Heslop, P. , & Glover, G. (2015). Mortality of people with ...
Welcome [] · both MPO and CRP had a 4.3-fold risk vs. patients with only one elevated marker...
Transcript of Welcome [] · both MPO and CRP had a 4.3-fold risk vs. patients with only one elevated marker...
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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Your Host: Karen Riba
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use the “Q & A” link at the top of your screen
Questions will be answered at the end of the
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Welcome
This presentation is not to be copied or distributed without the specific permission
of PAML LLC
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.
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This presentation is not to be copied or distributed without the specific permission
of PAML LLC
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
This presentation is not to be copied or distributed without the specific permission
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
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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
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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
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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®
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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
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This presentation is not to be copied or distributed without the specific permission
of PAML LLC
Questions
This presentation is not to be copied or distributed without the specific permission
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
This presentation is not to be copied or distributed without the specific permission
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
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This presentation is not to be copied or distributed without the specific permission
of PAML LLC
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)
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