ATEF ELBAHRY,FACA,FICA,MISCP,FVBWG.

Transcription

1 Hyperglycemia and Coronary Events: where is the link? ATEF ELBAHRY,FACA,FICA,MISCP,FVBWG. Cardiovascular (CV) disease is the primary complication of diabetes ~65% of deaths are due to CV disease Coronary heart disease deaths 2- to 4-fold Cardiovascular complications of T2DM Stroke risk 2- to 4-fold T2DM = type 2 diabetes mellitus Heart failure 2- to 5-fold Bell DSH. Diabetes Care. 23;26: Centers for Disease Control (CDC). 1

2 CHD risk appears to begin at low blood glucose levels N = 17,869 men, aged 4 64 years; follow-up 33 years CHD mortality (log hazard ratios) mg/dl OGTT blood glucose (mg/dl) Relative to baseline group of all men with blood glucose <83 mg/dl Brunner EJ et al. Diabetes Care. 26;29: Even mild glucose elevations increase mortality in patients undergoing PCI N = 1612 with CAD; mean age 62 years 12 1 P-trend < Mortality NFG IFG Undx DM2 DM2 FG (mg/dl) < NFG = normal FG Undx DM2 = undiagnosed type 2 diabetes Muhlestein JB et al. Am Heart J. 23;146:

3 IVUS shows greater atherosclerotic disease burden in diabetes N = 654 with CHD; 128 (19.6%) with diabetes 1 P =.3 % P =.2 P =.1 2 Percent atheroma volume Percent abnormal cross sections Percent area stenosis Diabetes No diabetes IVUS = intravascular ultrasound Nicholls SJ et al. J Am Coll Cardiol. 26;47: New-onset hyperglycemia linked to highest rate of in-hospital mortality A retrospective study of medical records of 23 consecutive hospitalized patients 4 Newly Diagnosed 3 Mortality 2 1 Normoglycemia Known diabetes New hyperglycemia CCU patients Non-CCU patients P <.1 vs normoglycemia and known diabetes Umpierrez GE et al. J Clin Endocrinol Metab. 22;87:

4 Admission glucose in AMI associated with mortality, independent of T2DM diagnosis N = 141,68 hospitalized with AMI 6 3 days 1 year Mortality >11-14 >14-17 >17-24 >24 11 >11-14 >14-17 >17-24 >24 Admission glucose (mg/dl) Diabetes No diabetes AMI = acute myocardial infarction Kosiborod M et al. Circulation. 25;111: Stress hyperglycemia in AMI: Association with mortality risk in patients without known diabetes Reference Hyperglycemia definition (mg/dl) O Sullivan 1991 >144 Lewandowicz Soler Oswald Bellodi 1989 >121 Ravid 1975 >121 Sewdarsen Pooled 3.9-fold higher risk of in-hospital mortality Unadjusted RR of in-hospital mortality after MI vs patients with normoglycemia Capes SE et al. Lancet. 2;355:

5 Admission glucose and glucose change within 24 hours predict mortality risk N = 1469 with AMI (n = 1219 without DM) 12 3-day mortality % in 3-day mortality per 11 mg/dl glucose in first 24 hr (P =.2) 2 < <14 14 <17 17 Baseline glucose (mg/dl) ΔGlucose (24 hr vs baseline) 3 mg/dl decrease No change to <3 mg/dl decrease Increase Multivariate analysis Goyal A et al. Eur Heart J. 26;27: Hyperglycemia in CORONARY EVENTS Deranged metabolism Serum FFA Insulin secretion Glycolysis Glucose oxidation Impaired perfusion Endothelial function No-reflow phenomenon Prothrombotic Platelet aggregation g Fibrinolysis Clotting factors Impaired LV function Ischemic preconditioning LV remodeling Inflammation Cytokines, chemokines, biomarkers FFA = free fatty acids LV = left ventricular Zarich SW. Rev Cardiovasc Med. 26;7(suppl 2).S Bauters C et al. Eur Heart J. 27;28:

6 Excessive myocardial triglyceride accumulation in IGT and T2DM N = Intramyocardial triglycerides (fat/water ratio, %) P <.1 vs lean individuals IGT = impaired glucose tolerance T2DM = type 2 diabetes mellitus Lean Normoglycemic IGT T2DM Obese McGavock JM et al. Circulation. 27;116: Hyperglycemia: Independent predictor of impaired myocardial blood flow in STEMI N = 57 Thrombolysis In Myocardial Infarction (TIMI) Initial TIMI flow grade vs admission glucose 14 vs <14 mg/dl TIMI -2 predictors 6 OR P 5 Glucose 14 mg/dl Patients No Flow Glucose 14 mg/dl (hyperglycemia) Worst Best Complete Perfusion TIMI flow grade Nonsmoking Male gender Age (per year) Diabetes history.5.15 Glucose <14 mg/dl P =.3 vs TIMI 1-3; P <.1 vs TIMI -2 After multivariate analysis Timmer JR et al. J Am Coll Cardiol. 25;45:

7 Hyperglycemia increases endothelial dysfunction N = 579 without diabetes or prior CV disease 1 Odds ratio for abnormal flowmediated brachial artery dilation (95% Cl) Fasting plasma glucose (mg/dl) Unadjusted Rodriguez CJ et al. Am J Cardiol. 25;96: Myocardial blood flow response to hyperemia in insulin-resistant states N = % 1.5 MBF (ml/min per g) 1. 35%.5. IS IR IGT DM DM + HTN In response to adenosine or dipyridamole P <.1 IS = insulin sensitive; IR = insulin resistant; MBF = myocardial blood flow Prior JO et al. Circulation. 25;111:

8 Myocardial blood flow response to cold pressor testing in insulin-resistant states N = P trend <.1.2 Δ MBF.1 (ml/min per g). -.1 IS IR IGT DM DM + HTN P <.1 vs IS; P <.5 vs IGT, DM, DM + HTN IS = insulin sensitive; IR = insulin resistant Prior JO et al. Circulation. 25;111: Hyperglycemia associated with increased inflammatory markers in AMI N = 18 CRP (mg/dl) IL-18 (pg/ml) New hyperglycemia New Known Normoglycemia hyperglycemia diabetes Known diabetes Normoglycemia P <.5 vs normoglycemia CRP = C-reactive protein; IL = interleukin Marfella R et al. Diabetes Care. 23;26:

9 Impact of hyperglycemia on platelet function Inhibition of Na/K ATPase Activation of PKC T2DM GlyLDL, HG, hyperinsulinemia Ca Ca Impaired Ca 2+ Ca homeostasis 2+ Platelet activation TXA 2 NO production GPIb/IX/V GPIV GPIIb-IIIa Non-enzymatic glycation of GPs ROS production TXA 2 PKC = protein kinase C; GlyLDL = glycated low-density, ROS = reactive oxygen species lipoproteins; GP = glycoproteins; TXA = thromboxane Ferroni P et al. J Thromb Haemost. 24;2: Take Home message 1. Hyperglycemia is an independent risk factor in patients with UA/NSTEMI. 2. Cardiovascular events occur in impaired glucose tolerance & undiagnosed DM subjects more than diagnosed ones 3. Hyperglycemia induces, endothelial dysfunction,impaired myocardial blood flow, platelet aggregation and increases inflammatory markers. 9