Early Identification of PAD: Evidence to Refute USPSTF Position on Screening

Early Identification of PAD: Evidence to Refute USPSTF Position on Screening Mehdi H. Shishehbor, DO, MPH, PhD Director Endovascular Services Interventional Cardiology & Vascular Medicine Department of Cardiovascular Medicine Cleveland Clinic

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Every Patient Should Have an ABI Test Or should they?

U.S. Preventive Services Task Force: Who Should Have an ABI Test? The No USPSTF one recommends without against routine symptoms! screening for peripheral arterial disease (PAD) On what basis? Screening for PAD among asymptomatic adults in the general population would have few or no benefits because: the prevalence of PAD in this group is low (!!) there is little evidence that treatment of PAD at this asymptomatic stage of disease improves health outcomes. screening asymptomatic adults with the ABI could lead to some small degree of harm, including false-positive results and unnecessary work-ups U.S. Preventive Services Task Force. Screening for Peripheral Arterial Disease: Recommendation Statement. 2015. http://www.ahrq.gov/clinic/uspstf05/pad/padrs.htm.

ACC/AHA Consensus Guidelines: Who should have an ABI test? Class I recommendation: The resting ABI should be used to establish the lower extremity PAD diagnosis in patients with: Exertional leg symptoms Non-healing wounds Asymptomatic patients at high risk Adults > 70 years of age Adults > 50 years of age with diabetes or tobacco use Hirsch, AT, et al. ACC/AHA Guidelines for the Management of Patients with PAD. 2005.

ADA Consensus Guidelines: Who should have an ABI test? Due to the high estimated prevalence of PAD in patients with diabetes, a screening ABI should be performed in patients > 50 years of age who have diabetes. If normal, the test should be repeated every 5 years. A screening ABI should be considered in diabetic patients < 50 years of age who have other PAD risk factors. American Diabetes Association Consensus Statement. Diabetes Care 2003; 12:3333.

Prevalence of PAD in U.S. Population: NHANES NHANES 1999-2000 Survey Selvin, E. et al. Circulation 2004;110:738-743 Overall Prevalence PAD in Population N=217470 Years = 14.5% 8-12 million Americans have PAD FG Fowkes, et al. Lancet (July, 2013) Globally, 202 million people were living with PAD in 2010, 69.7% of them in low or middle income countries

What is the Prevalence of PAD in a General Medicine Clinic? PARTNERS study (2001) 6,979 ambulatory care patients in 350 primary care practices ABIs measured for all enrolled patients Aged 70+ Aged 50-69+ with diabetes mellitus or tobacco history PAD prevalence 29% overall Hirsch AT, et al. JAMA. 2001;286;1317.

Ethnicity and PAD: San Diego Population Study 2.5 2.34 Adjusted OR - PAD 2 1.5 1 0.5 1.00 1.08 * 0.62 * N=2343 0 White Black Hispanic Asian Ethinicity - p=0.048 vs. White; * p -NS- vs. White Criqui, et al., Circulation, 2005;112:2703.

Natural History of PAD: Beware Death, MI, Stroke Population > 55 years of age Intermittent claudication 5% Peripheral vascular outcomes Other cardiovascular morbidity/total mortality Stable claudication 73% Worsening claudication 16% Lower extremity bypass surgery 7% Major amputation 4% Nonfatal cardiovascular event (MI/stroke) 20% 5-year mortality 30% Cardiovascular cause 75% Adapted from Weitz Jl et al. Circulation. 1996;94:3026.

0 Five-Year Mortality of PAD Comparable to Common Malignancies Cancer* Breast Disease* Hodgkin's PAD** Cancer* Rectal Colon and Cancer* Lung 20 40 15 18 28 38 60 80 100 Percent * American Cancer Society. Cancer Facts and Figures 1997 ** Kampozinski RP, Bernard VM. In: Rutherford RB (ed). Vascular Surgery. Philadelphia: WB Saunders, 1989: Chapter 53.) 86

Relative Risk (95% CI) PAD is a Marker of High Cardiovascular Risk 10.0 10.0 8.0 8.0 5.9 (3.0-11.4) 6.6 (2.9-14.9) 6.0 6.0 4.0 4.0 3.1 (1.9-4.9) 2.0 2.0 0.0 0.0 All Causes Cardiovascular Disease Cause of Death Coronary Heart Disease All Causes Cardiovascular Coronary Disease Heart Disease Criqui MH et al. N Engl J Med. 1992;326:386.

PAD = Marker of Widespread Atherosclerosis PAD = coronary risk equivalent 60-80% of patients with PAD have CAD in at least one coronary vessel 1,2 Up to 15-25% of patients with PAD have a significant carotid stenoses of >70% 3,4 21% of patients with PAD will have MI, stroke, cardiovascular death or hospitalization within 1 year 5 Compared to 15% of patients with established coronary artery disease and/or prior MI 1. Valentine RJ, et al. J Vasc Surg. 1994;19:668. 2. McFalls EO, et al. CARP Trial. N Engl J Med. 2004;351:2795. 3. Klop RB, et al. Eur J Vasc Surg. 1991;5:41-5. 4. Cheng Sw, et al. Cardiovasc Surg. 1999;7:303. 5. Steg, et al. REACH Registry. JAMA 2007.

