk prediction as measured by the Framingham Risk Score (FRS). Thus, the systematic review by Lin and colleagues includes assessment of 2 questions: Does the ABI provide clinically important prognostic information about CVD risk beyond that provided by the FRS, and does screening for PAD with the ABI followed by treatment of patients with the disease reduce cardiovascular event rates?

At first, the USPSTF's conclusion may seem surprising. Undiagnosed PAD is common, the ABI has excellent diagnostic and prognostic characteristics, and medications are available that decrease cardiovascular events in persons diagnosed with PAD. Currently, the ABI is used infrequently to screen for PAD in clinical practice in the United States, and the disease is commonly underdiagnosed. The PARTNERS (PAD Awareness, Risk, and Treatment: New Resources for Survival) study measured the ABI of patients in 350 primary care practices across the United States who were aged 70 years or older or aged 50 to 69 years with a history of diabetes mellitus or smoking (7). Of 6979 patients tested, 1865 (29%) had an ABI less than 0.9, which is consistent with PAD. Of note, 45% of those with an ABI less than 0.9 had no history of clinically diagnosed PAD, and only 11% had classic symptoms of intermittent claudication. The remaining participants who tested positive for PAD were asymptomatic or had atypical leg symptoms. These types of PAD were more common among persons newly diagnosed with the disease, suggesting that the high prevalence of asymptomatic disease and atypical leg symptoms contributes to underdiagnosis.

Consistent evidence shows that an ABI less than 0.9 is associated with increased all-cause mortality and cardiovascular morbidity and mortality compared with those in persons without PAD (3). Yet, Lin and colleagues found limited evidence to support adding the ABI to the FRS to predict risk for CVD. Therefore, the ABI may not provide additional clinically meaningful predictive information beyond that attainable by the FRS. This observation explains, in part, why the USPSTF concluded that the current evidence is insufficient to assess the balance of benefits and harms of PAD screening and CVD risk assessment with the ABI in adults.

To improve health and prevent cardiovascular events, ABI screening must identify a large number of individuals with an ABI less than 0.9 who are undertreated. In the PARTNERS study, 1040 of the 1865 participants found to have PAD (55%) had concomitant clinically evident CVD and 311 of the remaining 825 (38%) had diabetes. Of the 821 patients with newly diagnosed PAD, 365 (44%) had other CVD that was previously diagnosed and clinically evident and 150 (18%) had diabetes mellitus. Thus, 515 of the 821 participants with newly diagnosed PAD (63%) had other indications for intensive treatment of cardiovascular risk factors (7).

No randomized, controlled trials have assessed whether ABI screening followed by cardiovascular preventive therapies for all patients with PAD reduces cardiovascular event rates compared with usual care. The Aspirin for Asymptomatic Atherosclerosis trial used the ABI to screen 28 980 community-dwelling adults aged 50 to 75 years with no history of CVD (8). A total of 3350 participants diagnosed with PAD on the basis of ABI screening were randomly assigned to receive 100 mg of aspirin or placebo. No differences in the primary outcome of fatal or nonfatal cardiovascular events were seen between the aspirin and control groups at 8.2 years of follow-up (13.7 vs. 13.3 events per 1000 person-years). Similarly, all-cause mortality did not differ between the groups. Thus, in this cohort, ABI screening followed by aspirin prescription for a random sample of patients with PAD did not reduce cardiovascular events or all-cause mortality.

Several characteristics of Lin and colleagues’ systematic review are worth noting. First, by definition, screening applies only to individuals without signs or symptoms of disease. Thus, the authors limited their review to persons without leg symptoms. Yet, atypical leg symptoms are common in PAD and it is well-established that the disease is underdiagnosed in persons who are not asymptomatic (7). Targeted ABI testing for patients with atypical leg symptoms may be beneficial but was not addressed in the review. Second, Lin and colleagues identified the Aspirin for Asymptomatic Atherosclerosis trial as a primary study that informed assessment of the benefits and harms of ABI screening; however, that trial used aspirin to prevent cardiovascular events in persons identified with PAD (8). Recent evidence raises questions about the efficacy of aspirin for preventing cardiovascular events in patients with PAD (9). A study that evaluated the effectiveness of alternative or multiple cardiovascular prevention interventions might have found benefit associated with screening. Third, PAD is associated with increased rates of functional decline and mobility loss in addition to cardiovascular events (10). The USPSTF did not address whether ABI screening can prevent mobility loss in persons found to have PAD.

Establishing whether ABI screening improves outcomes is a global imperative for the growing number of persons with undiagnosed PAD. A definitive randomized, controlled trial is needed to determine whether ABI screening improves health outcomes in persons at risk for PAD.

References

Allison MA, Ho E, Denenberg JO, Langer RD, Newman AB, Fabsitz RR, et al. Ethnic-specific prevalence of peripheral arterial disease in the United States. Am J Prev Med. 2007; 32:328-33.
PubMed
CrossRef
 
Fowkes FGR, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, et al.  Global estimates of prevalence and risk factors for peripheral artery disease: systematic analysis comparing high-income and low and middle-income countries in 2000 and 2010. Lancet. [Forthcoming].
 
