October 6, 2014

Screening ABIs in Asymptomatic Adults

Guideline Recommendations

In 2013, the US Preventive Services Task Force (USPTF) updated its 2005 guidelines to state that there was insufficient evidence to support screening ankle-brachial index measurement (ABI) in asymptomatic adults, regardless of age or risk factors  (grade I statement). (1) This recommendation contradicted the endorsement made in the 2011 American College of Cardiology Foundation (ACCF) / American Heart Association (AHA) guidelines, which recommended screening all adults over age 65, regardless of symptoms or risk profile, and all adults over 50 with a history of either smoking of diabetes (class I, grade B). (2) In addition, the 2009 Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease (TASC-II), similar to the 2005 ACCF/AHA guidelines, had advised screening all patients >70 years regardless of comorbidities and all patients >50 years of age with at least one risk factor.

Why the disagreement, especially over a test that has long been praised for its low cost and rapid point-of-care administration?

Epidemiologic Studies

Each committee highlighted different sources of evidence to justify their recommendations.

The 2011 ACCF/AHA guidelines updated their screening recommendations because of a single, large observational study: the German Epidemiologic Trial on Ankle Brachial Index Study Group. (3) This study enrolled 6880 unselected adults >65 years of age in Germany, all of whom were interviewed to assess for vascular disease and underwent resting ABI with a cutoff of <0.90. Patients were classified as having peripheral arterial disease (PAD) if they were asymptomatic with an abnormal ABI or symptomatic with a history of intervention or amputation.

With this case definition, the study found that 21% of adults over the age of 65 had some form of PAD. Of those, 12.3% were asymptomatic, and 8.7% symptomatic. About a quarter of the symptomatic patients had undergone any intervention. And symptomatic patients had a higher risk of vascular events, but not overall mortality, compared with asymptomatic patient. But, over 5 years of follow-up, asymptomatic patients with PAD had a higher overall mortality than patients without PAD (19.5 vs. 41.7 patients per 1000 patient-years; HR 1.66; 95% CI 1.38-2.00), a finding echoed in prior studies.

Though this study was available to them at the time of writing, the USPTF did not reference the German Epidemiologic Trial. Instead, the committee referenced the National Health and Nutrition Examination Survey (NHANES), which showed that only 5.9% of patients >40 years of age or 17.5% of patients over 75 had PAD, as defined solely by a low ABI (<0.90), a less sensitive case definition. (4)

Benefits of Early Treatment

The USPTF paper stated, “[we] found no evidence that screening for and treatment of PAD in asymptomtic patients leads to clinically important benefits.” It further suggested that while adding ABIs to the Framingham Risk Score (FRS) results in patient risk reclassification (19% of men and 26% of women), there is uncertainty about improving clinical outcomes as a result of this adjustment. (5) USPTF primarily cites the Aspirin for Asymptomatic Atherosclerosis trial, which randomized 4941 asymptomatic patients with ABI <0.95 to aspirin or placebo and found no significant benefit in cardiovascular outcomes (myocardial infarction, stroke, or revascularization). (6)

On the other hand, the ACCF/AHA guidelines recommended aggressive risk factor modification, enhanced patient follow-up, and pharmacological therapy, with emphasis on statin (IB) and angiotensin converting enzyme inhibitor (ACEi) (IIB) treatment. The Heart Protection Study included 6748 patients with PAD who did not have coronary disease; those randomized to 40mg of simvastatin benefited from a significant 25% reduction in vascular events compared with placebo. (7) Based on this and other trials showing a comparable reduction in CV events, the new 2013 ACC/AHA cholesterol guidelines also recommended high-intensity statin therapy in any patient with PAD. (8)

Discussion

Detecting the presence of PAD is critical. Its diagnosis alters a patient’s risk profile and will cause clinicians to follow patients more closely and have a heightened sensitivity to associated conditions, especially concomitant coronary disease, which is present in >60% of patients with PAD. (9) The diagnosis also helps the clinician emphasize important risk factor modification efforts, such as tobacco cessation, weight loss, exercise, and cholesterol management. Its presence may be the sole impetus to start a statin. In addition, distinguishing between symptomatic and asymptomatic patients can be challenging, particularly in patients who do not exercise enough to produce symptoms. (9) And thus screening elderly patients with a baseline risk of around 20% will likely identify both those patients who are truly asymptomatic as well as those who did not know they were symptomatic until they were actually tested.

Take home message: asymptomatic adults >65 years of age regardless of risk factors or >50 years of age with risk factors should be screened with a simple, office-based ankle-brachial index study

References

(1) 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 Sep 3;159(5):342-8.

(2) 2011 ACCF/AHA Focused Update of the Guideline for the Management of patients with peripheral artery disease (Updating the 2005 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011 Nov 1;124(18):2020-45.

(3) Diehm C, Allenberg JR, Pittrow D, et al. Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease. Circulation. 2009;120:2053– 61.

(4) Joosten MM, Pai JK, Bertoia ML, Rimm EB, Spiegelman D, Mittleman MA, et al. Associations between conventional cardiovascular risk factors and risk of peripheral artery disease in men. JAMA. 2012; 308:1660-7.

(5) 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.

(6) 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.

(7) Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.

(8) Cholesterol Treatment Trialists Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomized trials. Lancet 2010; 376: 1670-1681.

(9) ACC/AHA 2005 Practice Guidelines for the Management of Patients with Peripheral Arterial Disease. Circulation 2006; 113: e463-e654.