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