1. health and fitness
2. disease
3. cholesterol

Managing the Patient with High Triglycerides:
Assessment and Treatment Strategies
February 6, 2014
Ft. Lauderdale, FL
Faculty
Harold E. Bays, MD, FTOS, FACE, FNLA
Michael Miller, MD, FACC, FAHA
Session 5: Managing the Patient with High Triglycerides:
Assessment and Treatment Strategies
Learning Objectives
1.
2.
3.
4.
Discuss the role of elevated triglyceride (TG) levels in the assessment and diagnosis of dyslipidemia,
including cardiovascular risk factors
Apply best practices in the attainment of TG levels, including the role of fasting and nonfasting states in accurate
evaluation
Evaluate the management of hypertriglyceridemia through greater adherence to evidenced based practices and
accepted guidelines
Select potential new and emerging therapeutic approaches to manage TG-based dyslipidemia, mixed dyslipidemia,
and associated cardiovascular risk
Faculty
Harold E. Bays, MD, FTOS, FACE, FNLA
Medical Director and President
Louisville Metabolic and Atherosclerosis Research Center
Louisville, Kentucky
Dr Harold Bays is medical director and president of Louisville Metabolic and Atherosclerosis Research Center (L-MARC) in
Louisville, Kentucky. He earned his medical degree and completed his internship and residency in internal medicine, He
then received his fellowship in endocrinology and metabolism at the University of Louisville School of Medicine. Dr Bays
has served as an investigator in over 400 Phase I through IV clinical trials for treatments for high cholesterol and other
dyslipidemias, obesity, diabetes mellitus, hypertension, osteoporosis, and other metabolic and hormonal disorders. He
has written, or served as a contributing author for, over 180 scientific manuscripts and book chapters; and authored over
100 scientific abstracts. His publications have appeared in such peer reviewed journals as the New England Journal of
Medicine, Obesity/Obesity Research, Journal of Clinical Endocrinology and Metabolism, and Cell Metabolism.
Michael Miller, MD, FACC, FAHA
Professor, Departments of Medicine, Epidemiology & Public Health
University of Maryland School of Medicine
Director, Center for Preventive Cardiology
University of Maryland Medical Center
Baltimore, Maryland
Dr Michael Miller is a professor in the departments of medicine, epidemiology & public health at the University of
Maryland School of Medicine, Baltimore, Maryland. In addition, he is director of the center for preventive cardiology at the
University of Maryland Medical Center. Dr Miller earned his MD from The University of Medicine and Dentistry of New
Jersey. Following a medical residency at the University of Cincinnati Hospital, he completed two fellowships at Johns
Hopkins, one in lipoprotein metabolism and the second in cardiovascular disease. His major research interests are
disorders of lipid and lipoprotein metabolism, molecular studies of HDL cholesterol, triglycerides and the postprandial
response to dietary fat, nontraditional coronary risk factors, and clinical trials to reduce atherosclerosis. Dr Miller has
authored more than 250 original articles, book chapters and other publications. Original research articles have appeared
in BMJ, Circulation, JACC, JAMA, NEJM, PNAS, and Science. He is the coauthor of “The Practice of Coronary Disease
Prevention” and the “AMA Guide to Preventing and Treating Heart Disease.”
Faculty Financial Disclosure Statements
The presenting faculty reports the following:
Dr Bays receives research grants from Alere, Amarin, Amgen, Ardea Inc., Boehringer Ingelheim, California Raisin Board,
Catabasis, Eisai, Elcelyx, Eli Lilly, Esperion, Forest, Gilead, Given, GlaxoSmithKline, High Point Pharmaceuticals, LLC,
Hoffman LaRoche, Home Access, Isis, Janssen, Merck, Micropharma Limited, Nektar, Novartis, Novo Nordisk, Omthera,
Orexigen Therapeutics, Pfizer, Pronovo, Regeneron, Takeda, TIMI, Transtech Pharma, Inc., Trygg Pharmaceuticals, VIVUS,
WPU, and Xoma; Consulting Fees from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Catabasis, Daiichi Sankyo, Inc.,
Eisai, Isis, Merck, Novartis, Pronovo, VIVUS, and WPU; and speaker fees from Amarin, Bristol-Myers Squibb, Daiichi Sankyo,
Inc., Eisai, Merck, and VIVUS.
Dr Miller receives consulting fees from Amarin.
Education Partner Financial Disclosure Statement
The content collaborators at Medtelligence, LLC report the following:
Ben Caref, PhD, Managing Partner and Chief Medical Officer, develops content and has no financial relationships to
disclose.
Pamela J. Clark, Director of Editorial Services, provides editorial assistance and has no financial relationship to disclose.
Suggested Reading List
American Diabetes Association. Standards of medical care in diabetes–2012. Diabetes Care. 2012;35(Suppl 1):S11-S63.
Ballantyne CM, Bays HE, Kastelein JJ, et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in
statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110(7): 984-992.
Bays HE, Ballantyne CM, Kastelein JJ, et al. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high
triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an openlabel Extension [MARINE] trial). Am J Cardiol. 2011;108(5):682-690.
Brinton EA, Ballantyne CM, Bays HE, et al. Effects of icosapent ethyl on lipid and inflammatory parameters in patients with
diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR
study. Cardiovasc Diabetol. 2013;12(1):100.
Brunzell JD, Davidson M, Furberg CD, et al. Lipoprotein management in patients with cardiometabolic risk: consensus
conference report from the American Diabetes Association and the American College of Cardiology Foundation. J Am
Coll Cardiol. 2008;51(15):1512-1524.
James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults:
Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2013;Dec 18 [Epub
ahead of print].
Jellinger PS, Smith DA, Mehta AE, et al; for the AACE Task Force. American Association of Clinical Endocrinologists'
Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis. Endocr Pract. 2012;18(Suppl 1):1-78.
Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: a scientific statement from the American
Heart Association. Circulation. 2011;123(20):2292-2333.
Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density
lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes.
2011;4(3):337-345.
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association
Task Force on Practice Guidelines. Circulation. 2013; Nov 12. [Epub ahead of print]
Sarwar N, Sandhu MS, Recketts SL, et al: for the Triglyceride Coronary Disease Genetics Consortium and Emerging Risk
Factors Collaboration. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet.
2010;375(9726):1634-1639.
