Detection and Treatment of
Asymptomatic Atherosclerosis
for Primary Prevention of CVD
Morteza Naghavi, M.D.
Society for Heart Attack Prevention and Eradication (SHAPE)
SHAPE 2012 Summit
AHA 2012 Satellite Symposium
November 2, 2012
Cedars Sinai Medical Center
Los Angeles, California
http://www.theheart.org/article/1459893.do
The Problem
> 15 Million Heart Attacks Each Year
Source:
World
Heart
Federation
The AEHA 2005 VP Summit
Unpredicted
In >50% of victims,
the first symptom of
asymptomatic
atherosclerosis is a
sudden cardiac
death or acute MI.
Sudden Cardiac Death or Acute MI
as Initial Presentation of CHD
Men
62%
42%
Women
0
10
20
30
40
50
Patients Diagnosed with CHD (%)
60
70
Murabito et al
Circulation 1993
Of 136,905 patients hospitalized with CAD, 77% had normal LDL levels
below 130 mg/dl
Modified from Sachdeva et al. AHJ, Vol 157, 111-117 Jan 2009
Chapter 1: Preventive Cardiology; the SHAPE of the Future in Naghavi et al. Asymptomatic Atherosclerosis: Pathophysiology,
Detection and Treatment. Humana Press, 2009
Of 136,905 patients hospitalized with CAD, 45.4% had normal HDL levels
above 40 mg/dl
Modified from Sachdeva et al. AHJ, Vol 157, 111-117 Jan 2009
Chapter 1: Preventive Cardiology; the SHAPE of the Future in Naghavi et al. Asymptomatic Atherosclerosis: Pathophysiology,
Detection and Treatment. Humana Press, 2009
Of 136,905 patients hospitalized with CAD, 61.8% had normal triglyceride
levels below 150 mg/dl
Modified from Sachdeva et al. AHJ, Vol 157, 111-117 Jan 2009
Chapter 1: Preventive Cardiology; the SHAPE of the Future in Naghavi et al. Asymptomatic Atherosclerosis: Pathophysiology,
Detection and Treatment. Humana Press, 2009
Traditional Risk Factors Miss the Majority of
High Risk Patients
Akosah et al. JACC 2003:41 1475-9
1998 – 2002. 222 patients with 1st acute MI, no prior
CAD, no DM. Men <55 y/o (75%), Women <65. 40%
hypertensive
What was NCEP risk before the MI? Would they have
received statin therapy or more intensive statin therapy?
10 yr risk >20%
Goal LDL<100 mg/dL
(optional < 70 mg/dL)
10 yr risk 10 - 20%
Goal LDL<130 mg/dL
(optional < 100 mg/dL)
% of total
would qualify for statin Rx
would not qualify for statin Rx
10 yr risk <10%
Goal LDL<160 mg/dL
70%
61%
75% would not qualify for statin Rx.
18%
12%
6%
High Risk
6%
8%
10%
Moderately High Risk
9%
Slide Source:
Lipids Online
www.lipidsonline.org
Lower / Moderate Risk
CONCLUSION:
Relying on risk factors of
atherosclerosis (i.e.
cholesterol & blood
pressure) mislead
physicians and patients.
A direct assessment of
atherosclerosis is needed.
Who Has More Cardiovascular Risk Factors?
Sir Winston Churchill, 91 
Jim Fixx, 53 
Unexpected Sudden Death
of Famous Cardiologists
Helmut Drexler
death with 58 years
Philip Alexander Poole-Wilson
death with 66 years March 4, 2009
Two weeks after Update in Cardiology
In Davos
Bottom Line:
Status Quo IS
Unacceptable
~50%
Apparently
Healthy
People
(New)
~50%
CHD
Patients
(Recurrent)
CVD Genotyping?
Naghavi et al. Circulation. 2003;108:1664
~50%
Apparently
Healthy
People
(New)
~50%
CHD
Patients
(Recurrent)
CVD Genotyping?
