1. health and fitness
2. disease
3. cholesterol

Managing the Patient with High Triglycerides:
Assessment and Treatment Strategies
March 20, 2014
Houston, TX
Faculty
JoAnne M. Foody, MD, FACC, FAHA
Gregory S. Pokrywka, MD, FACP, FNLA, NCMP
Session 1: 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
JoAnne M. Foody, MD, FACC, FAHA
Medical Director, Pollin Cardiovascular Wellness Program
Brigham and Women's Hospital
Associate Professor of Medicine
Harvard Medical School
Boston, MA
Dr JoAnne Foody is the medical director of the Pollin Cardiovascular Wellness Center at Brigham and Women’s Hospital
and an associate professor of medicine at Harvard Medical School, Boston, Massachusetts. She earned her medical
degree from the University of Chicago Pritzker School of Medicine, completed her internship and a residency in internal
medicine at Brigham and Women’s Hospital, and held a fellowship in cardiology at the Cleveland Clinic Foundation. Dr
Foody’s research focuses on identifying and fostering greater use of clinical strategies that prevent adverse
cardiovascular events in people with and without coronary artery disease. She has had leadership roles in multiple quality
improvement projects of the centers for medicare and medicaid services. A fellow of the American College of Cardiology
(ACC) and the American Heart Association, Dr Foody is the author of over 100 peer reviewed articles, editor of the
authoritative text Preventive Cardiology and serves as editor in chief of CardioSmart.org, the ACC’s patient website.
Gregory S. Pokrywka, MD, FACP, FNLA, NCMP
Assistant Professor of Medicine
Johns Hopkins University School of Medicine
Director, Baltimore Lipid Center
Diplomate, American Board of Clinical Lipidology
Baltimore, MD
Dr Gregory Pokrywka earned his medical degree from the University of Maryland Medical School and was chief resident
in internal medicine at Mercy Hospital, Baltimore. He formed the Baltimore Lipid Center in 2001, and has further pursued
his interest in menopausal lipidology through certification as a credentialed menopause practitioner by the North
American Menopause Society (NAMS). He is a 2005 inaugural diplomate of the American Board of Clinical Lipidology and
is one of a handful of US physicians double certified in menopause and lipidology. In 2009, Dr Pokrywka was elected by
his peers to the honor of fellow of the National Lipid Association (NLA). Fellowship is reserved for NLA members who
have made significant regional and/or national contributions to the science and practice of clinical lipidology. Since 2004,
Dr Pokrywka has conducted over 100 lipid/lipoprotein educational programs per year. He serves on the editorial board of
the Journal of Clinical Lipidology and as assistant professor for the Johns Hopkins University School of Medicine, as well as
conducting clinical research with the IRC clinical research center.
Session 1
Faculty Financial Disclosure Statements
The presenting faculty reported the following:
Dr Foody receives honoraria from Amarin.
Dr Pokrywka receives honoraria from Aegerion, Amarin, AstraZeneca, Genzyme, Health Diagnostic Laboratory, Kowa,
LipoScience, and Sanofi.
Education Partner Financial Disclosure Statement
The content collaborators at Medtelligence, LLC have reported the following:
Ben Caref, PhD, Managing Partner and Chief Medical Officer, develops content and has no financial relationship to report.
Pamela J. Clark, Director of Editorial Services, provides editorial assistance and has no financial relationship to report.
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. 2014;311(5):507520].
Jellinger PS, Smith DA, Mehta AE, et al. 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. Circulation. 2013; Nov 7. [Epub ahead of print]
Sarwar N, Sandhu MS, Ricketts SL, et al; for 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.
Session 1
Drug Names
Managing the Patient with High
Triglycerides: Assessment and
Treatment Strategies
March 20, 2014
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
Pravastatin
Pravachol, Pravastatin
Sodium, Pravigard PAC
Rosuvastatin
Crestor, Rosuvastatin
Calcium, Rosuvastatin
Zinc
Simvastatin
Zocor, simvastatin
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
Tamoxifen
Nolvadex, Soltamox,
Tamoxifen Citrate
Thiazide diuretic
various
Learning Objectives
• Discuss the role of elevated triglyceride (TG) levels in the
assessment and diagnosis of dyslipidemia, including
cardiovascular risk factors
What Is the Relationship of
Hypertriglyceridemia to Increased CVD Risk?
