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VAP+ Lipid Profiling
Comprehensive Lipid Profiling to Personalize
Treatment and Improve Outcomes
Presentation Overview

Cardiometabolic
Disease: Current
Challenges and
Methodology
Limitations

Advancements
in
Cardiovascular
Risk
Assessment: The
VAP+
Lipid Panel
Your Partner for
Cardiometabolic
Disease
Management:
Personalized
Treatment and
Patient Education

VAP+ Lipid Panel:
Clinical Evidence
Continues
to Substantiate
VAP Technology

2
Cardiometabolic Disease
Current Challenges
and Methodology Limitations
CVD Is an Epidemic

Cardiovascular
Disease

Metabolic
Disease

• 1 in 3 US adults has 1 or more types of CVD1
• Heart disease accounts for 25% of all US mortalities2
• 811,940 yearly deaths from CVD
• CVD kills more women each year than the next 3 causes
of death combined3

• Diabetes affects 25.8 million people of the US population
• Diabetes markedly increases the risk of MI, stroke, amputation, and death
as a result of metabolic abnormalities4
• At least 65% of people with diabetes die from some form of heart disease
or stroke5
• NCEP ATP III established diabetes as a CVD risk equivalent in mandating
aggressive antiatherosclerotic therapy4,6

NCEP ATP III=National Cholesterol Education Program Adult Treatment Panel III.
1.
2.
3.

Roger VL, et al. Circulation. 2011;123(4):e18-e209.
Gutstein DE, et al. Clin Pharmacol Ther. 2012;91(1).
WomenHeart. Available at: http://c.ymcdn.com/sites/www.womenheart.org/resource/
resmgr/docs/women,_heart_disease,_and_di.pdf. Accessed September 4, 2013.

4.
5.
6.

Beckman JA, et al. JAMA. 2002;287(19).
NDEP. Available at: http://ndep.nih.gov/media/CVD_FactSheet.pdf.
Accessed August 13, 2013.
NCEP Adult Treatment Panel III. Circulation. 2002;106(25):3143-3421.

4
Defining Cardiometabolic Risk
Assessing cardiometabolic risk is necessary
to establish personalized treatment strategies to improve outcomes
Metabolic Syndrome
Traditional
Risk Factors

• Abdominal obesity
• Hypertriglyceridemia
•  HDL-C
•  Blood pressure
•  Glycemia or diabetes

• Age
• Family history
• Gender
•  Blood pressure
•  Cholesterol
• Diabetes
• Smoking

Nontraditional
Risk Factors
• Genetics
• Prothrombotic state
• Inflammatory profile

Cardiometabolic Risk
Evidence-based guidelines recommend a personalized treatment strategy through
cardiometabolic risk stratification and comprehensive lipid profiling.
Adapted from: Tremblay M, et al. J Can Dent Assoc. 2011;77:b125.

5
Accurate CVD Identification and Management
Remain a Challenge
•
•
•
•

CVD remains challenging to diagnose, treat, and prevent1
Many patients do not achieve therapeutic goals for LDL-C, HDL-C, and TGs2
Statin adherence is <50% after 4 years in patients 65 and older3
Basic lipid panel utilization of the Friedewald formula significantly
underestimates LDL-C and may lead to undertreatment of at-risk patients4

50% of men and
64% of women
who die suddenly
from heart disease
have no previous
warning signs5

50% of people
who have a CVD
event have
normal cholesterol6

Estimated values
from basic lipid
panels miss 60%
of those at risk
for CVD4

TG=triglycerides.
1.
2.
3.

Roger VL, et al. Circulation. 2011;123(4):e18-e209.
Stacy TA, Egger A. J Manag Care Pharm. 2006;12(9).
Bemmer JS, et al. JAMA 2002;288.

4.
5.
6.

Martin SS, et al. J Am Coll Cardiol. 2013.
Gutstein DE, et al. Clin Pharmacol Ther. 2012;91(1).
Sachdeva A, et al. Am Heart J. 2009;157(1):111-117 e112.

6
The Basic Lipid Panel Fails to Identify 60%
of At-Risk Patients
Basic Lipid Panel
Does Not Identify 60%
of Those at Risk for CVD

• BLP developed by Friedewald in 19721
• Generally agreed to be inaccurate in non-fasting
state and when

-70

• Problematic patients for BLP/Friedewald include 5
◦
◦
◦
◦
◦
◦

Frederickson class I, III, or V hyperlipoproteinemia1
Nonselective beta blocker users
Diabetes, insulin resistance, or metabolic syndrome
Liver disease
Nephrotic syndrome or chronic renal insufficiency
Hormone replacement6

% Error in LDL-C

-60

◦ Fasting 12 hours
◦ TG 150 mg/dL2-3
◦ LDL-C 100 mg/dL4

-50
-40

-30
-20
-10
0
<100 mg/dL

100-149
mg/dL

150-199
mg/dL

200-399
mg/dL

Triglycerides

1.
2.
3.

Friedewald WT, et al. Clin Chem. 1972;18(6).
Lindsey CC, et al. Pharmacotherapy. 2004;24(2).
Martin SS, et al. J Am Coll Cardiol. 2013.