ABI: Independent Predictor of Survival 1.0 0.8 Cumulative 0.6 N=1592 Edinburgh Artery Study probability of survival ABI 0.4 1.01-1.1 >1.1 0.2 0.91-1.0 0.71-0.9 <0.7 0.0 0 1 2 3 4 5 6 Time (yrs) Leng GC, et al. BMJ

ABI: Independent Predictor of Survival N=744 vascular lab patients ABI >0.85 ABI 0.4-0.85 ABI <0.4 Year McKenna M, Wolfson S, Kuller L. Atherosclerosis. 1991;87:119-128.

Event-free Survival 1.0 Low ABI Predicts CV Events Regardless of Symptoms 0.9 0.8 0.7 0.6 PAD no/unknown Asymptomatic PAD Symptomatic PAD N=6880 patients >65 years German get ABI study PAD = ABI < 0.9 0.5 0 1 2 3 4 5 Time after baseline (years) Diehm C, et al. Circulation 2009;120:2053.

PAD is a Morbid Disease Major risk factor for lower extremity amputation < 5% at 5 years among stable claudicants 1 Risk increases dramatically among those with critical limb ischemia (as high as 30-40%/year) 2 QOL impairment more severe than CHF or recent MI 3 Functional impairment is common, even among patients with atypical leg symptoms 4-7 Decreased walking distance Decreased walking velocity 1 Weitz Jl et al. Circulation. 1996;94:3026. 2 Hirsch AT, et al. ACC/AHA Guidelines. Critical limb ischemia 2.6.3. 3 Schneider JR et al. Ann Vasc Surg. 1993;7:419. 4-7 McDermott MM et al. Ann Intern Med. 2002;136:873. Circulation. 2000;101:1007. JAMA. 2001;286:13 J Gen Intern Med 1999;14:173. 8 Arseven A, et al. Vasc Med. 2001;6:229.. Objective evidence of depression twice as common among patients with PAD 8

Est. Population Intermittent Claudication Impairs Quality of Life Intermittent Claudication Congestive Heart Failure Chronic Lung Disease Average Adult Average Well Adult 30 34 36 38 40 50 55 SF-36 Physical Function Component Scores Ware JE Ann Rev Pub Health 1995; 16:327-354

Thousands Percentage PAD is Common But Your Patient Has Never Heard of it! Disease Prevalence Disease Awareness 9000 8000 7000 6000 5000 4000 3000 9 million 4 45 40 35 30 25 20 15 42 36 29 26 2000 1000 0 300K 1 20K 2 30K 3 10 5 0 Multiple Sclerosis Lou Gehrig s Disease Cystic Fibrosis PAD 1 Multiple Sclerosis: Hope Through Research, NINDS. NIH Publication No. 96-75. September 1996. 2 Amyotrophic Lateral Sclerosis Fact Sheet. NINDS. NIH Publication No. 00-916. April 2003. 3 Cystic Fibrosis Foundation Fact Sheet, 06/07 4 Am J Prev Med 2007;32:328-33

The Clinical Spectrum of PAD Asymptomatic Claudication Atypical leg symptoms Critical limb ischemia Rest pain, tissue loss Acute limb ischemia Painful, pulseless leg

Intermittent Claudication Recurring burning, aching, fatigue, or heaviness in the leg muscles with predictable level of walking, that resolves with a predictable duration of rest (< 10 minutes)

Simple Screening Tool for Claudication #1 Do you get pain in either leg when you walk? #2 Does the pain go away when you stop walking (within 10 minutes)? If answers are Yes to both questions, the likelihood of PAD is > 95% Adapted from Rose, FA. Bulletin of the WHO. 1962;27:645

Claudication is the Exception Rather than the Rule: PARTNERS Study 11% N=1857 Patients with ABI < 0.9 34% No Pain Atypical Leg Pain Classic Claudication 55% Hirsch, et al. PARTNERS Study. JAMA 1999; 286:1317

Screening for Claudication Alone is Inadequate to Detect PAD Intermittent Claudication Atypical or No Symptoms

Function 5 Categories Pain with exertion, doesn t require stopping Pain with exertion, resolves promptly with rest (classic intermittent claudication) Pain with exertion and rest (?multifactorial) Asymptomatic, but develop pain with 6 MWT Asymptomatic, always Non-lifestyle limiting pain equates to sometimes asymptomatic Quality of Life Criqui MH, etal, Vasc Med 1996;1:65; McDermott MM, etal. Circulation 2008;117:2484-2149

Mm@2 P=<.0001 McDermott MM, etal. Circulation 2008;117:2484-2149

Mm2 P=.0004 McDermott MM, etal. Circulation 2008;117:2484-2149

Kinematic dysfunction (gait abnormality) Celis R,etal. JVS 2009;49:127 Myers SA, etal, JVS 2009;49:924 Crowther AG, etal, Hum Mov Sci 2009: May 10, Epub Persists after 12 month SET Axonal polyneuropathy Weber etal. Muscle Nerve 2002;26:471 Muscle myopathy with mitochondrial changes Pipinos II, etal. Vasc Endo Surg 2008;41:481 Pipinos II, etal. Vasc Endo Surg 2008;42:101 Pipinos II, etal. Free Rad Biol Med 2006;41:262

P=<.0001 McDermott MM, etal. Circulation 2008;117:2484-2149

Total Mortality Disease Mortality Cardiovascular McDermott MM, etal.j Am Coll Card 2008; 51(15):1482

Changes in Medicine Come Slow. JNC 1977 SBP 159mmHg No treatment, re-evaluate in 6 months NCEP 1988 LDL < 130mg/dL Considered optimal

The Ankle-Brachial Index: The Cornerstone of PAD Diagnosis

Partners in PAD Advocacy Vascular Disease Foundation Society of Vascular Medicine and Biology