screening and treatment of coronary artery disease matthew j. budoff, md, facc associate professor...

Screening and Treatment of Screening and Treatment of Coronary Artery DiseaseCoronary Artery Disease

Matthew J. Budoff, MD, FACCMatthew J. Budoff, MD, FACC

Associate Professor of MedicineAssociate Professor of Medicine

Division of Cardiology, Division of Cardiology,

Harbor-UCLA Medical Center, Torrance, CADISCLOSURE INFORMATION:The following relationships exist related to this presentation:

Electron Beam Computerized Tomography

Crystal-photodiodes

Preamplifiers

Sourcecollimator

Target ring

Vacuum envelope

Patient crosssection

47cm scanfield

Target rings

Sourcecollimator

Radiationshield

Vacuumchamber

Heart

Detectors

Coronary Artery Scanning

NORMAL CONDITION


SEVERECALCIFICATION

CAC vs HISTOLOGYCAC vs HISTOLOGY

High correlation of score (r=0.96) and area (r=0.95) with histomorphometry (p<0.0001)

“.. the amount of coronary calcium increases as the extent of atherosclerosis increases”

Mautner GC et al: Radiology 1994;192:619-623

20%20%

80%80%

Total Coronary Artery PlaqueTotal Coronary Artery Plaqueand EBCT Coronary Calciumand EBCT Coronary Calcium

80%80%

PlaquePlaqueDetectableDetectableby IVUS,by IVUS,PathologyPathology

Lipid RichLipid Rich

FibroticFibrotic

CalcifiedCalcified 20%20%

80%80%

Calcium ScoreCalcium Score

Total PlaqueTotal PlaqueBurdenBurden

Total Coronary Artery Plaque Burden andTotal Coronary Artery Plaque Burden andEBCT Coronary Calcium Score:EBCT Coronary Calcium Score:

defining the tip of the atherosclerotic icebergdefining the tip of the atherosclerotic iceberg

Mild Plaque SevereModerate

Framingham Risk in the Young

222 patients with AMI (men < 55, women <65)

Only 25% qualified for pharmacotherapy based on 10-year risk prior to MI

Only 18% of women met criteria

Akosah – JACC 2003

Prediction of Cardiac Events in AsymptomaticPrediction of Cardiac Events in AsymptomaticPatients by EBTPatients by EBT

Pohle, Heart 2003:89:625-628Pohle, Heart 2003:89:625-628

102 patients with AMI, age < 60 years 95.1% had calcification present Only 5.8% of controls had calcification present

(p<0.0001) Agatston >50% score – present in 87% By extrapolation, this test may allow identification of

87-95% of the 650,000 patients whose first presentation is Myocardial infarction or cardiac death

Refining Framingham Risk ScoreRefining Framingham Risk Score

EBT derived “Arterial Age”

a man is as old as his coronaries…

Syndenham 1689

EBT derived “Arterial Age”

a man is as old as his coronaries…

Syndenham 1689

EBCT CORONARY CALCIUM SCORES AS FUNCTION OF AGE AND GENDER

MALES

0100200300400500600700800900

1000

30-39 40-49 50-59 60-69 70+

10th25th50th75th90th

EBCT CORONARY CALCIUM SCORES AS FUNCTION OF AGE AND GENDER

FEMALES

0

100

200

300

400

500

600

700

800

900

30-39 40-49 50-59 60-69 70+

10th25th50th75th90th

A

Negative Predictive Power of EBT

1764 persons underwent EBT and angiogram Sensitivity for Obstruction (any calcium)

99.4% in men, 100% in women Negative predictive power > 99% Can be used as a ‘filter’ prior to angiography

to help avoid negative angiograms

Haberl et al. JACC Feb 2001

EBCT “Screening” in the Emergency Room:EBCT “Screening” in the Emergency Room:Results in the Mayo Clinic “chest pain unit”Results in the Mayo Clinic “chest pain unit”