Naghavi et al. Circulation. 2003;108:1664
The Vulnerable Patient Consensus Statement Preceding
the SHAPE Initiative
Naghavi et. al. Circulation Journal Vol108, No14; October 7, 2003
The Vulnerable Patient Consensus Statement Preceding
the SHAPE Initiative
Naghavi et. al. Circulation Journal Vol108, No14; October 7, 2003
First SHAPE Symposium
SHAPE Task Force Meeting
SHAPE Guidelines Published
SHAPE Guidelines Published
SHAPE v.s. Status Quo
Existing Guidelines (Status Quo):
• Screen for Risk Factors of Atherosclerosis
• Treat Risk Factors of Atherosclerosis
The SHAPE Guidelines:
• Screen for Atherosclerosis (the Disease)
Regardless of Risk Factors
• Treat based on the Severity of the Disease
and its Risk Factors
ROC Curve, its AUC and Corresponding Odds Ratio
hs-CRP
LDL
HDL
Smoking
Hypertension
Diabetes
etc.
Risk Factors
Based on the paper by Pepe e. al. Am J Epidemiol 2004; 159:882-890.
ROC Curve, its AUC and Corresponding Odds Ratio
Structural
CAC +FRS
IMT+FRS
hs-CRP
LDL
HDL
Smoking
Hypertension
Diabetes
etc.
Risk Factors
Based on the paper by Pepe e. al. Am J Epidemiol 2004; 159:882-890.
ROC Curve, its AUC and Corresponding Odds Ratio
Structural
Combined structural & functional?
CAC +FRS
IMT+FRS
hs-CRP
LDL
HDL
Smoking
Hypertension
Diabetes
etc.
Risk Factors
Based on the paper by Pepe e. al. Am J Epidemiol 2004; 159:882-890.
The 1st S.H.A.P.E. Guideline
Conceptual Flow Chart
Apparently Healthy At-Risk Population
Step 1
Atherosclerosis Test
Test for
Presence of the
Disease
Positive
Negative
No Risk Factors
+ Risk Factors
<75th
Percentile
75th-90th
Percentile
≥90th
Percentile
Moderately
High Risk
High
Risk
Very
High Risk
Step 2
Stratify based on the
Severity of the Disease and
Presence of Risk Factors
Step 3
Treat based on
the Level of
Risk
Lower
Risk
Moderate
Risk
The 1st SHAPE Guidelines
Apparently Healthy Population Men>45y Women>55y1
Very Low Risk3
Step 1
Exit
Exit
All >75y receive unconditional treatment2
• Coronary Artery Calcium Score (CACS)
or
• Carotid IMT (CIMT) & Carotid Plaque4
Atherosclerosis Test
Step 2
Negative Test
Positive Test
• CACS =0
• CIMT <50th percentile
No Risk Factors5
Step 3
Lower
Risk
+ Risk Factors
Moderate
Risk
• CACS ≥1
• CIMT 50th percentile or Carotid Plaque
• CACS <100 & <75th%
• CIMT <1mm & <75th%
& no Carotid Plaque
Moderately
High Risk
• CACS 100-399 or >75th%
• CIMT 1mm or >75th%
or <50% Stenotic Plaque
ABI<0.9
CRP>4mg
Optional
• CACS >100 & >90th%
or CACS 400
• 50% Stenotic Plaque6
High
Risk
Very
High Risk
LDL
Target
<160 mg/dl
<130 mg/dl
<130 mg/dl
<100 Optional
<100 mg/dl
<70 Optional
<70 mg/dl
Re-test Interval
5-10 years
5-10 years
Individualized
Individualized
Individualized
1: No history of angina, heart attack, stroke, or peripheral arterial disease.
2: Population over age 75y is considered high risk and must receive therapy without testing for
atherosclerosis.
3: Must not have any of the following: Chol>200 mg/dl, blood pressure >120/80 mmHg, diabetes,
smoking, family history, metabolic syndrome.
4: Pending the development of standard practice guidelines.
