1. ASCORE : An up-to-date cardiovascular risk score for hypertensive patients reflecting. contemporary clinical practices developed. using the ASCOT trial database .
D Prieto-Merino1, AK Gupta2, J Dobson2, CL Chang2, SE Mastorantonakis2, PS Sever2, B Dahlof3, H Wedel S Pocock1, NR Poulter2on behalf of the ASCOT investigators
1 London School of Hygiene and Tropical Medicine
2 ICCH, Imperial College London
3 Sahlgrenska University Hospital, Sweden
4 Nordic School of Public Health, Goteborg, Sweden

2. Introduction
Guidelines recommend total CV risk estimation for CV patients1
Various risk assessment tools available
Framingham2 QRisk NHANES SCORE ASSIGN PROCAM INDANA3
Need for a new score for patients with multiple CV risk factors
1Mancia G et al. J Hypertens 2007;25: Anderson KM et al. Am Heart J 1991;121: Pocock SJ et al BMJ 2001;323:75-81

3. ASCOT Study design  160/100 mmHg untreated,  140/ 90 mmHg treated
Age years
No previous MI or current clinical CHD
3 or more CV risk factors
Let us remember briefly ASCOT’S study design:
Patients included were years old, had no history of MI or current CHD, had grade 2 hypertension and at least 3 other CV risk factors.
Sever PS et al. J Hypertens 2001;19:

4. ASCOT Study design 19,257 hypertensive patients ASCOT-BPLA
5.5 years follow-up
atenolol ± bendroflumethiazide
amlodipine ± perindopril
PROBE
design
placebo
atorvastatin 10 mg
Double-blind
ASCOT-LLA
3.3 years follow-up
10,305 patients
TC ≤ 6.5 mmol/L (250 mg/dL)
Sever PS et al. J Hypertens 2001;19:

5. ASCORE Study design
Study population: ASCOT patients excluding those with history of CV disease at baseline
Primary composite endpoint: first CV event (Death, MI or Stroke)
Statistical analysis: Cox proportional hazard models with backward stepwise variable selection

6. ASCORE Study design Baseline variables defined a priori: Sex Age
Ethnicity
Education
Smoking
Diabetes
Prev. antihypert. treatment
Prev. lipid lowering treatment
Aspirin use
SBP
DBP
Heart rate
Height
Weight
BMI
Microalbuminuria / proteinuria
Renal dysfunction
Total cholesterol
HDL
Fasting LDL
Fasting TGs
Fasting glucose
Creatinine
GFR

7. ASCORE Results ASCOT ASCORE 19,257 15,955 Endpoints at 5 years 1,114
-3302 excluded
ASCORE
15,955
Endpoints at 5 years
1,114

8. ASCORE and ASCORE-S

9. Model calibration ASCORE ASCORE-S Predicted by ASCORE
.15
Predicted by ASCORE
.15
Predicted by ASCORE-S
Observed (KM)
Observed (KM)
ASCORE ASCORE-S
.10
.10
P-value of Chi2 = 0,22
P-value of Chi2 = 0,49
Risk of having the event in 5 years
Risk of having the event in 5 years
.05
.05
.00
.00 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9
Deciles of predicted risk
Deciles of predicted risk

10. ROC curves and AUC Sensitivity ASCORE area: 0.664 area: 0.648 ASCORE-S
1.00
0.75
ASCORE
Sensitivity
area:
area:
0.50
ASCORE-S
P-value for comparison <
0.25
0.00
1-Specificity
0.00
0.25
0.50
0.75
1.00

11. External validation
INDANA (INdividual Data ANalysis of Antihypertensive intervention trials)
53000 patients antihypertensive trials15-20 years ago
Interventions Primarily ß-blockers and diuretics vs placebo

12. External validation Subset of 13335 patients with no CV history
aged y, not randomized to placebo
Complete data on CV endpoints
Complete data for all variables of ASCORE-S

13. Risk of CV event in 5 years.2
Average risk predicted with ASCORE-S
Observed risk in INDANA database
.15
Risk of CV event in 5 years .1
.05 1 2 3 4 5 6 7 8 9
Patients by deciles of risk

14. SBP T.C. ASCOT INDANA Mean change after 5 years20 1 10
0.5
-10
-0.5
Mean change after 5 years
-20 -1
ASCOT
-30
-1.5
-40 -2
INDANA
-50
-2.5
-60 -3
<150
>190
<4
4-6
6-8
>8
SBP at baseline T. Cholesterol at baseline
Dahlof B et al. Lancet 2005; 366: , Sever PS et al. Lancet 2003; 361:

15. Risk of CV event in 5 years.2
Average risk predicted with ASCORE-S
Expected risk in INDANA if treatment was as in ASCOT
Observed risk in INDANA database
.15
Risk of CV event in 5 years .1
.05 1 2 3 4 5 6 7 8 9
Patients by deciles of risk

16. 1-0.9985 exp(0.1*total risk score)
We converted the ASCORE and ASCORE-S models into ‘user-friendly’ integer scores for the 5-year risk of the primary composite endpoint.
To calculate the total score for a patient, start with the score corresponding to the relevant combination ## of sex and age group.
Next add the corresponding points if the patient is ## diabetic (differs depending on sex), a recent ## smoker (differs depending on age group), or ## was on previous anti-hypertensive treatment.
For ## SBP and for the laboratory measures (ASCORE only) a scale of points from +0 to +8 is shown under which the values of the variable are given.
The estimated probability of cardiovascular death, MI or stroke within 5 years is then equal to the equation ## for ASCORE and ## for ASCORE-S. or derives form the conversion of the total risk score to 5 year probability of CV death, MI or Stroke according to the table ##
exp(0.1*total risk score)

17. 1-0.9985 exp(0.1*total risk score)

18. Score conversion to 5 year risk
Total Risk score
ASCORE
ASCORE-S
0.15%
0.34% 10
0.41%
0.92% 12
0.50%
1.12% 14
0.61%
1.37% 16
0.74%
1.67% 18
0.90%
2.04% 20
1.10%
2.49% 22
1.35%
3.03% 24
1.64%
3.68% 26
2.00%
4.48% 28
2.44%
5.45% 30
2.97%
6.61% 32
3.62%
8.02% 34
4.40%
9.70% 36
5.35%
11.72% 38
6.49%
14.12% 40
7.87%
16.97% 42
9.53%
20.32% 44
11.51%
24.23% 46
13.87%
28.74% 48
16.67%
33.89% 50
19.97%
39.68%

19. ASCORE Summary ASCORE and ASCORE-S models and easy to use score charts
5 year risk prediction in hypertensive patients under treatment
Internal and External validation (ASCORE-S)
Consistency with contemporary treatment guidelines
Established predictors in an up-to-date model
ASCORE
and ASCORE-S