4.
5.
6.

Scharnagl H, et al. Clin Chem Lab Med. 2001;39(5):426-431.
NCEP ATP III. Circulation. 2002;106(25).
Legault C, et al. J Clin Epidemiol. 1999;52(12).

7
Magnitude of Underestimation
in the basic lipid panel/Friedewald LDL-C
In the Johns Hopkins VLDL study of 1.3 million adults, misclassification of VLDL was significant in
the following classes of patients:
• Patients with abnormal TG levels: 25-60% should be reclassified into a higher risk category
• Patients with normal TG levels: 10-20% should be reclassified into a higher risk category

60

Discordance in BLP/Friedewald and Direct LDL-C by TG
59.4%
Strata
51.9%

50
LDL-C 70-99 mg/dL

39.1%

Error (%)

40

39.1 %

n=13,265

n=10,838

LDL-C <70 mg/dL

30
20.3%

20
10.4%

10
0

n=8042

n=2678

<100 mg/dL

n=11,456

n=10,544

100-149 mg/dL

150-199 mg/dL

n=24,988

n=19,677

200-399 mg/dL

Triglycerides

The basic lipid panel misclassifies patient risk
Martin SS, et al. J Am Coll Cardiol. 2013.

8
Advancements in
Cardiovascular Risk Assessment:
The VAP+ Lipid Panel
Interactive Question
What are the emerging risk factors outlined in the
national guidelines?
1. Lp(a)
2. Small LDL pattern
3. ApoB and remnant lipoproteins
4. All of the above

10
Evidence-Based Guidelines Recommend
Comprehensive Risk Factor Assessment
• LDL-C accounts for 30% of the risk of premature CVD, while the remaining 70%
represents residual risk factors1
• Residual risk can be attributed to LDL-C subclasses, remnant lipoproteins, and other
HDL-C components2-4
• Cardiometabolic risk stratification and personalized approach to management
are recommended2-4
National Guidelines2-5
• Direct LDL-C measurement
• Secondary targets of therapy
◦ Non–HDL-C and metabolic syndrome
• Emerging risk factors
◦ Lp(a), HDL-C subclasses, small LDL pattern, ApoB, and remnant lipoproteins

VAP+ is the first comprehensive lipid profile
to comply with NCEP ATP III, ADA, and AACE guidelines
1.
2.
3.

Kreisberg RA, Oberman A. J Clin Endocrinol Metab. 2002;87(2).
NCEP ATP III. Circulation. 2002;106(25).
Brunzell JD, et al. Diabetes Care. 2008;31(4).

4.
5.

Grundy SM, et al. Circulation. 2004;110(2).
Jellinger PS, et al. Endocr Pract. 2012;18(suppl 1):

11
The Comprehensive VAP+ Lipid Panel
Is Essential to Cardiometabolic Risk Stratification
• The VAP+ Lipid Panel provides the most accurate risk
assessment, enabling personalized treatment based on 3 key
indicators not measured by the basic lipid panel

Heredity
Identifies Lp(a),
a hereditary marker
of risk

Cholesterol
Directly measures
LDL-C, LDL-P,
and HDL-C

Triglycerides
Identifies TG-rich disorders, including
non–HDL-C, even in patients with
seemingly normal TG levels

12
HEREDITY
TRIGLYCERIDES
CHOLESTEROL

VAP+ Lipid Panel Uncovers Residual
Cardiometabolic Risk and Drives Personalized Therapy
CVD RISK ASSESSMENT
The CVD Risk Assessment
LDL
TGs
LOWER Lp(a)
gives a snapshot of the
• Consider LDL-C
Statins acid
patient’s cardiovascular
Nicotinic
risk. • goals below
Caution 3
• Resins markers on
Omega
the side indicate risk level;
• current guidelines
Cholesterol
fatty acids
absorption
• Consider
additional information in
• Fibric acid
inhibitors
nicotinic acid
the sections below further
• Low-sugar diet
• Consider risk.
Diet low in
clarifies patient baby
• aspirin if not
Exercise fat
saturated
and fried food
contraindicated
• Exercise

The VAP+ Lipid Panel offers detailed results that
enable personalized treatment to directly target
underlying problems
13
Global Risk Assessment Mandates
VAP+ Technology
• The VAP+ Lipid Panel uses direct measurement by ultracentrifugation;
therefore, is accurate in non-fasting or fasting patients
• All lipoproteins are physically separated and reacted with an enzymatic
cholesterol reagent, measuring all lipoproteins directly, which increases
the accuracy of the method1

• VAP+ simultaneously measures cholesterol concentrations of ALL
5 lipoprotein classes
The VAP+ Lipid Panel now includes the proprietary
Vertical Lipoprotein Particle (VLP+) technology, which allows
for accurate particle measurement

1.

Kulkarni KR. Clin Lab Med. 2006;26(4).

