Wolfgang Koenig, MD, FACC Wolfgang Koenig, MD, FACC Dept. of Internal Medicine II - Cardiology Dept. of Internal Medicine II - Cardiology University of Ulm Medical Center, Ulm, University of Ulm Medical Center, Ulm, Germany Germany Is the Framingham model sufficient fo Is the Framingham model sufficient fo prediction of coronary events? prediction of coronary events? Should CRP be added to Should CRP be added to Framingham Risk Score? Framingham Risk Score? How about calcium score? How about calcium score? 1 1 st st „Vulnerable Patient“ Satellite Symposium, „Vulnerable Patient“ Satellite Symposium, American Heart Association American Heart Association Orlando, USA, November 11, 2003 Orlando, USA, November 11, 2003
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Wolfgang Koenig, MD, FACCWolfgang Koenig, MD, FACCDept. of Internal Medicine II - CardiologyDept. of Internal Medicine II - Cardiology
University of Ulm Medical Center, Ulm, GermanyUniversity of Ulm Medical Center, Ulm, Germany
Is the Framingham model sufficient for Is the Framingham model sufficient for prediction of coronary events?prediction of coronary events?
Should CRP be added to Should CRP be added to Framingham Risk Score?Framingham Risk Score?
How about calcium score? How about calcium score?
11stst „Vulnerable Patient“ Satellite Symposium, „Vulnerable Patient“ Satellite Symposium,American Heart Association American Heart Association
Orlando, USA, November 11, 2003Orlando, USA, November 11, 2003
Pre-test Probability of CHD Event in 10 YrsPre-test Probability of CHD Event in 10 Yrs
Post
-test
Pro
babi
lity o
f CHD
Eve
nt in
10
Yrs
Post
-test
Pro
babi
lity o
f CHD
Eve
nt in
10
Yrs
modified after Greenland et al. Circulation 2001;104:1863-1867modified after Greenland et al. Circulation 2001;104:1863-1867
Low-Risk Intermediate-Risk High-RiskLow-Risk Intermediate-Risk High-Risk(~35 % of Pts.) (~40% of Pts.) (~25% of Pts.)(~35 % of Pts.) (~40% of Pts.) (~25% of Pts.)
CHD Risk Assessment in CHD Risk Assessment in Asymptomatic Patients: Asymptomatic Patients:
Selective Use of Noninvasive TestingSelective Use of Noninvasive TestingModification of Probability Estimates of Modification of Probability Estimates of
CHD by Non-invasive TestingCHD by Non-invasive Testing
Assessment by multivariable Assessment by multivariable statistical models: e.g.statistical models: e.g. Framingham Risk Score or Framingham Risk Score or PROCAM scorePROCAM score
Clear guidelines for high or low Clear guidelines for high or low risk subjects, but not so for risk subjects, but not so for those at intermediate riskthose at intermediate risk
C-Reactive Protein C-Reactive Protein Modulates Risk PredictionModulates Risk Prediction
Can CRP ChangeCan CRP Change Our Practice? Our Practice?
C-Reactive Protein Modulates Risk Prediction:C-Reactive Protein Modulates Risk Prediction:
MONICA/KORA Augsburg Cohort 1984-98MONICA/KORA Augsburg Cohort 1984-98 3,435 men aged 45-74 years, participating in the three 3,435 men aged 45-74 years, participating in the three
MONICA surveys 1984/85, 1989/90, 1994/95MONICA surveys 1984/85, 1989/90, 1994/95 Exclusion of prevalent CHD Exclusion of prevalent CHD Standardized assessment of cardiovascular risk factors: Standardized assessment of cardiovascular risk factors:
Total cholesterol, HDL-C, blood pressure, smoking, BMI, Total cholesterol, HDL-C, blood pressure, smoking, BMI, physical activity, social class, diabetes mellitus, alcohol physical activity, social class, diabetes mellitus, alcohol consumption.consumption.
Endpoint determination according to the MONICA protocol Endpoint determination according to the MONICA protocol (fatal and non-fatal MI and sudden cardiac death) (fatal and non-fatal MI and sudden cardiac death)
Determination of CRP by a hs-IRMA (Hutchinson et al. Clin Determination of CRP by a hs-IRMA (Hutchinson et al. Clin Chem 2000) with a detection limit of 0.05 mg/L (CV < 12%).Chem 2000) with a detection limit of 0.05 mg/L (CV < 12%).
