This document summarizes key points from a task force report on identifying and treating asymptomatic patients vulnerable to heart attack. It introduces a new paradigm focused on outcomes studies, measuring disease activity, and identifying the vulnerable plaque and patient. The report was chaired by Morteza Naghavi and had writing contributions from experts in cardiovascular imaging, risk assessment, and prevention. It aims to advance the field beyond traditional risk factor assessment alone.

1. 96% of deaths from CHD
or stroke occur in people
aged 55 and over*
*Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than
80%. BMJ. 2003;326:1419-

3. Circulation 2004;110:227-39Circulation 2004;110:227-39

4. Circulation 2004;110:227-39Circulation 2004;110:227-39
§ Almost all people with zero or 1 risk factor have a 10-year risk <10%,§ Almost all people with zero or 1 risk factor have a 10-year risk <10%,
and 10-year risk assessment in people with zero or 1 risk factorand 10-year risk assessment in people with zero or 1 risk factor
is thus not necessary.is thus not necessary.

5. Low riskLow risk
• S-chol <200 mg/dlS-chol <200 mg/dl
• BPBP <<120/80120/80
• No smokingNo smoking
• No diabetesNo diabetes
JAMA 1999;282:2012-8

6. Low riskLow risk
• S-chol <200 mg/dlS-chol <200 mg/dl
• BPBP <<120/80120/80
• No smokingNo smoking
• No diabetesNo diabetes
<10% of population<10% of population
JAMA 1999;282:2012-8

7. Low riskLow risk
• S-chol <200 mg/dlS-chol <200 mg/dl
• BPBP <<120/80120/80
• No smokingNo smoking
• No diabetesNo diabetes
<10% of population<10% of population
High negativeHigh negative
predictive value!predictive value!
JAMA 1999;282:2012-8

8. CirculationCirculation 1999;100:1481-14921999;100:1481-1492
(no prehypertension)
(Optimal)

9. CirculationCirculation 1999;100:1481-14921999;100:1481-1492

12. 96% of deaths from CHD
or stroke occur in people
aged 55 and over*
*Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than
80%. BMJ. 2003;326:1419-
Trajectory:
How early?

13. Susceptibility
VulnerableVulnerable
PatientPatient
~10% risk/y~10% risk/y
Risk factors:
Categorical levels

14. Susceptibility
VulnerableVulnerable
PatientPatient
~10% risk/y~10% risk/y
Vulnerability:
• Relative
• Absolute (VP)
Risk factors:
Categorical levels

15. Susceptibility
VulnerableVulnerable
PatientPatient
~10% risk/y~10% risk/y
Vulnerability:
• Relative
• Absolute (VP)
Risk factors:
Categorical levels
Tool-
dependent

16. VulnerableVulnerable
PatientPatient
~10% risk/y~10% risk/y
Susceptibility

17. Susceptibility
VulnerableVulnerable
PatientPatient
~10% risk/y~10% risk/y

18. Vulnerability
VulnerableVulnerable
PatientPatient
~10% risk/y~10% risk/y

21. Madjid et al. ATVB 2004;24:1775-82

22. ThrombusThrombus
Lipid-rich core
Vulnerable Plaque + Thrombosis+ Thrombosis →→ 
Fibrous
cap
Inflammation
(macr, MMP)
smcsmc
Expansive growth
(remodeling)
AngiogenesisAngiogenesis

24. Figure 1. Occurrence of a first coronary event within 10Occurrence of a first coronary event within 10
yearsyears, estimated by Cox proportional hazards models in
percentages.
Left, Percentage estimated by a model with FRS (5
categories) adjusted for survey.
Right, Percentage estimated for each of 5 FRS categories by
a model with CRP (3 categories) adjusted for FRS
(continuous) and survey. Probability values indicate significance status
of CRPCRP in the Cox model.
Wolfgang Koenig, SHAPE Report 2005

26. Clinical utility of very high (>10 mg/L) as well as very low (<0.5 mg/L) levels of
hsCRP among those with 10-year Framingham estimated risks <10% (left) and
between 10% and 20% (right). Circulation 2004;109:2818-25

27. Pepe et al. Am J Epidemiol 2004;159:882-90Pepe et al. Am J Epidemiol 2004;159:882-90

28. CRPCRP
MPOMPO
!!
Pepe et al. Am J Epidemiol 2004;159:882-90Pepe et al. Am J Epidemiol 2004;159:882-90

29. Pepe et al. Am J Epidemiol 2004;159:882-90Pepe et al. Am J Epidemiol 2004;159:882-90

30. Circulation 2004 Dec 14;110:e532

31. Targeted therapy,
proportionate to the severity of the disease

32. Causal factors
Targeted therapy,
proportionate to the severity of the disease

33. Mosca L. N Engl J Med 2002;347:1615-7. Editorial

34. Circulation 2000;101:111-6Circulation 2000;101:111-6
Physical inactivity

35. Table 1. Direct medical costs (not charges) for numerous cardiovascular imaging and cardiac diagnostic tests as
based upon the published evidence and as synthesized in the recent 34th Bethesda Conference of the American
College of Cardiology and from the recent European Society for Cardiology’s Consensus Panel Report on
cardiovascular magnetic resonance imaging
$39Outpatient Office Visit
$712Added Cost of Intravascular Ultrasound
$296Single Photon Emission Computed Tomography
$67Exercise ECG
$247Advanced Lipid Analysis
$13C-Reactive Protein Laboratory Measurement
$13Cholesterol panel
Comparative Costs
$1,810Right / Left Heart Cateterization
$1,272Positron Emission Tomography
$450Magnetic Resonance Imaging*
$283Other Computed Tomography
$91Rest Echocardiography
$87Electron Beam Tomography / Computed Tomography Coronary
Calcium Scan
$71Carotid Ultrasound
$61Ankle Brachial Index
CV Imaging Costs
*Costs vary widely from ~$200 to $1,100 depending upon the procedure.
SHAPE: Cost-Effectiveness
Leslee Shaw, SHAPE Report 2005