14
Lipoprotein Metabolism
Treatment Options:

Omega 3 Fatty Acids

Statins, Bile Acid
Sequestrants, Ezetimibe

Fibrate, Niacin, Omega 3 Fatty Acids

Large, Buoyant
Pattern A

VLDL

Healthy
Food

IDL

LDL

Chylomicrons

Small
Intestines
intestines

Liver
Lp(a)

Atherogenic
Small, Dense
Pattern B

Unhealthy
Food

LDL
Chylomicrons
VLDL1+2

VLDL3

IDL

(Increased LDL-P
Concentration)

15
VAP+ Lipid Panel:
The Importance of LDL Pattern
• LDL patterns carry different CHD risks

Pattern A: Characterized by
larger, more buoyant
lipoprotein particles (LDL1,2)1

Pattern B: Characterized by
smaller, denser lipoprotein
particles (LDL3,4)1

• Although total LDL-C concentration can be similar in pattern A or B patients, pattern B
patients present with a higher concentration of LDL-P2
• Pattern B particles are more easily taken up by arterial tissue than pattern A particles 2
• Due to altered properties of the surface lipid layer, pattern B particles are more
susceptible to oxidation2

1.
2.

Austin MA, et al. Circulation. 1990;82(2).
Rizzo M, Berneis K. QJM. 2006;99(1).

16
Significance of LDL Particle Concentration
• This animation illustrates that 2 individuals with the same total
LDL-C can have different LDL-P concentrations, leading to different
CHD risk levels

Pattern A
B

Individuals with high LDL-P
Individuals with low
have predominantly small and dense
usually have large, buoyant, pattern A
pattern B LDL-C particles
LDL-C particles
*Note both individuals have same amount of TC.

17
LDL Particle Concentration Indicates Risk
• In practical application, 2 patients have identical LDL-C—which
patient is at greater risk?
Lower Risk

Higher Risk

B
20 mg/dL

A
100 mg/dL
Large LDL-C
(Pattern A)

LDL-C=100 mg/dL
LDL-P=1100 nmol/L

B
20 mg/dL

B
20 mg/dL

B
20 mg/dL

B
20 mg/dL

Small LDL-C
(Pattern B)

LDL-C=100 mg/dL
LDL-P=1800 nmol/L

Assessment of true LDL-P using the VAP+ Lipid Panel allows for isolation of the actual cause
of increased total LDL-P number to help personalize treatment and improve outcomes
18
Appropriate Patients to Consider for VAP+ Testing

Moderate- and
higher-risk
individuals and
those at risk
for CVD

Any patient with
NCEP ATP III
risk factors
(5 established):
• Family history of
premature CHD
• Age (men 45
years; women
55 years)
• Cigarette smoking
• Hypertension
• Low HDL-C
( 40 mg/dL)

Established
atherosclerotic
vascular disease

Diabetes mellitus
and/or metabolic
syndrome

Framingham Risk
Score (FRS)
over 5% or
Reynolds
Risk Score

An elevated
inflammatory
biomarker

19
VAP+ Lipid Panel
Clinical Evidence Continues
to Substantiate VAP Technology
Interactive Question
Which of the following is true about residual risk after
statin therapy?
1. Residual risk for CVD remains despite a significant reduction
in CV events and mortality with statin therapy.
2. Substantial residual risk persists even after patients are treated
with intensive statin therapy to reduce LDL-C.
3. High TGs and low levels of HDL-C appear to be major contributors
to residual risk, even at optimal LDL-C levels.
4. All of the above are correct.
21
VAP+ Lipid Panel Evidence Summary
HDL-C subclass is
an independent risk factor

The basic lipid panel
misclassifies CVD risk
• The BLP/Friedewald formula consistently
underestimates LDL-C, resulting in
undertreatment of high-risk patients1

• Framingham Heart Study: Increased
HDL3-C revealed a 40% lower risk for
CHD and 36% lower risk for hard CHD4
(primary prevention)

• Intermountain Heart Collaborative Study:
A large percentage of patients with heart
disease remain at high residual risk despite
having achieved basic lipid panel target
LDL-C treatment goals2
(secondary prevention)

• TRIUMPH Study: Low HDL3-C revealed
a 50% higher mortality risk5
(secondary prevention)
• Jackson Heart Study: Increased HDL3-C
revealed a 68% lower risk for hard CHD
and a 35% lower risk for CHD6
(primary prevention)

• Low HDL2-C reveals CV risk in 6 times as
many patients as the basic lipid panel3
(primary prevention)

1.
2.
3.

Martin SS, et al. J Am Coll Cardiol. 2013.
May HT, et al. Presented at: ACC 59th Annual Scientific Sessions; 2010.
Sailam V, et al. Clin Cardiol. 2008;31(11):542-545.

4.
5.
6.

Toth P. et al Impact of HDLC and its subfractions. 2012.
Martin SS. Presented at: AHA Scientific Sessions; 2012.
Joshi P, et al. Presented at: AHA Scientific Sessions; 2012.