• Apply best practices in the attainment of TG levels,
including the role of fasting and non-fasting states in
accurate evaluation
Gregory S. Pokrywka, MD, FACP, FNLA, NCMP
Assistant Professor of Medicine
Johns Hopkins University School of Medicine
Director, Baltimore Lipid Center
Diplomate, American Board of Clinical Lipidology
Baltimore, MD
• 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
Prevalence (%) of HTG by Age, Sex, and
Ethnicity in NHANES 1999–2008
Three Atherogenic Consequences
of HTG
TG Cut Points, mg/dLa
Demographic
Overall (age ≥20 yrs)
≥150
≥200
≥500
31
16
1.1
Men
35
20
1.8
Womenb
27
13
0.5
Mexican American
35
20
1.4
Non-Hispanic, black
16
8
0.4
Non-Hispanic, white
33
18
1.1
Use of TG-lowering
medicationsc
“Atherogenic
Dyslipidemia”
1 ↑TG / VLDL-C
1.
2 SD LDL / ↑LDL-P
2.
3 ↓HDL-C & Apo A-I
3.
TG
Central
Adiposity
1
FFA /TG
VLDL-C
Fatty
Fatty
liver
liver
FFA/TG
and
Fructose
(glucose)
CE
CETP
VLDL
↑VLDL
Synthesis
Hepatic
Lipase
HDL
3
TG
CE
CETP
2
TG
18
LDL
70 million persons, or ~1/3 of US adults, have elevated TG (≥150 md/dL)d
Hepatic
Lipase
SD
LDL
Kidney
Rapid Loss
of Apo A-I
SD
HDL
HDL-C, HDL-P,
& Apo A-I
LDL size
Apo B & LDL-P
Fatty liver & ↑VLDL synthesis are key to ↑TG and consequences
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.
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.
1
Postprandial TG (Remnants) Increased in
CAD Patients
With HTG, LDL-C Underestimates ↑CVD
Risk
Small, dense LDL-C
Large LDL-C
LDL=
130 mg/dL
CAD (n=61)
†
No CAD (n=40)
*
Apo B
†
300
More Apo B
CE
200
100
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
0
0
2
4
6
8
Hours after meal
*P=0.025; †P0.001.
CVD=cardiovascular (CV) disease; LDL-C=low-density lipoprotein cholesterol; TC=total cholesterol.
Otvos JD et al. Am J Cardiol. 2002;90:22i-29i.
CAD=coronary artery disease. Patsch JR et al. Arterioscler Thromb. 1992;12:1336-45.
Association Between BMI and HTG
NHANES 1999–2004
Enlarged Waist Combined with Elevated TG May
Predict CVD as Well as MetS in Menopausal Women
25 to <30
Cumulative Survival
BMI (kg/m2)
<25
≥30
<200 (n=4057)
39.0
33.3
27.7
≥200 (n=937)
17.5
39.6
42.9
1.1
1.1
Percent of participants within a TG category as a function of BMI status
TG (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
EWET –
1.0
Cumulative Survival
Plasma TG (mg/dL)
400
0.9
EWET +
0.8
CV
0
2
4
6
8
0.9
MetS-NCEP +
0.8
0.7
10
-2
BMI=body mass index.
AHA Scientific Statement. Miller M et al. Circulation. 2011;123:2292-333.
Low HDL-C and High TG Increase CVD Risk
Even when LDL-C Levels Are Well-Controlled
Achieving both low LDL-C and low TG (<150 mg/dL) may be important
therapeutic strategies in patients after acute coronary syndrome (ACS)
TNT Study
Patients with LDL-C ≤70 mg/dL on statina,b
N=4162
5-yr Risk of Major
CVD Events (%)
24
18
12
6
Referent
LDL-C ≥70 mg/dL
TG ≥150 mg/dL
Event Rate=17.9%
HR: 0.84
P=0.192
HR: 0.72
P=0.017
200
TG=186
TG=166
TG=147
TG=139
150
TG=122
100
TG values
(mean)
in mg/dL
50
0
0
CHD Eventa Rate
after 30 Daysc (%)
39% Lower Risk
LDL-C <70 mg/dL
TG <150
10
EWET=enlarged waist with elevated TG; MetS=metabolic syndrome; NCEP=National Cholesterol Education Program.
