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

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 and cardiovascular illness  Prevalence has increased by 42% in developed world and quadrupled in developing countries (Amos Diabetic Medicine 1997;14:s5:S1-S85)  One third of individuals born after 2000 will be diabetic when adult (ADA statement 2003)  DM magnifies risk of cardiovascular mortality and morbidity and  is associated with three fold increase in CV events (Stein Circulation 1995;91:979-81) Amos Diabetic Medicine 1997;14:S5:S1-S85

7. Obesity and type 2 diabetes Chan et al (1994) and Colditz et al (1995)

8. Insulin Resistance and the Metabolic Syndrome  Insulin Resistance Resistance to the action of insulin occurring in the adipocyte, skeletal muscle and the liver Resistance to the action of insulin occurring in the adipocyte, skeletal muscle and the liver  Metabolic Syndrome Insulin Resistance plus clustering of inflammatory atherothrombotic cardiovascular risk Insulin Resistance plus clustering of inflammatory atherothrombotic cardiovascular risk  Type 2 Diabetes Metabolic Syndrome plus dysglycaemia Metabolic Syndrome plus dysglycaemia

9. Cardiovascular Risk Clustering in Viscerally Obese Patients. Hypertriglyceridemia. Low HDL-cholesterol. High apolipoprotein B. Small, dense LDL particles. Inflammatory profile. Insulin resistance. Hyperinsulinemia. Glucose intolerance. Impaired fibrinolysis. Endothelial dysfunction

10. 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

11. Coronary heart disease and diabetes  Studied using –epidemiology –post-mortem –electrocardiography –Angiography  High prevalence of subclinical atherosclerosis  CAD more prevalent, more extensive, more diffuse, increased calcification  High prevalence of Lt. Main disease, less collaterals  High prevalence of ‘silent ischemia’

12. Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved. 12 Table 2. Risk of Coronary Heart Disease based on the UKPDS model* Kirk et al. Coronary Artery Disease 2007,18:595-600 Follow-up point † WhiteMexican AmericanBlack 5-year 10-year 15-year 20-year 11.0% (9.5-12.4) 23.0% (20.4-25.7) 35.8% (32.1-39.5) 48.7% (44.3-53.0) 9.6% (7.9-11.4) 20.0% (16.7-23.3) 31.0% (26.4-35.6) 42.3% (36.7-47.9) 10.1% (8.1-12.2) 21.5% (17.7-25.4) 33.6% (28.3 -38.9) 45.8% (39.6-52.0) Values are accompanied by 95% CI (in parentheses) CHD = Coronary Heart Disease, UKPDS = United Kingdom Prospective Diabetes Study. *UKPDS model assuming all participants are white, † All comparisons non-significant (NS)

13. Mortality in Diabetes Diabetic patients without previous MI have as high a risk of MI as non-diabetic patients with previous MI New England Journal of Medicine 1998;339:229–234. Without previous MI previous MI With previous MI previous MI 7-year incidence of MI (%) 7 year follow-up

14. 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

15. 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 (“good”) cholesterol –high LDL (“bad”) cholesterol 4

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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.

22. 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 (%)

23. 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

24. v

26. Plaque Disruption & Thrombosis Journal of medicine

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

28.   PCI Case

29. Optimising medical therapy   Metformin : reduced incidence of diabetes by 31% (Knowler NEJM 2002;346:393)   Ramipril : by 34% (HOPE JAMA 2001;286:1882)   Lipid lowering : by 22% (Collins Lancet 2003;361:2005)   Blood pressure control : SBP<140

30. 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.

31. 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

32. 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

33. 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

34. 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

35. 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.