Presenter Disclosure Information
SESSION 5
The following relationships exist related to this presentation:
2:30–3:45pm
► Dr Bays receives research grants from Alere, Amarin, Amgen, Ardea
Inc., Boehringer Ingelheim, California Raisin Board, Catabasis, Eisai,
Elcelyx, Eli Lilly, Esperion, Forest, Gilead, Given, GlaxoSmithKline,
High Point Pharmaceuticals, LLC, Hoffman LaRoche, Home Access,
Isis, Janssen, Merck, Micropharma Limited, Nektar, Novartis, Novo
Nordisk, Omthera, Orexigen Therapeutics, Pfizer, Pronovo,
Regeneron, Takeda, TIMI, Transtech Pharma, Inc., Trygg
Pharmaceuticals, VIVUS, WPU, and Xoma; Consulting Fees from
Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Catabasis,
Daiichi Sankyo, Inc., Eisai, Isis, Merck, Novartis, Pronovo, VIVUS,
and WPU; and speaker fees from Amarin, Bristol-Myers Squibb,
Daiichi Sankyo, Inc., Eisai, Merck, and VIVUS.
Managing the Patient with High
Triglycerides: Assessment and
Treatment Strategies
SPEAKERS
Harold E. Bays, MD, FTOS, FACE, FNLA
Michael Miller, MD, FACC, FAHA
► Dr Miller receives consulting fees from Amarin.
Presenter Disclosure Information
Off-Label/Investigational Discussion
► In accordance with pmiCME policy, faculty have been asked to
disclose discussion of unlabeled or unapproved use(s) of drugs or
devices during the course of their presentations.
Managing the Patient with High
Triglycerides: Assessment and
Treatment Strategies
February 6, 2014
Drug Names
Learning Objectives
Generic name
Brand name(s)
Generic name
Brand name(s)
Atorvastatin
Atorvastatin Calcium, Caduet,
Lipitor
Metformin
various
Bezafibrate
none
Niacin
Niacin/laropiprant
various
Estrogen
various
Omega-3-acid
ethyl esters
Lovaza, Omacor, Vascepa
Ezetimibe
various
Fenofibrate
Antara, Fenoglide, Lipofen, Tricor,
Triglide, Trilipix
Fluvastatin
Fluvastatin Sodium, Lescol,
Lescol XL
Gemfibrozil
Gemfibrozil, Lopid
Icosapent Ethyl
Vascepa
Isotretinoin
various
Lovastatin
Advicor, Altoprev, Lovastatin,
Mevacor
Pravastatin
Pravachol, Pravastatin
Sodium, Pravigard PAC
Rosuvastatin
Crestor, Rosuvastatin
Calcium, Rosuvastatin
Zinc
Simvastatin
Zocor, simvastatin
Tamoxifen
Nolvadex, Soltamox,
Tamoxifen Citrate
Thiazide diuretic
various
• Discuss the role of elevated triglyceride (TG) levels in the
assessment and diagnosis of dyslipidemia, including
cardiovascular risk factors
• Apply best practices in the attainment of TG levels,
including the role of fasting and non-fasting states in
accurate evaluation
• Evaluate the management of hypertriglyceridemia (HTG)
through greater adherence to evidence based practices
and accepted guidelines
• Select potential new and emerging therapeutic
approaches to manage TG-based dyslipidemia, mixed
dyslipidemia, and associated cardiovascular risk
1
Prevalence (%) of HTG by Age, Sex, and
Ethnicity in NHANES 1999–2008
TG Cut Points, mg/dLa
Demographic
≥150
≥200
≥500
Overall (age ≥20 yrs)
31
16
1.1
Men
35
20
1.8
Michael Miller, MD, FACC, FAHA
Womenb
27
13
0.5
Professor, Departments of Medicine, Epidemiology, & Public Health
University of Maryland School of Medicine
Director, Center for Preventive Cardiology
University of Maryland Medical Center
Baltimore, MD
Mexican American
35
20
1.4
Non-Hispanic, black
16
8
0.4
Non-Hispanic, white
33
18
1.1
What Is the Relationship of
Hypertriglyceridemia to Increased CVD Risk?
Use of TG-lowering
medicationsc
18
70 million persons, or ~1/3 of US adults, have elevated TG (≥150 md/dL)d
a Percentage of participants. bExcludes pregnant women. Miller M et al. Circulation. 2011;123:2292-333.
c Includes fenofibrate, gemfibrozil, niacin, or statin. Ford ES et al. Arch Intern Med. 2009;169:572-8.
dUS Census Age 20 and above, July 1, 2010, was 226,113,653.
HTG=hypertriglyceridemia; NHANES=National Health and Nutrition Examination Survey; TG=triglyceride(s); yrs=years.
Three Atherogenic Consequences
of HTG
Central
Adiposity
1
FFA /TG
VLDL-C
Fatty
Fatty
liver
liver
FFA/TG
and
Fructose
(glucose)
CE
CETP
VLDL
↑VLDL
Synthesis
CE
CETP
2
TG
LDL
Hepatic
Lipase
SD
HDL
HDL
3
SD
LDL
400
Rapid Loss
of Apo A-I
Hepatic
Lipase
TG
CAD (n=61)
Kidney
Plasma TG (mg/dL)
“Atherogenic
Dyslipidemia”
1 ↑TG / VLDL-C
1.
2 SD LDL / ↑LDL-P
2.
3 ↓HDL-C & Apo A-I
3.
TG
Postprandial TG (Remnants) Increased in
CAD Patients
HDL-C, HDL-P,
& Apo A-I
*
200
100
0
0
2
4
6
8
Hours after meal
*P=0.025; †P0.001.
Apo=apolipoprotein; CE=cholesterol ester; CETP=CE transfer protein; FFA=free fatty acid; HDL=high-density lipoprotein;
HDL-C=HDL cholesterol; HDL-P=HDL particle; LDL=low-density lipoprotein; LDL-P=LDL particle; SD=small dense;
VLDL=very-low-density lipoprotein; VLDL-C=VLDL cholesterol.
CAD=coronary artery disease. Patsch JR et al. Arterioscler Thromb. 1992;12:1336-45.
Elevated TG Associated with
↑SD LDL-P, ↓HDL-C, and ↑Non-HDL-C
Association Between BMI and HTG
NHANES 1999–2004
Percent of participants within a TG category as a function of BMI status
More Particles
LDL=
130 mg/dL
Apo B
†
300
LDL size
Apo B & LDL-P
Fatty liver & ↑VLDL synthesis are key to ↑TG and consequences
Fewer Particles
No CAD (n=40)
†
TG Concentration (mg/dL)
More Apo B
BMI
(kg/m2)
<150
<200
≥150
(n=3250) (n=4057) (n=1744)
≥200
(n=937)
CE
Fasting Lipid Panel:
TC
198 mg/dL
LDL-C
130 mg/dL
TG
90 mg/dL
HDL-C
50 mg/dL
Non-HDL-C 148 mg/dL
Fasting Lipid Panel:
TC
210 mg/dL
LDL-C
130 mg/dL
TG
250 mg/dL
HDL-C
30 mg/dL
Non-HDL-C 180 mg/dL
<25
42.7
39.0
20.1
17.5
25 to <30
31.6
33.3
39.9
39.6
≥30
25.6
27.7
39.9
42.9
BMI=body mass index.