Tankó LB et al. Circulation. 2005;111:1883-90.
TG <150 mg/dL Associated with Lower Risk
of CHD Eventsa Independent of LDL-C Level
11.7%
8
6
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.
~2.5 greater
prevalence
16.5%
4
2
0
Follow-up Time (yrs)
Follow-up Time (yrs)
PROVE ITTIMI 22 Trialb
P<0.001
CV
P<0.001
0.7
-2
MetS-NCEP –
1.0
TG ≥150
HDL-C
Quintilesa
(mg/dL)
TG level (mg/dL)
Q1
<37
HR vs Q1*
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; 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.
aOn-treatment
Q2
37 to <42
Q3
42 to <47
Q4
47 to <55
Q5
≥55
0.85
0.57
0.55
0.61
level (3 months statin therapy), n=2661.
bMean LDL-C 58 mg/dL, mean TG 126 mg/dL.
*P=0.03 for differences among quintiles of HDL-C.
2
TNT=Treating to New Targets.
Barter P et al. N Engl J Med. 2007;357:1301-10.
AHA Scientific Statement on TG
Classification
TG Levels and CHD Risk:
Meta-analysis of 29 Studies
N=262,525
TG Revisions between 1984 and 2001
CHD Cases
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
CHD Risk Ratio* (95% CI)
TG Designation
1984 NIH
Consensus Panel
Desirable*
<250
<200
<150
250–499
200–399
150–199
High*
500–999
400–999
200–499
>1000
>1000
>500
Decreased
Risk
AHA Statement in 2011 classified TG <100 mg/dL as “optimal”
1.72 (95% CI 1.56–1.90)
Overall CHD Risk Ratio*
1
Increased
Risk
2001 NCEP
ATP III
Borderline High*
Very High*
4469
5689
1993 NCEP
ATP II
2
*All measurements in mg/dL.
AHA=American Heart Association; ATP=Adult Treatment Panel; NIH=National Institutes of Health.
Miller M et al. Circulation. 2011;123:2292-33.
*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.
Can HTG Cause Atherosclerosis?
Meta-analysis of 61 Studies Reaffirms Link
between Blood TG and CVD/All-cause Mortality
• TG-rich lipoproteins are atherogenic (esp. cholesterol-rich
remnants)
• 33 studies with data on CVD mortality (17,018 deaths in 726,030 subjects)
• 38 studies with data on all-cause mortality (58,419 deaths in 330,566 subjects)
• TG lipolysis by lipoprotein lipase (LPL) → pro-inflammatory FFA
(uptake by CD36 & FA binding proteins to nucleus)
TG level (mg/dL)
• HTG causes atherogenic changes in LDL and HDL
<90
• TG-lowering drugs ↓CVD in HTG / low HDL-C patients
90 to <150
• TG ~100–800 mg/dL is OFTEN associated with hyper-Apo B
(ie, pro-atherogenic state)
CVD mortality
All-cause mortality
RR
P
RR
P
0.83
0.001
0.94
0.15
1.00 (referent)
1.00 (referent)
150–200
1.15
0.015
1.09
0.011
>200
1.25
0.013
1.20
0.011
Median duration of study follow-up was 12.0 years.
Studies that focused on patients with diabetes, CVD, dyslipidemia or cancer were excluded.
RR=relative risk. Liu J et al. Lipids Health Dis. 2013;12:159.
FA=fatty acid. Miller M et al. Circulation. 2011;123:2292-333.
Genetics: Current Concepts On
Relationship of HTG and CVD
• Common variants of LDL-C consistently show an
association with CVD
How Should We Use Lipid Measures,
Including Triglycerides, to Assess CV
Risk in Patients with Dyslipidemia?
