An update on the state of the art in vascular health. Based on current ACC/AHA guidelines.

1. Peripheral Arterial Disease or P.A.D. GUIDELINES

3. 1. Meijer WT, et al. Arterioscler Thromb Vasc Biol . 1998;18:185-192. 2. Criqui MH, et al. Circulation . 1985;71:510-515 . Rotterdam Study San Diego Study 0 10 20 30 40 50 60 Patients With PAD (%) 55-59 60-64 65-69 70-74 75-79 80-84 85-89 Age (years) Prevalence of PAD Increases With Age ABI=ankle-brachial index

4. Gender Differences in the Prevalence of PAD Adapted from Diehm C. Atherosclerosis . 2004;172:95-105 with permission from Elsevier . Prevalence (%) Women Men 6880 Consecutive Patients (61% Female) in 344 Primary Care Offices <70 0 2 4 6 8 10 12 14 16 70 – 74 75–79 80–84 >85 Age (years) 18

5. Ethnicity and PAD: The San Diego Population Study NHW = Non-hispanic white. Reprinted with permission from Criqui, et al. Circulation. 2005:112:2703-07. NHW Black Hispanic Asian 0 1 2 3 4 5 6 7 8 9 10 Fraction of Population With PAD (%)

6. Diabetes Increases the Risk of PAD 22.4* 19.9* 12.5 0 5 10 15 20 25 Normal Glucose Tolerance Impaired Glucose Tolerance Diabetes Prevalence of PAD (%) Impaired glucose tolerance was defined as oral glucose tolerance test value ≥140 mg/dL but <200 mg/dL. *P  .05 vs. normal glucose tolerance. Reprinted with permission from Lee AJ, et al. Br J Haematol. 1999;105:648-654. www.blackwell-synergy.com

7. Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192 . Relative Risk Smoking Diabetes Hypertension Hypercholesterolemia Hyperhomocysteinemia C-Reactive Protein Risk Factors for PAD 1 2 3 4 5 6 0 Reduced Increased

11. PAD Prognosis

13. Natural History of Atherosclerotic Lower Extremity PAD PAD Population (50 years and older) Initial clinical presentation Asymptomatic PAD 20%-50% Atypical leg pain 40%-50% Claudication 10%-35% Critical limb ischemia 1%-2% Progressive functional impairment 1-year outcomes Alive w/ 2 limbs 50% Amputation 25% CV mortality 25% 5-year outcomes (to next slide) Reprinted with permission from Hirsch AT, et al. Circulation. 2006;113:e463-654 .

14. Claudication 10%-35% 5-year outcomes Limb morbidity Stable claudication 70%-80% Worsening claudication 10%-20% Critical limb ischemia 1%-2% Amputation (see CLI data) CV morbidity & mortality Nonfatal CV event (MI or stroke) 20% Mortality 15%-30% CV causes 75% Non-CV causes 25% Reprinted with permission from Hirsch AT, et al. Circulation. 2006;113:e463-654. Asymptomatic PAD 20%-50% Atypical leg pain 40%-50% For each of these PAD clinical syndromes CLI=critical limb ischemia; CV=cardiovascular; MI=myocardial infarction

15. Long-Term Survival in Patients With PAD Criqui MH et al. N Engl J Med. 1992;326:381-386. Copyright © 1992 Massachusetts Medical Society. All rights reserved. Normal subjects Asymptomatic PAD Symptomatic PAD Severe symptomatic PAD Survival (%) Year 100 75 50 25 0 2 4 6 8 10 12

16. Association Between ABI and All‑Cause Mortality* Baseline ABI Total Mortality (%) Age range=mid- to late-50s; ABI=ankle-brachial index; *Median duration of follow-up was 11.1 (0.1–12) years. Adapted from O’Hare AM et al. Circulation . 2006;113:388-393 . N=5748 Risk increases at ABI values below 1.0 and above 1.3

17. Cardiovascular Risk Increases With Decreases in ABI >1.1 1.1–1.01 1.0–0.91 0.9–0.71 <0.7 ABI CHD Event Outcomes per Year (%) 0 1 2 3 4 5-year risk: 10% 5-year risk: 19% Framingham “High Risk” = 20% at 10 years Every patient with PAD is at “very high risk” *Fatal or nonfatal MI. ABI=ankle-brachial index; CHD=chronic heart failure 2% 3.8% 1.4% Leng GC, et al. Brit Med J. 1996;313:1440-44 . PAD

18. Critical Limb Ischemia (CLI) Fate of Patients With CLI After Initial Treatment Summary of 6-month outcomes from 19 studies Dormandy JA, Rutherford RB. J Vasc Surg . 2000;31:S1-S296. Critical limb ischemia is defined as ischemic rest pain, nonhealing wounds, or gangrene. Dead 20% Alive without amputation 45% Alive with amputation 35%

19. Applying Classification of Recommendations and Level of Evidence Class III Risk ≥ Benefit No additional studies needed Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL Class IIb Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED Class IIa Benefit >> Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure/administer treatment Class I Benefit >>> Risk Procedure/ Treatment SHOULD be performed/ administered Level B Limited (2-3) population risk strata evaluated Level A Multiple (3-5) population risk strata evaluated General consistency of direction and magnitude of effect Level C Very limited (1-2) population risk strata evaluated

34. ABI Procedure http://www.nhlbi.nih.gov/health/dci/Diseases/pad/pad_diagnosis.html

37. Using the ABI: An Example ABI=ankle-brachial index; DP=dorsalis pedis; PT=posterior tibial; SBP=systolic blood pressure. Right ABI 80/160=0.50 Brachial SBP 160 mm Hg PT SBP 120 mm Hg DP SBP 80 mm Hg Brachial SBP 150 mm Hg PT SBP 40 mm Hg DP SBP 80 mm Hg Left ABI 120/160=0.75 Highest brachial SBP Highest of PT or DP SBP ABI (Normal >0.90)

44. Individual at PAD risk: No leg symptoms or atypical leg symptoms Perform a resting ankle-brachial index measurement Confirmation of PAD diagnosis ABI ≥ 1.30 (abnormal) ABI ≤ 0.90 (abnormal) Pulse volume recording Toe-brachial index (Duplex ultrasonography) Abnormal results Evaluate other causes of leg symptoms Decreased post-exercise ABI Normal post-exercise ABI: No PAD Measure ABI after exercise test ABI 0.91 to 1.30 (borderline & normal) Normal results: No PAD Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192.