22
VAP+ Lipid Panel Evidence Summary
Remnant lipoproteins predict heart attack risk
• Jackson Heart Study: Remnant lipoproteins are 28% more likely to reveal a significant, independent
risk factor for heart attack1 (primary prevention)
• Framingham Heart Study: Remnant lipoproteins were an independent risk factor for incident CHD
events2 (primary prevention)
• Framingham Heart Study: Pattern B revealed double the risk for hard CHD and a 40% increased risk
for CHD3 (primary prevention)
• Atherogenic lipoprotein phenotype (LDL-C pattern B) reveals double the risk for hard CHD and 40%
increased risk for CHD and is strongly associated with CIMT progression4

Elevated Lp(a) plays a significant role in atherogenesis and is closely
associated with HDL-C, VLDL-C, and TGs
• Studies by Konerman’s group utilizing the VAP+ cholesterol test have shown that Lp(a) is strongly
associated with markers of HDL-C, VLDL-C, and TGs, and highlight Lp(a)’s role in atherogenesis5
(primary and secondary prevention)
CIMT=carotid intima media thickness.
1.
2.

Khokar A, et al. J Am Coll Cardiol. 2013;61(10S).
Toth PP, et al. Presented at: ACC Scientific Sessions; 2013. Impact of Lipoprotein Remnants
on 12 Year Risk for CHD in the Framingham Offspring Population.

3.
4.
5.

Toth PP. Presented at: AHA Scientific Sessions; 2012. Impact of LDL patterns on risk for CHD
in the Framingham Offspring Population.
Maki KC, et al. Vasc Health Risk Manag. 2012;8.
Konerman M, et al. J Clin Lipidol. 2012;6(1).

23
VAP+ Lipid Panel Improves Outcomes
and Reduces Cost for Managed Care
• Use of the VAP+ Lipid Panel permitted WellMed Medical Group to
detect more cases of dyslipidemia than the basic lipid panel, enabling
more appropriate and effective therapy to be prescribed
and, ultimately, leading to better outcomes1,2
◦ Repeated VAP testing and therapy adjustments led to lower LDL-C, higher
HDL3-C, reduced inpatient (IP) stays, and fewer emergency department (ED) visits
Utilization and Cost Comparisons

IMPROVED
PATIENT
OUTCOMES
REDUCED COSTS
TO MANAGED
CARE BY

35%

VAP
Test
Group

Control

Test
Results

P-Value

Mean total cost
year 1

$4307.70

$5146.02

-1.34*

0.1157

Mean total cost
year 2

$4852.62

$7413.18

-2.24*

0.0255

Mean ED cost
both years

$22.24

$33.15

-1.92*

0.0561

Mean IP cost
both years

$732.80

$876.20

-1.80*

0.0722

Cost

*t-test.
1.
Atherotech Inc. Available at: http://www.atherotech.com/information/viewinformation.asp?informationid=179. Accessed August 13, 2012.
2.
McAna JF, et al. Popul Health Manag. 2012;15(1).

24
Improving Health Outcomes
Through Cardiometabolic
Testing and Patient Education
Our Healthy Heart Patient Education Program
Our Healthy Heart is a unique service offered by
Atherotech at no additional charge with a
VAP+ Lipid Panel.

The service provides patients with personalized
lifestyle modification education, compliance
strategies, and coaching from licensed health
coaches to promote heart health through the
continuum of care.

Our licensed health coaches can design a
personalized program based on physician
recommendations, patient needs, and
VAP+ results.
Call 1-866-VAP-TEST or 1-866-827-8378
toll-free to enroll your patient.

26
Atherotech Offers Customizable Disease
State Panels
These disease state panels are provided as
examples only. Physicians should only order
tests that are medically necessary and
reasonable for the diagnosis or treatment of a
patient for which reimbursement is claimed. All
tests included in Atherotech panels or physiciancreated panels may be ordered individually.

Through proprietary technologies, including
the VAP+ Lipid Panel, Atherotech supports a
full offering of disease state panels that can
be customized by the clinician.

CARDIOMETABOLIC AND GENETIC TESTS FROM ATHEROTECH
CVD Risk Panel
•
•
•
•
•
•

VAP+ Lipid Panel
CMP
Lp-PLA2
Hs-CRP
Homocysteine
Cystatin C

CVD Treatment
Panel
•
•
•
•
•
•
•
•

VAP+ Lipid Panel
CMP
Lp-PLA2
Hs-CRP
Homocysteine
Cystatin C
TSH
Uric acid

Diabetes/Metabolic
Syndrome Panel
•
•
•
•
•
•
•
•

VAP+ Lipid Panel
CMP
A1C
GlycoMark
GGT
Uric acid
Cystatin C
Insulin

Heart Failure
Panel
•
•
•
•
•

VAP+ Lipid Panel
BMP
NTproBNP
Galectin 3
Cystatin C

Myalgia Panel
•
•
•
•
•

VAP+ Lipid Panel
B12
TSH
Vitamin D
Uric acid

27
In Conclusion
Comprehensive care is essential to effectively manage cardiometabolic risk and
improve outcomes

Basic lipid panels have led to misclassification of as many as 60% of
patients, potentially resulting in ineffective treatment for patients most at risk
Evidence-based guidelines recommend cardiometabolic risk stratification via
comprehensive cholesterol profiling so a personalized treatment strategy can
be implemented
The VAP+ Lipid Panel uncovers residual cardiometabolic risk, which provides
actionable information to improve patient outcomes
Atherotech provides over 100 routine and cardiometabolic specialty tests and
customizable disease state panels to offer clinicians a single source laboratory

Atherotech goes beyond diagnostics to offer personalized provider and patient
education for disease management

28
“If something doesn’t
make sense perhaps you
should look further”.