• Variants in HDL-C are not associated with LDL-C
or TG
– May not be an important contributor to CVD
• Variants of TG are associated with atherogenic
LDL-C and CVD
TG levels play a more important role in ASCVD than HDL-C levels
Do R et al. Nat Genet. 2013;45:1345-52. Global Lipids Genetics Consortium. Nat Genet. 2013;45:1274-83.
Varbo A et al. J Am Coll Cardiol. 2013;61:427-36.
3
American Association of Clinical Endocrinologists
(AACE) Recommendation on Elevated TG
Current TG Level Designations
2011 AHA Scientific Statement
TG
Designation*
TG
Designation*
mg/dL
Optimal
<100
Normal
Normal
<150
Mild HTG
mg/dL
<150
• TG levels that are even moderately elevated (>150 mg/dL)
may identify individuals at risk for the insulin resistance
syndrome
150–199
Borderline
High
150–199
Moderate HTG
High
200–499
Severe HTG
1000–1999
≥500
Very Severe
HTG
≥2000
Very High
• Increasing clinical evidence suggests that elevated TG
may be an independent risk factor for CAD; therefore,
AACE recommends screening of TG as a component of
lipid screening
2012 Endocrine Society
200–999
• TG levels 200 mg/dL or greater may indicate a substantial
increase in CAD risk
*All measurements fasting.
Berglund L et al. J Clin Endocrinol Metab. 2012;97:2969-89. Miller M et al. Circulation. 2011;123:2292-33.
Jellinger PS et al. Endocr Pract. 2012;18(Suppl 1):1-78.
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.
Predicting a First Atherosclerotic
CV Event
2013 ACC/AHA Guideline on the Treatment of Blood
Cholesterol to Reduce Atherosclerotic CV Risk
Four Statin Benefit Groups
Individuals with clinical
atherosclerotic
cardiovascular
disease (ASCVD) –
acute coronary
syndromes, or a
history of myocardial infarction,
stable or unstable angina, coronary
or other arterial revascularization,
stroke, TIA, or peripheral arterial
disease presumed to be of
atherosclerotic origin – without New
York Heart Association (NYHA) class
II-IV heart failure or receiving
hemodialysis.
1
2
3
4
Individuals with primary
elevations of low-density
lipoprotein cholesterol
(LDL-C) 190 mg/dL.
•Estimates the 10-year primary risk of ASCVD
among patients ages 40–79 without CVD
Individuals 40–75 years of
age with diabetes, and
•Patients are considered to be at "elevated" risk if
predicted risk is ≥7.5%
LDL-C 70–189 mg/dL
without clinical ASCVD.
•Replaces the Framingham Risk 10-year CVD
calculation
Individuals without clinical ASCVD
or diabetes, who are 40–75 years
of age with LDL-C 70–189
mg/dL, and have an estimated
10-year ASCVD risk of 7.5%
or higher.
Goff DC Jr et al. Circulation. 2013; Nov 12. [Epub ahead of print].
ACC=American College of Cardiology.
http://my.americanheart.org/professional/StatementsGuidelines/PreventionGuidelines/Prevention-Guidelines_UCM_457698_SubHomePage.jsp
CardioSource. http://www.cardiosource.org//~/media/Images/Advocacy/I13116_INFOGRAPHIC_Lipids_Guidelines_v2.pdf
4
AACE Guidelines: Lipid Goals for
Patients at Risk for CAD
Optimal Levels of LDL-C and Non-HDL-C
for Primary Prevention
Lipid Parameter
Goal (mg/dL)
TC
<200
LDL-C
HDL-C
<100; <70 (all very high risk patients)
Non-HDL-C
30 above LDL-C goal
TG
<150
Apo B
• Optimal levels
– LDL-C
– Non-HDL-C
As high as possible, but at least >40 in both
men and in women
<100 mg/dL (2.6 mmol/L)
<130 mg/dL (3.4 mmol/L)
• Optimal levels not goals of therapy
• Cholesterol-lowering goals determined by
clinical judgment
<90 (patients at risk of CAD, including
those with diabetes)
<80 (patients with established CAD or
diabetes plus 1 additional risk factor)
AACE=American Association of Clinical Endocrinologists.
