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Vulnerable Plaque SymposiumVulnerable Plaque Symposium
Patients with High CRP & HighPatients with High CRP & HighCT Calcium Score are at Higher Risk:CT Calcium Score are at Higher Risk:
How Can Calcium ScoreHow Can Calcium ScoreImprove Your Practice?Improve Your Practice?
John A. Rumberger, PhD, MD, FACCJohn A. Rumberger, PhD, MD, FACCClinical 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, OhioChicago, ILChicago, IL
March 29, 2003March 29, 2003© 2003 John A Rumberger, MD
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 thePhysicians Health Study
Risk of MI in Apparently Healthy PeopleRisk of MI in Apparently Healthy People
Values in the Highest Quartile Compared to Lowest Quartile
hs C-Reactive Proteinhs C-Reactive Protein
At At 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 ByElevated BP ETOH consumption Elevated BP ETOH consumption BMI Aerobic exerciseBMI Aerobic exerciseMetabolic syndrome Weight lossMetabolic syndrome Weight lossHormone use Medications:Hormone use Medications:Chronic infections statins, fibrates,Chronic infections statins, fibrates,Chronic inflammation niacinChronic inflammation niacin
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
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
©
CT Coronary Artery CalciumCT Coronary Artery Calcium
No CalcificationNo Calcification Severe CalcificationSevere Calcification
Left Main
LAD
LCX
AoAo
LALA
PAPA
Coronary Calcium Area by EBT andCoronary Calcium Area by EBT andCoronary Artery Plaque AreaCoronary Artery Plaque Area
0
2
4
6
8
10
12
14
16
0 2 4 6 8Square Root Sum of Calcium Areas
Squa
re R
oot S
um o
f Pl
aque
Are
as
Rumberger, Circ 1995:92:2157-62
n = 38n = 38r = 0.90r = 0.90p < .001p < .001
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 calcified No. of calcified coronarycoronary
segments/pt.segments/pt. (EBCT)(EBCT)
0
1
2
3
4
5
6
7Y = -0.67 + (0.90 * X)r = 0.86p < 0.0001 N = 40 patientstotal 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 alAJC 1998; 81:AJC 1998; 81:141-146141-146
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 calcium The amount of calcium correlates DIRECTLYcorrelates DIRECTLY to to
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
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 diabetes for 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
Rel
ativ
e R
isk
(RR
)R
elat
ive
Ris
k (R
R)
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 0.991.38
1.922.64
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
Annual Annual AbsoluteAbsolute Risk Risk
EBT CVS EBT CVS (volume score)(volume score) Progression and MI Progression and MIRaggi, Shaw, Callister, Budoff; JACC 2003 Raggi, Shaw, Callister, Budoff; JACC 2003 (retrospective analysis)(retrospective analysis)
0
10
20
30
40
50
60
No MI MI
Mea
n C
hang
e in
CV
S/ye
arM
ean
Cha
nge
in C
VS/
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 ModelIndependent Predictors of MI Elevated cholesterol Diabetes Initial EBT-CVS % Change in EBT-CVS
Initially asymptomatic patients with CVS > 30 and repeat EBT Scans
Coronary Artery CalcificationCoronary Artery Calcification
At At 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
RR of non-fatal MI/Cardiac Death: EBT Score and hs-CRP
6.3 4.3
1.74.9
1.8 10
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
Rel
ativ
e R
isk
Rel
ativ
e R
isk
6.4 yr. f/u, n = 967initially asymptomatic,non-diabetic individuals
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
LowLowRiskRisk
IntermediateIntermediateRiskRisk
HighHighRiskRisk
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
LowLowRiskRisk
IntermediateIntermediateRiskRisk
HighHighRiskRisk
CRPCRP
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
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/uLowLowLow
Mod.Mod.Mod.
HighHighHigh
<25th Low>25th-<75th Intermed.
>75th High
<25th Low>25th-<75th Intermed.
>75th High
<25th Low>25th-<75th Intermed.
>75th High
Primary RoutinePrimary Routine
Secondary Close
Primary RoutinePrimary Close
Secondary Close
Primary CloseSecondary Close
Secondary Close
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 testingare are ComplementaryComplementary to each other to each other
and the combination of bothand the combination of bothcan be used to refinecan be used to refine
Clinical-Decision making in such patientsClinical-Decision making in such patients