Miller M et al. Circulation. 2011;123:2292-333.
TC=total cholesterol. Otvos JD et al. Am J Cardiol. 2002;90:22i-29i.
2
~2.5 greater
prevalence
TG <150 mg/dL Associated with Lower Risk
of CHD Eventsa Independent of LDL-C Level
Enlarged Waist Combined with Elevated TG May
Predict CVD as Well as MetS in Menopausal Women
0.9
EWET +
0.8
CV
0
2
MetS-NCEP +
0.8
8
6
P<0.001
CV
P<0.001
4
0.7
10
-2
4
2
0
6
8
10
Lipid values in mg/dL
LDL-C <70
TG <150
TG ≥150
aDeath, myocardial infarction (MI), and recurrent ACS. bACS patients on atorvastatin 80 mg or pravastatin 40 mg. cAdjusted for age,
gender, low HDL-C, smoking, hypertension (HTN), obesity, diabetes, prior statin therapy, prior ACS, peripheral vascular disease, and
treatment. CHD=coronary heart disease; HR=hazard ratio; LDL-C=LDL cholesterol; PROVE IT-TIMI=Pravastatin or Atorvastatin
Evaluation and Infection Therapy Thrombolysis In Myocardial Infarction. Miller M et al. J Am Coll Cardiol. 2008;51:724-30.
CVD=CV disease; EWET=enlarged waist with elevated TG; MetS=metabolic syndrome;
NCEP=National Cholesterol Education Program. Tankó LB et al. Circulation. 2005;111:1883-90.
TG Levels and CHD Risk:
Meta-analysis of 29 Studies
Low HDL-C and High TGs Increase CVD Risk
Even when LDL-C Levels Are Well-Controlled
N=262,525
TNT Study
CHD Cases
Patients with LDL-C ≤70 mg/dL on statina,b
5-yr Risk of Major
CVD Events (%)
HR: 0.72
P=0.017
LDL-C ≥70
Kaplan-Meier curves indicating cardiovascular (CV) event rates in women with (n=88) or
without (n=469) EWET or with (n=100) or without (n=433) MetS as per 2001 NCEP.
EWET=Waist ≥88 cm and TG ≥128 mg/dL.
39%
Lower
Risk
TG=186
TG=168
TG=150
TG=142
Q1
<37
Q2
37 to <42
Q3
42 to <47
Q4
47 to <55
Q5
≥55
0.85
0.57
0.55
0.61
TG=124
TG values in mg/dL
Duration of Follow-up
≥10 yrs
<10 yrs
5902
4256
Sex
Male
Female
7728
1994
Fasting Status
Fasting
Non-fasting
7484
2674
Adjusted for HDL-C
Yes
No
4469
5689
CHD Risk Ratio* (95% CI)
1.72 (95% CI 1.56–1.90)
Overall CHD Risk Ratio*
HR vs Q1*
aOn-treatment
level (3 months statin therapy), n=2661.
LDL-C 58 mg/dL, mean TG 126 mg/dL.
*P=0.03 for differences among quintiles of HDL-C.
bMean
Decreased
Risk
1
Increased
Risk
2
*Individuals in top vs bottom third of usual log-TG values, adjusted for at least age,
sex, smoking status, lipid concentrations, and (in most studies) blood pressure (BP).
CI=confidence interval. Sarwar N et al. Circulation. 2007;115:450-8.
TNT=Treating to New Targets.
Barter P et al. N Engl J Med. 2007;357:1301-10.
AHA Scientific Statement on TG
Classification
Can HTG Cause Atherosclerosis?
Con
TG Revisions between 1984 and 2001
TG Designation
HR: 0.84
P=0.192
Follow-up Time (yrs)
Follow-up Time (yrs)
HDL-C
Quintilesa
(mg/dL)
N=4162
Referent
HR: 0.85
P=0.180
0.9
0.7
-2
PROVE ITTIMI 22 Trialb
1.0
CHD Eventa Rate
after 30 Daysc (%)
EWET –
1.0
MetS-NCEP –
Cumulative Survival
Cumulative Survival
Achieving both low LDL-C and low TG (<150 mg/dL) may be important
therapeutic strategies in patients after acute coronary syndrome (ACS)
1.1
1.1
• HTG → CVD weaker than LDL-C, partly HDL-C dependent
• Severe HTG from ↑chylomicrons not related to ↑CVD
1984 NIH
Consensus Panel
1993 NCEP
ATP II
2001 NCEP
ATP III
<250
<200
<150
Borderline High*
250–499
200–399
150–199
Pro
High*
500–999
400–999
200–499
• TG-rich lipoproteins are atherogenic (esp. cholesterol-rich remnants)
>1000
>1000
>500
Desirable*
Very High*
• TG accumulation not seen in atherosclerotic plaque
• TG-lowering drugs not completely proven to ↓CVD
• TG lipolysis by lipoprotein lipase (LPL) → pro-inflammatory FFA
(uptake by CD36 & FA binding proteins to nucleus)
• HTG causes atherogenic changes in LDL and HDL
AHA Statement in 2011 classified TG <100 mg/dL as “optimal”
(SD LDL becomes much more prevalent with TG >100 mg/dL)
• TG-lowering drugs ↓CVD in HTG / low HDL-C patients
• TG ~100–800 mg/dL is OFTEN associated with hyper-Apo B
(ie, pro-atherogenic state)
*All measurements in mg/dL. AHA=American Heart Association; ATP=Adult Treatment Panel; NCEP=National Cholesterol
Education Program; NIH=National Institutes of Health. Miller M et al. Circulation. 2011;123:2292-33.
FA=fatty acid. Miller M et al. Circulation. 2011;123:2292-333.
3
Predicting a First Atherosclerotic CV Event
•Calculator uses the Pooled Cohort Equations to
estimate the 10-year primary risk of ASCVD among
patients without pre-existing cardiovascular disease
who are between 40 and 79 years of age
How Should We Use Lipid Measures
to Assess CV Risk in Patients with
Dyslipidemia?
