How to identify patients at high
risk of stroke
C. Weimar
Department of Neurology
University of Duisburg-Essen
Percentage Breakdown of Deaths From
Cardiovascular Diseases
53%
13%
0.4%
0%
1% 4%
0.5%
17%
6%
Coronary Heart Disease
HF Failure
Heart
Diseases of the Arteries
Coronary
Heart
Disease Heart Disease
Rheumatic
Fever/Rheumatic
6%
Stroke
High Blood Pressure
Congenital Cardiovascular Defects
Stroke
Other
Heart Failure
High Blood Pressure
Diseases of the Arteries
Congenital Cardiovascular Defects
Rheumatic Fever/Rheumatic Heart Disease
Other
Source: CDC/NCHS and NHLBI
Billions of Dollars
Estimated Direct and Indirect Costs of Major
Cardiovascular Diseases and Stroke
160
140
120
100
80
60
40
20
0
142.5
57.9
63.5
29.6
rt
a
He
ry
a
on se
r
Co isea
D
ke
o
r
St
ive
s
n
tr e
e se
p
Hy isea
D
a
F
rt
a
He
re
u
il
Source: Heart Disease and Stroke Statistics – 2006 Update.
Prevalence of Stroke by Age and Sex
Percent of Population
14
12,0
11,5
12
10
8
6,6 6,3
6
4
2
0,4 0,3
3,1 3,0
2,1
1,1 0,8
1,2
35-44
45-54
0
20-34
55-64
65-74
75+
Ages
Men
Women
Source: CDC/NCHS and NHLBI
Modifiable Risk Factors for Stroke
Relative risk
Risk Factor
Arterial hypertension
Cigarette smoking
Diabetes mellitus
Obesity
Physical inactivity
Hyperlipidemia
Heavy alcohol intake (>80 g/day)
Hyperhomocystemia
2.0 – 4.0
1.8 – 2.5
1.8 – 2.8
1.5 – 2.0
1.2 – 1.5
3.0 – 4.0
1.5 – 2.0
1.5 – 2.0
.
Ischemic Stroke Etiologies
Intracranial
Atherosclerosis
1
Small Vessel Disease
5
Carotid Plaque with
Arteriogenic Emboli
2
Flow Reducing
Carotid Stenosis
6
Atrial Fibrillation
Aortic Arch Plaque
3
7
Valve Disease
8
Cardiogenic emboli
4
9
Left Ventricular
Thrombi
Albers et al., Chest 2001; 119 (Suppl): 300-20
Risk Factors for Intracerebral
Hemorrhage
Risk Factor
Male gender
Arterial hypertension
Chronic alcohol intake
Age per decade
Cerebral amyloid angiopathy
Relative risk
3.73
3.68
3.36
1.97
?
Ariesen et al. Stroke 2003;34:2060
Percent of Population
Prevalence of High Blood Pressure
in Americans by Age and Sex
90
80
70
60
50
40
30
20
10
0
74.0
46.6
55.5
83.4
69.2
60.9
34.1 34.0
11.1
21.3 18.1
5.8
20-34
35-44
45-54
55-64
65-74
75+
Ages
Men
Women
Source: CDC/NCHS and NHLBI
Diastolic blood pressure and stroke
7 prospective observational studies: 843 events
4,00
Relative Risk for stroke
2,00
1,00
0,50
0,25
76
84
91
98
105
Mean baseline diastolic blood pressure
(mmHg)
MacMahon et al., Lancet 1990;335:766.
Risk of Stroke in Diabetes
RR=2,50
(1,73-3,60)
0,06
0,05
RR=1,47
(1,07-2,03)
0,04
Rate of eventrs
0,03
RR=1,40
(0,80-2,43)
0,02
RR=1,00
0,01
0
3
6
9
12
15
18
21
24
Months
Diabetes/CVD(+)
Diabetes/CVD(-)
No Diabetes/CVD(+)
No Diabetes/CVD(-)
Malmberg et al., For the OASIS Investigators, Circulation 2000;102:1014.
Fatal strokes per 100.000 patient years
during 7-year follow-up
Incidence of Fatal Stroke stratified by
prior stroke and diabetes
25
Diabetes
20
15
Diabetes
10
5
WIthout
Diabetes
WIthout
Diabetes
0
Without prior stroke
After prior stroke
Haffner et al., NEJM 1998;339:229-234.
