Vp presentation jar 3 29 03

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


0

1

2

3

4

5

6

7

0 10 20 30 40 50 60 70 80 90


LowLowRiskRisk

IntermediateIntermediateRiskRisk

HighHighRiskRisk


0

1

2

3

4

5

6

7

0 10 20 30 40 50 60 70 80 90


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


>75th High


>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

Vp presentation jar 3 29 03

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