Jellinger PS et al. Endocr Pract. 2012;18(Suppl 1):1-78.
International Atherosclerosis Society. http://www.athero.org/slidelibrary.asp.
Secondary Prevention: Achieving an
Optimal Atherogenic Cholesterol Level
2013 ACC/AHA Guideline:
Hypertriglyceridemia
• The optimal LDL-C in patients with established
ASCVD is <70 mg/dL (1.8 mmol/L)
(or non-HDL-C of <100 mg/dL [2.6 mmol/L])
• “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.”
• Most patients with ASCVD deserve maximal statin
therapy when it is tolerated
• To achieve an LDL-C <70 mg/dL (1.8 mmol/L)
some patients will require add-on drugs to statins
(ie, ezetimibe and/or bile acid resins)
International Atherosclerosis Society. http://www.athero.org/slidelibrary.asp.
Stone NJ et al. Circulation. 2013; Nov 12. [Epub ahead of print].
Targets for Therapy after LDL-C
Goal in Patients with TG 200 mg/dL
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
Summary and Conclusions
HTG (and low HDL-C)
• 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
• Both HTG and low HDL-C strongly predict CVD risk,
even with excellent LDL-C control on a statin
RF=risk factor.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-97.
T2DM=type 2 diabetes mellitus.
5
2013 ACC/AHA Guideline
Recommendations
After assessing for ASCVD with risk calculator,
guideline recommendations for statin Rx include
How Should HTG be Managed?
1. Individuals with clinical ASCVD
2. Individuals with primary elevations of LDL ≥190 mg/dL
JoAnne M. Foody, MD, FACC, FAHA
3. Individuals 40–75 years of age with diabetes and an
LDL 70–189 mg/dL without clinical ASCVD
Medical Director, Pollin Cardiovascular Wellness Program
Brigham and Women’s Hospital
Associate Professor of Medicine, Harvard Medical School
Boston, MA
4. Individuals without clinical ASCVD or diabetes who are
40–75 years of age with LDL 70–189 mg/dL and a 10year 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].
ATP III Treatment Recommendations
for Elevated TG
TG
(mg/dL)
ATP III
Classification
150–199
Borderline high
Primary
Target of
Therapy
Pharmacologic Therapy for Very
High TG Levels
Treatment Recommendations
High TG Indications*
Drug Class
LDL-C goal Weight and Physical activity
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
Weight and Physical activity
200–499
≥500
Fenofibratea
Consider non-HDL-C goal:
LDL-C goal
LDL-C with statin or VLDL-C with
niacin or fibrate
Sugar and carbs*
High
Very high
TG
to prevent
acute
pancreatitis
Extendedrelease
Niacin
(ERN)b
Very low fat diet (fat ≤15% total calories)
Weight and Physical activity
Add niacin or fibrates
(+OM-3 as per FDA indication*)
*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.
*Not in ATP III statement. carbs=carbohydrates; FDA=US Food and Drug Administration; OM=omega.
NCEP ATP III. Circulation 2002;106:3143-421.
Pharmacologic Therapy for Very
High TG Levels
Lipid Effects of Drug Classes in Subjects with Primary
Hyperlipidemia / Mixed Dyslipidemia and Isolated HTG
Type of dyslipidemia/
medication
High TG Indications*
Drug Class
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
Mixed dyslipidemia
• Statins
• OM-3 fatty acids
• Fenofibrate, fenofibric acid
and gemfibrozil
• Niacin
Isolated hypertriglyceridemia
• Statins
• OM-3 fatty acids
• Fenofibrate, fenofibric acid
and gemfibrozil
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; DHA=docosahexaenoic acid; EPA=eicosapentaenoic acid.
Fredrickson DS et al. Ann Intern Med. 1975;82:150-7. Miller M et al. Circulation. 2011;123:2292-333.
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
–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
TG*
–10 to –37
–19 to –44
–24 to –36
*Range, %.
NR=not reported.