EBCT ResultsPositive Negative Total

Other Cardiac Test Results (Score > 0) (Score = 0)

Positive Dx of CAD 14 0 14Negative Dx of CAD 32 54 86

Total

EBCT Results:

SensitivitySpecificity

Negative Predictive Value

46

100%63%

100%

54 100

NPV for “Significant”CAD of 100%

50% women, 98% Caucasian

All events occurred in those with CAC

Annals of Em Med, 1999

CARDIOMYOPATHYCARDIOMYOPATHY Evaluate Cardiomyopathy of Unknown Etiology

using EBT

The sensitivity of coronary calcium depicting an ischemic cardiomyopathy was 99% (score >0 = presumed ischemic CM) 1

Better than echocardiography or stress testing at distinguishing ischemic from dilated CM2

1Budoff et al. JACC 1999

2Le T. Clin Card 2000

Sensitivity of Calcium for Future Cardiovascular Events

0%

10%

20%

30%

40%

50%60%

70%

80%

90%

100%

RiskFactors

Detrano Greenland Raggi Arad Wong Agatston Detrano Georgio Keelan

Rusty Pipe Model of Atherosclerosis

NormalNormalvesselvessel

MinimalMinimalCADCAD

ProgressionProgression

Artery can compensate for up Artery can compensate for up to 40% plaque volume (lumen to 40% plaque volume (lumen

size remains constant)size remains constant)

Artery atArtery atmaximummaximumexpansion:expansion:

lumen narrowslumen narrows

SevereSevereCADCAD

ModerateModerateCADCAD

Glagov S et al, Glagov S et al, N Engl J MedN Engl J Med, 1987., 1987.

Glagov Hypothesis: Coronary Remodeling

Glagov Hypothesis: Coronary Remodeling

False Negative Coronary Angiography

Diffuse Atherosclerosis despite negative angiogram

Images supplied by Steven E. Nissen, MD, Cleveland Clinic.

Asymptomatic PersonsAsymptomatic Persons Nuclear Imaging Nuclear Imaging

0 0 2.6

11.3

46

0 03.1

6.6

40.4

0

10

20

30

40

50

Zero 1 10 11-100 101-400 400-1000

Total Calcium Score

Per

cent

age

Pos

itiv

e

Pos MIBI Cath

Hu, Circulation 2000

Historical Development of a Coronary Artery Plaque

This process, in various stages of development, can be seen in manyareas of the coronary artery system, consistent with the “diffuse” natureof coronary artery disease

EBCT “positive” for coronary calcium

DATA TAKEN FROM “THE DAWN OF A NEW ERA -NON-INVASIVE CORONARY IMAGING” R. ERBEL HERZ 1996; 21, 75-77

DIAGNOSTIC SENSITIVITY

0% 20% 45% 60% 70% 90%

INVASIVEMODALITIES

STRESS ECG $300

STRESS ECHO $900

PET SCANNING $2200

ELECTRON BEAM CT $400

NON-INVASIVE MODALITIES

INTRAVASCULAR ULTRASOUND $3,000

CORONARY ANGIOGRAPHY $5,000

STRESS THALLIUM $1600

The challenge in diagnosis of coronary heart disease

““The majority of people destined to die The majority of people destined to die suddenly will not have a positive exercise test. suddenly will not have a positive exercise test. The likely reason that they will die suddenly is The likely reason that they will die suddenly is that only a mild, non-flow -limiting coronary that only a mild, non-flow -limiting coronary plaque will have been present before the plaque will have been present before the sudden development of an occlusive sudden development of an occlusive thrombus.”thrombus.”

