UNCLASSIFIED
22d Medical Group
Lp-PLA2 Testing
PLAC
SAFMLS, MARCH 2010
Capt J. Brian Clark
SSgt James Baluyot
McCONNELL AFB, KS (AMC)
UNCLASSIFIED
1
Agenda
DiaDexus Slides Used With
Definitions
Permission
Background
Relativity to Customers
Evidence
Case Studies
Make vs Buy
Bringing In-House
Coordination
Testing Requirements
Translating to AFMS Importance
Testing Recommendations
Review
Questions
2
Definitions
Lp-PLA2
Lipoprotein-Associated Phospholipase A2
Stenosis
A Marker of Risk for Coronary Events and Strokes
Hardening of the Arteries
Plaque
Stable
Unstable
Ruptured
Illustration
3
Stenotic Plaques May Be Stable or
Unstable
Thick Cap with Small
Necrotic Lipid Core:
“Stable Plaque”
Early Plaque
with Lipid Pool
Thin Cap: Unstable
or “Rupture-Prone”
Plaque
4
Ruptured Plaque
with Thrombus
in Lumen
Adapted from Kolodgie F, et al. Arterioscler Thromb Vasc Biol 2006. Copyright 2009 diaDexus, Inc. All rights reserved.
Contrasting Histopathological
Characteristics
of a Stable versus Ruptured Plaque
Minimal Necrotic
Lipid Pool
Thick Fibrous Cap
Large Necrotic
Lipid Pool
Thin Fibrous Cap
Lumen
Lp-PLA2
Lumen
Lp-PLA2
Stable Plaque
Ruptured Plaque
• Low Lp-PLA2 content (dark staining)
• High Lp-PLA2 content (dark staining)
• May have significant stenosis
• May have minimal stenosis
• Thick fibrous cap / high collagen content
• Thin fibrous cap / low collagen content
• Minimal necrotic lipid pool
• Large necrotic lipid pool
• Few inflammatory cells
• Many inflammatory cells
5 Davidson MH, Jones PH. Am J Card Suppl 2008.
Copyright 2009 diaDexus, Inc. All rights reserved.
Relativity to Customers
Its Relative to Everyone!
TRICARE Beneficiaries
Active Duty
Guard/Reserve
Retirees
Dependents
Not Limited to Any Certain Age Group
Enables Lab to Provide MORE Information to HCPs
Can Help Diagnose and Treat High Risk Patients
Test Focuses on Prevention & Tracking vs Reaction
Test Can Help Track Plaque Progression/Regression
6
Evidence
Heart Disease is the Leading Cause of Death in the United States, Stroke is Third
1,000,000
Total Leading Causes
of Death in the US
Leading Causes of Death
for American Women
800,000
350,000
300,000
631,636
600,000
315,000
559,888
250,000
200,000
400,000
150,000
137,119
71,000
121,599
72,449
0
65,000
41,000
50,000
0
Heart
Disease
Cancer
Stroke
Accidents
Diabetes
National Center for Health Statistics 2006.
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82,000
100,000
200,000
Heart
Disease
Stroke
Lung
Cancer
COPD
Breast
Cancer
National Heart, Lung and Blood Institute, 2006
Copyright 2009
diaDexus, Inc.
Evidence…Continued
Coronary Artery Disease (CAD):
The Diagnosis Often Comes Too Late
Myocardial Infarction (MI) or Death as Initial
Presentation of CAD
Men
62%
Women
46%
0%
20%
40%
60%
Percentage of Patients
Adapted from Levy et al in Textbook of Cardiovascular Medicine, 1998.
8
Copyright 2009 diaDexus, Inc. All rights reserved.
More Evidence…
Rupture-Prone Plaque, not Severe Stenosis,
Causes most Acute MI and Cardiac Death
Up to 76% of all CV Events are due to Plaque Rupture
Sudden Cardiac Death
100%
Proportion (%)
76%
80%
60%
40%
24%
20%
0%
Rupture-prone plaque
Severe Stenosis
Type of culprit lesion
9
Kolodgie F, et al. ATVB 2006.
Copyright 2009 diaDexus, Inc. All rights reserved.
Case Studies
Miranda
age 45
Smoker
Total Cholesterol 200 mg/dL
HDL Cholesterol 49 mg/dL
Systolic BP 138 mm/Hg
Not on blood pressure medications
Family history of premature CVD
LDL 121 mg/dL
BMI 31 kg/m2
Triglycerides 150 mg/dL
Fasting Blood Glucose 98 mg/dL
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Anna
age 67
Paul
age 55
•
•
•
•
•
•
•
•
•
•
•
•
Non-Smoker
Total Cholesterol 204 mg/dL
HDL Cholesterol 35 mg/dL
Systolic BP 128 mm/Hg
Not on blood pressure medications
No family history of premature CVD
LDL 128 mg/dL
BMI 32 kg/m2
Triglycerides 205 mg/dL
Non-HDL = 170 mg/dL
>3 Met Synd Diagnostic Criteria
Fasting Blood Glucose 110 mg/dL
•
•
•
•
•
•
•
•
•
•
Non-Smoker
Total Cholesterol 160 mg/dL
HDL Cholesterol 42 mg/dL
Systolic BP 136 mm/Hg
On blood pressure medications
Family history of premature CVD
LDL 88 mg/dL
BMI 27 kg/m2
Triglycerides 150 mg/dL
Fasting Blood Glucose 92 mg/dL
Copyright 2009 diaDexus, Inc. All rights reserved.