•Patients are considered to be at "elevated" risk if the
Pooled Cohort Equations predicted risk is ≥7.5%
•The Pooled Cohort Equations have been proposed
to replace the Framingham Risk 10-year CVD
calculation
ACC/AHA 2013 Prevention Guidelines CV Risk Calculator. http://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx.
Goff DC Jr et al. Circulation. 2013; Nov 12. [Epub ahead of print].
2013 ACC/AHA Guideline:
Hypertriglyceridemia
Targets for Therapy after LDL-C
Goal in Patients with TG 200 mg/dL
• “Although elevations in LDL-C often occur simultaneously with
elevated triglyceride levels, the Panel did not conduct a systematic
review on lifestyle and drug therapies for the treatment of elevated
triglyceride levels.”
• “Marked exacerbations of triglycerides >1,000 mg/dL may indicate
those who may develop very marked triglyceride elevations that could
trigger hyperlipidemic pancreatitis. Because of the increased risk for
pancreatitis at these triglyceride levels, drug therapy specifically to
lower triglycerides is advised. The fibrates—fenofibrate and
gemfibrozil—are considered first-line agents for triglyceride lowering
(see Safety). Marine omega-3 fatty acids (docosahexaenoic acid
[DHA] and EPA) in doses of 3 to 4 g and niacin 2 g also have been
shown to reduce triglycerides in individuals with severe
hypertriglyceridemia.”
Patient Category
LDL-C target
(mg/dL)
Non-HDL-C target
(mg/dL)
No CHD, <2 RFs
<160
<190
No CHD, ≥2 RFs
<130
<160
CHD or CHD risk
equivalent
<100
<130
RF=risk factor.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-97.
EPA=eicosapentaenoic acid. Stone NJ et al. Circulation. 2013; Nov 12. [Epub ahead of print].
Summary and Conclusions
Summary and Conclusions
HTG (and low HDL-C)
After assessing for ASCVD with risk calculator,
guideline recommendations for statin Rx include
• HTG and low HDL-C (with high Apo B, LDL-P, and
SD LDL) is the “atherogenic dyslipidemia” common
in insulin resistance/MetS and T2DM
1. Individuals with clinical ASCVD
2. Individuals with primary elevations of LDL ≥190 mg/dL
• Both HTG and low HDL-C strongly predict CVD risk,
even with excellent LDL-C control on a statin
3. Individuals 40 to 75 years of age with diabetes and an
LDL 70 to 189 mg/dL without clinical ASCVD
4. Individuals without clinical ASCVD or diabetes who are
40 to 75 years of age with LDL 70 to 189 mg/dL and a
10-year ASCVD risk of 7.5% or higher
ACC/AHA 2013 Prevention Guidelines CV Risk Calculator. http://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx. Goff
DC Jr et al. Circulation. 2013; Nov 12. [Epub ahead of print]. Stone NJ et al. Circulation. 2013; Nov 12. [Epub ahead of print].
T2DM=type 2 diabetes mellitus.
4
ATP III Treatment Recommendations
for Elevated TG
How Should HTG be Managed?
TG
(mg/dL)
ATP III
Classification
150–199
Borderline high
Primary
Target of
Therapy
Treatment Recommendations
LDL-C goal Weight and Physical activity
Weight and Physical activity
Harold E. Bays, MD, FTOS, FACE, FNLA
Medical Director and President
Louisville Metabolic and Atherosclerosis Research Center
Louisville, KY
200–499
High
LDL-C goal
≥500
Very high
TG
to prevent
acute
pancreatitis
Consider non-HDL-C goal:
LDL-C with statin or VLDL-C with
niacin or fibrate
Sugar and carbs*
Very low fat diet (fat ≤15% total calories)
Weight and Physical activity
Add niacin or fibrates
(+OM-3 as per FDA indication*)
*Not in ATP III statement. carbs=carbohydrates; FDA=US Food and Drug Administration; OM=omega.
NCEP ATP III. Circulation 2002;106:3143-421.
Secondary Causes of HTG
Primary Causes of HTG
Relatively common
• Familial combined hyperlipidemia (FCHL)
– Variable phenotype (↑TG alone, or ↑TC alone, or both increased)
– Associated with ↑↑CVD and ↑central obesity
– Multiple genetic associations of unclear causal significance
– “Hyper-Apo B”
• Familial HTG (FHTG)
– ↑TG alone (not TC)
– Associated with ↑CVD if ↑central obesity / MetS
– Largely due to ↑hepatic VLDL production
– Apo B is usually normal
Note: FCHL and FHTG may
NOT be distinct entities
• Apo C-II deficiency
Clinically useful details
Positive energy balance
Saturated fat or Glycemic index content
Carbohydrate intake
Simple sugars (fructose, sucrose, etc.) & dietary fiber
Adiposopathy (especially
visceral adiposity)
Impaired adipogenesis, adipocyte hypertrophy, & adipose tissue
dysfunction
Diabetes mellitus
Especially if poorly controlled
Hypothyroidism
Only if not adequately controlled with thyroid replacement
therapy
Nephrotic syndrome
Rare
• LPL deficiency
Cause
Medications
Antiretroviral regimens (for HIV)
Some phenothiazines and 2nd-generation antipsychotics
Nonselective beta-blockers
Thiazide diuretics
Oral estrogen, tamoxifen
Glucocorticoids and Isotretinoin
Recreational drugs
Alcohol (esp. with fatty liver) and marijuana (Apo C-III)
• Familial dysbetalipoproteinemia (Type III)
• GPIHBP1 deficiency
GPIHBP=glycophosphatidylinositol-anchored HDL-binding protein. Bays HE. In: Kwiterovich PO Jr, ed.
The Johns Hopkins Textbook of Dyslipidemia. 1st ed. Lippincott Williams & Wilkins;2010:245-57.
HIV=human immunodeficiency virus. Bays HE. In: Kwiterovich PO Jr, ed. The Johns
Hopkins Textbook of Dyslipidemia. 1st ed. Lippincott Williams & Wilkins;2010:245-57.