Maki KC, Bays HE, Dicklin MR. J Clin Lipidol. 2012;6:413-26.
6
Risk Difference vs Placebo of Hypertriglyceridemic
Subgroups from Large-scale, Primary and Secondary CVD
Prevention Trials that Used Statins
Drug
Median
follow-up
Pravastatin
5 yrs
Statin Trials
WOSCOPS
High TG subgroup
CARE
High TG subgroup
Pravastatin
PPP Project
Highest TG tertile subgroup
JUPITER
Older subjects with TG subgroup
–31%
–17, –43 (<0.001)
–32%
–12, –47 (0.003)
–24%
–9, –36 (0.003)
5–6 yrs
Simvastatin
5 yrs
Rosuvastatin
5 yrs
Simvastatin/
pravastatin/ lovastatin/
atorvastatin/ fluvastatin
CTT Collaborators
Highest TG tertile subgroup
95% CI
(P-value)
5 yrs
Pravastatin
4S
Dyslipidemic subgroup
Risk difference
vs placebo
5 yrs
Risk Difference vs Placebo of Hypertriglyceridemic
Subgroups from Large-scale, Primary and Secondary CVD
Prevention Trials
Trial
(drug)
Primary endpoint:
entire cohort (P)
Lipid subgroup criterion
Primary endpoint:
subgroup post-hoc (P)
–34% (<0.02)
TG >204 mg/dL
LDL-C/HDL-C ratio >5.0
–72% (0.005)
BIP
(bezafibrate)
–9% (0.26)
TG ≥200 mg/dL
–39.5% (0.02)
VA-HIT
(gemfibrozil)
–22% (0.006)
TG ≥150 mg/dL
–27% (0.01)
–11% (0.16)
TG ≥204 mg/dL
HDL-C <40 mg/dL (men) or
<50 mg/dL (women)
–27% (0.005)
–8% (0.32)
TG ≥204 mg/dL
HDL-C ≤34 mg/dL
Prespecified –31%
(<0.05)
–19% (0.011)
TG ≥150 mg/dL
HDL-C <40 mg/dL
–53% (.043)
+2% (0.79)
TG ≥200 mg/dL
HDL-C <32 mg/dL
–36% (0.032)
HHS
(gemfibrozil)
–15%
1, –29 (0.07)
–23%
–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)*
ACCORD
(fenofibrate)
–21%
–19, –23 (<0.001)
–24%
–17, –23 (<0.001)
JELIS
(EPA)
FIELD
(fenofibrate)
AIM-HIGH
(niacin)
*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.
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.
Guyton JR et al. J Am Coll Cardiol. 2013;62:1580-4. Maki KC, Bays HE, Dicklin MR. J Clin Lipidol. 2012;6:413-26.
AIM-HIGH Primary Endpoint: CHD Death, Non-fatal MI,
Ischemic Stroke, High-risk ACS, Hospitalization for
Coronary or Cerebrovascular Revascularization
HPS2-THRIVE: Randomized Placebocontrolled Trial of ERN and LRPT
N=25,673 with Pre-existing CVD
Effect of ERN / LRPT on
Major Vascular Events (MVEs)*
Baseline Lipids on Statin-based Rx
Combination Therapy
Monotherapy
40
HR 1.02, 95% CI 0.87–1.21
Log-rank P value=0.79
20
16.4%
2
3
Time (years)
Monotherapy 1696
1581
1381
910
436
1606
1366
903
428
Non-HDL-C
27
TC
296
VLDL-C
175
LDL-C
89
Median Change from Baseline (%)
Change in Median Levels
45.0
P=0.0002
9.1
6.7
P=0.0015
P=0.0059
P<0.0001
0.0
–13.8
Placebo
– 0.9
– 1.7
–3.6
–45.0
14.5%
10
5
0
Placebo
ERN / LRPT
0
2
1
3
4
Years of Follow-up
Statin + EPA+DHA: COMBOS Primary
and Secondary Efficacy Results
P<0.0001
P<0.0001
Risk ratio 0.96 (95% CI 0.90–1.03)
Log-rank P=0.29
15.0%
15
*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.
