This document discusses how coronary artery calcium scoring using computed tomography (CT) and levels of the inflammatory marker C-reactive protein (CRP) can be used together to predict cardiovascular risk. It finds that higher calcium scores and CRP levels each indicate greater risk of future heart attacks and cardiac deaths. The combination of an intermediate calcium score and elevated CRP may identify patients who would benefit from more aggressive prevention treatment and closer follow-up. The document recommends using calcium scoring and CRP testing together in asymptomatic individuals to help refine clinical decision making and prevention strategies.

1. Vulnerable Plaque SymposiumVulnerable Plaque Symposium
Patients with High CRP & HighPatients with High CRP & High
CT Calcium Score are at Higher Risk:CT Calcium Score are at Higher Risk:
How Can Calcium ScoreHow Can Calcium Score
Improve Your Practice?Improve Your Practice?
John A. Rumberger, PhD, MD, FACCJohn A. Rumberger, PhD, MD, FACC
Clinical Professor of Medicine, Ohio State UniversityClinical Professor of Medicine, Ohio State University
Medical DirectorMedical Director
Physician’s Prevention and Wellness CenterPhysician’s Prevention and Wellness Center
Columbus, OhioColumbus, Ohio
Chicago, ILChicago, IL
March 29, 2003March 29, 2003© 2003 John A Rumberger, MD

2. 1.25
1.6
1.6
1.8
2.15
2.35
2.5
5
0 2 4 6 8 10
Lp(a)
Homocysteine
TC
Fibr
t-PA Ag
TC/HDL
hs-CRP
hs-CRP + TC/HDL
RR in men from the
Physicians Health Study
Risk of MI in Apparently Healthy PeopleRisk of MI in Apparently Healthy People
Values in the Highest Quartile Compared to Lowest Quartile

3. hs C-Reactive Proteinhs C-Reactive Protein
AtAt PRESENTPRESENT the following has been established:the following has been established:
o Values in the upper tercile (or quartile) confer a 2+ risk MI/SCDValues in the upper tercile (or quartile) confer a 2+ risk MI/SCD
o Marker likely for “endothelial dysfunction”Marker likely for “endothelial dysfunction”
o May have a role in “promoting atherogenesis”May have a role in “promoting atherogenesis”
o Values altered by:Values altered by: Increased By Decreased ByIncreased By Decreased By
Elevated BP ETOH consumptionElevated BP ETOH consumption
BMI Aerobic exerciseBMI Aerobic exercise
Metabolic syndrome Weight lossMetabolic syndrome Weight loss
Hormone use Medications:Hormone use Medications:
Chronic infections statins, fibrates,Chronic infections statins, fibrates,
Chronic inflammation niacinChronic inflammation niacin

4. hs C-Reactive Proteinhs C-Reactive Protein
o May or may not be related to the severity or extent of diseaseMay or may not be related to the severity or extent of disease
o This could be due to differences in chronicity or “pattern”This could be due to differences in chronicity or “pattern”
o CRP may be more related to “acceleration of atherosclerosis”CRP may be more related to “acceleration of atherosclerosis”
rather than its extentrather than its extent

5. VTVT
VT = “vulnerable threshold”VT = “vulnerable threshold”
““vulnerability”vulnerability”
TimeTime
Patient APatient A
Patient BPatient B
MI/SCDMI/SCD
The “Vulnerable Threshold”
CRPCRP
CRPCRP
CRPCRP
©
© 2003 John A Rumberger, MD
©

6. CT Coronary Artery CalciumCT Coronary Artery Calcium
No CalcificationNo Calcification Severe CalcificationSevere Calcification
Left Main
LAD
LCX
AoAo
LALA
PAPA

7. Coronary Calcium Area by EBT andCoronary Calcium Area by EBT and
Coronary Artery Plaque AreaCoronary Artery Plaque Area
0
2
4
6
8
10
12
14
16
0 2 4 6 8
Square Root Sum of Calcium Areas
SquareRootSumof
PlaqueAreas
Rumberger, Circ 1995:92:2157-62
n = 38n = 38
r = 0.90r = 0.90
p < .001p < .001

8. No. of coronary segments/pt. with plaques (IVUS)No. of coronary segments/pt. with plaques (IVUS)
0 1 2 3 4 5 6 7
No. of calcifiedNo. of calcified
coronarycoronary
segments/pt.segments/pt.
(EBCT)(EBCT)
0
1
2
3
4
5
6
7
Y = -0.67 + (0.90 * X)
r = 0.86
p < 0.0001 N = 40 patients
total of 222 coronary
segments examined
# of segments with EBT calcium vs. # of segments with any plaque# of segments with EBT calcium vs. # of segments with any plaque
Schmermund et alSchmermund et al
AJC 1998; 81:AJC 1998; 81:
141-146141-146

9. EBT and Coronary Artery CalciumEBT and Coronary Artery Calcium
 Define the extent of ASO disease?Define the extent of ASO disease?
YESYES
 The amount of calciumThe amount of calcium correlates DIRECTLYcorrelates DIRECTLY toto
the amount of measurable coronary disease by:the amount of measurable coronary disease by:
1) direct histopathologic comparison1) direct histopathologic comparison
2) with intravascular ultrasound2) with intravascular ultrasound