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Atherotech VAP+ cardiovascular testing

  • 1. VAP+ Lipid Profiling Comprehensive Lipid Profiling to Personalize Treatment and Improve Outcomes
  • 2. Presentation Overview Cardiometabolic Disease: Current Challenges and Methodology Limitations Advancements in Cardiovascular Risk Assessment: The VAP+ Lipid Panel Your Partner for Cardiometabolic Disease Management: Personalized Treatment and Patient Education VAP+ Lipid Panel: Clinical Evidence Continues to Substantiate VAP Technology 2
  • 4. CVD Is an Epidemic Cardiovascular Disease Metabolic Disease • 1 in 3 US adults has 1 or more types of CVD1 • Heart disease accounts for 25% of all US mortalities2 • 811,940 yearly deaths from CVD • CVD kills more women each year than the next 3 causes of death combined3 • Diabetes affects 25.8 million people of the US population • Diabetes markedly increases the risk of MI, stroke, amputation, and death as a result of metabolic abnormalities4 • At least 65% of people with diabetes die from some form of heart disease or stroke5 • NCEP ATP III established diabetes as a CVD risk equivalent in mandating aggressive antiatherosclerotic therapy4,6 NCEP ATP III=National Cholesterol Education Program Adult Treatment Panel III. 1. 2. 3. Roger VL, et al. Circulation. 2011;123(4):e18-e209. Gutstein DE, et al. Clin Pharmacol Ther. 2012;91(1). WomenHeart. Available at: http://c.ymcdn.com/sites/www.womenheart.org/resource/ resmgr/docs/women,_heart_disease,_and_di.pdf. Accessed September 4, 2013. 4. 5. 6. Beckman JA, et al. JAMA. 2002;287(19). NDEP. Available at: http://ndep.nih.gov/media/CVD_FactSheet.pdf. Accessed August 13, 2013. NCEP Adult Treatment Panel III. Circulation. 2002;106(25):3143-3421. 4
  • 5. Defining Cardiometabolic Risk Assessing cardiometabolic risk is necessary to establish personalized treatment strategies to improve outcomes Metabolic Syndrome Traditional Risk Factors • Abdominal obesity • Hypertriglyceridemia •  HDL-C •  Blood pressure •  Glycemia or diabetes • Age • Family history • Gender •  Blood pressure •  Cholesterol • Diabetes • Smoking Nontraditional Risk Factors • Genetics • Prothrombotic state • Inflammatory profile Cardiometabolic Risk Evidence-based guidelines recommend a personalized treatment strategy through cardiometabolic risk stratification and comprehensive lipid profiling. Adapted from: Tremblay M, et al. J Can Dent Assoc. 2011;77:b125. 5
  • 6. Accurate CVD Identification and Management Remain a Challenge • • • • CVD remains challenging to diagnose, treat, and prevent1 Many patients do not achieve therapeutic goals for LDL-C, HDL-C, and TGs2 Statin adherence is <50% after 4 years in patients 65 and older3 Basic lipid panel utilization of the Friedewald formula significantly underestimates LDL-C and may lead to undertreatment of at-risk patients4 50% of men and 64% of women who die suddenly from heart disease have no previous warning signs5 50% of people who have a CVD event have normal cholesterol6 Estimated values from basic lipid panels miss 60% of those at risk for CVD4 TG=triglycerides. 1. 2. 3. Roger VL, et al. Circulation. 2011;123(4):e18-e209. Stacy TA, Egger A. J Manag Care Pharm. 2006;12(9). Bemmer JS, et al. JAMA 2002;288. 4. 5. 6. Martin SS, et al. J Am Coll Cardiol. 2013. Gutstein DE, et al. Clin Pharmacol Ther. 2012;91(1). Sachdeva A, et al. Am Heart J. 2009;157(1):111-117 e112. 6
  • 7. The Basic Lipid Panel Fails to Identify 60% of At-Risk Patients Basic Lipid Panel Does Not Identify 60% of Those at Risk for CVD • BLP developed by Friedewald in 19721 • Generally agreed to be inaccurate in non-fasting state and when -70 • Problematic patients for BLP/Friedewald include 5 ◦ ◦ ◦ ◦ ◦ ◦ Frederickson class I, III, or V hyperlipoproteinemia1 Nonselective beta blocker users Diabetes, insulin resistance, or metabolic syndrome Liver disease Nephrotic syndrome or chronic renal insufficiency Hormone replacement6 % Error in LDL-C -60 ◦ Fasting 12 hours ◦ TG 150 mg/dL2-3 ◦ LDL-C 100 mg/dL4 -50 -40 -30 -20 -10 0 <100 mg/dL 100-149 mg/dL 150-199 mg/dL 200-399 mg/dL Triglycerides 1. 2. 3. Friedewald WT, et al. Clin Chem. 1972;18(6). Lindsey CC, et al. Pharmacotherapy. 2004;24(2). Martin SS, et al. J Am Coll Cardiol. 2013. 4. 5. 6. Scharnagl H, et al. Clin Chem Lab Med. 2001;39(5):426-431. NCEP ATP III. Circulation. 2002;106(25). Legault C, et al. J Clin Epidemiol. 1999;52(12). 7