Hospitalizations first within
6 months due to stroke (%)
Risk of Stroke after Myocardial Infarction
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
4.17
3.58
2.72
2.08
0.93
0
1.43
1
2
3
4
>5
Number of Risk Factors
Risk Factors: age>75, black race, atrial fibrillation, prior stroke, Diabetes, arterial hypertension, PAD
Lichtman JH et al. Circulation 2002; 105: 1082-7
Stroke Risk Stratification
• Primary prevention
– Framingham
– SCORE
– SPAF-III, CHADS2 index (Atrial fibrillation)
• Secondary prevention
– Recurrent Stroke Risk Scores
– High grade carotid stenosis
Framingham Risk Score
• Subjects free of stroke
• age 55 to 84 years
• Followed for 10 years
• Variables: age, SBP (treated/untreated),
Diabetes, smoking, CVD, AF, LVH
D´Agostino et al. Stroke 1994;25:40
Estimated 10-Year Rate(%)
Estimated 10-Year Stroke Risk in 55Year-Old Adults According to Levels of
Various Risk Factors
30
27
25
22.4
19.1
20
14.8
15
8.4
10
5
2.6
5.4
4
3.5
2
1.1
6.3
0
A
B
C
Men
Systolic BP [mmHg]
Diabetes
Cigarettes
Prior Atrial Fib.
Prior CVD
A
95-105
No
No
No
No
D
E
F
Women
B
C
D
E
F
130-148 130-148 130-148 130-148 130-148
No
Yes
Yes
Yes
Yes
No
No
Yes
Yes
Yes
No
No
No
Yes
Yes
No
No
No
No
Yes
Framingham Heart Study. Stroke 1991;22:312-318.
Average 10-year Probability of Stroke
Age Group, years
Men
Women
55 - 59
60 - 64
65 - 69
70 - 74
75 - 79
80 - 84
Age adjusted
5.9
7.8
11.0
13.7
18.0
22.3
9.6
3.0
4.7
7.2
10.9
15.5
23.9
6.5
D´Agostino et al. Stroke 1994;25:40
Systemic Coronary Risk Evaluation
Conroy et al. Eur Heart J 2003;24:987
Systemic Coronary Risk Evaluation
Conroy et al. Eur Heart J 2003;24:987
Stroke Risk Score for Atrial Fibrillation
CHADS2
Prior stroke or TIA
Age >75 years
Hypertension
Diabetes mellitus
Heart failure
2
1
1
1
1
High risk
Moderate risk
Low risk
4-6
2-3
0-1
Gage et al. JAMA 2001;285:2864
Ankle Brachial Index = ABI
130 mmHg
126 mmHg
145 mmHg
80 mmHg
145 / 130 = 1,1
80 / 130 = 0,62
Death / severe cardiovascular
events stratified by ABI
Diehm et al. Eur Heart J 2006;27:1743
Predictive Accuracy of low ABI for
cardiovascular events
Doobay AV et al. Arterioscler Thromb Vasc Biol 2005;25(7):1463-9.
Intima-Media Thickness
Relative Risk for Myocardial Infarction
or Cardiac Death
Carotid Intima-Media Thickness and
clinical coronary events
8
7
6
5
4
3
2
1
< 0,566
0,567- 0,635
0,636-0,732
≥ 0,733
Intima-Media-Thickness (mm)
Hodis H, et al., Ann Intern Med 1998;128:262-269.
Carotid Stenosis:
Angioplasty und Stenting
before
after PTA/Stenting
ACST: 5-year risk of ipsilateral stroke
Conservative group 11,78 %
Operative group 6,42 %
Stroke free survival (%)
100
95
90
ARR = 5,35 % (KI 2,96-7,75)
p = 0,00001
85
0
0
1
2
3
4
5
years
ACST, Lancet 2004; 363:1491-1502.
ACST: 5-year risk of disabling stroke
Conservative group 6,07 %
Operative group 3,53 %
Stroke free survival (%)
100
95
90
ARR = 2,54 % (KI 0,77 - 4,32)
p = 0,004
85
0
0
1
2
3
4
5
years
ACST, Lancet 2004; 363:1491-1502.
Effect of Surgery by Sex
in ACST and ACAS
events/patients
Subgroup
surgical
medical
Odds ratio
95 % Cl
Men
ACST
ACAS
51/1.021
18/544
97/1.023
38/547
0,50
0,46
0,35-0,72
0,26-0,81
Total
69/1.565
135/1.570
0,49
0,36-0,66
Women
ACST
ACAS
31/539
15/281
34/537
14/287
0,90
1,10
0,55-1,49
0,52-1,82
Total
46/820
48/824
0,96
0,63-1,45
0
0,5
1
1,5
Odds ratio
(95 % KI)
Lancet 2004;364:1123.
Risk factors of first stroke
in asymptomatic carotid stenosis
• Increasing degree of carotid stenosis
• Progression of stenosis
• Asymptomatic embolization as detected by TCD
• Diabetes mellitus
45% of strokes unrelated to carotid stenosis
Rockman, J Vasc Surg 1997;25:423. Molloy, Stroke 1999;30:1440. Inzitari, NEJM 2000;342:1693
Patent foramen ovale:
To close or not to close
Recurrent Stroke Risk
after IS
after TIA
30 Tage
3 – 10 %
4 – 10,5 %
1 Jahr
10 – 14 %
12 – 13 %
5 Jahre
25 – 40 %
Sacco Neurology. 1997;49(suppl 4):S39.
