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Mater Dei Hospital, Malta. Cardiovascular Disease & Mortality in Diabetes. Stephen Fava MD, MRCP(UK), FEFIM, FACP, FRCP (Lond), MPhil (Malta), PhD (Exeter) Consultant Physician, Diabetologist & Endocrinologist Head of Diabetes & Endocrine Centre, Mater Dei Hospital, Malta.
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Mater Dei Hospital, Malta Cardiovascular Disease & Mortality in Diabetes Stephen Fava MD, MRCP(UK), FEFIM, FACP, FRCP (Lond), MPhil (Malta), PhD (Exeter) Consultant Physician, Diabetologist & Endocrinologist Head of Diabetes & Endocrine Centre, Mater Dei Hospital, Malta
Overall summary estimates of relative risks and 95% confidence intervals for fatal coronary heart disease in men and women with and without diabetes in 22 studies that reported both age and multiple adjusted coefficients Huxley, R. et al. BMJ 2006;332:73-78
Glycaemia and Mortality log rank test P < 0.0001 Kaplan-Meier survival curves according to quartiles of HBA1c Menon V et al. Glycosylated hemoglobin and mortality in patients with nondiabetic chronic kidney disease . J Am Soc Nephrol. 2005 Nov;16(11):3411-7
Isolated post-challenge hyperglycaemia and mortality Pooled data from 3 population-based longitudinal studies (in Mauritius, Fiji and Nauru) 1.0 Normal 0.9 Isolated fasting hyperglycaemia Cumulative survival (males) Combined fasting / postprandial hyperglycaemia 0.8 Isolated postprandial hyperglycaemia Known DM 0.7 0 1000 2000 3000 4000 Time (days) Shaw JE et al. Diabetologia 1999;42:1050
Outcome Of AMIin Diabetes • 196 T2 diabetic subjects and 196 age- & sex- matched non-diabetic controls with AMI were recruited • Patients with IGT were excluded • Biochemical & clinical parameters were measured at baseline & during hospital stay (Fava S et al, Diabetes Care 16:1615-8, 1993)
Outcome Of AMI 3-month mortality p<0.05 (Fava S et al, Diabetes Care 16:1615-8, 1993)
p< 0.001 p< 0.05 (Fava S et al, Diabetes Care 16:1615-8, 1993)
Loss of ‘R’ to ‘R’ variability and Mortality p<0.05 (Fava S et al, Diabetes Care 16:1615-8, 1993)
Loss of ‘R’ to ‘R’ variability and LVF p<0.02 (Fava S et al, Diabetes Care 16:1615-8, 1993)
Thrombolysis p<0.05 (Fava S et al, Diabetes Care 16:1615-8, 1993)
Mortality after AMI: Recent Data Murcia AMet al: Impact of Diabetes on Mortality in Patients With Myocardial Infarction and Left Ventricular Dysfunction. Arch Intern Med. 2004;164:2273-2279.
Outcome Of Unstable Angina p=0.014 p=0.029 Fava S et al, Diabet Med, 14:209-213, 1997
Drug Rx After Unstable Angina NS NS NS p=0.008 Nitrates CCB Aspirin β-Blockers Fava S et al, Diabet Med, 14:209-213, 1997
Invasive Procedures at 1 year After Unstable Angina p= 0.04 p= 0.002 NS Fava S et al, Diabet Med, 14:209-213, 1997
Impact of Albuminuria Gerstein HC et al: Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001 Jul 25;286(4):421-6
Kaplan-Meier survival plot Parents of with T1 DM without nephropathy Log-rank test p= 0.008 Parents of patients with T1 DM with nephropathy Tarnow L et al, Diabetes Care 23 :30–33, 2000
SURVIVAL IN DIABETIC NEPHROPATHY AND ACE GENOTYPE p<0.05 Fava S et al, Diabetes Care 24:2115-20, 2001
Circadian Variation in Onset of AMI χ2 = 1.66, NS χ2 = 13.9, P < 0.005 Non-diabetic subjects Diabetic subjects Fava S et al, Heart 1995;74;370-372
Circadian Variation in Onset of AMI Rana JS et al: Circadian Variation in the Onset of Myocardial Infarction. Effect of Duration of Diabetes. Diabetes 52:1464-1468, 2003
Circadian Variation in Onset of Acute Pulmonary Oedema APE χ2 = 9.38, P < 0.005 AMI χ2 = 0.34, NS Fava S & Azzopardi J. Am J Cardiol 1997
Plasma Glucose in Diabetic Patients with AMI r = 0.92, p< 0.04 Fava S et al: The prognostic significance of Blood Glucose in Diabetic Patients with Acute Myocardial Infarction. Diabetic Med , 1996:13: 80-83
DIGAMI RR 0.72 (0.55 to 0.92), p=0.011 Actuarial mortality curves during long term follow up in patients receiving insulin-glucose infusion and in control group among total DIGAMI cohort. Absolute risk reductionwas 11% Malmberg, K. BMJ 1997;314:1512
Conclusions (1) Mater Dei Hospital, Malta • Diabetes is associated with increased mortality after AMI and unstable angina • Loss of ‘R’ to ‘R’ variability and PG on admission are associated with increased mortality in diabetic patients with AMI • Outcome after AMI may be improved with tight glycaemic control in the acute stage
Conclusions (2) Mater Dei Hospital, Malta • Diabetic patients with ACS should be managed aggressively to lower this risk • Diabetic patients with renal disease are at a particularly risk; this is probably partly genetically mediated • There is loss of circadian rhythm in the onset of AMI & APE in diabetic patients~ ? implications for chronopharmacology