1. 1 “Diabetic foot” Sensory Autonomic Motor

2. 2 Neuropathic: 45-60% Purely ischaemic: 10% Mixed neuroischaemic: 25-40% Diabetic foot ulceration

3. 3 Diabetes and PAD Spectrum of disease Intermittent claudication Intermittent claudication Rest pain Rest pain Ulceration/gangrene Ulceration/gangrene Incidental/Screening Incidental/Screening

4. 4 Intermittent claudication

5. 5 Intermittent Claudication Prevalence: 5.3% in patients aged 45-74yrs Prevalence: 5.3% in patients aged 45-74yrs Quality of life: Significantly impaired Quality of life: Significantly impaired Limb Outlook: Relatively benign Limb Outlook: Relatively benign 10% require intervention to prevent limb loss 10% require intervention to prevent limb loss 1% per year require amputation 1% per year require amputation Life expectancy: 2-4 X ↑ mortality Life expectancy: 2-4 X ↑ mortality

6. 6 Peripheral Arterial Disease and All- Cause Mortality Normal subjects Asymptomatic PAD † Symptomatic PAD † Severe symptomatic PAD † 1.00 0.75 0.50 0.25 0.00 024681012 Survival Year *Kaplan-Meier survival curves based on mortality from all causes *Kaplan-Meier survival curves based on mortality from all causes † Large-vessel PAD † Large-vessel PAD 1. Criqui MH. Vasc Med 2001; 6(suppl 1): 3–7. 1. Criqui MH. Vasc Med 2001; 6(suppl 1): 3–7.

7. 7 Odds ratio for risk factors for intermittent claudication Male gender (cf female) Age (per 10 years) Diabetes Smoking Hypertension Hypercholesterolemia Fibrinogen Alcohol -201234 ProtectiveHarmful Odds Ratio Dormandy JA et al. J Vasc Surgery. 2000;31(1 Part 2):S1-S296.

8. 8 Intermittent Claudication and diabetes Prevalence: 2 x ↑ Prevalence: 2 x ↑ Diabetics – 20% of PAD population Diabetics – 20% of PAD population Limb Outlook: Worse Limb Outlook: Worse 2x ↑ rest pain, 6x ↑gangrene 2x ↑ rest pain, 6x ↑gangrene 80% of amputations occur in diabetics 80% of amputations occur in diabetics Life expectancy: 8 x ↑ mortality Life expectancy: 8 x ↑ mortality

9. 9 Diagnosis: History  Intermittent claudication cramp like pain in muscles cramp like pain in muscles Location: buttock, thigh, calf,foot Location: buttock, thigh, calf,foot occurs on exercising occurs on exercising relieved by rest relieved by rest Atypical symptoms Atypical symptoms are common are common

10. 10 Diagnosis – clinical examination Examination of pulses Examination of pulses Peripheral pulses- HIGHLY SUBJECTIVE Rotterdam study Rotterdam study 60% inaccurate

11. 11 Pulses & PAD Collins 206, 403 pts screened Collins 206, 403 pts screened PAD prevalence :16.6% PAD prevalence :16.6% Sensitivity of a non detectable pedal pulse -18% Sensitivity of a non detectable pedal pulse -18% Specificity: 98% Specificity: 98% Post tibial pulse: sensitivity 33%, specificity 66% ( Brealey S et al) Post tibial pulse: sensitivity 33%, specificity 66% ( Brealey S et al) Probability of agreement of an absent pedal pulse between experienced examiners : 0.49-0.59 (Marinelli et al) Probability of agreement of an absent pedal pulse between experienced examiners : 0.49-0.59 (Marinelli et al)

12. 12 Ankle Brachial Pressure Index (ABPI)

13. 13 Ankle Brachial Pressure Index (ABPI) Ankle pressure (mm Hg) Brachial pressure (mm Hg) ABPI = Value <0.9 indicates PAD

14. 14 Figure 1.5 ABPI – DIAGNOSIS & PROGNOSIS McKenna et al, atherosclerosis, 1991

15. 15 ABPI Reliable Reliable Positive predictive value -95% Positive predictive value -95% Negative predictive value-99% Negative predictive value-99% But a normal ABPI at rest and classical symptoms may indicate need for exercise ABPI But a normal ABPI at rest and classical symptoms may indicate need for exercise ABPI ESSENTIAL FOR DIAGNOSIS ESSENTIAL FOR DIAGNOSIS Do we have expertise in the community? Do we have expertise in the community?