Pharmacologic Therapy for Very
High TG Levels
Pharmacologic Therapy for Very
High TG Levels
High TG Indications*
High TG Indications*
Drug Class
Fenofibratea
Extendedrelease
Niacin
(ERN)b
Drug Class
TG
>500
mg/dL
Type IV
Hyperlipidemia
Select Adverse Effects (AEs)


Dyspepsia, various upper gastrointestinal
complaints, cholesterol, gallstones, myopathy


Flushing, pruritus, diarrhea, vomiting,
hyperglycemia, hyperuricemia or gout, dyspepsia
and exacerbation of peptic ulcer, hepatotoxicity
TG
>500
mg/dL
Type III
Hyperlipidemia
Type IV
Hyperlipidemia
Select Adverse Effects
OM-3 FA
(EPA / DHA)a

Eructation, dyspepsia, taste
perversion
OM-3 FA
(EPA only)a

Arthralgia
Statins
b
c
Myalgia, myopathy (rare),
rhabdomyolysis (very rare), A1c,
cognitive impairment
*Data from individual product labeling for each drug in patients with very TG. a4 grams per day. bAtorvastatin,
rosuvastatin, and simvastatin. cAtorvastatin and simvastatin. A1c=glycosylated hemoglobin.
Fredrickson DS et al. Ann Intern Med. 1975;82:150-7. Miller M et al. Circulation. 2011;123:2292-333.
*Data from individual product labeling for each drug in patients with very TG. a145 mg per day. b2 grams per day.
Fredrickson DS et al. Ann Intern Med. 1975;82:150-7. Miller M et al. Circulation. 2011;123:2292-333.
5
Risk Difference vs Placebo of Hypertriglyceridemic
Subgroups from Large-scale, Primary and Secondary CVD
Prevention Trials that Used Statins
Lipid Effects of Drug Classes in Subjects with Primary
Hyperlipidemia / Mixed Dyslipidemia and Isolated HTG
Type of dyslipidemia/
medication
Mixed dyslipidemia
• Statins
• Omega-3 fatty acids
• Fenofibrate, fenofibric acid
and gemfibrozil
• Niacin
Isolated hypertriglyceridemia
• Statins
• Omega-3 fatty acids
• Fenofibrate, fenofibric acid
and gemfibrozil
LDL-C*
HDL-C*
NonHDL-C*
–26 to –63
–6 to +25
–5 to –31
+5 to +16
–5 to +7
+10 to +16
–44 to –60
–1 to –7
–17
TG*
–10 to –37
–19 to –44
–24 to –36
Statin Trials
–5 to –38
–3 to –17
+10 to +26
NR
–21 to –52
–26 to –52
–46 to –62
–27 to –45
+17 to +49
+3 to +47
+3 to +22
+9 to +14
+18 to +23
–29 to –52
–10 to –14
NR
Pravastatin
5 yrs
CARE
High TG subgroup
Pravastatin
5 yrs
PPP Project
Highest TG tertile subgroup
Pravastatin
5–6 yrs
4S
Dyslipidemic subgroup
Simvastatin
5 yrs
Rosuvastatin
5 yrs
Simvastatin/
pravastatin/ lovastatin/
atorvastatin/ fluvastatin
5 yrs
JUPITER
Older subjects with TG subgroup
CTT Collaborators
Highest TG tertile subgroup
Drug
Median
follow-up
Risk difference
vs placebo
Gemfibrozil
5 yrs
–34%
–72%
–71%
–8.2, –52.6 (<0.02)
NR (<0.05)*
–43, –85 (<0.001)
NR (NS)
NR (0.02)
–9%
–40%
VA-HIT
High TG subgroup
Gemfibrozil
5 yrs
–22%
–27%
–7, –35 (0.006)
–7, –42 (0.01)
FIELD
High TG subgroup
High TG, low HDL-C subgroup
Fenofibrate
5 yrs
–11%
–23%
–27%
–25, 5 (NS)
–6, –37 (<0.01)
–9, –42 (0.005)
ACCORD
High TG, low HDL-C subgroup
Fenofibrate
5 yrs
–8%
–31%
–21, 8 (NS)
NR (<0.05)*
EPA
5 yrs
Niacin
3 yrs
Fish oil trial: JELIS
High TG, low HDL-C subgroup
–19%
–5, –31 (0.011)
–53%
–2, –77 (0.043)
+2%
Cumulative % with Primary Outcome
6 yrs
–31, 21 (NS)
HDL-C
44 (11)
TG
–18, –28 (<0.001)
–15%
–2, –26 (0.029)
–34%
–25, –41 (<0.001)
–52%
–31, –67 (<0.001)
–44%
–31, –54 (<0.001)
–21%
NR (NS)*
–21%
–19, –23 (<0.001)
–24%
–17, –23 (<0.001)
125 (74)
The average patient had NONE of
the usual lipid indications for niacin
14.5%
10
5
0
Placebo
ERN / LRPT
0
1
2
16.4%
16.2%
10
0
1
2
3
Time (years)
4
1581
1381
910
436
1606
1366
903
428
3
TG
816
HDL-C
22
Non-HDL-C
27
TC
296
VLDL-C
175
LDL-C
89
P<0.0001
Risk ratio 0.96 (95% CI 0.90–1.03)
Log-rank P=0.29
15.0%
15
HR 1.02, 95% CI 0.87–1.21
Log-rank P value=0.79
20
Monotherapy 1696
Baseline
(mg/dL)
Effect of ERN / LRPT on
Major Vascular Events (MVEs)*
20
30
OM-3 Ethyl Esters and Lipid Levels in
Patients with TG >500 mg/dL
Change in Median Levels
Mean (SDM) at
baseline, mg/dL
Patients Suffering Events (%)
Baseline Lipids on Statin-based Rx
63 (17)
1, –29 (0.07)
–23%
Combination Therapy 1718
N=25,673 with Pre-existing CVD
128 (22)
–9, –36 (0.003)
–15%
MI=myocardial infarction. Boden WE et al. N Engl J Med. 2011;365:2255-67.
HPS2-THRIVE: Randomized Placebocontrolled Trial of ERN and LRPT
Direct LDL
–12, –47 (0.003)
–24%
Combination Therapy
Monotherapy
40
0
N at risk
*Actual P-value was not reported. ACCORD=Action to Control Cardiovascular Risk in Diabetes; AIM-HIGH=Atherothrombosis Intervention
in MetS with Low HDL/High TGs: Impact on Global Health Outcomes; BIP=Bezafibrate Infarction Prevention; FIELD=Fenofibrate
Intervention and Event Lowering in Diabetes; HHS=Helsinki Heart Study; JELIS=Japan EPA Lipid Intervention Study; VA-HIT=Veterans
Affairs HDL Intervention Trial. Maki KC, Bays HE, Dicklin MR. J Clin Lipidol. 2012;6:413-26.
