Management of Dyslipidemia in Patients with Peripheral Arterial Disease: an update from Guidelines Oman International Vascular Conference Al-Bustan Palace Hotel Muscat– Sultanate of Oman 12 th - 14 th March 2012 Khalid Al-Rasadi, MD

Event-free survival by PAD status at 5 years for 6880 patients Kaplan–Meier estimates showing all-cause mortality or severe vascular events Curt Diehm, Circulation November 24, 2009

Logistic Regression Estimates and Odds Ratios for Significant Risk Factors in the Intermittent Claudication Profile in Subjects Aged 45 to 84: Framingham Heart Study Risk FactorOdds Ratio (95% CI)P Male sex1.7 (1.3, 2.1).0001 Age (per 10 years)1.5 (1.3, 1.6).0001 High normal blood pressure (0.9, 1.8).1384 Stage 1 hypertension (1.1, 2.0).0091 Stage 2+ hypertension (1.7, 3.0).0001 Diabetes2.6 (2.0, 3.4).0001 Cigarettes (per 10 cigarettes)1.4 (1.3, 1.5).0001 Cholesterol (per 40 mg/dL)1.2 (1.1, 1.3).0001 CHD2.7 (2.2, 3.4).0001 Circulation 1997; 96: 44–49.

Prevalence of and Risk Factors for Peripheral Arterial Disease in the United States : Results From the National Health and Nutrition Examination Survey, 1999 −2000 Circulation August 10, 2004

Values of plasma lipid and lipoprotein concentrations in male cases with PAD and healthy controls B.F. Mowat et al. : Atherosclerosis 131 (1997) 161–166

Lipoprotein(a) and PAD in a Community-Based Sample of Older Men and Women (the InCHIANTI Study) Am J Cardiol 2010;105:1825–1830

Heart Protection Study: Vascular Events by Baseline Disease Baseline feature Simvastatin (n=10,269) Placebo (n=10,267) Previous MI Other CHD (not MI) No prior CHD CVD PVD Diabetes All patients 2042 (19.9%) 2606 (25.4%) Collins R. Presented at AHA, Anaheim, California, 13 November Risk ratio and 95% CI Statin better Statin worse  24 ± 2.6% (2P < )

The effect of intensified lipid-lowering therapy on long-term prognosis in patients with peripheral arterial disease (1374 patients, followed for 6.4 ± 3.6 years) J Vasc Surg 2007;45:936-43

hs-CRP and Risk of Developing PVD in Apparently Healthy Men Ridker PM et al. Circulation 1998;97: 1998 Lippincott Williams & Wilkins. None hs-CRP (mg/dL) Intermittent Claudication Peripheral Artery Surgery

Patients with statin use had significantly less inflammatory activity in 515 patients with severe PAD European Heart Journal (2004) 25, 742–748

Statin therapy improves cardiovascular outcome of patients with severe PAD European Heart Journal (2004) 25, 742–748

Peripheral Arterial Disease (PAD) Studies of patients with atherosclerotic PAD support the concept that PAD, regardless of diagnosis by ABI, lower limb blood flow studies, or clinical symptoms, is a CHD risk equivalent

Guidelines for Lipid Management in PAD Guideline source LDL-CHDL-CTriglycerides ACCF/AHA Class 1: LDL <100 mg/dl, for all patients with PAD using HMG-CoA reductase inhibitor (statin) Class 2a: LDL <70 mg/dl, for those at high risk of ischemic events Class 2a: low HDL, consider treatment with fibric acid derivative Class 2a: elevated triglycerides, consider treatment with fibric acid derivative TASC II LOE A: LDL <100 mg/dl, for all patients with PAD LOE B: LDL <70 mg/dl, for patients with atherosclerosis in other territories LOE A: statin drugs should be the primary agent used LOE B: low HDL, consider treatment with niacin or fibrates LOE B: elevated triglycerides, consider treatment with fibrates ESC Class 1: LDL 50% LDL reduction, if target level cannot be reached Not addressed in guidelines

Centralized pan-Middle East Survey on the undertreatment of hypercholesterolemia: Results from the CEPHEUS Study in Arabian Gulf States CEPHEUS, unpublished data

Lipid-lowering treatment in hypercholesterolaemic patients: the CEPHEUS Pan-Asian survey European Journal of Cardiovascular Prevention & Rehabilitation 0(00) 1–14

Conclusion & Future Perspective Exciting advances have been made in the treatment of lower extremity PAD to reduce morbidity and mortality as well as to improve functional capacity. Continued investigation is needed to better understand the relationship between dyslipidemia, endothelial dysfunction, inflammation and hyperglycemia as they relate to an individual's exercise capacity and symptoms. Lastly, large clinical trials are needed to better understand the impact of statin therapy and resulting LDL reduction on exercise performance in patients with PAD.