16. 16 Diabetes and ABPI Medial calcification: non compressible (nc) arteries Medial calcification: non compressible (nc) arteries ABPI in diabetics : 5-10% too high ABPI in diabetics : 5-10% too high Alternatives: Elevate foot Alternatives: Elevate foot Toe pressures Toe pressures

17. 17 Toe pressures Cuff placed around proximal phalanx Cuff placed around proximal phalanx Normal pressures are less than ankle pressures Normal pressures are less than ankle pressures average 24± 7 – 41± 17mmHg average 24± 7 – 41± 17mmHg Normal ratios compared to brachial 0.72-0.91 Normal ratios compared to brachial 0.72-0.91

18. 18 First line : Prolong life First line : Prolong life Risk factor management Improve symptoms Improve symptomsExercise Medical therapy Revascularisation CLAUDICATION: SURGICAL TREATMENT

19. 19Treatment *Statin for all *Statin for all *Screen for diabetes/ Glycaemic control *Screen for diabetes/ Glycaemic control *BP control *BP control Smoking cessation: NRT Smoking cessation: NRT Anti-platelet therapy Anti-platelet therapy Increase exercise Increase exercise ACE inhibitor (HOPE study) ACE inhibitor (HOPE study) Review: ? For revascularisation Review: ? For revascularisation

20. 20 VASCULAR EVENT by PRIOR DISEASE MRC/BHF Heart Protection Study Risk ratio and 95% CISTATINPLACEBOBaseline feature (10269)(10267)STATIN betterSTATIN worse Previous MI10071255 Other CHD (not MI)452597 No prior CHD CVD182215 PVD332427 Diabetes279369 ALL PATIENTS20422606 (19.9%)(25.4%) 24%SE 2.6 reduction (2P<0.00001) 0.40.60.81.01.21.4

21. 21 Diabetes and PAD No clinical trials have been set up specifically to investigate glycaemic control. No clinical trials have been set up specifically to investigate glycaemic control. Type 2 diabetes,  glycaemia (HbA1C)   risk of cardiovascular morbidity and mortality (1) Type 2 diabetes,  glycaemia (HbA1C)   risk of cardiovascular morbidity and mortality (1) Each 1% difference in HbA1C  21% (95% CI 15-27%) change in the risk of diabetes-related death and a 14% reduction in fatal and nonfatal myocardial infarction over 10 years (2) Each 1% difference in HbA1C  21% (95% CI 15-27%) change in the risk of diabetes-related death and a 14% reduction in fatal and nonfatal myocardial infarction over 10 years (2) Turner RC, et al.. BMJ 1998; 316: 823-8. Stratton IM et al,. BMJ. 2000;321(7258):405-12.

22. 22 HOPE study Effects of ramipril on patients with Effects of ramipril on patients with 1. symptomatic PAD 2. Asymptomatic PAD (ABPI ≤ 0.9) plus an additional coronary risk factor were analysed. Only 50% of the patients were defined as hypertensive. Only 50% of the patients were defined as hypertensive. In both groups-  ~ 25% reduction in the primary combined outcome of cardiovascular mortality, myocardial infarction or stroke with ramipril. In both groups-  ~ 25% reduction in the primary combined outcome of cardiovascular mortality, myocardial infarction or stroke with ramipril. (ABPI) was measured unconventionally (ABPI) was measured unconventionally Ostergren J, et al. Eur Heart J 2004; 25: 17-24.

