1. Diabetes and its Cardiovascular Impact Dr Rashid Iqbal Consultant Cardiologist Surrey and Sussex Healthcare NHS Turst St Georges Hospitals NHS Trust Spire Gatwick Park Hospital

2. Aims  Epidemiology of DM  Coronary Artery Disease in Diabetes  How to protect Diabetic Heart?

3. Diabetes Prevalence Worldwide  In 2000 2.8% (171 million)  By 2030 4.4% (366 million)  A 36 % increase in 30 years Wild S et al Diabetes Care 2004;27:1047-53

4. 0 1995200020052010201520202025 2030 100 150 300 350 50 200 250 Diabetes – Prevalence Year 2000: 177 million Year 2030: 370 million. equivalent to 2/3 rd of Europe population

6. Diabetes Doubles Risk for MI Mortality Despite Advances in Cardiac Care

8. Glycemic disorders Dyslipidemia - Low HDL - Small, dense LDL - Hypertriglyceridemia -Postprandial lipemia Hypertension Impaired thrombolysis -  PAI-1, fibrinogen Endothelial dysfunction/ inflammation -  CRP, MMP-9,  adiponectin Microalbuminuria Visceral Obesity Insulin Resistance  Free Fatty Acids Atherosclerosis The Metabolic Syndrome: A Network of Atherogenic Factors Brunzell J, Hokanson J. Diabetes Care. 1999;22(Suppl 3):C10-C13. McFarlane S, et al. J Clin Endocrinol Metab. 2001;86(2):713-718. Frohlich M, et al. Diabetes Care. 2000;23(12):1835-1839. Kuusisto J, et al. Circulation. 1995;91:831-837. Parulkar AA, et al. Ann Intern Med. 2001;134:61-71. Hseuh WA, et al. Diabetes Care. 2001;24(2):392-397. Lebovitz H. Clin Chem. 1999;45(8B):1339-1345.

9. Cardiovascular Mortality Associated With Metabolic Syndrome Diabetes Care 2001;24:683 p < 0.001

10. Cardiovascular Disease   Early, aggressive interventions for risk reduction   New, more effective therapies for treatment of HTN and hyperlipidemia   Dramatic improvement in cardiovascular interventions   Reduction in smoking ? Yet the increase in prevalence of obesity and diabetes is epidemic, with CVD the leading complication of DM

11. ACS Treatment   STMI- Aim for PPCI   NSTMI- Aim to catheterise within 72hours   Secodary prevention:   DAPT, Aspirin for life, Clopidogrel/Prasugrel/Ticagrelol 12 MONTHS   High dose Statin +/- Ezatemibe ( In-Practice Study and NICE guidance.   Betablocker/ACE Inhibition   Smoking cessation   Cardiac Rehab

17.   PCI Case

18. Diabetes and Heart Failure: Current Knowledge

19. Stenting in Diabetes: Clinical and Angiographic Outcomes BARI – Mortality after CABG vs. PTCA, 2000

20. Co-morbidity (PVD , CRF  ) Peri-procedural complications  Worse long-term clinical outcomes death , MI , stroke  Excessive restenosis intimal hyperplasia  negative remodeling  Accelerated atherosclerosis progression of disease  small vessel/diffuse disease  Revascularization in Diabetes: BARI 2-D All-cause mortality CVD mortality & MI Angina, employment Retinopathy Neuropathy Nephropathy PVD HbA1c, BP, cholesterol Cost-effectiveness

21. Blood Glucose Relates to Mortality and Risk for Heart Failure in MI

22. Glycemic Control and Risk of Development of HF in Diabetes

23. Syst-Eur: Reduction in Event Rate in Adults (  60 Years) With Diabetes

24. HOT: Cardiovascular Events by Target DBP in Diabetes Subgroup

27. ACE Inhibitor Therapy for Patients With Diabetes

28. HOPE: Outcomes in Patients With Diabetes

29. BIP:  -Blocker Treatment Improves Survival of Patients With Diabetes

30. Costs - Fact File  Studies have shown that diabetes is a costly disease  Type 2 diabetes accounted for between 3% and 6% of total healthcare expenditure in eight European countries  Hospital in-patient costs are the largest single contributor to direct healthcare costs

31. Diabetes-CVD Facts   More than 65% of all deaths in people with diabetes are caused by cardiovascular disease.   Heart attacks occur at an earlier age in people with diabetes and often result in premature death. 3

