Giuseppe Biondi Zoccai Ospedale San Giovanni Battista “Molinette” Università di Torino

1. Minicorso GISE:Interventistica per gli arti inferiori e per il piede diabetico EPIDEMIOLOGY, PATHOPHYSIOLOGY AND NATURAL HISTORY OF ARTERIOPATHY OF THE LOWER LIMB & ISCHEMIC DIABETIC FOOT Giuseppe Biondi Zoccai Ospedale San Giovanni Battista “Molinette” Università di Torino gbiondizoccai@gmail.com Genova, martedì 2 ottobre 2007 – 13.20-13.35

2. DISCLOSURE • Consultant: Boston Scientific, Cordis, Mediolanum Cardio Research • Lecture fees: Bristol-Myers Squibb

3. LEARNING GOALS • Epidemiology • Pathophysiology • Natural history of lower limb atherosclerotic disease and ischemic diabetic foot

4. LEARNING GOALS • Epidemiology • Pathophysiology • Natural history of lower limb atherosclerotic disease and ischemic diabetic foot

5. ACUTE ISCHEMIA IS NOT THE FOCUS OF THIS MINICOURSE ACC/AHA, Circulation 2005

6. CLINICAL PRESENTATION OF PAD PATIENTS

7. THE TIP OF THE ICEBERG

8. Transient ischemic attack Ischemic stroke Angina pectoris (Stable, Unstable angina) Myocardial infarction Renovascular HTN, Ischemic renal injury Peripheral arterial disease Critical limb ischemia, claudication, gangrene, necrosis BURDEN OF PAD

9. CLASSIFICATION Mukherjee et al, AHJ 2005

10. CASE FATALITY OF PAD

11. LONG-TERM PROGNOSIS 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995, with follow-up complete to March 1998 Caro et al, BMC Cardiovasc Dis 2005

12. OVERLAP IN ATHEROTHROMBOSIS TASC, EJVES 2007

13. PAD IN ITALY

14. COMPARING SEVERITY

15. ATHEROSCLEROSIS

16. LARGE VS SMALL VESSELS

17. RISK FACTORS FOR PAD TASC, EJVES 2007

18. TASC, EJVES 2007

19. LEARNING GOALS • Epidemiology • Pathophysiology • Natural history of lower limb atherosclerotic disease and ischemic diabetic foot

20. CRITICAL LIMB ISCHEMIA

21. CLASSIFICATION Mukherjee et al, AHJ 2005

22. CRITICAL LIMB ISCHEMIA

23. DIABETES AND ULCER • Diabetes is 1st cause of lower extremity amputation in Europe • Lifetime risk of ulcer: 15% (up to 25%) • Foot disorders • Major cause of morbidity • A leading cause of hospitalization • Costly when result in amputation: > $6 billion

24. PRIMARY REASONS FOR FOOT PROBLEMS IN DIABETES • Microvascular: Peripheral neuropathy & loss of protective sensation • ~50% of people having diabetes > 15 years have a peripheral sensory neuropathy, lack protective sensation • Vulnerable to physical & thermal trauma • Macrovascular: Vascular insufficiency (peripheral vascular disease) -> risk of limb ischemia • Metabolic disorders: Hyperglycemia -> dries skin, facilitates growth of pathogens; contributes to microvascular • Impaired immune system: Decreased host response • Trauma: Repetitive and acute • Foot deformities: Excess plantar pressures

25. PATHOPHYSIOLOGY OF PAD/ISCHEMIC DIABETIC FOOT • Older age • Male gender • Diabetes (especially diabetes duration, HbA1c, insulin use, and retinopathy) • Chronic kidney failure • Hyperuricemia • Smoke • Body weight (BMI, WHR) • Dyslipidemia • History of CAD

26. CLAUDICATION IN DIABETICS?

27. CAUSES OF FOOT ULCERS TASC, EJVES 2007

28. CAUSES OF ULCERS % Causal Pathways NEUROPATHY Neuropathy: 78%  Minor trauma: 79% DEFORMITY Deformity: 63%  Behavioral issues ? MINOR TRAUMA - Mechanical (shoes) POOR SELF- - Thermal FOOT CARE - Chemical ULCER Diabetes Care 1999; 22:157