OM-3 Ethyl Esters and Lipid Levels in
Patients with TG >500 mg/dL
HDL-C
22
44 (11)
125 (74)
20
“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.”
Boden WE et al. N Engl J Med. 2011;365:2255-67.
TG
816
63 (17)
The average patient had NONE of
the usual lipid indications for niacin
4
Combination Therapy 1718
128 (22)
Direct LDL
TG
0
1
TC
HDL-C
16.2%
10
0
N at risk
Baseline
(mg/dL)
Mean (SDM) at
baseline, mg/dL
Lipid
30
Patients Suffering Events (%)
Cumulative % with Primary Outcome
50
– 4.8
– 9.7
– 42.0
OM-3 Acid Ethyl Esters (4 g/day)
5
TG
NonHDL-C
LDL-C
VLDL-C
0.7‡
HDL-C
3.4*
0
–2.2
–5
–2.8
–6.3
–10
–9.0*
OM-3 (Rx) 4 g/d + simvastatin 40 mg/d (n=123)
Placebo + simvastatin 40 mg/d (n=133)
–25
–29.5*
–27.5*
Note: OM-3 AEEs are not FDA approved
for TG 200–500 mg/dL
*P<0.0001 between groups.
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.
7
–1.9
–4.2†
Additions to baseline simvastatin therapy:
–20
–30
–1.2
–7.2
–15
†P=0.0232
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.
Apo B
JELIS Patient Subgroup:
TG >150 mg/dL and HDL-C <40 mg/dL
Cumulative Incidence of Major
Coronary Events (%)
JELIS: Effect of EPA on Major Coronary
Events in Hypercholesterolemic Patients
4
↓
Primary endpoint: sudden cardiac death, fatal and
non-fatal MI, unstable angina pectoris, angioplasty,
stenting, or CABG
Statin + EPA
2
HR and P-value adjusted for age, gender, smoking,
diabetes, and HTN
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
–19%
Statin only
3
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.
CABG=coronary artery bypass graft; HTN=hypertension.
Saito Y et al. Atherosclerosis. 2008;200:135-40.
Yokoyama M et al. Lancet. 2007;369:1090-8.
MARINE: EPA: Median Placebo-adjusted Change
from Baseline for Efficacy Endpoints
ANCHOR: EPA Median Placebo-adjusted Change
from Baseline for Efficacy Endpoints
The ANCHOR Study: TG ≥200 and <500 mg/dL
ITT Population
The MARINE Study: TG >500 mg/dL
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
NS
1.5
TC
-2.3
NS
-2.6
NS
-6.8
*
-8.5
†
-13.6
‡
-33.1
ǁ
VLDL-TG hsCRP
-3.6
NS
-10.1
NS
-16.3
ǁ
-17.3
NS
Icosapent Ethyl
-28.6
‡
TG
HDL-C
Median Placebo-adjusted Change (%)
Median Placebo-adjusted Change (%)
LDL-C
4 g/day (n=76)–FDA approved dose
-25.8
†
2 g/day (n=73)
-36.0
†
†P<0.01. ‡P<0.001. ǁP<0.0001.
*P<0.05.
NS = P≥0.05.
P-values reflect differences between icosapent ethyl vs placebo.
265 254
NonHDL-C
128 128
Apo B
LDL-C
HDL-C
93
82
37
91
– 3.8
*
– 5.5
†
– 9.3
ǁ
– 10.1
‡
– 13.6
ǁ
– 6.2
†
82
– 3.6
NS
– 4.5
†
EPA
Baseline
values
(mg/dL)
Note: EPA is not
FDA approved for
TG 200–500 mg/dL
4 g/day (n=233)
2 g/day (n=236)
–21.5
ǁ
38
– 2.2
NS
*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.
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.
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.
Select EPA+DHA CVD Outcome Studies
EPA CVD Outcome Studies
GISSI-P1-2
ORIGIN3
Risk and
Prevention Study4
STRENGTH5
JELIS1
OM-3
Type/dose
EPA+DHA
1 g/day
EPA+DHA
1 g/day
EPA+DHA
1 g/day
EPA+DHA
4 g/day
OM-3 Type/dose
EPA
1.8 g/day
EPA
4 g/day
Population
N
Gender
Italian
11,324
85% male
International
12,536
65% male
Italian
12,513
61% male
International
Estimated 13,000
?
