Welcome [] · both MPO and CRP had a 4.3-fold risk vs. patients with only one elevated marker 1Modified from Heslop CL et al. Myeloperoxidase and C-reactive protein have combined

2/11/2014

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This presentation is not to be copied or distributed without the specific permission

of PAML LLC

Inflammation Testing for

Assessing Heart Disease Risk

Presented by Dr. Marc Penn, MD, PhD, FACC

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webinar. Toll Free: 1-800-867-0864. Entry Code: 40191308.

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Your Host: Karen Riba

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For technical difficulties please e-mail

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For questions you have during the presentation

use the “Q & A” link at the top of your screen

Questions will be answered at the end of the

presentation

Welcome


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Welcome

P.A.C.E. credit may be obtained by submitting

your completed evaluation form at the end of

the webinar

CE credit may be obtained by downloading

the “Certificate of Completion”

PAML employees will be able to receive one

hour of continuing education.

2/11/2014

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At the end of this presentation participants

will be able to:

Summarize the value of assessing inflammation to

define cardiovascular risk.

Describe various inflammatory biomarker tests to

assess a patient’s risk of disease, presence of

disease, and disease activity.

State the value of a multi-marker approach-based on

biomarker physiology to provide additive utility and

synergies when risk stratifying patients.

Learning Objectives


of PAML LLC

Dr. Marc Penn, MD, PhD, FACC

Director of Research,

Summa Cardiovascular Institute

Chief Medical Officer,

Cleveland HeartLab, Inc.

Dr. Penn is also a Professor of

Medicine and Integrative Medical

Sciences at the Skirball Laboratory of

Cardiovascular Cellular Therapeutics

Biomarkers to define risk

Long-Term

Risk

Mid-Term

Risk

Near-Term

Risk

Life Long Decade(s) Years

Classic

Lipid Panel

Advanced

Lipid Testing

Inflammatory

Markers

CHL’s Unique

Focus Also offered through CHL

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Why monitor inflammation?

1Ross R et al. Atherosclerosis-An inflammatory disease. N Engl J Med. 1999; 340: 115-126.

Atherosclerosis is a chronic inflammatory

disease1

Markers of inflammation help refine cardiovascular risk estimation

Russell Ross’s response

to injury hypothesis

1976

Injury

Cholesterol

• Developed statins

which reduce events

• Advanced testing to

help identify risk (ApoB,

ApoA1, LDL-P)

Response

Inflammation

• Landmark JUPITER

Trial

• Advanced testing to

help identify risk (MPO,

hsCRP, Lp-PLA2,

F2-IsoPs, MicroAlb)

Approximately 50% of

individuals who experience

heart attack or stroke have

normal lipids

Why monitor inflammation?

1Ridker et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008; 359: 2195-2207 2Libby et al. Inflammation in atherosclerosis: From pathophysiology to practice. J Am Coll Cardiol. 2009; 54: 2129-2138.

Treatment benefits occur when you reduce

both LDL and hsCRP2

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The CVD Risk Panel

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• Lifestyle markers (inversely related to conditioning)

Exercise daily & eat healthy

Low F2-IsoPs

Sedentary lifestyle, eat poorly & smoke

High F2-IsoPs

What are F2-IsoPs?

The CVD Risk Panel

12

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OxLDL association with future metabolic

syndrome

From: 1889 participants in

The CARDIA Study

Holvoet, P. et al. Future Lipidol. 2008 December; 3: 637–649

OxLDL association with future metabolic

syndrome

Rao et al. Cardiology Research and Practice. 2011

Indian Atherosclerosis Study

2316 patients without CAD

The CVD Risk Panel

15

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Baseline hsCRP levels in apparently healthy

men can predict the risk of first myocardial

infarction or ischemic stroke1

1Ridker PM et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997; 336: 973-979.

Physicians’ Health Study

• 1,086 men (>8 yrs)

• hsCRP measured at baseline

hsCRP is a stronger predictor of cardiovascular

events in women than LDL-C and adds prognostic

information to Framingham risk scores1

1Ridker PM et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the

prediction of first cardiovascular events. N Engl J Med. 2002; 347: 1557-1565.

Women’s Health Study

• 28,345 women (8 yrs.; 15,745 were

not on HRT)

• hsCRP and LDL-C measured at

baseline

Elevated levels of microalbuminuria are a robust

independent continuous risk factor for

cardiovascular events and death1

The HOPE study

• 5,545 (w/o DM ;

history of CVD)

• 3,498 (w/ DM + at

lease 1 risk factor)

1Gerstein HC et al. Albuminuria and risk of cardiovascular events, death, and heart failure in

diabetic and non-diabetic individuals. JAMA. 2001; 286: 421-426.

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The CVD Risk Panel

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What does Lp-PLA2 measure?

• The amount of plaque within the artery wall due to

accumulation of oxidized LDL

Lipoprotein-Associated Phospholipase-A2

(Lp-PLA2; The PLAC® Test)

Clinical implications of The PLAC® Test

1Ballantyne CM et al. Lp-PLA2, hsCRP, and risk for incident coronary artery disease in middle-aged men and

women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 2004; 109: 837-842.

• Elevated Lp-PLA2 levels are independently associated with

high stroke risk in individuals who have low LDL-C levels

The ARIC study

• 960 middle-aged men

and women

• Follow-up ~6-8 yrs.

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Log-rank test: p=0.007

First tertile (lowest)

Second tertile

Third tertile (highest)

HR: 2.38 (95% CI: 1.47-2.98) for

top vs bottom MPO tertile

1Modified from Heslop CL et al. Myeloperoxidase and C-reactive protein have combined utility for long-term

prediction of cardiovascular mortality after coronary angiography. J Am Coll Cardiol . 2010; 55:1102-1109.