45. Risk factor normalization : Immediate smoking cessation Treat hypertension Treat lipids Treat diabetes mellitus: HbA 1c less than 7% Pharmacological Risk Reduction : Antiplatelet therapy (ACE inhibition) Confirmation of PAD diagnosis Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192. ACE=angiotensin-converting enzyme; JNC-7=Joint National Committee on Prevention ; NCEP=National Cholesterol Education Program – Adult Treatment Panel III .

46. Antihypertensive Therapy Antihypertensive therapy should be administered to hypertensive patients with lower extremity PAD to a goal of less than 140/90 mm Hg (non-diabetics) or less than 130/80 mm Hg (diabetics and individuals with chronic renal disease) to reduce the risk of myocardial infarction, stroke, congestive heart failure, and cardiovascular death. Beta-adrenergic blocking drugs are effective antihypertensive agents and are not contraindicated in patients with PAD.

47. Lipid Lowering Therapy Treatment with a HMG coenzyme-A reductase inhibitor (statin) medication is indicated for all patients with peripheral arterial disease to achieve a target LDL cholesterol of less than 100 mg/dL. Treatment with a HMG coenzyme-A reductase inhibitor (statin) medication to achieve a target LDL cholesterol level of less than 70 mg per dl is reasonable for patients with lower extremity PAD at very high risk of ischemic events † . † Factors that define “very high risk” in individuals with established PAD are: (a) multiple major risk factors (especially diabetes), (b) severe and poorly controlled risk factors (especially continued cigarette smoking), (c) multiple risk factors of the metabolic syndrome and (d) individuals with acute coronary syndromes. HMG coenzyme=3-hydroxy-3-methylglutaryl coenzyme I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B

48. PAD Care Standards for Patients With Diabetes Proper foot care, including use of appropriate footwear, chiropody/podiatric medicine, daily foot inspection, skin cleansing, and use of topical moisturizing creams, should be encouraged and skin lesions and ulcerations should be addressed urgently in all diabetic patients with lower extremity PAD. Treatment of diabetes in individuals with lower extremity PAD by administration of glucose control therapies to reduce the hemoglobin HbA1C to less than 7% can be effective to reduce microvascular complications and potentially improve cardiovascular outcomes. I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III B I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III c

49. Risk Reduction of Clopidogrel vs. Aspirin in Patients With Atherosclerotic Vascular Disease Reprinted with permission from CAPRIE Steering Committee. Lancet . 1996;348:1329-1339. Stroke 0 10 20 -10 -20 MI PAD All patients Aspirin favored -30 30 40 Clopidogrel favored N=19,185

50. Classic Claudication Symptoms : Muscle fatigue, cramping, or pain that reproducibly begins during exercise and that promptly resolves with rest Document pulse examination ABI Exercise ABI (TBI, segmental pressure, or Duplex ultrasound examination) Chart document the history of walking impairment (pain-free and total walking distance) and specific lifestyle limitations Confirmed PAD diagnosis ABI greater than 0.90 ABI less than or equal to 0.90 No PAD or consider arterial entrapment syndromes Normal results Abnormal results Cont’d Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192. ABI=ankle-brachial index; TBI=toe-brachial index .

51. Risk factor normalization : Immediate smoking cessation Treat hypertension Treat lipids Treat diabetes mellitus: HbA1c less than 7% Pharmacological risk reduction : Antiplatelet therapy (ACE inhibition) Confirmed PAD diagnosis Treatment of Claudication Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192. ACE=angiotensin-converting enzyme; JNC-7=Joint National Committee on Prevention ; NCEP=National Cholesterol Education Program – Adult Treatment Panel III .

55. Chronic CLI symptoms : Ischemic rest pain, gangrene, nonhealing wound Ischemic etiology must be established promptly by examination and objective vascular studies Implication : Impending limb loss History and physical examination : Document lower extremity pulses; Document presence of ulcers or infection ABI, TBI, or Duplex US Evaluation of source (ECG or Holter monitor; TEE; and/or abdominal US, MRA, or CTA); or venous Duplex Consider atheroembolism, thromboembolism, or phlegmasia cerulea dolens No or minimal atherosclerotic arterial occlusive disease Assess factors that may contribute to limb risk: diabetes, neuropathy, chronic renal failure, infection Severe lower extremity PAD documented: ABI less than 0.4; flat PVR waveform; absent pedal flow Cont’d Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192. ABI=ankle-brachial index; CLI=critical limb ischemia; CTA=computed tomographic angiography; ECG=electrocardiogram; MRA=magnetic resonance angiography; PVR=pulse volume recording; TEE=transesophageal echocardiogram; TBI=toe-brachial index; US= ultrasound.

62. Individual “at risk” or with PAD seeks care (primary care) Individual “at risk” or with PAD receives vascular care The Ideal Clinical Synergy: When an Informed Patient Seeks an Informed Clinician Public Awareness of Peripheral Arterial Disease Clinician Awareness of Peripheral Arterial Disease The PAD Coalition & PAD Guideline

63. NMHI Vascular: 843-2525