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Peripheral Artery Disease. Part 1: Clinical Evaluation and Noninvasive Diagnosis Joe F

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Peripheral Artery Disease. Part 1: Clinical Evaluation and Noninvasive Diagnosis Joe F REVIEWS Peripheral artery disease. Part 1: clinical evaluation and noninvasive diagnosis Joe F. Lau, Mitchell D. Weinberg and Jeffrey W. Olin Abstract | Peripheral artery disease (PAD) is a marker of systemic atherosclerosis. Most patients with PAD also have concomitant coronary artery disease (CAD), and a large burden of morbidity and mortality in patients with PAD is related to myocardial infarction, ischemic stroke, and cardiovascular death. PAD patients without clinical evidence of CAD have the same relative risk of death from cardiac or cerebrovascular causes as those diagnosed with prior CAD, consistent with the systemic nature of the disease. The same risk factors that contribute to CAD and cerebrovascular disease also lead to the development of PAD. Because of the high prevalence of asymptomatic disease and because only a small percentage of PAD patients present with classic claudication, PAD is frequently underdiagnosed and thus undertreated. Health care providers may have difficulty differentiating PAD from other diseases affecting the limb, such as arthritis, spinal stenosis or venous disease. In Part 1 of this Review, we explain the epidemiology of and risk factors for PAD, and discuss the clinical presentation and diagnostic evaluation of patients with this condition. Lau, J. F. et al. Nat. Rev. Cardiol. 8, 405–418 (2011); published online 31 May 2011; doi:10.1038/nrcardio.2011.66 of systemic atherosclerosis and is, therefore, associated Continuing Medical Education online with substantial morbidity and mortality.1–2 The major‑ This activity has been planned and implemented in accordance ity of patients with PAD also have concomitant coronary with the Essential Areas and policies of the Accreditation Council artery disease (CAD), and a large burden of morbidity and for Continuing Medical Education through the joint sponsorship of mortality in patients with PAD is related to myo­cardial Medscape, LLC and Nature Publishing Group. Medscape, LLC is 1 accredited by the ACCME to provide continuing medical education infarction (MI), ischemic stroke, or cardio­vascular death. for physicians. Indeed, in a series of 1,000 coronary angiograms of patients Medscape, LLC designates this Journal-based CME activity for who were under consideration for vascular surgery for a maximum of 1 AMA PRA Category 1 Credit(s)TM. Physicians abdominal aortic aneurysm (n = 263), carotid artery disease should claim only the credit commensurate with the extent of (n = 295), or PAD (n = 381) only 8% demonstrated normal their participation in the activity. coronary arteries.3 Also note­worthy is that patients with All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME PAD but no clinical evidence of CAD have the same rela‑ activity: (1) review the learning objectives and author disclosures; tive risk of death from cardiac or cerebrovascular causes as (2) study the education content; (3) take the post-test and/or those whose main diagnosis is CAD, which is consistent complete the evaluation at http://www.medscape.org/journal/ with the systemic nature of the disease.1,4 Furthermore, nrcardio; (4) view/print certificate. PAD is associ­ated with depression, a profound reduction in Released: 31 May 2011; Expires: 31 May 2012 functional capacity (as measured by 6‑min walk distance, Learning objectives 4‑m fast-walking velocity, and performance on a series of Upon completion of this activity, participants should be able to: tests that measure balance and mobility), and overall poor 1 Analyze the epidemiology of PAD. quality of life.5–6 Notably, patients with PAD who already 2 Evaluate risk factors for PAD. 3 Describe the clinical presentation of PAD. exhibit the greatest declining functional performance as The Zena and 4 Apply imaging studies for PAD effectively. measured by these tests (lowest tertile) possess the great‑ Michael A. Wiener Cardiovascular Institute est risk for loss of mobility, and have the highest risk for & Marie-José and all-cause and cardiovascular mortality.7 Henry R. Kravis Introduction The same risk factors that contribute to CAD and Cardiovascular Health Center, Mount Sinai For the purposes of this Review, the definition of peripheral cerebro­vascular disease, such as advancing age, hyper­ School of Medicine, artery disease (PAD) is atherosclerosis of the aorta, and the tension, hyperlipidemia, diabetes mellitus, and a current One Gustave L. Levy Place, Box 1033, New iliac and lower extremity arteries. PAD is a manifestation or prior history of smoking, also lead to the development York, NY 10029‑6574, of PAD.8 Additional risk factors that have been associated USA (J. F. Lau, M. D. Weinberg, Competing interests 9 with PAD include chronic kidney disease, low serum J. W. Olin). J. W. Olin declares associations with the following companies: 25-hydroxy-vitamin D levels,10,11 and the presence of Bristol-Myers Squibb, Genzyme, Merck & Co., and Sanofi– several inflammatory biomarkers, such as homocysteine, Correspondence to: Aventis. See the article online for full details of the relationships. J. W. Olin J. F. Lau, M. D. Weinberg, the journal Chief Editor B. Mearns and C‑reactive protein (CRP), beta-2-microglobulin, and jeffrey.olin@ CME questions author C. P. Vega declare no competing interests. cystatin C.12,13 PAD is underdiagnosed owing to the lack msnyuhealth.org NATURE REVIEWS | CARDIOLOGY VOLUME 8 | JULY 2011 | 405 © 2011 Macmillan Publishers Limited. All rights reserved REVIEWS Key points Among participants of the Cardiovascular Health Study, who were aged 65 years or older and had no previously ■■ Most patients with peripheral artery disease (PAD) also have concomitant coronary artery disease; morbidity and mortality in patients with PAD are often known cardiovascular disease, total and cardiovascular related to myocardial infarction and ischemic stroke mortality after 6 years of follow-up was higher in those with an initial ABI <0.9 when compared with those with ■■ Risk factors for coronary artery and extracranial cerebrovascular disease also promote the development of PAD; smoking and diabetes mellitus are normal (1.0–1.4) ABI (all-cause mortality: 25.4% versus 2 particularly prevalent among patients with PAD 8.7%; cardiovascular mortality: 6.9% versus 1.7%). These ■■ Only a small percentage of patients with PAD present with classic Rose differences between the two groups were statistically claudication, as approximately 70–90% have atypical leg symptoms or are signifi­cant. A decline in ABI within this population also asymptomatic correlated with the increased prevalence of modifiable risk 31 ■■ The ankle–brachial index remains the initial noninvasive diagnostic tool of factors, such as tobacco use, hypertension, and dia­betes. choice for PAD screening, with 95% sensitivity and 99% specificity In the Strong Heart Study,32 a population-based study of ■■ Segmental limb pressures, pulse–volume recordings, and exercise treadmill American Indians aged 45–74 years, cardio­vascular mortal­ testing can help localize the diseased arterial segment(s), and provide ity over an 8‑year follow-up period was significantly higher information about the functional limitations of the patient in subjects with an initial ABI <0.9 or >1.4 when com‑ ■■ Duplex ultrasound can identify the site, extent, and severity of PAD from the pared with counter­parts with normal ABIs. The U‑shaped aorta to the feet association between ABI and cardiovascular mortality correlated with the increased prevalence of diabetes and hyper­tension in both low and high ABI groups. Both high of education about PAD during medical school and post‑ (>1.4 or noncompressible) and low ABIs (<0.9) have been graduate medical training, and the high prevalence of closely associated with chronic kidney disease, suggesting asymptomatic disease.4 Excellent noninvasive imaging that arterial stiffness could be an important mechanism modalities are available to assist the clinician in the diagnosis for PAD in patients with this disease.33 Indeed, large-scale and management of PAD. syste­matic reviews affirmed the high specificity of the ABI In Part 1 of this Review, we focus on the epidemiology to predict future cardiovascular outcomes.34,35 of and risk factors for PAD, and the clinical presentation and diagnostic evaluation of patients with this condition. In Risk factors Part 2,14 we cover the medical and endovascular manage­ment The risk factors that contribute to atherosclerosis in of these patients. the carotid and coronary arteries also contribute to the develop­ment of PAD. Several population studies and Epidemiology observational analyses have identified major risk factors for An estimated 27 million people in Western Europe and PAD, such as increasing age, African-American or Hispanic North America, including 8–10 million Americans, have ethnicity, current or past tobacco use, and the presence of PAD. This figure represents approximately 16% of the total diabetes, dyslipidemia, hypertension, and chronic kidney population of both the USA and Western Europe aged disease.4,36–39 Of these risk factors, smoking and diabetes over 55 years.15 Approximately 10–35% of patients with pose the greatest risk for the development and progression PAD present with classic claudication and 20–40% have of PAD (Figure 2).40,41 atypical leg pain.1 Nearly 50% of all patients with PAD are asymptomatic and PAD is only detected by measuring Age the ankle–brachial index (ABI), which is the ratio of the Multiple studies have
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