The Burden of the Diabetic Heart

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1 The Burden of the Diabetic Heart Dr. Ghaida Kaddaha (MBBS, MRCP-UK, FRCP-london) Diabetes Unit Rashid Hospital Dubai U.A.E Risk of CVD in Diabetes Morbidity and mortality from CVD is 2-4 fold higher than in age & sex-matched individuals without diabetes. 5% of diabetics have evidence of CVD at diagnosis. 8% of diabetes-related deaths are due to cardiovascular complications. Diabetes is considered a CVD equivalent in the (NCEP) ATP- III guidelines. ١

2 OASIS Study Mortality by Diabetes and CVD Status.25 Diabetes/CVD (n=1,148) No Diabetes/CVD (n=3,53) RR=2.88 ( ) Event rate Diabetes/No CVD (n=569) No Diabetes/No CVD (n=2,796) RR=1.99 ( ) RR=1.71 ( ).55 RR= Malmberg K, et al. Circulation. 2;12: Months OASIS=Organization to Assess Strategies for Ischemic Syndromes CVD=cardiovascular disease RR=relative risk (95% confidence intervals) Incidence of myocardial infarction (MI) in subjects with and without diabetes 7-year follow-up 45 Fatal or non-fatal MI incidence e dur ring follow-up (%) Prior MI No MI Prior MI No MI Non DM DM Haffner SM et al. N Engl J Med 1998;339: ٢

3 Increased CHF Prevalence in Diabetics Diabetic subjects Control subjects < CHF=congestive heart failure Age at baseline Nichols GA, et al. Diabetes Care. 21:24; Copyright 22, American Diabetes Association. Reprinted with permission. Relative risks for Mortality in Categories of HbA 1c (Hoorn-Study) All-cause CVD * Relative risk * < *p<.5 HbA 1c (%) Adjusted for age and sex De Vegt F et al. Diabetologia 1999;42: ٣

4 Lowering HbA1c Reduces Risk of Complications* Reduction in Risk (%) Any diabetes - related endpoint -5 Microvascular endpoint -15 p= MI p= Cataract -25 p=.15 extraction p=.9 p=.46-3 Retinopathy p=.5 Albuminuria at years *Percent risk reduction for.9% decrease in HbA1C UKPDS 33. Lancet 1998; 352:837. DCCT/EDIC: Early intensive therapy reduced the risk of nonfatal MI, stroke or death from CVD.12 Cumulative incidence of tal MI, stroke or death fro om CVD nonfat % risk reduction (P=.2; 95% CI:12 79%) Conventional treatment Intensive treatmentt t n at risk: Years since entry Intensive treatment Conventional treatment DCCT/EDIC Study Research Group. N Engl J Med 25;353: ٤

5 Trials examining glycemic targets The ACCORD 257 died in the intensive-treatment group died 23 within the standard-treatment group A difference of 54 deaths. This translates to a 2% higher rate of death in This translates to a 2% higher rate of death in the intensive than the standard group. ٥

6 PERISCOPE 543 patients with type 2 diabetes underwent coronary IVUS and then were randomized to receive either glimepiride (1-4 mg) or pioglitazone (15-45 mg) for 18 months, at which time IVUS studies were repeated. Mean percent atheroma volume decreased by.16% in pioglitazone-treated subjects but increased by.73% in glimepiride-treated patients. Pioglitazone also produced favourable changes in HDL and triglyceride levels The CHICAGO Study 18-month, multicenter, randomized study that enrolled 462 patients with type 2 diabetes, all from the Chicago area. The primary goal was to compare the effects of ACTOS versus glimepiride,, on carotid intima-media thickness (CIMT), The CHICAGO analysis demonstrated a similar result on the y progression of atherosclerosis as was observed in PERISCOPE. ٦

7 Time to Primary Composite Endpoint Kaplan-Meier event rate.25.2 placebo pioglitazone N events: 572 / / year estimate: 23.5% 21.% 1% RR HR 95% CI p value pioglitazone vs placebo.94.82, N at Risk: (228) Time from randomisation (months) Dormandy J et al. Lancet 25; 366: 1279 Time to Death, MI (Excluding Silent) or Stroke Kaplan-Meier event rate.15 placebo N events: 358 / year estimate: 14.4% 4% 16% RRR.1 pioglitazone 31 / %.5 HR 95% CI p value pioglitazone vs placebo , N at Risk: (256) Time from randomisation (months) Dormandy J et al. Lancet 25; 366: 1279 ٧

8 Ticking Clock Hypothesis For Microvascular complications Macrovascular complications The clock starts ticking At onset of hyperglycemia Before the diagnosis of hyperglycemia WHO. Diabetologia 1985;28:615-64; Haffner SM et al. JAMA 199;263: Incidence of first CV events 5 ITT Cum mulative incidence (%) 4 Placebo 3 49%, p=.4 2 Acarbose 1 p=.4 log rank Time (years after randomisation) Chiasson JL, et al. JAMA 23;29: ٨

9 Does Treatment of IGT Affect Macrovascular Disease? (NAVIGATOR), Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (DREAM), Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (ACT NOW); pioglitazone Actos Now for the Prevention of Type 2 Diabetes (ORIGIN); insulin glargine). Outcome Reduction with Initial Glargine Intervention The NAVIGATOR trial The largest diabetes prevention trial to date, involving 7,5 subjects The only diabetes prevention trial also powered to show a reduction in CVD Will involve 8 investigator centers in 4 countries around the globe ٩

10 Primary objectives NAVIGATOR will tell us: Whether the oral antidiabetic (nateglinide) or the angiotensin II receptor blocker (valsartan) can Delay type 2 diabetes Prevent CVD in people who have IGT and are at high risk of CVD ١٠

11 UKPDS Event Rates for Select Endpoints With Tight vs Less Tight Blood Pressure Control Even nts per 1 patient yrs P=.5 Any diabetes-related endpoint P=.2 Diabetesrelated death Tight (n=758) mean achieved BP 144/82 mmhg Less tight (n=39) mean achieved BP 154/87 mmhg P=.1 Stroke P=.9 Microvascular complications UKPDS Group. BMJ. 1998;317: Diabetes: Tight Glucose vs Tight BP Control and CV Outcomes in UKPDS ion In Relative Risk % Reducti Stroke 5% 44% * Any Diabetic Endpoint 12% DM Deaths 1% Tight Glucose Control (Goal <6. mmol/l or 18 mg/dl) Microvascular Complications 24% * 32% 32% * 37% *P <.5 compared to tight glucose control * Tight BP Control (Average 144/82 mmhg) Bakris GL, et al. Am J Kidney Dis. 2;36(3): Reprinted by permission, Harcourt Inc. ١١

12 Steno-2: effect of intensive vs. conventional treatment on cardiovascular complications oint* (%) Primary composite endpo What do we need to do? Conventional therapy 1 Intensive therapy Months of follow-up n Conventional Intensive ~5% reduction Hazard ratio.47 (95% CI.24.73) *Primary composite endpoint of death from cardiovascular causes, non-fatal myocardial infarction, coronary-artery bypass grafting, percutaneous coronary intervention, non-fatal stroke, amputation or surgery for peripheral atherosclerotic artery disease Gaede P, et al. N Engl J Med 23; 348: What do we need to do? Public awareness (Obesity & Diabetes) Targeting children & adolescents Early screening of high risk individual Exercise & diet (DPP, Finnish, India DPP) ١٢

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