  • 8. Magnitude of Underestimation in the basic lipid panel/Friedewald LDL-C In the Johns Hopkins VLDL study of 1.3 million adults, misclassification of VLDL was significant in the following classes of patients: • Patients with abnormal TG levels: 25-60% should be reclassified into a higher risk category • Patients with normal TG levels: 10-20% should be reclassified into a higher risk category 60 Discordance in BLP/Friedewald and Direct LDL-C by TG 59.4% Strata 51.9% 50 LDL-C 70-99 mg/dL 39.1% Error (%) 40 39.1 % n=13,265 n=10,838 LDL-C <70 mg/dL 30 20.3% 20 10.4% 10 0 n=8042 n=2678 <100 mg/dL n=11,456 n=10,544 100-149 mg/dL 150-199 mg/dL n=24,988 n=19,677 200-399 mg/dL Triglycerides The basic lipid panel misclassifies patient risk Martin SS, et al. J Am Coll Cardiol. 2013. 8
  • 9. Advancements in Cardiovascular Risk Assessment: The VAP+ Lipid Panel
  • 10. Interactive Question What are the emerging risk factors outlined in the national guidelines? 1. Lp(a) 2. Small LDL pattern 3. ApoB and remnant lipoproteins 4. All of the above 10
  • 11. Evidence-Based Guidelines Recommend Comprehensive Risk Factor Assessment • LDL-C accounts for 30% of the risk of premature CVD, while the remaining 70% represents residual risk factors1 • Residual risk can be attributed to LDL-C subclasses, remnant lipoproteins, and other HDL-C components2-4 • Cardiometabolic risk stratification and personalized approach to management are recommended2-4 National Guidelines2-5 • Direct LDL-C measurement • Secondary targets of therapy ◦ Non–HDL-C and metabolic syndrome • Emerging risk factors ◦ Lp(a), HDL-C subclasses, small LDL pattern, ApoB, and remnant lipoproteins VAP+ is the first comprehensive lipid profile to comply with NCEP ATP III, ADA, and AACE guidelines 1. 2. 3. Kreisberg RA, Oberman A. J Clin Endocrinol Metab. 2002;87(2). NCEP ATP III. Circulation. 2002;106(25). Brunzell JD, et al. Diabetes Care. 2008;31(4). 4. 5. Grundy SM, et al. Circulation. 2004;110(2). Jellinger PS, et al. Endocr Pract. 2012;18(suppl 1): 11
  • 12. The Comprehensive VAP+ Lipid Panel Is Essential to Cardiometabolic Risk Stratification • The VAP+ Lipid Panel provides the most accurate risk assessment, enabling personalized treatment based on 3 key indicators not measured by the basic lipid panel Heredity Identifies Lp(a), a hereditary marker of risk Cholesterol Directly measures LDL-C, LDL-P, and HDL-C Triglycerides Identifies TG-rich disorders, including non–HDL-C, even in patients with seemingly normal TG levels 12
  • 13. HEREDITY TRIGLYCERIDES CHOLESTEROL VAP+ Lipid Panel Uncovers Residual Cardiometabolic Risk and Drives Personalized Therapy CVD RISK ASSESSMENT The CVD Risk Assessment LDL TGs LOWER Lp(a) gives a snapshot of the • Consider LDL-C Statins acid patient’s cardiovascular Nicotinic risk. • goals below Caution 3 • Resins markers on Omega the side indicate risk level; • current guidelines Cholesterol fatty acids absorption • Consider additional information in • Fibric acid inhibitors nicotinic acid the sections below further • Low-sugar diet • Consider risk. Diet low in clarifies patient baby • aspirin if not Exercise fat saturated and fried food contraindicated • Exercise The VAP+ Lipid Panel offers detailed results that enable personalized treatment to directly target underlying problems 13
  • 14. Global Risk Assessment Mandates VAP+ Technology • The VAP+ Lipid Panel uses direct measurement by ultracentrifugation; therefore, is accurate in non-fasting or fasting patients • All lipoproteins are physically separated and reacted with an enzymatic cholesterol reagent, measuring all lipoproteins directly, which increases the accuracy of the method1 • VAP+ simultaneously measures cholesterol concentrations of ALL 5 lipoprotein classes The VAP+ Lipid Panel now includes the proprietary Vertical Lipoprotein Particle (VLP+) technology, which allows for accurate particle measurement 1. Kulkarni KR. Clin Lab Med. 2006;26(4). 14
  • 15. Lipoprotein Metabolism Treatment Options: Omega 3 Fatty Acids Statins, Bile Acid Sequestrants, Ezetimibe Fibrate, Niacin, Omega 3 Fatty Acids Large, Buoyant Pattern A VLDL Healthy Food IDL LDL Chylomicrons Small Intestines intestines Liver Lp(a) Atherogenic Small, Dense Pattern B Unhealthy Food LDL Chylomicrons VLDL1+2 VLDL3 IDL (Increased LDL-P Concentration) 15