10. 3
4.4
8.8
0
2
4
6
8
10
Score 0 Score 1-15 Score 16-
80
Score 81-
270
Score
>271
Relative Risk for Future CV Events using EBCT:Relative Risk for Future CV Events using EBCT:
926 initially asymptomatic patients926 initially asymptomatic patients
1st Quartile1st Quartile 2nd Quartile2nd Quartile 3rd Quartile3rd Quartile 4th Quartile4th Quartile
* AdjustedAdjusted for age, gender, hypertension, past/current smoking, and diabetesfor age, gender, hypertension, past/current smoking, and diabetes
Wong and Detrano, et al [Am J Cardiol 2000;86:495-498Wong and Detrano, et al [Am J Cardiol 2000;86:495-498
RelativeRisk(RR)RelativeRisk(RR)

11. Prediction of MI/SCD in Asymptomatic Patients:Prediction of MI/SCD in Asymptomatic Patients:
EBTEBT
Raggi et al AHJ 2001;141:193-199Raggi et al AHJ 2001;141:193-199
0.36 0.51 0.71
0.99
1.38
1.92
2.64
3.62
4.9
6.54
0
1
2
3
4
5
6
7
0 10 20 30 40 50 60 70 80 90
Percentile Rank for Baseline EBCT Calcium ScorePercentile Rank for Baseline EBCT Calcium Score
676 initially asymptomatic patients676 initially asymptomatic patients
3232++7 months f/u7 months f/u
AnnualAnnual AbsoluteAbsolute RiskRisk

12. EBT CVSEBT CVS (volume score)(volume score) Progression and MIProgression and MI
Raggi, Shaw, Callister, Budoff; JACC 2003Raggi, Shaw, Callister, Budoff; JACC 2003 (retrospective analysis)(retrospective analysis)
0
10
20
30
40
50
60
No MI MI
MeanChangeinCVS/yearMeanChangeinCVS/year
26+1.5%
47.5+7.5% *
n = 833, 2.1+1.4 yr f/u,
45 documented MI (2.2%/yr)
Stepwise Cox Model
Independent Predictors of MI
 Elevated cholesterol
 Diabetes
 Initial EBT-CVS
 % Change in EBT-CVS
Initially asymptomatic patients with CVS > 30 and repeat EBT Scans

13. Coronary Artery CalcificationCoronary Artery Calcification
AtAt PRESENTPRESENT the following has been established:the following has been established:
o Coronary calcium IS AtherosclerosisCoronary calcium IS Atherosclerosis
o The magnitude of the calcium score relates to the severity of ASO diseaseThe magnitude of the calcium score relates to the severity of ASO disease
o The calcium score as well as the percentile rank provide informationThe calcium score as well as the percentile rank provide information
in which to view risk factors, rather than the other way aroundin which to view risk factors, rather than the other way around
o The data on examining progression of CAD with CT are consistent withThe data on examining progression of CAD with CT are consistent with
the potential for the calcium score/rank to be used as the “goal” of therapythe potential for the calcium score/rank to be used as the “goal” of therapy

14. RR of non-fatal MI/Cardiac Death:
EBT Score and hs-CRP
6.3 4.3
1.74.9
1.8 1
0
2
4
6
8
High CAC Med. CAC Low CAC
Lowest quartile
hs-CRP
Highest quartile
hs-CRP
Park et al.
Circ. 2002;106-2073-2077
6.3
RelativeRiskRelativeRisk
6.4 yr. f/u, n = 967
initially asymptomatic,
non-diabetic individuals

15. Prediction of MI/SCD in Asymptomatic Patients:Prediction of MI/SCD in Asymptomatic Patients:
EBTEBT
0
1
2
3
4
5
6
7
0 10 20 30 40 50 60 70 80 90
Percentile Rank for Baseline EBCT Calcium ScorePercentile Rank for Baseline EBCT Calcium Score
LowLow
RiskRisk
IntermediateIntermediate
RiskRisk
HighHigh
RiskRisk

16. Prediction of MI/SCD in Asymptomatic Patients:Prediction of MI/SCD in Asymptomatic Patients:
EBTEBT
0
1
2
3
4
5
6
7
0 10 20 30 40 50 60 70 80 90
Percentile Rank for Baseline EBCT Calcium ScorePercentile Rank for Baseline EBCT Calcium Score
LowLow
RiskRisk
IntermediateIntermediate
RiskRisk
HighHigh
RiskRisk
CRP
CRP

17. Clinical Questions in PreventionClinical Questions in Prevention
In the asymptomatic individual
How aggressive should I be?
 Primary versus secondary prev. goals
How closely should I follow up?
 Routine versus close & repeat testing

18. hs-CRP CAC Range Level of Aggression, f/u
< 1 mg/L
> 1-3 mg/L
> 3 mg/L
hs-CRP & CAC Scoringhs-CRP & CAC Scoring
Value Range Percentile Range Aggression Clinical f/u
Low
Low
Low
Mod.
Mod.
Mod.
High
High
High
<25th
Low
>25th
-<75th
Intermed.
>75th
High
<25th
Low
>25th
-<75th
Intermed.
>75th
High
<25th
Low
>25th
-<75th
Intermed.
>75th
High
Primary Routine
Primary Routine
Secondary Close
Primary Routine
Primary Close
Secondary Close
Primary Close
Secondary Close
Secondary Close

19. hs-CRP & CAC Scoringhs-CRP & CAC Scoring
In “intermediate” risk asymptomatic individualsIn “intermediate” risk asymptomatic individuals
CAC Scanning with CTCAC Scanning with CT
&&
hs-CRP testinghs-CRP testing
areare ComplementaryComplementary to each otherto each other
and the combination of bothand the combination of both
can be used to refinecan be used to refine
Clinical-Decision making in such patientsClinical-Decision making in such patients