Prevention of

cardiovascular risk in
diabetes
Applying evidence based
medicine to clinical care
Cardiovascular disease is the biggest killer in UK

Number of deaths (000’s)

Coronary heart disease 124,037

Stroke 60,666

Other circulatory diseases 18,165

Lung cancer 33,634

Colo-rectal cancer 16,216

Breast cancer 12,762

Respiratory disease 103,431

Injuries and poisoning 19,996

All other causes 96,195

0 20 40 60 80 100 120 140

National Institute for Health and Clinical Excellence, 2005

Leading causes of death and disability in UK
Disability adjusted life years
1990 2020
Rank Cause % Rank Cause %

1 Lower respiratory infections 8.2 1 Ischaemic heart disease 5.9

2 Diarrhoeal diseases 7.2 2 Major depression 5.7

3 Perinatal conditions 6.7 3 Road traffic accidents 5.1

4 Major depression 3.7 4 Cerebrovascular disease 4.4

5 Ischaemic heart disease 3.4 5 COPD 4.2

6 Cerebrovascular disease 2.8 6 Lower respiratory infections 3.1

7 Tuberculosis 2.8 7 Tuberculosis 3.0

8 Measles 2.7 8 War 3.0

9 Road traffic accidents 2.5 9 Diarrhoeal diseases 2.7

10 Congenital abnormalities 2.4 10 HIV 2.6

National Institute for Health and Clinical Excellence, 2005

Patients with one CV risk factor are likely
to have additional risk factors

+1 RF 26% +2 RFs 25% +1 RF 27% +2 RFs 24%

No additional RF +3 RFs 22% No additional RF +3 RFs 20%

19% 17%

+ ≥ 4 RFs + ≥ 4 RFs

8% 12%

Men Women

Kannel WB. Am J Hypertens 2000; 13: 3S-10S

Synergistic interaction of traditional
multiple risk factors on CVD risk
50 SBP (mm Hg)
44%
110 150
120 160
40
130 170
140 180 33%
5-year
CVD risk 30
24%
per 100
people 20 18%
12%
10 6%
3%
<1%
0
Reference TC = Smoker HDL = Male Diabetes 60 years
270 mg/dL 39 mg/dL of age

TC = total cholesterol Additive risk factors

Jackson R et al. Lancet. 2005;365:434-41

PROCAM: Combination of risk factors
increases risk of MI
120
In c id e n c e o f M I/1 0 0 0 p ts

100

80

60

40

20

o ne ly s+ +
N on l y n ia i a
n on rte tes em em +/
-
s io te
s e
p be id
a
da s
n e Hy dia ls ip pi rten tes
rte ia
b l i
s e e
p e D Dy Dy yp iab
Hy h d
Prevalence (%): 54.9 22.9 2.6 2.3 9.4 8.0

Assmann G, Schulte H. Am Heart J 1988;116:1713-24

Patients with Type 2 diabetes are a high
cardiovascular risk group
Nondiabetic patients
50
Patients with type 2 diabetes
45
7-year incidence of cardiovascualr events (%)

40
35 -MI: no prior myocardial infarction /
+MI: prior myocardial infarction
30
25
20

15
10
5
0
-MI +MI -MI +MI -MI +MI -MI +MI -MI +MI -MI +MI
Myocardial infarction Stroke Cardiovascular death

Haffner SM et al. NEJM 1998; 339: 229-34

 Cardiovascular risk factors in
type 2 diabetes
Dyslipidaemia Hypertension Obesity
Nondiabetic Diabetic
50
30 30
1000 patient-years

40
CHD deaths/

30 20 20

20
10 10
10

0
0 0

4 .2 6 .8 6 .8
<2 . 2-
2 >2
24
Serum cholesterol (mmol/L) SBP (mmHg) BMI (kg/m2)

Adlerberth AM et al. Diabetes Care 1998;21:539-45

Eschwege E. Diabetes Metab 2003;29:6S19-27
Diabetes is a CHD risk equivalent

0.25
Event rate (Total mortality)

0.20
diabetes + CVD (n=1448)

diabetes + no CVD (n=569)

0.15
no diabetes + CVD (n=3503)
0.10
no diabetes/CVD (n=2796)
0.05

0 3 6 9 12 15 18 21 24

Months follow-up

Malmberg K et al. OASIS. Circulation 2000;102:1014–1019

Worldwide prevalence of diabetes
expected to increase
Diabetes prevalence
140 155%
~171 million in 2000
120 ~366 million in 2030

100
102% 99%
Diabetes 80
prevalence
(in millions) 180% 44%
60

40 160%
20

0
Africa Americas E Medit Europe SE Asia W Pacific
2000 2030

World Health Organization. www.who.org.

Hyperglycaemia and vascular
complications in type 2 diabetes
60
% Incidence/1000 patient-years

50

40 Myocardial
infarction
30
Microvascular
disease
20

10

0
<6 6-<7 7-<8 8-<9 9-<10 10+
Updated HbA1C (%)
Stratton IM et al. BMJ 2000;321:405-12
Type 2 diabetes: Vascular complications

By 10 years:

Microvascular
23% have had a significant microvascular
complication (mainly retinal or macular)

Macrovascular
 28% have died from a diabetes related cause
 27% have had a myocardial infarction
 10% have had a stroke

Marshall SM, Flyvbjerg A. BMJ 2006 333: 475-480

Johansen OE, Birkeland KI . Am J Cardiovasc Drugs. 2003: 283-97
Post-MI survival
Diabetes
No diabetes

100 Men 100 Women

90 90

Survival (%)
Survival (%)

80 n=1628 80 n=568
70 70

60 60

50 50 n=156
n=228
40 40
0 10 20 30 40 50 60 0 10 20 30 40 50 60
Months Post-MI Months Post-MI

Sprafka JM et al. Diabetes Care 1991;14:537–543.

Mortality after coronary intervention
CABG PTCA
35

30
5-years mortality (%)

25

20

15

10

0
No diabetes Diabetes
(n=1476) (n=353)

BARI Investigators. N Engl J Med 1996:335:217–225.

Sources of excess mortality in diabetes
NHANES I cohort
50
Age-standardised mortality
per 100,000 person-years

40
Diabetes
30 No diabetes
20
10
0

Death from
Gu K et al. Diabetes Care 1998;21:1138-45