Feinberg et al. Stroke. 1994;25:1320.
Survival free of event
Stroke and cardiovascular events
following TIA
1.0
Stroke 10.5%
0.9
0.8
All events 25.1% (Stroke,
recurrent TIA, cardiovascular
event, death)
0.7
0.6
0
7
30
Days after TIA
60
90
Johnston et al. JAMA 2000; 284:2901-06.
Stroke and cardiovascular events
following TIA
30,0%
25,0%
20,0%
15,0%
12,7%
10,5%
10,0%
5,0%
0,0%
bis
90 Tage
5,3%
2,6%
2,6%
bis
48 h
Stroke
recurrent cardiovasc.
event
TIA
death
Johnston SC et al. JAMA 2000;284:2901
Validated scores for risk stratification
Primary
Secondary prevention
Titel
Framingham
SPI II
ABCD
Essen
Prediction given
10 years
2 years
7 days
2 years
Index event
asymptomatic
IS or TIA
TIA
IS or TIA
Range
0 – 38
0 – 15
0–6
0–9
High-risk group
> 17
>7
>4
>2
Items
•Age
•diabetes
•systolic RR
•antihypertens. TX
•smoking
•Cardiac disease
•atrial fibrillation
•left ventricular
hypertrophy
•age >70
•diabetes
•prior stroke
•coronary heart
disease
•cardiac failure
•stroke index event
(vs. TIA)
•age ≥60
•arterial
hypertension
•hemiparesis
•aphasia
•duration of
symptoms >10min /
>1h
•age ≥65 />75
•Diabetes
•arterial
hypertension
•Prior MI
•Other cardiovascular disease
•PAD
•Smoking
•prior IS / TIA
Reference
D‘Agostino. Stroke
1994;25:40-3.
Kernan. Stroke
2000;31:456-62
Rothwell. Lancet
2005;366:29-36
Diener. Exp Opin
Pharmacother
2005;6(5):755-764.
Essen Stroke Risk Score
• Developed in the CAPRIE study population with IS
(N=6400)
• Validated in the ESPS II population (N=6602)
– Simple 10-point score
– Sum of clinical variables
– Linear risk increase between 0 – 6 points
Diener et al. Exp Opin Pharmacother 2005;6(5):755-764. Diener. Aging Health 2005; 1:19-26
Essen Stroke Risk Score:
Calculation
Age >65-75 years / > 75 years :
Arterial hypertension:
Diabetes mellitus:
Prior myocardial infarction:
Other cardiovascular disease*:
Peripheral arterial disease:
Smoking:
Additional Ischemic stroke or TIA
Max. Score
1/2
1
1
1
1
1
1
1
--------9
* Except myocardial infarction and atrial fibrillation
Diener et al. Exp Opin Pharmacother 2005;6(5):755
Rate of recurrent stroke in CAPRIE
Diener et al. Expert Opin Pharmacother. 2005;6:755
Rate of recurrent stroke in ESPS 2
25
Annual event rate
20
15
DP+ASA
ASA
10
5
0
0
1
2
3
4
Essen Risk Score
5
6
7-8
Diener et al. Aging Health 2005; 1:19-26
Essen Stroke Risk Score:
Interpretation
Score
9
8
7
6
5
4
3
2
1
0
risk
very high
high:
Stroke risk ≥ 4% / year
low:
Stroke risk < 4% / year
Diener et al. Exp Opin Pharmacother 2005;6(5):755-764. Diener. Aging Health; 1:19-26
2-year risk of stroke in ECST
(symptomatic carotid stenosis)
Rothwell, Stroke 2000;31:615-621
Predictors of stroke
in NASCET and ECST
Hazard rate
p
Women vs. men
0,79 (0,64 - 0,97)
0,03
Age 65-74
> 75
1,23 (1,00 - 1,51)
1,70 (1,28 - 2,56)
<0,0001
Monocular blindness
vs. hemisph. TIA
vs. hemisph. stroke
Diabetes
1
1,88 (1,38 - 2,55)
2,33 (1,74 - 3,13)
1,31 (1,05 - 1,65)
Subgruppe
Irregular or
1,35 (1,11 - 1,64)
ulcerated plaque
< 2h weeks since last event
1
2–4
0,80 (0,61 – 1,06)
4 – 12
0,69 (0,55 – 0.88)
> 12
0,61 (0,46 – 0,82)
<0,0001
0,02
0,003
<0,0001
Rothwell, Lancet 2004;363:915.
Rothwell, Neurol Res 2005;27:S18
5-year risk reduction by CarotidEndarterectomie in NASCET and ECST
5-year absolute risk reduction (%)
40
30
70-90 % Stenosis
50-69 % Stenosis
30,2
20
14,8
17,6
11,4
8,9
10
4,0
3,3
0
-2,9
-10
0-2
2-4
4-12
> 12
Time from event to randomization
Rothwell, Lancet 2004;363:915
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