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 Wedel4. 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

Introduction Guidelines recommend total CV risk estimation for CV patients1 Various risk assessment tools available Framingham2 QRisk2 NHANES SCORE ASSIGN PROCAM INDANA3 Need for a new score for patients with multiple CV risk factors 1Mancia G et al. J Hypertens 2007;25:1751-62 2Anderson KM et al. Am Heart J 1991;121:293-8 3Pocock SJ et al BMJ 2001;323:75-81

ASCOT Study design  160/100 mmHg untreated,  140/ 90 mmHg treated Age 40-79 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 40-79 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;19:1139-47

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;19:1139-47

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

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

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

ASCORE and ASCORE-S

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

ROC curves and AUC Sensitivity ASCORE area: 0.664 area: 0.648 ASCORE-S 1.00 0.75 ASCORE Sensitivity area: 0.664 area: 0.648 0.50 ASCORE-S P-value for comparison < 0.0001 0.25 0.00 1-Specificity 0.00 0.25 0.50 0.75 1.00

External validation INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) 53000 patients 10 antihypertensive trials15-20 years ago Interventions Primarily ß-blockers and diuretics vs placebo

External validation Subset of 13335 patients with no CV history aged 40-80 y, not randomized to placebo Complete data on CV endpoints Complete data for all variables of ASCORE-S

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

SBP T.C. ASCOT INDANA Mean change after 5 years 20 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 <150 150-170 170-190 >190 <4 4-6 6-8 >8 SBP at baseline T. Cholesterol at baseline Dahlof B et al. Lancet 2005; 366: 895-906, Sever PS et al. Lancet 2003; 361: 1149-58

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

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 ## 1-0.9985 exp(0.1*total risk score)

1-0.9985 exp(0.1*total risk score)

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%

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