36. Screen Testing
Evaluating the Cost and Effectiveness of Strategies for Atherosclerotic Detection
and Prevention
The SHAPE EquationThe SHAPE Equation
N = nN = n00 ×× ffcc ×× ffss ×× ffdd ×× fftt ×× ffee
N Number of prevented atherosclerotic events
n0
Number of atherosclerotic events in the baseline population
fc
Fraction of candidates in the baseline population
fs
Fraction of candidates who are screened
fd
Fraction of screened candidates who are detected for treatment
ft
Fraction of detected subjects who are effectively treated
fe
Fraction of effectively treated subjects in whom events are prevented
George A. Diamond, SHAPE Writing Group

37. Raymond Bahr, SHAPE Report 2005
Early Heart Attack Care (EHACEHAC) and
Chest Pain Centers ED

40. Raggi et al. AHJ 2001;141:375-82Raggi et al. AHJ 2001;141:375-82

41. Fatal and nonfatal MI
risk and OR for each decile of calciumrisk and OR for each decile of calcium
score (CS)score (CS)
Raggi et al. AHJ 2001;141:375-82Raggi et al. AHJ 2001;141:375-82
n=676, age ~52y

42. Author N Mean
Age, y
(years
)
Follow-up
Duration,
y
(years)
Calcium
Score Cutoff
Comparator
Group for RR
Calculation
Relative
Risk
Ratio
Arad (11) 1,173 53 3.6 CAC
>160
CAC
< 160
20.2
Detrano (12) 1,196 66 3.4 CAC >44 CAC <44 2.3
Park (13) 967 67 6.4 CAC >142.1 CAC <3.7 4.9
Raggi (14) 632 52 2.7 Top
Quartile*
Lowest Quartile 13
Wong (15) 926 54 3.3 Top Quartile
(>270)
First Score
Quartile
8.8
Arad (16) 5,585 59 4.3 CAC ≥ 100 CAC <100 10.7
Kondos (17) 5,635 51 3.1 CAC No CAC 10.5
Greenland (18) 1,312 66 7.0 CAC>300 No CAC 3.9
Shaw (19) 10,377 53 5 CAC >400 CAC <10 8.4**
Pletcher (20)
(meta-analysis)
3,970 56 3.3 CAC >400 CAC=0 10.0
Harvey Hecht, SHAPE Report 2005
Predictive studies: Characteristics and Risk Ratio for Follow-
Up Studies Using
EBCT in Asymptomatic Persons

43. NEJM 2003;NEJM 2003;
349:465-73349:465-73
RR>10RR>10
Office-basedOffice-based
risk assessmentrisk assessment

44. NEJM 1999;340:14-22

45. O’Leary et al. NEJM 1999;340:14-22

46. O’Leary et al. NEJM 1999;340:14-22

47. Figure 2: B-mode imaging of right carotid artery,
bifurcation and internal and external carotid
arteries. Images are obtained with ultrasound beam
perpendicular to the vessel wall showing near wall,
lumen and far wall. Distal 1 cm of common carotid,
1 cm of carotid bulb and 1 cm of proximal internal
carotid artery are imaged for IMT measurement
and detection of plaque.and detection of plaque.
Naqvi and Douglas, SHAPE Report 2005

48. Best Marker of Susceptibility to CHD
prevalent arterial diseaseprevalent arterial disease
CHD risk equivalentsCHD risk equivalents
NCEP ATP III

49. 96% of deaths from CHD
or stroke occur in people
aged 55 and over*
*Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than
80%. BMJ. 2003;326:1419-
Future research:
• Outcome studies
• Disease activity
• Search for the VP

51. From Vulnerable Plaque to Vulnerable Patient – Part III
Introducing a New Paradigm for the Prevention of Heart Attack;
Identification and Treatment of the Asymptomatic Vulnerable Patient
Screening for Heart Attack Prevention and Education (SHAPE)
Task Force Report
Chairman… Editorial Committee… Writing Group … Advisors…
Morteza Naghavi,
…… Harvey S. Hecht, Jay Cohn, Michael Jamieson, Daniel Berman, Ole Faergeman,
Matthew J. Budoff, Zahi Fayad, John Rumberger, George A. Diamond, Leslee Shaw,
Tasneem Z. Naqvi, Pamela Douglas, Raymond Bahr, Wolfgang Koenig, Jasenka
Demirovic, Dan Arking, Victoria L.M. Herrera, Juan Badimon, Sanjay Kaul, Juhani
Airaksinen, Yoram Rudy, Arturo G. Touchard, Robert S. Schwartz, Daniel Lane, Henrik
Sillesen, Roger Blumenthal, Roxana Mehran, Stephane Carlier, Allen J. Taylor, ……
Prediman K. Shah.

52. From:From: Morteza Naghavi, M.D.Morteza Naghavi, M.D. [mailto:mn2@vp.org]
Sent:Sent: Thu 3/3/2005 1:29 AMThu 3/3/2005 1:29 AM
To: Erling Falk
Subject:
Erling, please note the yellow box is Lower Risk not Low Risk, … . Mort

53. Risk assessment and stratification
Risk factor/office-basedNCEP
, 10-year risk
Intermediate Risk
10-20%
High Risk
>20%
Low(er) Risk
<10%
RR ~2RR ~2
Pletcher et al
Arch Intern Med
2004;164:1285-92