29. DIABETIC NEUROPATHY

30. NEUROPATHY VS ISCHEMIA TASC, EJVES 2007

31. CHARCOT FOOT

32. FOOT TRAUMA

33. DIABETIC FOOT TRIAD TRAUMA Neuropathy Infection ULCER Ischemia

34. BILATERAL INVOLVEMENT

35. RISK FACTORS FOR CLI TASC, EJVES 2007

36. PATHOPHYSIOLOGY OF DIABETIC FOOT ULCERS • The development of a foot ulcer has traditionally been considered to result from a combination of peripheral vascular disease (PVD), peripheral neuropathy (PNP) and infection • There has been no convincing evidence that infection is a direct cause, but it rather complicates an established ulcer and impedes its healing • Other factors have been identified such as repetitive stress and pressure on insensitive feet, poor glycaemic control and others

37. PATHOPHYSIOLOGY OF DIABETIC FOOT ULCERS • Patients with DM have a high risk of atherosclerotic PVD. • PVD alone is rarely a cause of ulceration but usually in • combination with PNP and minor trauma leads to tissue • Breakdown. • It also has a major role in delayed wound healing and the development of • gangrene. • Reduced lower limb transcutaneous oxygen tension • (TcPO2) and reduced large vessel perfusion were • associated with the increased risk of DFU. • A TcPO2 < 30 Hg was a very strong predictor for DFU. • Diabetic patients also appear to have an increased risk of • coagulability and thrombosis and this may have a role in • the impairment of tissue perfusion. • Foot deformities such as Charcot deformity and claw toes • are also risk factors for DFU.

38. Peripheral sensory neuropathy Structural foot deformity Trauma and improperly fitted shoes Callus History prior ulcers/amputations Prolonged, elevated pressures on foot Limited joint mobility Uncontrolled hyperglycemia Duration of diabetes Blindness/partial sight Chronic renal disease Older age RISK FACTORS FOR DIABETIC FOOT ULCERS

39. RISK FACTORS FOR DIABETIC FOOT ULCERS • Diabetes mellitus (DM) is one of the most important and common metabolic disorders affecting 2–5% of the population in Europe and between 1 and 20% of the population in various other parts of the world • It is characterised by multiple long-term complications affecting almost every system in the body • Foot ulcers are one of the main complications of DM, with a 15% lifetime risk for foot ulcers in all diabetic patients • There is wide variation reported in the incidence and • prevalence of diabetic foot ulcers (DFU), with the incidence • ranging from 1.0 to 4.0% and prevalence between 5.3 and • 10.5%. • Twenty percent of diabetic patients are admitted to hospital • because of foot problems. • DFU precede 85% of lower extremity amputations (LEAs). • There is a two-fold increase in mortality rate in patients with • DFU.

41. WOUND CLASSIFICATION

42. DIABETIC VASCULOPATHY

43. ATHEROSCLEROSIS: DIABETICS VS NON-DIABETICS

44. FOOT ULCERS IN DIABETES Precipitate 85% of amputations: “Rule of 15” • 15% of diabetes patients Foot ulcer in lifetime • 15% of foot ulcers Osteomyelitis • 15% of foot ulcers Amputation Clinical Care of the Diabetic Foot, 2005

45. AMPUTATIONS IN DIABETES Tragic “Rules of 50” • 50% of amputations transfemoral/transtibial level • 50% of patients 2nd amputation in  5y • 50% of patients Die in  5y Clinical Care of the Diabetic Foot, 2005

46. RISK FACTORS FOR AMPUTATION • 􀂄􀂄 Absence of protective sensation • 􀂄􀂄 Arterial insufficiency: ABI<0.45 • 􀂄􀂄 Foot deformity / decreased joint mobility • 􀂄􀂄 Autonomic neuropathy • 􀂄􀂄 Poor glucose control • 􀂄􀂄 Low HDL • 􀂄􀂄 Infection • 􀂄􀂄 Lack of diabetes education • 􀂄􀂄 Decreased vision • 􀂄􀂄 Obesity • 􀂄􀂄 Improper foot wear • 􀂄􀂄 Foot ulcer or previous amputation

47. PROGNOSIS OF CLI TASC, EJVES 2007

48. PROBABILITY OF HEALING Documento di Consenso internazionale sul Piede Diabetico 1999

49. QUESTIONS?

50. TAKE HOME MESSAGES • PAD prevalence and incidence are increasing in developed countries • PAD may be asymtomatic, symptomatic for claudication, or critical limb ischemia • Diabetes is one of the most important pathophysiologic factors underlying PAD and CLI • A comprehensive appraisal of causes and mechanisms of PAD and CLI, beyond revascularization, is pivotal to maximize clinical success