TC
–32%
50
Bezafibrate
Lipid
–17, –43 (<0.001)
95% CI (P-value)
BIP
High TG subgroup
Niacin trial: AIM-HIGH
95% CI
(P-value)
–31%
AIM-HIGH Primary Endpoint: CHD Death, Non-fatal MI,
Ischemic Stroke, High-risk ACS, Hospitalization for
Coronary or Cerebrovascular Revascularization
Risk Difference of Hypertriglyceridemic Subgroups vs
Placebo from Large-scale, Primary and Secondary CVD
Prevention Trials that Used Fibrates, Fish Oil, and Niacin
Fibrate trials:
HHS
High TG, high LDL-C/HDL-C subgroup
High TG, high BMI subgroup
Risk difference
vs placebo
*Actual P-value was not reported; CARE=Cholesterol and Recurrent Events Trial; CTT=Cholesterol Treatment Trialists;
JUPITER=Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin; NS=not
significant; PPP=Prospective Pravastatin Pooling; 4S=Scandinavian Simvastatin Survival Study; WOSCOPS=West of
Scotland Coronary Prevention Study. Maki KC, Bays HE, Dicklin MR. J Clin Lipidol. 2012;6:413-26.
*Range, %.
NR=not reported.
Maki KC, Bays HE, Dicklin MR. J Clin Lipidol. 2012;6:413-26.
Trial
Median
follow-up
Drug
WOSCOPS
High TG subgroup
4
Years of Follow-up
“Significant excesses of serious AEs due to known and unrecognised side-effects of niacin.
Over 4 years, ER niacin / laropiprant caused serious AEs in ~30 patients per 1000.”
45.0
P<0.0001
P=0.0015
P=0.0059
P<0.0001
0.0
–13.8
–45.0
– 0.9
– 1.7
–3.6
Placebo
*Non-fatal MI or coronary death, any non-fatal or fatal stroke, coronary or non-coronary artery surgery or angioplasty. HPS2-THRIVE=Heart
Protection Study 2 Treatment of HDL to Reduce the Incidence of Vascular Events; LRPT=laropiprant; SDM=standard deviation of the mean.
Armitage J. Paper presented at ACC.13: American College of Cardiology 62nd Annual Scientific Session. March 9, 2013.
P=0.0002
9.1
6.7
– 4.8
– 9.7
– 42.0
OM-3 Acid Ethyl Esters (4 g/day)
Pooled analysis (N=82).
Harris WS et al. J Cardiovasc Risk 1997;4:385-91 and Pownall HJ et al. Atherosclerosis 1999;143:285-97.
6
5
NonHDL-C
TG
LDL-C
VLDL-C
0.7‡
JELIS: Effect of EPA-only on Major Coronary
Events in Hypercholesterolemic Patients
Cumulative Incidence of Major
Coronary Events (%)
Median Change from Baseline (%)
Statin + EPA+DHA: COMBOS Primary
and Secondary Efficacy Results
Apo B
HDL-C
3.4*
0
–2.2
–5
–10
–1.2
–2.8
–6.3
–1.9
–4.2†
–7.2
–9.0*
–15
Additions to baseline simvastatin therapy:
OM-3 (Rx) 4 g/d + simvastatin 40 mg/d (n=123)
–20
Placebo + simvastatin 40 mg/d (n=133)
–25
–29.5*
–30
↓
–19%
Statin only
3
Statin + EPA
2
1
0
HR (95% CI): 0.81 (0.69–0.95)
P=0.011
0
1
2
3
Control
9319
8931
8671
8433
8192
7958
EPA
9326
8929
8658
8389
8153
7924
No. at Risk
Note: OM-3 AEEs are not FDA approved
for TG 200–500 mg/dL
–27.5*
4
4
5
Years
18,645 patients with TC ≥251 mg/dL recruited in Japan between 1996 and 1999 received 1800 mg of EPA
daily with statin or statin only. Statin dose was up to 20 mg pravastatin or 10 mg simvastatin.
*P<0.0001 between groups. †P=0.0232 between groups. ‡P=0.0522 between groups.
AEEs=acid ethyl esters; COMBOS=Combination of Prescription Omega-3 with Simvastatin.
Davidson MH et al. Clin Ther. 2007;29:1354-67.
Yokoyama M et al. Lancet. 2007;369:1090-8.
MARINE: Icosapent Ethyl (Pure EPA): Median
Placebo-adjusted Change from Baseline for
Efficacy Endpoints
JELIS Patient Subgroup:
TG >150 mg/dL and HDL-C <40 mg/dL
ITT Population
The MARINE Study: TG >500 mg/dL
LDL-C
Median Placebo-adjusted Change (%)
Primary endpoint: sudden cardiac death, fatal
and non-fatal MI, unstable angina pectoris,
angioplasty, stenting, or CABG
HR and P-value adjusted for age, gender,
smoking, diabetes, and HTN
NS
5.2
TG
Non-HDL-C
VLDL-C
Lp-PLA2
-5.1
NS
-8.1
*
-19.7
†
-15.3
*
-17.7
ǁ
Apo B
HDL-C
NS
1.5
TC
-2.3
NS
-2.6
NS
-6.8
*
-8.5
†
-13.6
‡
-10.1
NS
-16.3
ǁ
-17.3
NS
Icosapent Ethyl
-28.6
‡
-33.1
ǁ
VLDL-TG hsCRP
-3.6
NS
4 g/day (n=76)–FDA approved dose
-25.8
†
2 g/day (n=73)
-36.0
†
*P<0.05. †P<0.01. ‡P<0.001. ǁP<0.0001. NS = P≥0.05.
P-values reflect differences between icosapent ethyl vs placebo.
hsCRP=high-sensitivity C-reactive protein; ITT=intention to treat; Lp-PLA=lipoprotein-associated phospholipase A; MARINE= Multi-center,
Placebo-controlled, Randomized, Double-blind, 12-week Study with an Open-label Extension. Bays HE et al. Am J Cardiol. 2011;108:682-90.
Bays HE et al. Paper presented at: European Society of Cardiology (ESC) Congress 2011; August 29, 2011; Paris, France.
CABG=coronary artery bypass graft; HTN=hypertension.
Saito Y et al. Atherosclerosis. 2008;200:135-40.
