1. 22d Medical Group 1 Lp-PLA 2 Testing PLAC Capt J. Brian Clark SSgt James Baluyot McCONNELL AFB, KS (AMC) UNCLASSIFIED SAFMLS, MARCH 2010

2. 2 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. 3 Definitions Lp-PLA 2 Lipoprotein-Associated Phospholipase A 2 Lipoprotein-Associated Phospholipase A 2 A Marker of Risk for Coronary Events and Strokes A Marker of Risk for Coronary Events and Strokes Stenosis Stenosis Hardening of the Arteries Hardening of the Arteries Plaque Stable Unstable Ruptured Illustration

4. 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.

5. Copyright 2009 diaDexus, Inc. All rights reserved. 5 Contrasting Histopathological Characteristics of a Stable versus Ruptured Plaque Stable Plaque Low Lp-PLA 2 content (dark staining) May have significant stenosis Thick fibrous cap / high collagen content Minimal necrotic lipid pool Few inflammatory cells Ruptured Plaque High Lp-PLA 2 content (dark staining) May have minimal stenosis Thin fibrous cap / low collagen content Large necrotic lipid pool Many inflammatory cells Minimal Necrotic Lipid Pool Large Necrotic Lipid Pool Lp-PLA 2 Thin Fibrous CapThick Fibrous Cap Lumen Davidson MH, Jones PH. Am J Card Suppl 2008.

6. 6 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

7. Copyright 2009 diaDexus, Inc. All rights reserved. 7 Evidence Heart Disease is the Leading Cause of Death in the United States, Stroke is Third National Center for Health Statistics 2006. 315,000 82,000 71,000 65,000 41,000 0 50,000 100,000 150,000 200,000 250,000 300,000 350,000 Heart Disease StrokeLung Cancer COPDBreast Cancer National Heart, Lung and Blood Institute, 2006 Total Leading Causes of Death in the US Leading Causes of Death for American Women

8. Copyright 2009 diaDexus, Inc. All rights reserved. 8 Evidence…Continued Coronary Artery Disease (CAD): The Diagnosis Often Comes Too Late Adapted from Levy et al in Textbook of Cardiovascular Medicine, 1998.

9. Copyright 2009 diaDexus, Inc. All rights reserved. 9 More Evidence… Rupture-Prone Plaque, not Severe Stenosis, Causes most Acute MI and Cardiac Death Proportion (%) 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 plaqueSevere Stenosis

10. Copyright 2009 diaDexus, Inc. All rights reserved. 10 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/m 2 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/m 2 Triglycerides 150 mg/dL Fasting Blood Glucose 92 mg/dL Paul age 55 Anna age 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/m 2 Triglycerides 150 mg/dL Fasting Blood Glucose 98 mg/dL Miranda age 45

11. 11 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

12. Copyright 2009 diaDexus, Inc. All rights reserved. 12 Bringing the Test In-House PLAC Test for Lp-PLA 2 The diaDexus PLAC Test for Lp-PLA 2 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

13. Copyright 2009 diaDexus, Inc. All rights reserved. 13 Bringing the Test In-House PLAC Test for Lp-PLA 2 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

14. 14 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

15. 15 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

16. 16 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…

17. Copyright 2009 diaDexus, Inc. All rights reserved. Pre-Summary Lp-PLA 2 as a Biomarker in CHD and Stroke Lp-PLA 2 is specific for vascular inflammation and is a circulating measure of the progression of rupture- prone plaque. Therapeutic intervention can lower Lp-PLA 2. Lp-PLA 2 levels can be used to identify patients who require more aggressive treatment, including lipid-lowering therapy. 17

18. Copyright 2009 diaDexus, Inc. All rights reserved. 18 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-PLA 2 Testing Lp-PLA 2 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 Risk 0-1 risk factors Moderate CV Risk 2+ risk factors High CV Risk CHD, or CHD Risk Equivalent Very High CV Risk LDL-C Goal < 160 mg/dL LDL-C Goal < 70 mg/dL LDL-C Goal < 130 mg/dL LDL-C Goal < 100 mg/dL > 200 ng/mL  200 ng/mL Lp-PLA 2 TESTING Assess Treat  200 ng/mL > 200 ng/mL Lp-PLA 2 TESTING Test

19. Copyright 2009 diaDexus, Inc. All rights reserved. 19 Patient Candidates for Lp-PLA 2 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-PLA 2.

20. 20 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

21. 21 www.plactest.com