Determination of total cholesterol and HDL-C by routine Determination of total cholesterol and HDL-C by routine enzymatic methods (CV < 4%)enzymatic methods (CV < 4%)
Methods: Patient Population and AssaysMethods: Patient Population and Assays
Koenig et al. AHA 2003Koenig et al. AHA 2003
< 6 6-10 11-14 15-19 < 6 6-10 11-14 15-19 202000
11
22
33
44
55
66
77
88
< 6 6-10 11-14 15-19 < 6 6-10 11-14 15-19 202000
11
22
33
44
55
66
77
88
P=0.20P=0.20P=0.26P=0.26
P=0.02P=0.02
P=0.03P=0.03
P=0.09P=0.09<1.0<1.01.0 – 3.01.0 – 3.0> 3.0> 3.0
CRP CRP mg/Lmg/L
18 18 32 32 35 50 5635 50 56
Population at risk Population at risk 809 914 650 526 536809 914 650 526 536
Framingham Estimate of 10-Year Risk (%)Framingham Estimate of 10-Year Risk (%)
Mul
tivar
iabl
e R
elat
ive
Ris
kM
ultiv
aria
ble
Rel
ativ
e R
isk
AIC 2776AIC 2776AIC 2789AIC 2789
RR of CHD According to the Estimated 10-Yrs RR of CHD According to the Estimated 10-Yrs Risk Alone and in Combination With CRP: Risk Alone and in Combination With CRP:
Risk of a First Coronary Event Risk of a First Coronary Event by Cox Model w/o and With CRP for by Cox Model w/o and With CRP for
the FRS With 3 and 5 Categories the FRS With 3 and 5 Categories FactorFactor Events/nEvents/n HR (95%CI)HR (95%CI) P-valueP-value HR (95%CI)HR (95%CI) P-valueP-value
AIC, Akaike’s Information Criterion; ΔAIC, AIC (model without CRP) – AIC (model with CRP); AIC, Akaike’s Information Criterion; ΔAIC, AIC (model without CRP) – AIC (model with CRP); AUC, Area under the curve AUC, Area under the curve Koenig et al. AHA 2003Koenig et al. AHA 2003
Coronary Calcification and Atherosclerotic Coronary Calcification and Atherosclerotic Cardiovascular Disease Events: Cardiovascular Disease Events:
St. Francis Heart StudySt. Francis Heart Study Prospective, longitudinal, population-based study of asymp-Prospective, longitudinal, population-based study of asymp-
tomatic men and women aged 50 to 70 with no prior history, tomatic men and women aged 50 to 70 with no prior history, symptoms or signs of atherosclerotic CVDsymptoms or signs of atherosclerotic CVD
Subjects on or with indication for lipid-lowering therapy Subjects on or with indication for lipid-lowering therapy excludedexcluded
Coronary calcium measured by EBCT scanning, Agatston Coronary calcium measured by EBCT scanning, Agatston methodmethod
Events verified by independent Endpoints Adjudication Events verified by independent Endpoints Adjudication Committee, blinded to coronary calcium scoreCommittee, blinded to coronary calcium score
A total of 5,585 subjects were scannedA total of 5,585 subjects were scanned Risk factors measured in 1,817Risk factors measured in 1,817 4.3 years follow-up, 96% complete4.3 years follow-up, 96% complete 122 subjects (0.6%/year) with 122 subjects (0.6%/year) with 1 atherosclerotic CVD event 1 atherosclerotic CVD event
Arad et al. ACC, Chicago 2003Arad et al. ACC, Chicago 2003
% per 10 years % per 10 years ((predicted)predicted)
% p
er y
ear
% p
er y
ear ((
obse
rved
)ob
serv
ed)
Arad et al. ACC, Chicago 2003Arad et al. ACC, Chicago 2003
Summary and ConclusionsSummary and Conclusions The addition of CRP to a prediction model of the FRS resulted The addition of CRP to a prediction model of the FRS resulted
in a better fit of the model containing CRP and significantly in a better fit of the model containing CRP and significantly improved prediction of incident CHD for the calculated FRSimproved prediction of incident CHD for the calculated FRS
The latter was particularly true for those at intermediate risk The latter was particularly true for those at intermediate risk (10-20% over 10 years)(10-20% over 10 years)
Thus, CRP measurement modulates coronary risk and may Thus, CRP measurement modulates coronary risk and may therefore modify the physician`s interpretation of the patient`s therefore modify the physician`s interpretation of the patient`s risk statusrisk status
Calcium scoring also seems to improve prediction based on Calcium scoring also seems to improve prediction based on the FRS the FRS
However, these findings have to be replicated in other However, these findings have to be replicated in other populationspopulations