ANCHOR: Icosapent Ethyl (Pure EPA): Median
Placebo-adjusted Change from Baseline for
Efficacy Endpoints
Select OM-3 CVD Outcome Studies
GISSI-P1-2
The ANCHOR Study: TG ≥200 and <500 mg/dL
Median Placebo-adjusted Change (%)
TG
265 254
NonHDL-C
128 128
Apo B
LDL-C
HDL-C
93
82
37
– 3.8
*
– 5.5
†
– 9.3
ǁ
– 10.1
‡
– 13.6
ǁ
91
– 6.2
†
82
– 3.6
NS
– 4.5
†
Icosapent Ethyl
4 g/day (n=233)
2 g/day (n=236)
–21.5
ǁ
38
– 2.2
NS
Baseline
values
(mg/dL)
Note: EPA is not
FDA approved for
TG 200–500 mg/dL
*P<0.05. †P<0.01. ‡P<0.001. ǁP<0.0001. NS = P≥0.05.
P-values reflect differences between icosapent ethyl vs placebo.
ORIGIN3
JELIS4
REDUCE-IT5
(Ongoing)
OM-3
Type/dose
EPA/DHA
1 g/day2
EPA/DHA
1 g/day
EPA
1.8 g/day
EPA
4 g/day
Population
N
Gender
Italian
11,324
85% male
International
12,536
65% male
Japanese
18,645
31% male
International
~8000
Accrual ongoing
Risk Profile
Recent MI (≤3 mos;
median 16 days)
High CV risk, and
IFG, IGT, or T2DM
80% 1o prev; TC ≥6.5 mM;
excl. MI ≤6 mos prior
TG >150 mg/dL
+CHD or ↑CHD risk
Follow-up
3.5 years
6.2 years (median)
4.6 years (mean)
4–6 years (planned)
Statin Use
Minimal
53% in n-3 FA arm,
55% in pbo arm
All on statins
(simvastatin or pravastatin)
All on background
statins
(LDL-C goal)
Primary
End Point
All-cause death, NF
MI, NF stroke
Death from CV
causes
Major adverse
cardiac event
Major adverse
cardiac event
Result
RRR 10%
(P=0.048)/
15% (P=0.023)
HR=0.98
P=0.72
LDL-C
2%–3% >control
groups
12% both arms
RRR 19% (no minimum Powered for 15%
TG level) P=0.011
RRR
25% in both groups
–
Note: Trial designs differ so results can not be directly compared.
1. GISSI-Prevenzione Investigators. Lancet. 1999;354:447-55. 2. www.trialresultscenter.org/study4440-GISSI-P.htm. 3. ORIGIN Investigators. N Engl J
Med. 2012;367:309-18. 4. Yokoyama M et al. Lancet. 2007;369:1090-8. 5. http://www.clinicaltrials.gov.
excl.=excluded; GISSI=Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico; IFG=impaired fasting glucose; IGT=impaired glucose
tolerance; mos=months; NF=non-fatal; ORIGIN=Outcome Reduction with an Initial Glargine Intervention; pbo=placebo; prev=prevention;
REDUCE-IT=Reduction of Cardiovascular Events with EPA-Intervention Trial; RR=relative risk; RRR=relative risk reduction.
12-week trial in high-risk statin-treated patients (N=702) with residually TG levels (≥200 and <500 mg/dL) despite LDL-C
control (≥40 and <100 mg/dL). ANCHOR=Effect of AMR101 (Ethyl Icosapentate) on Triglyceride (Tg) Levels in Patients on
Statins With High Tg Levels (≥200 and <500 mg/dL). Ballantyne CM et al. Am J Cardiol. 2012;110:984-92.
7
Reduction of CV Events with EPA –
Intervention Trial
Approximate Levels of EPA and DHA Through
Dietary Intake of Fish
Fish
N=8000
• Men & women ≥45 yo
• Prior CHD (70% patients)
or T2DM + ≥1 RF)
• Atherogenic dyslipidemia:
– Hx of ↑TC (at LDL-C
goal on statin)
– TG 150–500 mg/dL
Primary
endpoint:
Prevention of
1st major CV
event
AMR101 4 g/day
Placebo
AMR101=icosapent ethyl
• Secondary outcome measures: Incidence of additional CV events, lipid
and lipoprotein levels, subgroup analyses such as diabetes, etc.
1840
Salmon Atlantic farmed
2150
Salmon Chinook
1740
Salmon Coho wild
1060
Salmon Coho farmed
1280
Herring Atlantic
2000
Herring Pacific
2130
Mackerel Pacific and jack
1850
Mackerel Atlantic
1200
Mackerel king
Note: EPA is not
FDA approved for
TG 200–500 mg/dL
1180
Tuna bluefin
1500
Tuna yellowfin
280
Tuna skipjack
300
Bluefish
990
Pollock Alaskan
120‡
Cod Atlantic
160
Cod Pacific
280
Sablefish (black cod)†
• Anticipated completion 2016
Bass freshwater
1790
Bass sea
760
760
Whitefish
1610
Trout rainbow wild
Hx=history; yo=year(s) old.
NIH website. http://clinicaltrials.gov/ct2/show/NCT01492361?term=REDUCE-IT&rank=1.
100 g ≈ 3.5 oz, or
~¾ cup of flaked fish
470
Halibut Greenland
• Multinational trial
Approximate levels of
EPA and DHA in dry-heat
cooked fish*
400
Halibut Atlantic and Pacific
Study duration ~4–6 yrs
• Randomized, double-blind, parallel group design
EPA plus DHA (mg/100 g eaten)
Salmon Atlantic wild
990
Trout rainbow farmed
1150
*Cooked fish (dry heat) often has less OM-3 FA
content than raw fish: 100 g of fish would be ~4 oz,
which would be a bit larger than a deck of playing
cards. The amount of OM-3 FAs varies
considerably in the same type of fish, depending on
the environment and location.
†Sablefish or “black cod” is not part of the codfish
family.
‡Alaskan Pollock is the fish used in many fast-food
restaurants, where it is usually battered and fried.
Bays HE. Drugs Today (Barc). 2008;44:205-46.
Prescription vs Dietary Supplement OM-3
FDA product classification
FDA approval
Ingredients
Quantity of OM-3 per
capsule
Capsules/day to achieve
4g OM-3
OM-3 acid
ethyl esters
Icosapent
ethyl
Drug
Drug
Yes
Yes
No
DHA + EPA
EPA
Variable amounts of DHA + EPA
(may include other PUFAs)
1g
1g
Typically 300 mg – 800 mg EPA & DHA
Typically 100 – 400 EPA
4
4
Dietary Supplements
Food
Case 1: 62-yo Hispanic Woman with
T2DM, no Prior CHD Events, with
High TG
Typically 5 – 13 for EPA & DHA
Typically 10 – 40 EPA
In patients with CHD: Consume ~1 g of
EPA+DHA per day, preferably from oily fish.
EPA+DHA supplements could be considered in
consultation with the physician.