- Stephen Epstein - Stephen Epstein New England Medical Journal 1989New England Medical Journal 1989

RR of MI/SCD: EBT Score and hs-CRP

0

1

2

3

4

5

6

7

High CAC Med. CAC Low CACLow hs-CRP

High hs-CRP

Park et al.Circ. 2002;106-2073-2077

0

10

20

30

40

50

60

70

Events in PatientsWith CAC

Events in PatientsWithout CAC

CAC by EBT and Cardiac EventsCAC by EBT and Cardiac Events

n=6499%

n=11%

696 pts.53+11 yrs50% males2.7 year f/u

Raggi et alCirc 2/00

65 Cardiac Events(Cardiac Death,

MI, Revasc)

Event Rate: 6%/yr <.1%/year

Event Rates Based upon Scores

0.8

21

41

480

2040

60

Estimated10 Year Event

Rate

Zero 1 99 100-400 >400

EBT Calcium Score

Raggi, AHJ 2001

Eve

nt F

ree

Sur

viva

l %

0

10

20

30

40

50

60

70

80

90

100

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37

Months

Figure 1. Probability of survival free of events in 98 consecutive asymptomatic subjects with calcium score >1,000 on a screening electron beamtomography scan.

Wayhs R, Zelinger A, Raggi P, J Am Coll. Card., Vol 39: pp 225-230, 2002

High Coronary Artery Calcium Scores Pose anExtremely Elevated Risk for Hard Events

Relative Risk Of Future Cardiac Event using EBT

4.9

21 20

8.8 9.6710.8

13.4

0

5

10

15

20

25

Rel

ativ

e R

isk

Detrano Arad Kondos Georgiou Raggi Wong Detrano


Kondos et al, Circulation 2003;107:2571-2176Kondos et al, Circulation 2003;107:2571-2176

5635 asymptomatic, low to intermediate risk patients, 375635 asymptomatic, low to intermediate risk patients, 37++12 m f/u12 m f/u

Cardiac events: MI, SCD, revascularization, age 30-76, avg 51Cardiac events: MI, SCD, revascularization, age 30-76, avg 51++9 yrs.9 yrs.

1.01.00.750.75 1.251.25 1.501.50 3.03.0 30.030.0

Age: 1.04-1.07Age: 1.04-1.071.051.05

1.391.39Smoking: 1.04-1.87Smoking: 1.04-1.87

0.870.87Elevated TC: 0.65-1.07Elevated TC: 0.65-1.07

1.981.98DM: 1.19-3.28DM: 1.19-3.28

1.331.33HTN: 0.98-1.81HTN: 0.98-1.81

10.4610.46Presence of CAC: 3.85-28.4Presence of CAC: 3.85-28.4

RelativeRelativeRiskRisk


The St. Francis Heart Study, ACC 2003The St. Francis Heart Study, ACC 2003

SFHS 3SFHS 3

0.12

0.7

2

2.4

3.3

0

0.5

1

1.5

2

2.5

3

3.5

0 > 0 > 100 > 200 > 600

Baseline EBT Calcium ScoreBaseline EBT Calcium Score

An

nu

al E

ven

t R

ate

(%)

An

nu

al E

ven

t R

ate

(%)

Calcium Score >100 vs <100

Rel

ativ

e R

isk

9.5

AnyEvent

10.7

Cor.Event

9.9

MI/SCD

2.72 2

12.47

3.55

6.15

12.29

0

2

4

6

8

10

12

14

Rel

ativ

e R

isk

DM Smoke HTN <1010-100

101-400401-1000

>1000

EBT Coronary Calcium ScoreEBT Coronary Calcium Score

All Cause Mortality [NDR]All Cause Mortality [NDR]n = 10,377n = 10,377asymptomatic men and womenasymptomatic men and womenf/u = 5.0f/u = 5.0++3.5 yrs.3.5 yrs.

Shaw, Raggi et alIn Press, Radiology 2003

EBT found to be independentand incremental to risk factors

All Cause Mortality in PatientsAll Cause Mortality in PatientsWithout Known CADWithout Known CAD

5 Year Mortality

EBT 5 year All-Cause Mortality

Risk Stratification – Shaw et al.