32. Diabetes-CVD Facts   Up to 60% of adults with diabetes have high blood pressure.   Nearly all adults with diabetes have one or more cholesterol problems, such as: –high triglycerides –low HDL cholesterol –high LDL cholesterol 4

33. The Good News…   By managing the ABCs of diabetes, people with diabetes can reduce their risk for heart disease and stroke. A stands for A1C B stands for Blood pressure C stands for Cholesterol 5

34. Ask About Your A1C   A1C measures average blood glucose over the last three months.   Get your A1C checked at least twice a year. A1C Goal = less than 7% 6

35. Treating Cardiovascular risk factors…  Managing the ABCs of diabetes, people with diabetes can reduce their risk for heart disease and stroke. A stands for A1C B stands for Blood pressure C stands for Cholesterol 5

36. HbA 1c % 7.0% versus 7.9% Reduction in risk by: 25%for eye disease and early kidney disease 16%for Heart Attacks 24%for cataract surgery Reduction in risk by: 25%for eye disease and early kidney disease 16%for Heart Attacks 24%for cataract surgery

37. Risk Reduction With a 1% Reduction in HbA 1c : Any lower is therefore better! 16% Heart failure 43% Amputation / death from leg vessel problems 37% Eye and early kidney disease 12%Stroke 14% Heart Attacks 21% Deaths related to diabetes

38. Pharmacotherapy of Hypertension  Aim for 125/75-80  ACE inhibitors and ARBs have a favorable effect on renal and cardiovascular systems.  ß-blockers along with ACE inhibitors help in reducing myocardial infarction and heart failure.  Calcium channel blockers in combination with ACE inhibitors, ß-blockers, and diuretics help in controlling blood pressure.  Diuretics are recommended when BP control is still uncontrolled.

39. Cholesterol lowering reduces Heart Disease in Patients with Diabetes by up to 55% ! 1234560 0 20 40 60 80 100 Risk reduction reduction 55% Diabetic,simvastatin Diabetic, placebo Years since randomisation Patients with heart disease (%)

40. Multiple aetiology of atherosclerosis generation  increased inflammatory markers  hyperglycaemia induced endothelial dysfunction  increased vascular permeability  adventitial inflammation (of vasa vasorum)  impaired fibrinolysis  dysfunctional arterial remodelling

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43. Plaque Disruption & Thrombosis Journal of medicine

44. Atherothrombotic plaque in diabetic patients  More in number  More likely to rupture  More likely to have existing surface thrombus

45. Antiplatelets Aspirin 75mg once daily : Aspirin 75mg once daily : Diabetes UK advises aspirin treatment in all patients with diabetes over the age of 30 years with any of the following: Diabetes UK advises aspirin treatment in all patients with diabetes over the age of 30 years with any of the following: previous MI, angina, HT, diabetic eye disease, PVD, early kidney disease, raised cholesterol, family history of heart disease, obesity, south Asians smokers, DM duration > 10 years. Clopidogrel can be used as an alternative.

46. DES in Diabetes  Both Sirolimus- and Paclitaxel-eluting stents substantially reduce angiographic and clinical restenosis compared with BMS  DES have not eliminated the excess risk of restenosis in diabetics c/w non-diabetics

47. CABG: the “diabetic disadvantage” Society of Thoracic Surgeons database of 1.37 million patients undergoing cardiac surgery (1990-2000). Diabetic patients had higher rates of:   30 day mortality and   deep sternal wound infections   stroke   longer hospital stay   two-fold worse 10 year survival (36835 pts) Brown et al Semin Thorac Cardiovasc Surg 2006;18:281

48. PCI v CABG( SYNTAX)   No mortality difference at 1 year   Higher incidence of CVA after CABG   More frequent angina after PCI   More frequent angiography and repeat revascularisation after PCI

49. Reducing risk in patients undergoing PCI – what can we do?   Tight glycaemic control (HbA1c ≤7) pre and post procedure ( Corpus et al JACC 2004;43:8 )   Thiazolidinediones – may reduce neointimal proliferation and restenosis in T2DM receiving BMS   Antithrhrombotic therapy   Drug eluting stents

50. Conclusion Diabetic patients are different 1.Epidemiology: increasing prevalence worldwide 2.Pathology: their vasculature is different - plaques more frequent and more prone to rupture. 3.Outcomes: for patients with type 2 diabetes sustaining an acute myocardial infarction is poor particularly if they have documented coronary artery disease. 4.Treatment: Modern therapies have a favourable effect but there remains a residual risk not addressed by these therapies.