  • 16. VAP+ Lipid Panel: The Importance of LDL Pattern • LDL patterns carry different CHD risks Pattern A: Characterized by larger, more buoyant lipoprotein particles (LDL1,2)1 Pattern B: Characterized by smaller, denser lipoprotein particles (LDL3,4)1 • Although total LDL-C concentration can be similar in pattern A or B patients, pattern B patients present with a higher concentration of LDL-P2 • Pattern B particles are more easily taken up by arterial tissue than pattern A particles 2 • Due to altered properties of the surface lipid layer, pattern B particles are more susceptible to oxidation2 1. 2. Austin MA, et al. Circulation. 1990;82(2). Rizzo M, Berneis K. QJM. 2006;99(1). 16
  • 17. Significance of LDL Particle Concentration • This animation illustrates that 2 individuals with the same total LDL-C can have different LDL-P concentrations, leading to different CHD risk levels Pattern A B Individuals with high LDL-P Individuals with low have predominantly small and dense usually have large, buoyant, pattern A pattern B LDL-C particles LDL-C particles *Note both individuals have same amount of TC. 17
  • 18. LDL Particle Concentration Indicates Risk • In practical application, 2 patients have identical LDL-C—which patient is at greater risk? Lower Risk Higher Risk B 20 mg/dL A 100 mg/dL Large LDL-C (Pattern A) LDL-C=100 mg/dL LDL-P=1100 nmol/L B 20 mg/dL B 20 mg/dL B 20 mg/dL B 20 mg/dL Small LDL-C (Pattern B) LDL-C=100 mg/dL LDL-P=1800 nmol/L Assessment of true LDL-P using the VAP+ Lipid Panel allows for isolation of the actual cause of increased total LDL-P number to help personalize treatment and improve outcomes 18
  • 19. Appropriate Patients to Consider for VAP+ Testing Moderate- and higher-risk individuals and those at risk for CVD Any patient with NCEP ATP III risk factors (5 established): • Family history of premature CHD • Age (men 45 years; women 55 years) • Cigarette smoking • Hypertension • Low HDL-C ( 40 mg/dL) Established atherosclerotic vascular disease Diabetes mellitus and/or metabolic syndrome Framingham Risk Score (FRS) over 5% or Reynolds Risk Score An elevated inflammatory biomarker 19
  • 20. VAP+ Lipid Panel Clinical Evidence Continues to Substantiate VAP Technology
  • 21. Interactive Question Which of the following is true about residual risk after statin therapy? 1. Residual risk for CVD remains despite a significant reduction in CV events and mortality with statin therapy. 2. Substantial residual risk persists even after patients are treated with intensive statin therapy to reduce LDL-C. 3. High TGs and low levels of HDL-C appear to be major contributors to residual risk, even at optimal LDL-C levels. 4. All of the above are correct. 21
  • 22. VAP+ Lipid Panel Evidence Summary HDL-C subclass is an independent risk factor The basic lipid panel misclassifies CVD risk • The BLP/Friedewald formula consistently underestimates LDL-C, resulting in undertreatment of high-risk patients1 • Framingham Heart Study: Increased HDL3-C revealed a 40% lower risk for CHD and 36% lower risk for hard CHD4 (primary prevention) • Intermountain Heart Collaborative Study: A large percentage of patients with heart disease remain at high residual risk despite having achieved basic lipid panel target LDL-C treatment goals2 (secondary prevention) • TRIUMPH Study: Low HDL3-C revealed a 50% higher mortality risk5 (secondary prevention) • Jackson Heart Study: Increased HDL3-C revealed a 68% lower risk for hard CHD and a 35% lower risk for CHD6 (primary prevention) • Low HDL2-C reveals CV risk in 6 times as many patients as the basic lipid panel3 (primary prevention) 1. 2. 3. Martin SS, et al. J Am Coll Cardiol. 2013. May HT, et al. Presented at: ACC 59th Annual Scientific Sessions; 2010. Sailam V, et al. Clin Cardiol. 2008;31(11):542-545. 4. 5. 6. Toth P. et al Impact of HDLC and its subfractions. 2012. Martin SS. Presented at: AHA Scientific Sessions; 2012. Joshi P, et al. Presented at: AHA Scientific Sessions; 2012. 22
  • 23. VAP+ Lipid Panel Evidence Summary Remnant lipoproteins predict heart attack risk • Jackson Heart Study: Remnant lipoproteins are 28% more likely to reveal a significant, independent risk factor for heart attack1 (primary prevention) • Framingham Heart Study: Remnant lipoproteins were an independent risk factor for incident CHD events2 (primary prevention) • Framingham Heart Study: Pattern B revealed double the risk for hard CHD and a 40% increased risk for CHD3 (primary prevention) • Atherogenic lipoprotein phenotype (LDL-C pattern B) reveals double the risk for hard CHD and 40% increased risk for CHD and is strongly associated with CIMT progression4 Elevated Lp(a) plays a significant role in atherogenesis and is closely associated with HDL-C, VLDL-C, and TGs • Studies by Konerman’s group utilizing the VAP+ cholesterol test have shown that Lp(a) is strongly associated with markers of HDL-C, VLDL-C, and TGs, and highlight Lp(a)’s role in atherogenesis5 (primary and secondary prevention) CIMT=carotid intima media thickness. 