Diabetes and its Cardiovascular Impact

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. Year 2000: 177 million Diabetes – Prevalence 350 Year 2030: 370 million. 300 250 200 150 100 equivalent to 2/3rd of Europe population 50 0 2030 1995 2000 2005 2010 2015 2020 2025

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

8. The Metabolic Syndrome: A Network of Atherogenic Factors • 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 Insulin Resistance  Free Fatty Acids VisceralObesity Atherosclerosis 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 AssociatedWith Metabolic Syndrome p < 0.001 Diabetes Care 2001;24:683

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. Revascularization in Diabetes: • 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  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: b-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. Astands for A1C Bstands for Blood pressure Cstands for Cholesterol 5

36. HbA1c% 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

37. Amputation / death from leg vessel problems 43% Eye and early kidney disease 37% Deaths related to diabetes 21% Heart failure 16% Heart Attacks 14% Stroke 12% Risk Reduction With a 1% Reduction in HbA1c : Any lower is therefore better!

38. Pharmacotherapy of Hypertension • Aim for 125/75-80 • ACE inhibitors and ARBs have a favorable effecton renal and cardiovascular systems. • ß-blockers along with ACE inhibitors help in reducingmyocardial 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. 100 80 55% 60 Risk reduction Patients with heart disease (%) 40 Diabetic,simvastatin 20 Diabetic, placebo 0 0 1 2 3 4 5 6 Years since randomisation Cholesterol lowering reduces Heart Disease in Patients with Diabetes by up to 55% !

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