Recommended dose
4 g/day
4 g/day
In patients requiring TG lowering: 2–4 grams of
EPA+DHA per day provided as capsules under a
physician’s care
When using prescription OM-3 agents to reduce
TG levels: 4 grams of OM-3 FAs per day
Tested in clinical trials
Yes
Yes
Not required
Case 1: 62-yo Hispanic Woman with
T2DM, No Prior CHD Events, with HTG
ATP III Treatment Recommendations
for Elevated TG
Meds: None for lipids, BP, or platelets
Exam: BMI=31 kg/m2, BP=135/95 mm Hg, Waist=36”
Non-smoker
Labs:
TG
(mg/dL)
ATP III
Classification
Primary
Target of
Therapy
150–199
Borderline high
LDL-C goal
200–499
High
LDL-C goal
≥500
Very high
TG
to prevent
acute
pancreatitis
Fasting glucose 115 mg/dL
A1c
6.2%
TC
200 mg/dL
TG
559 mg/dL
HDL-C
27 mg/dL
LDL-C
118 mg/dL
Non-HDL-C
173 mg/dL
Treatment Recommendations
Weight and Physical activity
Weight and Physical activity
*Not in ATP III statement.
NCEP ATP III. Circulation 2002;106:3143-421.
8
Consider non-HDL-C goal:
LDL-C with statin or VLDL-C with niacin
or fibrate
Sugar/carbs*
Very low fat diet (fat ≤15% total calories)
Weight and Physical activity
Add niacin or fibrates
(+OM-3 as per FDA indication*)
Case 2: 49-yo Caucasian Man with T2DM, MI,
and PCI 2 yrs Ago with Modestly Elevated TG
Meds: Metformin 1000 mg bid, ASA 81 mg/d,
atorvastatin 40 mg/d
Case 2: 49-yo Caucasian Man with
T2DM, MI, and PCI 2 yrs Ago with
Modestly Elevated TG
Exam: BMI=29 kg/m2, BP=129/82 mm Hg, Waist=41”
Labs
A1c
TG
LDL-C
HDL-C
Non-HDL-C
Michael Miller, MD
6.5%
248 mg/dL
75 mg/dL
38 mg/dL
139 mg/dL
ASA=aspirin; PCI=percutaneous coronary intervention.
Case 2: 49-yo Caucasian Man with T2DM, MI,
and PCI 2 yrs Ago with Modestly Elevated TG
Case 2: Treatment Approach
Establish the patient’s risk status:
49-yo man, T2DM, previous MI with PCI 2 yrs ago, non-smoker
Meds: Metformin 1000 mg bid, ASA 81 mg/d,
atorvastatin 40 mg/d
Risk factor
Exam: BMI=29 kg/m2, BP=129/82 mm Hg, Waist=41”
Labs
A1c
TG
LDL-C
HDL-C
Non-HDL-C
6.5%
248 mg/dL
75 mg/dL
38 mg/dL
139 mg/dL
Patient
Gender: Male
Yes: Male
Age: >45 years
Yes: 49 years
Previous MI
Yes
T2DM
Yes: T2DM = CHD risk equivalent
MetS: 3 of 5 RFs
1. Waist >40”
2. Hyperglycemia
3. HDL-C <40 mg/dL
4. TG >150 mg/dL
5. High BP
Yes: MetS (4 of 5)
1. Yes, 41”
2. Yes
3. Yes, 38 mg/dL
4. Yes, 248 mg/dL
5. No: BP 129/82 mm Hg
This patient is very high risk
Risk status established, set goals for therapy
Residual CVD Risk in Major Statin Trials
Case 2: Goals for Therapy
Goal
Patients Experiencing
Major CHD Events, %
CHD events occur in patients treated with statins
28.0
Placebo
Statin
19.4
15.9
12.3
N
4444
13.2
9014
10.2
4159
Secondary
11.8
8.7
20,536
High Risk
14S
4HPS
2LIPID
5Shepherd
Group. Lancet. 1994;344:1383-9.
Study Group. N Engl J Med. 1998;339:1349-57.
3Sacks FM et al. N Engl J Med. 1996;335:1001-9.
7.9
10.9
6.8
5.5
6595
6605
Primary
LDL-C: <100 mg/dL, optional
<70 mg/dL
75 mg/dL
Is relatively low LDL-C misleading?
Why? What to do?
Non-HDL-C: <130 (<100
optional)
139 mg/dL
Non-HDL-C high on atorva 40!
Needs non-HDL-C statin adjunct
TG: <150 mg/dL (target)
248 mg/dL
Address 2o factors
Likely needs TG statin adjunct
HDL-C >40 mg/dL (target)
38 mg/dL
Waist: <40”
BMI: 18.5–24.9 kg/m2
(Obese: >30 kg/m2)
AFCAPS= Air Force Coronary Atherosclerosis Prevention Study; HPS=Heart Protection Study; LIPID= Long-term
intervention with pravastatin in ischemic disease; TexCAPS=Texas Coronary Atherosclerosis Prevention Study.
Treatment
129/82 mm Hg,
Not on BP Rx
A1c: <6.5%
Collaborative Group. Lancet. 2002;360:7-22.
J et al. N Engl J Med. 1995;333:1301-7.
6 Downs JR et al. JAMA. 1998;279:1615-22.
Patient
BP: Age ≥18 years with
T2DM: Initiate Rx treatment
when SBP is ≥140 mm Hg or
DBP is ≥90 mm Hg (JNC8)*
6.5%
41”
29 kg/m2
No treatment needed at this point
May need HDL-C statin adjunct
None: He is at goal on metformin
Physical activity: 30–60 minutes of
daily moderate aerobic activity
Diet: ↓sugars, calories & alcohol
*James PA et al. JAMA. 2013; Dec 18. [Epub ahead of print]. DBP=diastolic BP; JNC=Joint National Committee.
9
Status of the ABCs of Risk Management
Conclusions
Percent
Compliant
• Assess risk factor profile to determine
treatment goals
Aspirin
People at  risk of CV events
who are taking aspirin
47%
Blood pressure
People with HTN who have
adequately controlled BP
• In the setting of elevated TGs, LDL-C may be
misleadingly low
46%
• Non-HDL-C goal is a good lipid target to use,
especially in patients with TG >200 mg/dL
Cholesterol
People with cholesterol who
are effectively managed
33%
• Compliance is always an important treatment
issue
Smoking
People trying to quit smoking
who get help
23%
Centers for Disease Control (CDC). MMWR Morb Mortal Wkly Rep. 2011;60:1248-51.
Question & Answer
10