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
Coronary Artery Scanning
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
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
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
Prediction of Cardiac Events in AsymptomaticPrediction of Cardiac Events in AsymptomaticPatients by EBTPatients by EBT
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
Prediction of Cardiac Events in AsymptomaticPrediction of Cardiac Events in AsymptomaticPatients by EBTPatients by EBT
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.
Coronary Artery Scanning
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