Fowkes FG, Murray GD, Butcher I, Heald CL, Lee RJ, Chambless LE, et al, Ankle Brachial Index Collaboration. Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA. 2008; 300:197-208.
PubMed
 
Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006; 113:463-654.
PubMed
 
Lin JS, Olson CM, Johnson ES, Whitlock EP. The ankle-brachial index for peripheral artery disease screening and cardiovascular disease prediction among asymptomatic adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:333-41.
 
Moyer VA, U.S. Preventive Services Task Force. Screening for peripheral artery disease and cardiovascular disease risk assessment with the ankle-brachial index in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013; 159:342-8.
CrossRef
 
Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001; 286:1317-24.
PubMed
CrossRef
 
Fowkes FG, Price JF, Stewart MC, Butcher I, Leng GC, Pell AC, et al, Aspirin for Asymptomatic Atherosclerosis Trialists. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA. 2010; 303:841-8.
PubMed
 
Berger JS, Krantz MJ, Kittelson JM, Hiatt WR. Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials. JAMA. 2009; 301:1909-19.
PubMed
CrossRef
 
McDermott MM, Liu K, Greenland P, Guralnik JM, Criqui MH, Chan C, et al. Functional decline in peripheral arterial disease: associations with the ankle brachial index and leg symptoms. JAMA. 2004; 292:453-61.
PubMed
CrossRef
 

Figures

Tables

References

Allison MA, Ho E, Denenberg JO, Langer RD, Newman AB, Fabsitz RR, et al. Ethnic-specific prevalence of peripheral arterial disease in the United States. Am J Prev Med. 2007; 32:328-33.
PubMed
CrossRef
 
Fowkes FGR, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, et al.  Global estimates of prevalence and risk factors for peripheral artery disease: systematic analysis comparing high-income and low and middle-income countries in 2000 and 2010. Lancet. [Forthcoming].
 
Fowkes FG, Murray GD, Butcher I, Heald CL, Lee RJ, Chambless LE, et al, Ankle Brachial Index Collaboration. Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA. 2008; 300:197-208.
PubMed
 
Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006; 113:463-654.
PubMed
 
Lin JS, Olson CM, Johnson ES, Whitlock EP. The ankle-brachial index for peripheral artery disease screening and cardiovascular disease prediction among asymptomatic adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:333-41.
 
Moyer VA, U.S. Preventive Services Task Force. Screening for peripheral artery disease and cardiovascular disease risk assessment with the ankle-brachial index in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013; 159:342-8.
CrossRef
 
Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001; 286:1317-24.
PubMed
CrossRef
 
Fowkes FG, Price JF, Stewart MC, Butcher I, Leng GC, Pell AC, et al, Aspirin for Asymptomatic Atherosclerosis Trialists. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA. 2010; 303:841-8.
PubMed
 
Berger JS, Krantz MJ, Kittelson JM, Hiatt WR. Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials. JAMA. 2009; 301:1909-19.
PubMed
CrossRef
 
McDermott MM, Liu K, Greenland P, Guralnik JM, Criqui MH, Chan C, et al. Functional decline in peripheral arterial disease: associations with the ankle brachial index and leg symptoms. JAMA. 2004; 292:453-61.
PubMed
CrossRef
 

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Absolute systolic ankle blood pressures versus ankle brachial index
Posted on September 12, 2013
Dr Kirti Kain
Senior Lecturer, University of Leeds
Conflict of Interest: None Declared

With reference to the editorial by McDermott it might be a global imperative to conduct ‘A definitive randomized, controlled trial to determine whether absolute systolic ankle blood pressures screening independent of systolic brachial blood pressures improves health outcomes in persons at risk for peripheral arterial disease and cardiovascular disease. Peripheral arterial disease can be defined by abnormally low and high ankle brachial index and both increase cardiovascular mortality. Majority of studies have defined peripheral arterial disease with ankle brachial index < 0.9. Ankle brachial index does not discriminate between the independent predictive values of systolic ankle blood pressures and systolic brachial blood pressures and these might be different in different populations.

Although the benefits of screening for, and treating, high blood pressure in adults is established, U.S. Preventive Services Task Force screening recommendations based on threshold of systolic brachial blood pressures results in missing more than half of those who have undiagnosed diabetes (1) . Increased systolic ankle blood pressures are associated with diabetes and higher hazard-ratios for fatal and non-fatal cardiovascular events in Europeans (2;3).

South Asians (more than a billion globally) continue to have increasing rates of visceral obesity, diabetes and cardiovascular mortality at a younger age but the prevalence of hypertension and its association with cardiovascular disease is not significantly different to Europeans. It is known that prevalence of ABI < 0.9 is lower even in subjects with diabetes in south Asians but systolic ankle blood pressures increase with diabetes and this increase along with association with cardiovascular disease is greater in South Asians when compared to Europeans (4). Therefore, in certain populations’ value of increased systolic ankle blood pressures (as one of the earliest signs of subclinical atherosclerosis) might be greater than increased systolic brachial blood pressures at a relatively younger age with short lifetime exposure to risk factors.