Population
N
Gender
Japanese
18,645
31% male
International
~8000
Accrual ongoing
Risk Profile
Risk Profile
REDUCE-IT2
(Ongoing)
Recent MI (≤3 mos;
median 16 days)
High CV risk, and
IFG, IGT, or T2DM
High CV risk, and
CAD but no MI
High CV risk (50%), any
atherosclerotic CVD (50%)
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)
5 years (median)
5 years (median)
Follow-up
4.6 years (mean)
4–6 years (planned)
Statin Use
Minimal
53% in n-3 FA arm,
55% in pbo arm
41%
Estimated 100%
Statin Use
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
Death, non-fatal MI
and stroke
?
Primary End Point
Major adverse
cardiac event
Major adverse
cardiac event
Result
RRR 10%
(P=0.048)/
15% (P=0.023)
HR=0.98
P=0.72
HR=0.97
P=0.58
?
Result
RRR 19% (no minimum TG level)
P=0.011
Powered for 15% RRR
LDL-C
2%–3% >control
groups
12% both arms
NA
?
LDL-C
25% in both groups
–
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. The Risk and Prevention Study Collaborative Group. N Eng J Med. 2013;368;1800-08. 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; RRR=relative risk reduction.
1. Yokoyama M et al. Lancet. 2007;369:1090-8. 2. http://www.clinicaltrials.gov.
prev=prevention; REDUCE-IT=Reduction of Cardiovascular Events with EPA-Intervention Trial.
8
Major Dietary Sources of Long-Chain (n-3)
PUFAs EPA and DHA
REDUCE-IT Trial
• 8000 men and women aged ≥45 years
• Established CHD (70% pts)
or high-risk for CHD (diabetes + ≥1 RF)
• Atherogenic dyslipidemia:
– Hypercholesterolemia but at LDL-C goal
(all patients on statin)
– TG ≥150 mg/dL and <500 mg/dL
Anchovy
Herring, Atlantic
Salmon, farmed
Salmon, wild
Mackerel, Atlantic
Bluefish
Sardines, Atlantic
Trout
Goldenbass (tilefish)
Swordfish
Tuna, white (albacore)
Mussels
Striped bass
Shark
Pollock, Atlantic
Primary
endpoint:
Prevention of
1st major CV
event
EPA 4g/day
Placebo
Study duration ~4–6 years
• Randomized, double-blind, parallel group design
• Secondary outcome measures: Incidence of additional CV
events, lipid and lipoprotein levels, subgroup analyses such
as diabetes, etc.
Note: EPA is not
FDA approved for
TG 200–500 mg/dL
• International trial
• >6,000 patients enrolled as of September 25, 2013
• Anticipate results 2017
EPA*
DHA*
Combined
EPA+DHA*
763
1292
2055
909
1105
2014
862
1104
1966
411
1429
1840
504
699
1203
323
665
988
473
509
982
259
677
936
172
733
905
127
772
899
233
629
862
276
506
782
169
585
754
258
431
689
91
451
542
*mg/100 g. Mozaffarian D, Wu JHY. J Nutr. 2012;142:614S-625S.
(Data are from the USDA National Nutrition Database for Standard Reference Release 23, 2010.)
Hx=history. NIH website. http://clinicaltrials.gov/ct2/show/NCT01492361?term=REDUCE-IT&rank=1.
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
EPA+DHA
EPA
Dietary Supplements
Drug
Drug
Food
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
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
A recent study found that 20% of the 30 top-selling OM-3 products contained levels of OM-3s that averaged 30% less than stated
on their labels. http://well.blogs.nytimes.com/2014/01/22/whats-in-your-fish-oil-supplements/?_php=true&_type=blogs&_r=0.
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.
9
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
Gregory S. Pokrywka, MD, FACP, FNLA, NCMP
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
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 TG, 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.
10