23. 23 Diabetes and PAD Spectrum of disease Intermittent claudication Intermittent claudication Rest pain Rest pain Ulceration/gangrene Ulceration/gangrene Incidental/Screening Incidental/Screening

24. 24 Severe limb ischaemia Rest pain>2/52, Tissue loss ABPI <0.5

25. 25 Severe limb ischaemia Rest pain>2/52, Tissue loss ABPI <0.5 Critical limb ischaemia Absolute ankle pressure <50mmHg

26. 26 Neuropathic: 45-60% Purely ischaemic: 10% Mixed neuroischaemic: 25-40% Diabetic foot ulceration

27. 27 Figure 14.2

28. 28 Diabetes & foot ulcers 15% develop a foot ulcer 15% develop a foot ulcer 12-24% require amputation 12-24% require amputation Leading cause of lower limb amputation Leading cause of lower limb amputation

29. 29 Will the ulcer heal? Study of patients with foot ulcers and toe amputations Non-heeling occurred in (Ramsey et al) 92% of limbs with ankle pressure <80mmHg 92% of limbs with ankle pressure <80mmHg But also in 45% of limbs with higher ankle pressures But also in 45% of limbs with higher ankle pressures 95% of limbs with toe pressures <30mmHg 95% of limbs with toe pressures <30mmHg But only in 14% of limbs with higher toe pressures But only in 14% of limbs with higher toe pressures Toe pressures – greater prognostic value Toe pressures – greater prognostic value PPV 67%, NPV 77% (Kaloni et al, 1999;Diabetes Care) PPV 67%, NPV 77% (Kaloni et al, 1999;Diabetes Care)

30. 30 Investigation of PAD in patients with diabetes Duplex scan Duplex scan Angiography Angiography CT angiography CT angiography MRA/MRI MRA/MRI

31. 31 Figure 1.2 A B C D

32. 32 Diabetes: distribution of PAD Atherosclerosis in : Atherosclerosis in : Classical sites: aorto- iliac, Fem artery Classical sites: aorto- iliac, Fem artery Medium-sized vessels- peroneal/tibial vessels Medium-sized vessels- peroneal/tibial vessels Foot vessels spared Foot vessels spared

33. 33 Revascularisation Angioplasty Angioplasty By-pass By-pass

34. 34 Figure 3.8

35. 35

36. 36 Amputation Minor- infection, osteomyelitis Minor- infection, osteomyelitis Possible if good blood supply Possible if good blood supply Major – extensive soft tissue infection or Major – extensive soft tissue infection or Insufficient blood supply 80% of amputees have diabetes 80% of amputees have diabetes

37. 37 When to refer ? Symptoms: Symptoms: Intermittent claudication Intermittent claudication Rest pain ( nb neuropathy) Rest pain ( nb neuropathy) Signs: Signs: low/nc ABPIs low/nc ABPIs Ulceration Ulceration Gangrene Gangrene ? ? Screening – value for risk factor Mx ? ? Screening – value for risk factor Mx

38. 38 Asymptomatic PAD Relatively common Relatively common Associated with increased mortality Associated with increased mortality Can early treatment prevent events ? Can early treatment prevent events ? 2 Major trials will report ‘06/’07 2 Major trials will report ‘06/’07 Potential to save lives using ABPI: a simple non-invasive screening test Potential to save lives using ABPI: a simple non-invasive screening test

39. 39 Aspirin for Asymptomatic Atherosclerosis (AAA) Trial ABPI<0.95 N=3334 Study Population: men and women >50 years of age Study Population: men and women >50 years of age £ British Heart Foundation £ 3- 4 Year Follow-up Aspirin vs placebo Endpoints Cardiovascular Events Deaths Endpoints Fowkes & Douglas, personal communication 2002

40. 40 POPADAD ABPI <0.99 Diabetes Men & women aged>40 years N=8000 Low ABPI in 20.1% Royal College of Physicians Diabetic Registry Group Royal College of Physicians Diabetic Registry Group NO clinical evidence of vascular disease £ Medical Research Council £ Endpoints Cardiovascular Events Deaths Endpoints

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