Rationale for Use of CAC in Different Populations

Risk

Category

Population Number Shifted

Number Needed to

Scan

Low 35% 2% 50

Intermediate 40% 73% 1.3

High 25% 16% 7

Asymptomatic Patient Algorithm for Asymptomatic Patient Algorithm for Intermediate Risk PatientsIntermediate Risk Patients

Greenland P, et al. Circulation Oct 9, 2001

““measurement of coronary calcium is an option measurement of coronary calcium is an option for advanced risk assessment.for advanced risk assessment.High coronary calcium scores (e.g., >75High coronary calcium scores (e.g., >75 thth percentile for age and sex) denotes advanced percentile for age and sex) denotes advanced atherosclerosis and provides rationale for atherosclerosis and provides rationale for intensified LDL-lowering therapy.”intensified LDL-lowering therapy.”

NCEP ATP-III : Noninvasive TestingNCEP ATP-III : Noninvasive Testing

Prevention V Guidelines

Used a score >80 by EBT to implement aggressive drug treatment in Framingham intermediate risk patients

In patients with a zero score, “one would not be justified to intervene with costly lipid lowering drugs at this time”

Percent Volume Change vs LDL

+120%

0

–80%

60 120 200

LDL (mg/dL)

Treated Untreated Suboptimal Therapy (LDL >120 mg/dl)

Callister et al. N Engl J Med. 1998;339:1972-1978.

CA

C S

core

Ch

a ng

e

-40

-20

0

20

40

60

80

100%

An

nu

ali

ze

d C

ha

ng

e

EBT 1 - EBT 2 EBT 2 - EBT 3

Achenbach S, Circulation, Vol 106: Aug. 27, 2002

Rates of Progression of CAC

25%

8.8%

P<0.0001

n=66

Before Statin After Statin

-40

-20

0

20

40

60

80

100%

An

nu

ali

ze

d C

ha

ng

e

EBT 1 - EBT 2 EBT 2 - EBT 3

Achenbach S, Circulation, Vol 106: Aug. 27, 2002

32 Patients who achieved LDL <100 Mg/dL

27%

-3.4%

P=0.0001

n=32

Before Statin After Statin

Annual Event Rate with Progression

01.5

6.45

0

1

2

3

4

5

6

7

Ann

ual E

vent

Rat

es

No progression 1-20% Increase >20% Increase

Annual CAC Score Change Raggi, Budoff AJC 2003

13X Risk

Progression and Medical Intervention

0

50

100

150

200

250

300

Baseline 12 months 24 months 36 Months

COMPLIANCE

“Willpower lasts about two weeks….

And is usually soluble in alcohol”

Mark Twain/Sam Clemens

~50% of patients discontinue lipid-lowering therapy within 1 year.

~75% of patients discontinue lipid-lowering therapy within 2 years.

Compliance and Lipid-Lowering TherapyCompliance and Lipid-Lowering Therapy

Roberts, Am. J. Cardiol. 78:1996:377-378.


SEVERECALCIFICATION

Percentage of individuals maintaining Statin therapy at 3.6 years according to various levels of baseline CAC

No CAC CAC 1-99 CAC 100-399 CAC>4000

10

20

30

40

50

60

70

80

90

100

44

63

75

90

Odds ratio of maintaining statin therapy with various levels of baseline CAC

2nd Quartile 3rd Quartile 4th Quartile0

5

10

15

20

25

30

2.4

5.1

1.1

4.2

1.9

9.19.3

3.0

28.9

5 USES OF EBT

Use a calcium score to screen patients with moderate (intermediate) Framingham risk Positive EBT scans indicate incremental risk Alters therapeutic goal (LDL, BP, etc)

Identify patients who do not need further cardiac evaluation (scores of zero)

Consider serial imaging as ongoing management tool (progression)

Improve compliance Non-invasive Angiography

EBT Coronary Calcium

screening and treatment of coronary artery disease matthew j. budoff, md, facc associate professor...

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