If predictive value of increased absolute high systolic ankle blood pressures for diabetes and cardiovascular disease in South Asian population is confirmed then possibly they can be used as a non-invasive, cheap and simple primary prevention screening tool for apparently healthy South Asians to reduce cardiovascular morbidity and mortality. Chronic diseases have increasing public health implications globally and focus ought to be on prevention more so when faced with hard economic times. Moreover, the developing countries have to deal with expense of managing infectious diseases and complications of chronic diseases.

There are no conflicts of interest.

References

(1) Casagrande SS, Cowie CC, Fradkin JE. Utility of the u.s. Preventive services task force criteria for diabetes screening. Am J Prev Med 2013; 45(2):167-174.
(2) Hietanen H, Paakkonen R, Salomaa V. Ankle and exercise blood pressures as predictors of coronary morbidity and mortality in a prospective follow-up study. J Hum Hypertens 2010; 24(9):577-584.
(3) Sutton-Tyrrell K, Venkitachalam L, Kanaya AM, Boudreau R, Harris T, Thompson T et al. Relationship of ankle blood pressures to cardiovascular events in older adults. Stroke 2008; 39(3):863-869.
(4) Kain K, Brockway M, Ishfaq T, Merrick M, Mahmood H, Ingoe JC et al. Ankle pressures in UK South Asians with diabetes mellitus: a case control study. Heart 2013; 99(9):614-619.

Response
Posted on November 7, 2013
Mary McGrae McDermott, MD
Northwestern University
Conflict of Interest: None Declared



First, Dr. Kain expresses concern that the ankle brachial index (ABI), a ratio of Doppler-recorded systolic pressures in the ankle and brachial arteries, does not distinguish between the independent predictive values of the systolic ankle and the systolic brachial blood pressure. But because the ABI calculation requires measurement of both the ankle and the brachial systolic pressures, prior prospective studies relating the ABI to subsequent cardiovascular events and mortality have the ability to separately analyze the independent predictive value of the systolic ankle and brachial blood pressures for cardiovascular events and mortality. For example, a meta-analysis relating the ABI to cardiovascular events and mortality included 16 prospective studies, 48,295 participants, and 480,325 person years of follow-up (1). This meta-analysis alone provides a robust opportunity to evaluate the relative independent associations of the ABI, ankle systolic pressure, and brachial systolic pressure with cardiovascular events and mortality. Second, Dr. Kain states that systolic blood pressure screening fails to identify more than half of individuals with undiagnosed diabetes. He implies that measuring the ankle systolic pressure may identify a greater number of individuals with undiagnosed diabetes. While Dr. Kain may be correct that an elevated ankle systolic pressure is more sensitive for identifying diabetes than an elevated brachial systolic pressure, neither test is likely to achieve optimal sensitivity as a diagnostic test for diabetes. For example, in the Multi-Ethnic Study of Atherosclerosis (MESA), most of the men and women with diabetes mellitus did not have an ABI > 1.30, consistent with a high ankle pressure. Although further study is needed, these and other data suggest that most people with diabetes mellitus do not have an elevated ankle pressure (2,3). Third, given the high rate of diabetes and cardiovascular disease in South Asians (4), early diagnosis, treatment, and prevention of diabetes and cardiovascular disease in South Asians are public health imperatives. However, in 2013, relatively little is known about the utility of screening systolic ankle blood pressures for identifying individuals at high risk of cardiovascular events and preventing adverse outcomes. The study by Kain et al supporting the hypothesis that elevated ankle pressures may be useful for diagnosing diabetes and cardiovascular disease in South Asians (5) employs a case-control study design, a relatively weak study design. Further study, including longitudinal prospective studies and randomized trials, is needed before large-scale screening with ankle systolic pressures in high-risk groups, such as South Asians, can be recommended.

1. Ankle Brachial Index Collaboration. Ankle brachial Index Combined with Framingham Risk Score to Predict Cardiovascular Events and Mortality. JAMA 2008;300:197-208.
2. McDermott MM, Liu K Criqui MH et al. Ankle-brachial index and subclinical cardiac and carotid disease: The Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 2005;162:33-41.
3. Sutton-Tyrrell K, Venkitachalam L, Kanaya AM, et al. Relationship of ankle blood pressures to cardiovascular events in older adults. Stroke 2008;39:863-869.
4. Tillin T, Hughes AD, Mayet J et al. The relationship between metabolic risk factors and incident cardiovascular disease in Europeans, South Asians, and African Caribbean. J Am Coll Cardiol 2013;61:1777-1786.
5. Kain K, Brockway M, Ishfaq T et al. Ankle pressures in UK South Asians with diabetes mellitus: A case control study. Heart 2013;99:614-619.
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