Can a simple blood test help predict which patients are at a greater risk for heart attack or stroke? Yes. The PLAC Test can.

PLAC® Facts

®Lp-PLA2

The PLAC® Test is the only blood test cleared by the FDA to aid in assessing risk of both coronary heart disease and ischemic stroke associated with athersclerosis.

INNOVATIONS IN CLINICAL DIAGNOSTICS

WHAT IS THE PLAC TEST?

The PLAC Test is a simple blood test that measures Lp-PLA2, an enzyme highly specific to vascular inflammation and implicated in the formation of rupture-prone plaque.

WHY IS THE PLAC TEST DIFFERENT FROM OTHER TESTS?

Lp-PLA2 is independent of traditional cardiovascular risk factors.

• Lp-PLA2 is a vascular specific inflammatory enzyme, therefore it is not as affected by systemic inflammation (infections, obeseity, smoking) compared to other inflammatory markers such as hs-CRP.

• Because elevations in Lp-PLA2 are independent of traditional risk factors, including obesity, the results of the PLAC Test provide valuable additive information to help determine the appropriate care for your patients.

WHO SHOULD BE TESTED?

The PLAC Test may be used as a management tool in patients at moderate to high risk for coronary heart disease or ischemic stroke events. Suitable patients may include patients with two or more risk factors, such as family history of cardiovascular disease or hypertension, even if their overall lipid profile looks normal.

WHAT DO PLAC TEST RESULTS MEAN?

Published data suggests patients with higher values of Lp-PLA2 have an increased risk for cardiovascular disease. In a meta-analysis, Lp-PLA2 levels showed a continuous association with risk for VCD, in both primary and secondary prevention study populations. Lp-PLA2 was consistently associated with a higher cardiovascular risk, and the risk estimate appears to be relatively unaffected by adjustment for traditional CVD risk factors.

HOW CAN THE PLAC TEST TELL WHICH OF MY PATIENTS ARE AT INCREASED RISK FOR STROKE?

Stroke is the number 3 killer in the United States and cholesterol is NOT a reliable predictor for stroke. Now there is a simple blood test that can help you uncover hidden risk for both heart attack and stroke.

A patient with normal systolic blood pressure and elevated Lp-PLA2 levels is over 2 times more likely to have a stroke while a patient with both elevated systolic blood pressure and elevated Lp-PLA2 levels is almost 7 times more likely to have a stroke.

Low Lp-PLA2

Thick fibrous capLipid pool

High Lp-PLA2

Thin fibrous capExpanding

lipid pool ThrombusSite of plaque

rupture

High Lp-PLA2

LowLp-PLA2

ThickFibrousCap

SmallLipid Pool

HighLp-PLA2

ThinFibrousCap

LargeLipid Pool

HighLp-PLA2

ThrombusSiteof PlaqueRupture

75% of heart attacks and most strokes are caused by plaque rupture and thrombosis, not stenosis.

Stable Plaque Ruptured PlaqueRupture-Prone Plaque

For more information on the PLAC® Test, please visit www.diazyme.com or call 1-888-DIAZYME.

Lp-PLA2 ≤ 151nmol/min/mL

Lp-PLA2 = 152 - 194nmol/min/mL

Lp-PLA2 ≥ 195nmol/min/mL

Low Risk Medium Risk High Risk

Lp-PLA2 levels increase withplaque progression1

% Lp-PLA2 staining in varyingcoronary plaque morphologies

35

30

25

20

15

10

5

0PIT FA TCFA Rupture

PIT = pathologic intimal thickeningFA = fibroatheromaTCFA = thin-cap fibroatheroma

*P<0.05 vs FA or PIT**P<0.05 vs TCFA, FA and PIT

*

**

Lipid-modifying medicationsshown to lower Lp-PLA2

12-17

Ezetimibe12 Fenofibrate12,13 Average

Statin12,14,15,17Omega-3FA

+ Statin16

-15%-18~22%

-16~32%-30%

Red

uctio

n in

Lp-

PLA

2 Lev

els

Lp-PLA2 measurement before and during statin treatment. Tracking the reduction of Lp-PLA2 in response to therapy is a better indicator of future CVD events than the reduction of LDL-C levels alone15

0%

-10%

-20%

-30%

-40%

The higher the level of Lp-PLA2,the higher the risk for a CVevent – even with normal LDL

Coronary and CV event hazard ratios

Fully adjusted for traditional risk factors

2.5

2.0

1.5

1.0

1.32

2.15 2.20

ARIC2

(N=9,549) P=0.011

JUPITER3

(N=17,802) P=0.04

Bruneck 4

(N=765) P=0.019

< 113 mm/Hg

1. Gorelick PB, et al. AM J Card Suppl 2008.

> 130 mm/Hg113 - 130 mm/Hg

0.0

1.0

1.02.1

3.52.3

3.5

6.8HighLp-PLA2Level

LowLp-PLA2Level

2.0

3.0

4.0

5.0

6.0

7.0

Tertile of SBP

Ris

k R

atio

ARIC STUDY: LP-PLA2 INCREASES RISK OF ISCHEMICSTROKE AT ALL LEVELS OF BLOOD PRESSURE1

Low Risk

LDL-C Goal< 160 mg/dL

LDL-C Goal< 130 mg/dL

LDL-C Goal< 100 mg/dL

Medium Risk

Lp-PLA2 Testing Lp-PLA2 Testing

High RiskASSESSCV Risk

according toATP III Guidelines

ATP III Risk Factors• Cigarette smoking• Hypertension• Low HDL cholesterol (male < 40 mg/dL, female < 50 mg/dL)

• Family history of premature CHD• Age (men ≥ 45 years, women ≥ 55 years)

CHD Risk Factors• Other clinically manifest forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease, e.g. TIA or stroke)

• Diabetes

TESTfor Lp-PLA2 withthe PLAC Test

TREATto LDL-C Goal.