Elevated MPO levels predict cardiovascular

mortality at 13 yrs in patients with angiographic

evidence of CAD1

Log-rank test: p<0.001 for trend

MPO CRP

Low and Low

High or High

High and High

Patients with either a high

MPO or high CRP elevated had 5.3-fold higher mortality risk

Patients with high levels of

both MPO and CRP had a 4.3-fold risk vs. patients with

only one elevated marker

1Modified from Heslop CL et al. Myeloperoxidase and C-reactive protein have combined utility for long-term

prediction of cardiovascular mortality after coronary angiography. J Am Coll Cardiol . 2010; 55:1102-1109.

MPO and CRP have combined utility in predicting

cardiovascular mortality risk in patients with

angiographic evidence of CAD1

Lp-PLA2 and MPO identify

unique patients

Highest Risk

Vessel Wall

Risk

WBC Risk

MPO

PL

A2

6.2%

5.2%

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Anatomical and biological assessment of

cardiovascular risk

• Anatomy is important but hard to follow

• Biology is important and can be measured

routinely

• Additive risk stratification

Anatomical and biological assessment of

cardiovascular risk

• Anatomy is important but hard to follow

• Biology is important and can be measured

routinely

• Additive risk stratification

1Wong ND et al. Myeloperoxidase, subclinical atherosclerosis, and cardiovascular disease events. J Am

Coll Cardiol Img. 2009; 2: 1093-1099.

In apparently healthy individuals, mean MPO levels

were greater according to increasing CAC categories,

and the risk for CVD increased by quartiles of MPO1

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• In apparently healthy individuals, moderate and significant

CAC (100) and MPO levels (257 pm) demonstrated

increased risk for CVD1

MPO levels 257 pm

remained an independent

predictor of CVD events

even after adjusting for

various risk factors

(HR: 1.9, p=0.04)

Clinical implications of MPO testing

1Wong ND et al. Myeloperoxidase, subclinical atherosclerosis, and cardiovascular

disease events. J Am Coll Cardiol Img. 2009; 2: 1093-1099.

1Modified from Brevetti G et al. Myeloperoxidase, but not C-reactive protein, predicts

cardiovascular risk in peripheral arterial disease. Eur Heart J. 2008; 29: 224-230.

MPOx >183.7 pM had higher

hsCRP levels versus MPOx

≤183.7 pM

Elevated MPO levels predict a significantly

higher incidence of cardiovascular events in

patients with PAD1

1Modified from Brevetti G et al. Myeloperoxidase, but not C-reactive protein, predicts

cardiovascular risk in peripheral arterial disease. Eur Heart J. 2008; 29: 224-230.

Measurement of MPO, in addition to ABI,

improved the ability to identify PAD patients at

risk for MI and stroke1

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Hypertension Diabetes

& Obesity

Lipids &

Oxidation Coagulation

& Genetics

31

Year Long Approach Allows for Greater Engagement

with the Patient and Targeted Biomarker Testing

Myeloperoxidase

Lp-PLA2 (The PLAC® Test)

hsCRP

Urinary Microalbumin

OxLDL

F2-Isoprostanes, OxLDL

Target Risk

Factor Hypertension

Diabetes/

Obesity

Lipids/

Oxidation

Coagulation/

Genetics

Biomarker

Galectin-3

NT-proBNP

CMP

Vitamin D

Cystatin C

HbA1c

Adiponectin

Insulin

hsTNT

OGTT

NASH

Haptoglobin

Std. Lipid Panel

sdLDL

ApoB

ApoA1

CoQ10

dysHDL

Omega 3 & 6

Lp(a)

Factor V Leiden

Factor II

CYP2C19

ApoE

AspirinWorks®

32

0

10

20

30

AbnormalCholesterol

Hardened Arteries Increased RiskActive Plaque

Active HardenedArteries

Active Vessel Walland White Cell

Response

Pe

rce

nt P

art

icip

atin

g A

tte

nd

ee

s (%

)

121 135

13 24

1

All these patients have normal LDL cholesterol

Increasing Risk

LDL > 130 +hsCRP

+MPO

or

+Lp-PLA2

+MPO or

+Lp-PLA2

and

+hsCRP

+MPO

and

+Lp-PLA2

531 Patients at Symposium in Nashville

2/11/2014

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Questions


of PAML LLC

We offer the Heart Inflammation Panel as well

as the individual test components introduced

today

Test Code – HRTINF

Specimen Type – serum, random urine and

EDTA plasma

TAT – 3 - 7 days

Contact for questions – Client Services or your

sales representative

PAML Heart Inflammation Test Information


of PAML LLC

P.A.C.E. credit may be obtained by submitting

your completed evaluation form. You will find the

form by clicking on the “handouts” icon in the

upper right hand corner of your screen

CE credit may be obtained by downloading the

“Certificate of Completion” under the “handouts”

icon

PAML employees will be able to receive one hour

of continuing education credit by submitting your

attendance through CE Manager.

Thank You for Attending

2/11/2014

13


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Thank You for Attending

We will be leaving the webinar open for 15

minutes to allow you to download the handouts

This webinar has been recorded and will be

available by Tuesday, February 18th, at

www.paml.com

PAML’s next webinar is scheduled for May 13,

12:30 p.m. – 1:30 p.m. (PT)

Please send ideas for future webinar topics.

Documents

Welcome [] · both MPO and CRP had a 4.3-fold risk vs. patients with only one elevated marker 1Modified from Heslop CL et al. Myeloperoxidase and C-reactive protein have combined