1. 2. Khokar A, et al. J Am Coll Cardiol. 2013;61(10S). Toth PP, et al. Presented at: ACC Scientific Sessions; 2013. Impact of Lipoprotein Remnants on 12 Year Risk for CHD in the Framingham Offspring Population. 3. 4. 5. Toth PP. Presented at: AHA Scientific Sessions; 2012. Impact of LDL patterns on risk for CHD in the Framingham Offspring Population. Maki KC, et al. Vasc Health Risk Manag. 2012;8. Konerman M, et al. J Clin Lipidol. 2012;6(1). 23
  • 24. VAP+ Lipid Panel Improves Outcomes and Reduces Cost for Managed Care • Use of the VAP+ Lipid Panel permitted WellMed Medical Group to detect more cases of dyslipidemia than the basic lipid panel, enabling more appropriate and effective therapy to be prescribed and, ultimately, leading to better outcomes1,2 ◦ Repeated VAP testing and therapy adjustments led to lower LDL-C, higher HDL3-C, reduced inpatient (IP) stays, and fewer emergency department (ED) visits Utilization and Cost Comparisons IMPROVED PATIENT OUTCOMES REDUCED COSTS TO MANAGED CARE BY 35% VAP Test Group Control Test Results P-Value Mean total cost year 1 $4307.70 $5146.02 -1.34* 0.1157 Mean total cost year 2 $4852.62 $7413.18 -2.24* 0.0255 Mean ED cost both years $22.24 $33.15 -1.92* 0.0561 Mean IP cost both years $732.80 $876.20 -1.80* 0.0722 Cost *t-test. 1. Atherotech Inc. Available at: http://www.atherotech.com/information/viewinformation.asp?informationid=179. Accessed August 13, 2012. 2. McAna JF, et al. Popul Health Manag. 2012;15(1). 24
  • 25. Improving Health Outcomes Through Cardiometabolic Testing and Patient Education
  • 26. Our Healthy Heart Patient Education Program Our Healthy Heart is a unique service offered by Atherotech at no additional charge with a VAP+ Lipid Panel. The service provides patients with personalized lifestyle modification education, compliance strategies, and coaching from licensed health coaches to promote heart health through the continuum of care. Our licensed health coaches can design a personalized program based on physician recommendations, patient needs, and VAP+ results. Call 1-866-VAP-TEST or 1-866-827-8378 toll-free to enroll your patient. 26
  • 27. Atherotech Offers Customizable Disease State Panels These disease state panels are provided as examples only. Physicians should only order tests that are medically necessary and reasonable for the diagnosis or treatment of a patient for which reimbursement is claimed. All tests included in Atherotech panels or physiciancreated panels may be ordered individually. Through proprietary technologies, including the VAP+ Lipid Panel, Atherotech supports a full offering of disease state panels that can be customized by the clinician. CARDIOMETABOLIC AND GENETIC TESTS FROM ATHEROTECH CVD Risk Panel • • • • • • VAP+ Lipid Panel CMP Lp-PLA2 Hs-CRP Homocysteine Cystatin C CVD Treatment Panel • • • • • • • • VAP+ Lipid Panel CMP Lp-PLA2 Hs-CRP Homocysteine Cystatin C TSH Uric acid Diabetes/Metabolic Syndrome Panel • • • • • • • • VAP+ Lipid Panel CMP A1C GlycoMark GGT Uric acid Cystatin C Insulin Heart Failure Panel • • • • • VAP+ Lipid Panel BMP NTproBNP Galectin 3 Cystatin C Myalgia Panel • • • • • VAP+ Lipid Panel B12 TSH Vitamin D Uric acid 27
  • 28. In Conclusion Comprehensive care is essential to effectively manage cardiometabolic risk and improve outcomes Basic lipid panels have led to misclassification of as many as 60% of patients, potentially resulting in ineffective treatment for patients most at risk Evidence-based guidelines recommend cardiometabolic risk stratification via comprehensive cholesterol profiling so a personalized treatment strategy can be implemented The VAP+ Lipid Panel uncovers residual cardiometabolic risk, which provides actionable information to improve patient outcomes Atherotech provides over 100 routine and cardiometabolic specialty tests and customizable disease state panels to offer clinicians a single source laboratory Atherotech goes beyond diagnostics to offer personalized provider and patient education for disease management 28
  • 29. “If something doesn’t make sense perhaps you should look further”.