Make vs Buy?
Make:
Buy:
Perform the Test In-House?
Submit Test to Reference Lab?
Costs:
Make (In-House)
Buy (Ref Lab)
$40 Per Test
$151*
*Quest DoD Pricing Agreement
Instrument Acquisition:
N/A
Reagent Packs Available for Pre-Existing Analyzers
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Bringing the Test In-House
PLAC Test for Lp-PLA2
• The diaDexus PLAC Test for Lp-PLA2 is cleared by the FDA as an aid in
predicting risk for coronary heart disease and ischemic stroke.*
• Simple blood test that does not require fasting by patients.
• Used on common automated clinical chemistry analyzers that can be
found in most labs…No Need to Purchase New or Additional Analyzers!
• Team Comes to Your Lab for All Correlation & Validation Testing
• Submits Final Version to Laboratory Records
• Follow Established Protocols for New Test Implementation
12
* for complete indication see package insert
Copyright 2009 diaDexus, Inc. All rights reserved.
Bringing the Test In-House
PLAC Test for Lp-PLA2
• List of Analyzers:
• Hitachi/P
• Olympus AU 400/640/2700
• Cobas 6000/c501
• Abbott Architect
• BioLis 24i
• Beckman CX7/LX20/DXC
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* for complete indication see package insert
• SIEMENS
• ADVIA
1200/2400/1800/1650
• DIMENSION*
• RXL/XPAND+
• April 10, 22 MDG was
Beta Site for Dimension
Line
Copyright 2009 diaDexus, Inc. All rights reserved.
Coordination Within MTF
What Does This Information Mean and How Can it be
Translated?
Discuss With Lab/Medical Director
Advertise In Pro-Staff
Explain Importance and Relativity
Consult with RMO
Present in Various MTF Functions/Committees
Broadcast or Share With Peers/Colleagues
Breakout Sessions
SAFMLS
Track in Quality Assurance Minutes
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Testing Requirements
Serum Samples
Fasting Not Required
Sample Age Must be Between 3-10 Days
Cannot Test Same Day
Batch Test
Once per Week on the Previous Week’s Samples
Run Batch on Monday or Tuesday
Frequency is Workload Dependent
15
Translating to the AFMS
Recognize Demographic Relevances
One out of three strokes occur in people between the
ages of 45 and 65.
Incorporate Test Into PHA
Associate Test with Risk Factors
Family History
Blood Pressure
Lipids
Etc
Lipids are NOT a Reliable Predictor for Stroke
Risk Diagram…
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Pre-Summary
Lp-PLA2 as a Biomarker in
CHD and Stroke
Lp-PLA2 is specific for vascular inflammation and is
a circulating measure of the progression of ruptureprone plaque.
• Lp-PLA2 levels can be used to identify
patients who require more aggressive
treatment, including lipid-lowering therapy.
• Therapeutic intervention can lower Lp-PLA2.
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Copyright 2009 diaDexus, Inc. All rights reserved.
Expert Consensus Panel
Recommendation for Use of
Lp-PLA2 Testing
Low CV Risk
0-1 risk factors
Moderate
CV Risk
2+ risk factors
High CV Risk
CHD, or CHD Risk
Equivalent
Lp-PLA2 TESTING
Lp-PLA2 TESTING
Very High
CV Risk
Assess
Test
200 ng/mL
Treat
LDL-C Goal
< 160 mg/dL
> 200 ng/mL
LDL-C Goal
< 130 mg/dL
> 200 ng/mL
200 ng/mL
LDL-C Goal
< 100 mg/dL
LDL-C Goal
< 70 mg/dL
• Lp-PLA2 identifies which moderate and high risk individuals, as initially assessed by
traditional risk factors, may actually be at increased risk of heart attack or stroke.
• These individuals should be treated to a lower LDL-C goal, which has been proven to
further reduce cardiovascular events in higher risk persons.
Davidson MH, Alberts MJ, Anderson JL, Gorelick PB, Jones PH, Lerman A, McConnell JP, Weintraub H. Am J Cardiol Supplement 2008
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Copyright 2009 diaDexus, Inc. All rights reserved.
Patient Candidates for
Lp-PLA2 Testing
Intermediate risk persons with 2 traditional risk factors, Metabolic
Syndrome or bad single risk factors like smoking or age > 65.
High risk coronary risk equivalent patients, even if treated, to see if
their plaque is still unstable. When is the job done?
A “tie breaker” for borderline lipids. How aggressive should we be
if LDL is borderline 130 or HDL is borderline 40?
A “tie breaker” for apparently healthy persons with borderline
hypertension. Their risk for stroke may be 3.5 to 6.8 times higher
than those with low blood pressure and low Lp-PLA2.
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Copyright 2009 diaDexus, Inc. All rights reserved.
In Review
DiaDexus Slides Used With
Definitions
Permission
Background
Relativity to Customers
Evidence
Case Studies
Make vs Buy
Bringing In-House
Coordination within MTF
Testing Requirements
Translating to AFMS Importance
Testing Recommendations
20
www.plactest.com
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