5: High cholesterol, high blood pressure, diabetes, smoking, family history, metabolic syndrome.
6: For stroke prevention, follow existing guidelines.
Follow Existing
Guidelines
Angiography
Myocardial
IschemiaTest
Yes
No
SHAPE II Guidelines– Under Discussions
Step 1
Calculate 10yr Risk using Risk Calculators such as Framingham Risk Score1
10y Risk 6%-20%
10y Risk <6%
10yr Risk >20%
No test:
Follow Preventive
Recommendations
as in Low Risk
Diabetics >40yr or
family history of
premature coronary
artery disease
Optional
Atherosclerosis Test
Carotid IMT
& Plaque
Step 2
No test:
Follow Preventive
Recommendations
as in High Risk
CIMT >75th%
and (or?)
CIMT <75th % or
Plaque<1.5mm
Plaque>1.5mm
Coronary Artery Calcium Scan (CACS)
Step 3
Diet,Exercise,
Smoking Cessation,
BP and Diabetes
Control
Consider
LDL Target
Consider
HDL and
TG Rx
Very Low Risk2
Low Risk2
Intermediate Risk2
CACS =0
CACS <100 &<75th%
CACS 100-399 &<75th%
CACS 400 or  75th%
+++++
+++++
+++++
+++++
High Risk
<160 mg/dl
<130 mg/dl
<100 mg/dl
<75 mg/dl
No RX
Rx
Rx
Intensive RX
1 http://www.framinghamheartstudy.org/risk/hrdcoronary.html
2Elevate to High Risk if
See the SHAPE II Task
Force report for further
cardiac imaging tests
in selected High Risk
individuals.
1.4<Ankel Brachail Index <0.9
SHAPE II Guidelines– Under Discussions
Coronary Artery Calcium
Score (CACS)
or
Carotid Plaque Burden
Carotid Plaque
0 Carotid Plaque
Lowest Tertile
Carotid Plaque
Lowest Risk
Low Risk
CACS 100-399 &<75th%
CACS>400 or >75th%
Middle Tertile
Carotid Plaque
Highest Tertile
Carotid Plaque
Intermediate
Risk
High
Risk
Some of the Members of the SHAPE Task Force (left to right): Drs Budoff, Falk, Rumberger, Naghavi, Fayad, Hecht, and Berman
Current National Preventive
Care Reimbursement Policies
Do Not Match the Burden of
the Problem
Inadequate & Disproportionate
Why do we screen for
asymptomatic cancers
but ignore
asymptomatic CVD?
<$100 for # 1 killer
>$1000 for # 2 Killer
Cost Effectiveness of the SHAPE Guidelines
Number
(per year)
Estimated Impact
of SHAPE
(Sensitivity
Analysis Range)
Estimated
Change in
Cost
910,600
↓10%
(5%-25%)
($1.2 b)
MI (prevalence)
7,200,000
↓ 25%
(5%-35%)
($18.0 b)
Chest Pain Symptoms (ER visits)
6,500,000
↓ 5%
(2.5%-25%)
($4.1 b)
Hospital Discharge for Primary Diagnosis of CVD
6,373,000
↑ 10%
(5%-25%)
$3.8 b
Hospital Discharge for Primary Diagnosis of CHD
970,000
↓ 10%
(5%-25%)
($9.9 b)
↑ 50 %
(50%-65%)
8.00 b
CVD Deaths
Cholesterol Lowering Therapy
CV Imaging
8,700,000
↑ 10%
(5%-25%)
Angiography
6,800,000
↑ 15% - CTA
(2.5%-25%)
$600 m
PCI (percutaneous coronary interventions per year)
657,000
↓ 10%
(5%-50%)
($580 m)
CABS (coronary artery bypass surgeries per year)
515,000
↓ 5%
(2.5%-50%)
($672 m)
Total Δ in Cost
$358 m
($21.5 b)
WWW.SHAPESOCIETY.ORG
The 1st SHAPE Textbook Released at the ACC 2010