Intensify treatment ofnon-lipid risk factors

and therapeuticlifestyle change.

0-1 Risk Factors 2+ Risk Factors

= 152-194 nmol/min/mL ≥ 195 nmol/min/mL

CHD orCHD Risk Equivalent

Very High Risk

LDL-C Goal< 70 mg/dL

DZ111 (01/2017) MK162 Rev. A

PLAC® TEST FOR Lp-PLA2

RECOMMENDATION FOR USE OF LP-PLA2 TESTING1

References1. Davidson, MH, et al. Am J Card Suppl 2008* In most states, please visit www.plactest.com for a complete list.

HOW WILL THE PLAC TEST HELP IMPROVE PATIENT MANAGEMENT?

The PLAC Test helps identify patients who have “hidden” cardiovascular risk due to the formation of rupture-prone plaque.

• 1/2 of all heart attacks occur in patients with low to moderate cholesterol levels.

• While cholesterol is a useful tool in coronary heart disease, it is not a reliable predictor of stroke.

• 1/3 of all strokes affect individuals between 45 and 65 years of age.

• The PLAC Test enables you to gain additional information to identify patients in need of more aggressive treatment. High Lp-PLA2 can be a wake-up call to your patients to help improve compliance to therapy.

HOW DOES THE PATIENT PREPARE FOR THE PLAC TEST?

There is no preparation required; it requires a simple venous blood draw. The patient does not have to be fasting and can be on medications. The test results are highly specific for inflammation associated with atherosclerosis, and are not likely to be falsely elevated from infections, rheumatologic disorders or obesity.

PAYMENT FOR THE PLAC TEST

• Medicare currently reimburses $47.77* for the PLAC Test when medically necessary.

• CPT Code: 83698. • Many health plans reimburse for the PLAC Test. However,

some insurance companies may deny payment because the test is fairly new.

CONSIDER THIS CASE STUDY

Lp-PLA2 levels increase withplaque progression1

% Lp-PLA2 staining in varyingcoronary plaque morphologies

35

30

25

20

15

10

5

0PIT FA TCFA Rupture

PIT = pathologic intimal thickeningFA = fibroatheromaTCFA = thin-cap fibroatheroma

*P<0.05 vs FA or PIT**P<0.05 vs TCFA, FA and PIT

*

**

Lipid-modifying medicationsshown to lower Lp-PLA2

12-17

Ezetimibe12 Fenofibrate12,13 Average

Statin12,14,15,17Omega-3FA

+ Statin16

-15%-18~22%

-16~32%-30%

Red

uctio

n in

Lp-

PLA

2 Lev

els

Lp-PLA2 measurement before and during statin treatment. Tracking the reduction of Lp-PLA2 in response to therapy is a better indicator of future CVD events than the reduction of LDL-C levels alone15

0%

-10%

-20%

-30%

-40%

The higher the level of Lp-PLA2,the higher the risk for a CVevent – even with normal LDL

Coronary and CV event hazard ratios

Fully adjusted for traditional risk factors

2.5

2.0

1.5

1.0

1.32

2.15 2.20

ARIC2

(N=9,549) P=0.011

JUPITER3

(N=17,802) P=0.04

Bruneck 4

(N=765) P=0.019

< 113 mm/Hg

1. Gorelick PB, et al. AM J Card Suppl 2008.

> 130 mm/Hg113 - 130 mm/Hg

0.0

1.0

1.02.1

3.52.3

3.5

6.8HighLp-PLA2Level

LowLp-PLA2Level

2.0

3.0

4.0

5.0

6.0

7.0

Tertile of SBP

Ris

k R

atio

ARIC STUDY: LP-PLA2 INCREASES RISK OF ISCHEMICSTROKE AT ALL LEVELS OF BLOOD PRESSURE1

Low Risk

LDL-C Goal< 160 mg/dL

LDL-C Goal< 130 mg/dL

LDL-C Goal< 100 mg/dL

Medium Risk

Lp-PLA2 Testing Lp-PLA2 Testing

High RiskASSESSCV Risk

according toATP III Guidelines

ATP III Risk Factors• Cigarette smoking• Hypertension• Low HDL cholesterol (male < 40 mg/dL, female < 50 mg/dL)

• Family history of premature CHD• Age (men ≥ 45 years, women ≥ 55 years)

CHD Risk Factors• Other clinically manifest forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease, e.g. TIA or stroke)

• Diabetes

TESTfor Lp-PLA2 withthe PLAC Test

TREATto LDL-C Goal.

Intensify treatment ofnon-lipid risk factors

and therapeuticlifestyle change.

0-1 Risk Factors 2+ Risk Factors

= 152-194 nmol/min/mL ≥ 195 nmol/min/mL

CHD orCHD Risk Equivalent

Very High Risk

LDL-C Goal< 70 mg/dL

Miranda Age 45

Clinical Information• Smoker• Total Cholesterol 200 mg/dL• HDL Cholesterol 49 mg/dL• Systolic BP 138 mm/Hg• On blood pressure medications• Family history of premature CVD• LDL 121 mg/dL• BMI 31 kg/m2, waist 40 in.• Triglycerides 150 mg/dL• Fasting Blood Glucose 98 mg/dL

ASSESSModerate Risk

ATP III LDL Goal< 130 MG/dL

TREATReclassify as High Risk

Treat to new LDL-C Goal < 100 mg/dL

TESTLp-PLA2 278 ng/mL

What would you change?

DIAZYME LABORATORIES, INC.12889 Gregg Court, Poway, CA 92064PO Box 85608, San Diego, CA 92186Tel: 858-455-4768 888-DIAZYMEwww.diazyme.com sales@diazyme.com