22d Medical Group 1 Lp-PLA 2 Testing PLAC Capt J. Brian Clark SSgt James Baluyot McCONNELL AFB, KS...

22d Medical Group

1

Lp-PLA2 Testing PLAC

Capt J. Brian Clark

SSgt James Baluyot

McCONNELL AFB, KS (AMC)

UNCLASSIFIED

UNCLASSIFIED

SAFMLS, MARCH 2010

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Agenda

Definitions Background Relativity to Customers Evidence Case Studies Make vs Buy Bringing In-House Coordination Testing Requirements Translating to AFMS Importance Testing Recommendations Review Questions

DiaDexus Slides Used With Permission

3

Definitions

Lp-PLA2

Lipoprotein-Associated Phospholipase ALipoprotein-Associated Phospholipase A22

A Marker of Risk for Coronary Events and StrokesA Marker of Risk for Coronary Events and Strokes

StenosisStenosis Hardening of the ArteriesHardening of the Arteries

Plaque Stable Unstable Ruptured Illustration

Copyright 2009 diaDexus, Inc. All rights reserved.4

Stenotic Plaques May Be Stable or Unstable

Early Plaque with Lipid Pool

Thick Cap with Small Necrotic

Lipid Core:“Stable Plaque”

Thin Cap: Unstable or

“Rupture-Prone” Plaque

Ruptured Plaque with Thrombus

in Lumen

Adapted from Kolodgie F, et al. Arterioscler Thromb Vasc Biol 2006.


Contrasting Histopathological Characteristics

of a Stable versus Ruptured Plaque

Stable Plaque•Low Lp-PLA2 content (dark staining)

•May have significant stenosis

•Thick fibrous cap / high collagen content

•Minimal necrotic lipid pool

•Few inflammatory cells

Ruptured Plaque•High Lp-PLA2 content (dark staining)

•May have minimal stenosis

•Thin fibrous cap / low collagen content

•Large necrotic lipid pool

•Many inflammatory cells

Minimal NecroticLipid Pool

Large Necrotic Lipid Pool

Lp-PLA2 Lp-PLA2

Thin Fibrous CapThick Fibrous Cap

LumenLumen

Davidson MH, Jones PH. Am J Card Suppl 2008.

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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

Copyright 2009 diaDexus, Inc.

All rights reserved.

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EvidenceHeart Disease is the Leading Cause of Death in the United States,

Stroke is Third

631,636

559,888

137,119 121,599

72,449

0

200,000

400,000

600,000

800,000

1,000,000

HeartDisease

Cancer Stroke Accidents Diabetes

National Center for Health Statistics 2006.

315,000

82,00071,000 65,000

41,000

0

50,000

100,000

150,000

200,000

250,000

300,000

350,000

HeartDisease

Stroke LungCancer

COPD Breast Cancer

National Heart, Lung and Blood Institute, 2006

Total Leading Causesof Death in the US

Leading Causes of Death for American Women

Copyright 2009 diaDexus, Inc. All rights reserved.

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Evidence…ContinuedCoronary Artery Disease (CAD):

The Diagnosis Often Comes Too Late

Adapted from Levy et al in Textbook of Cardiovascular Medicine, 1998.

Myocardial Infarction (MI) or Death as Initial Presentation of CAD

46%

62%

0% 20% 40% 60%

Women

Men

Percentage of Patients


More Evidence…Rupture-Prone Plaque, not Severe Stenosis,

Causes most Acute MI and Cardiac Death

Pro

po

rtio

n (

%)

Kolodgie F, et al. ATVB 2006.

Type of culprit lesion

Sudden Cardiac Death

Up to 76% of all CV Events are due to Plaque Rupture

76%

24%

0%

20%

40%

60%

80%

100%

Rupture-prone plaque Severe Stenosis


• 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

Paulage 55

Annaage 67

Case Studies

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

Mirandaage 45

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Make vs Buy?

Make: Perform the Test In-House?

Buy: Submit Test to Reference Lab?

Costs:

Instrument Acquisition: N/A Reagent Packs Available for Pre-Existing Analyzers

Make (In-House) Buy (Ref Lab)

$40 Per Test $151**Quest DoD Pricing Agreement


Bringing the Test In-HousePLAC 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* for complete indication see package insert


Bringing the Test In-HousePLAC 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

* 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

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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

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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…

Copyright 2009 diaDexus, Inc. All rights reserved.

Pre-SummaryLp-PLA2 as a Biomarker in

CHD and Stroke

Lp-PLA2 is specific for vascular inflammation and is a circulating measure of the progression of rupture-prone plaque.

• Therapeutic intervention can lower Lp-PLA2.

• Lp-PLA2 levels can be used to identify patients who require more aggressive treatment, including lipid-lowering therapy.

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Davidson MH, Alberts MJ, Anderson JL, Gorelick PB, Jones PH, Lerman A, McConnell JP, Weintraub H. Am J Cardiol Supplement 2008

Expert Consensus Panel Recommendation for Use of

Lp-PLA2 Testing

• 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.

Low CV Risk0-1 risk factors

ModerateCV Risk

2+ risk factors

High CV RiskCHD, or CHD Risk

Equivalent

Very HighCV Risk

LDL-C Goal< 160 mg/dL




> 200 ng/mL 200

ng/mL

Lp-PLA2 TESTING

Assess

Treat

200 ng/mL

> 200 ng/mL

Lp-PLA2 TESTINGTest


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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In Review

Definitions Background Relativity to Customers Evidence Case Studies Make vs Buy Bringing In-House Coordination within MTF Testing Requirements Translating to AFMS Importance Testing Recommendations

DiaDexus Slides Used With Permission

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22d Medical Group 1 Lp-PLA 2 Testing PLAC Capt J. Brian Clark SSgt James Baluyot McCONNELL AFB, KS...

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