Cardiovascular Disease & Mortality in Diabetes Stephen Fava MD, MRCP(UK), FEFIM, FACP, FRCP (Lond),...
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Transcript of Cardiovascular Disease & Mortality in Diabetes Stephen Fava MD, MRCP(UK), FEFIM, FACP, FRCP (Lond),...
Cardiovascular Disease & Cardiovascular Disease & Mortality in DiabetesMortality in Diabetes
Stephen FavaStephen FavaMD, MRCP(UK), FEFIM, FACP, FRCP (Lond), MPhil (Malta),MD, MRCP(UK), FEFIM, FACP, FRCP (Lond), MPhil (Malta),
PhD (Exeter)PhD (Exeter)
Consultant Physician, Diabetologist & EndocrinologistConsultant Physician, Diabetologist & EndocrinologistHead of Diabetes & Endocrine Centre, Mater Dei Hospital, Head of Diabetes & Endocrine Centre, Mater Dei Hospital,
MaltaMalta
Mater Dei Hospital, Malta
Huxley, R. et al. BMJ 2006;332:73-78
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
Glycaemia and MortalityGlycaemia and Mortality
Kaplan-Meier survival curves according to quartiles of HBA1c
log rank test P < 0.0001
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 Isolated post-challenge hyperglycaemia and mortality hyperglycaemia and mortality
0.7
0.8
0.9
1.0
Cu
mu
lati
ve s
urv
ival
(male
s)
0 2000 4000 1000 3000
Time (days)
Normal
Isolated fasting hyperglycaemia
Combined fasting / postprandial hyperglycaemia
Isolated postprandial hyperglycaemia
Known DM
Shaw JE et al. Diabetologia 1999;42:1050
Pooled data from 3 population-based longitudinal studies (in Mauritius, Fiji and Nauru)
• 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
Outcome Of AMIOutcome Of AMIin Diabetesin Diabetes
(Fava S et al, (Fava S et al, Diabetes CareDiabetes Care 16:1615-8, 1993) 16:1615-8, 1993)
Outcome Of AMIOutcome Of AMI
17.3%
10.2%
0.0%
4.0%
8.0%
12.0%
16.0%
20.0%
DM Controls
3-month mortality
p<0.05
(Fava S et al, (Fava S et al, Diabetes CareDiabetes Care 16:1615-8, 1993) 16:1615-8, 1993)
38.3%
16.8%
9.7%
3.6%
0%
10%
20%
30%
40%
LVF Cardiogenicshock
DM
Controls
(Fava S et al, (Fava S et al, Diabetes CareDiabetes Care 16:1615-8, 1993) 16:1615-8, 1993)
p< 0.001
p< 0.05
Loss of ‘R’ to ‘R’ variability and Loss of ‘R’ to ‘R’ variability and MortalityMortality
11.1%
29.4%
0%
5%
10%
15%
20%
25%
30%
Survivors
Fatalities
p<0.05
(Fava S et al, (Fava S et al, Diabetes CareDiabetes Care 16:1615-8, 1993) 16:1615-8, 1993)
Loss of ‘R’ to ‘R’ variability and LVFLoss of ‘R’ to ‘R’ variability and LVF
9.1%
22.7%
0%
5%
10%
15%
20%
25%
no LVF
LVF
p<0.02
(Fava S et al, (Fava S et al, Diabetes CareDiabetes Care 16:1615-8, 1993) 16:1615-8, 1993)
ThrombolysisThrombolysis
23.5%
34.2%
0%
5%
10%
15%
20%
25%
30%
35%
DM Controls
(Fava S et al, (Fava S et al, Diabetes CareDiabetes Care 16:1615-8, 1993) 16:1615-8, 1993)
p<0.05
Mortality after AMI: Recent Data Mortality after AMI: Recent Data
Murcia AM et 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 AnginaOutcome Of Unstable Angina
8.6%
2.5%
16.7%
8.6%
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
3-monthmortality
1 year mortality
DM
Controls
p=0.014 p=0.029
Fava S et al, Fava S et al, Diabet MedDiabet Med, 14:209-213, 1997, 14:209-213, 1997
Drug Rx After Unstable AnginaDrug Rx After Unstable Angina
88
.9%
92
.6%
53
.1% 60
.5%
67
.9%
60
.5%
32
.1%
46
.3%
0%
20%
40%
60%
80%
100%Diabetic
Controls
Nitrates CCB Aspirin β-Blockers
Fava S et al, Fava S et al, Diabet MedDiabet Med, 14:209-213, 1997, 14:209-213, 1997
NS
NSNS
p=0.008
Invasive Procedures at 1 year After Invasive Procedures at 1 year After Unstable AnginaUnstable Angina
21.0%
30.9%
3.7%
13.2%11.1%
9.3%
0%
5%
10%
15%
20%
25%
30%
35%
CA PCI CABG
DM
Controls
p= 0.04
NS
p= 0.002
Fava S et al, Fava S et al, Diabet MedDiabet Med, 14:209-213, 1997, 14:209-213, 1997
Impact of AlbuminuriaImpact 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
Log-rank test p = 0.008
Kaplan-Meier survival plot
Parents of patients with T1 DM withnephropathy
Parents of with T1 DM without nephropathy
Tarnow L et al, Diabetes Care 23 :30–33, 2000
SURVIVAL IN DIABETIC SURVIVAL IN DIABETIC NEPHROPATHY AND ACE NEPHROPATHY AND ACE
GENOTYPEGENOTYPE
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 6 12 18 24 30 36
Months
Survival (%)
DD
I ID/II
Fava S et al, Diabetes Care 24:2115-20, 2001
p<0.05
Circadian Variation in Onset of AMICircadian Variation in Onset of AMI
0
5
10
15
20
25
30
35
40
45
2400-0559 0600-1159 1200-1759 1800-23590
10
20
30
40
50
60
2400-0559 0600-1159 1200-1759 1800-2359
χ2 = 13.9, P < 0.005χ2 = 1.66, NS
Non-diabetic subjects Diabetic subjects
Fava S et al, Heart 1995;74;370-372
Circadian Variation in Onset of AMICircadian 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 Circadian Variation in Onset of Acute Pulmonary OedemaAcute Pulmonary Oedema
0
5
10
15
20
25
30
2400-0559 0600-1159 1200-1759 1800-23590
5
10
15
20
25
2400-0559 0600-1159 1200-1759 1800-2359
χ2 = 9.38, P < 0.005 χ2 = 0.34, NS
Fava S & Azzopardi J. Am J Cardiol 1997
APE
AMI
Plasma Glucose in Diabetic Patients Plasma Glucose in Diabetic Patients with AMIwith AMI
Fava S et al: The prognostic significance of Blood Glucose in Diabetic Patients with Acute Myocardial Infarction. Diabetic Med , 1996:13: 80-83
r = 0.92, p< 0.04
Malmberg, K. BMJ 1997;314:1512
Actuarial mortality curves during long term follow up in patients receiving insulin-glucose infusion and in control group among total DIGAMI cohort. Absolute risk reduction was 11%
DIGAMI
RR 0.72 (0.55 to 0.92), p=0.011
Conclusions (1)Conclusions (1)
• 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
Mater Dei Hospital, Malta
Conclusions (2)Conclusions (2)
• 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
Mater Dei Hospital, Malta