the Lipid Spin (Winter 2013-14)

Transcription

Official Publication of the National Lipid Association
LipidSpin
Theme:
Obesity from a
Global Perspective
Also in this issue: New Pharmacologic Approaches to Obesity
The Adipocyte: Friend or Foe?
This issue sponsored by the Northeast Lipid Association
Volume 12 Issue 1
Winter 2013/2014
visit www.lipid.org
MORE THAN A
MEETING IN MAUI
Join us for the opening session of the 2014 Clinical Lipid Update Meeting
as world renowned thought leaders discuss Lipid Management and Metabolic Syndrome
in various populations from around the world.
W. Virgil Brown, MD, FNLA
Yuji Matsuzawa, MD, PhD
Shaukat Sadikot, MD
Cesare R. Sirtori, MD, PhD
GeraldWatts, DSc, MB, BS, PhD
This meeting features evidence-based sessions that include:
A debate from John Brunzell, MD and Sekar Kathiresan, MD
How Close are we to Personalizing CVD Prevention with Genetics?
Other key sessions include:
HDL: State of the Lipoprotein
Benjamin Ansell, MD, FNLA
Cardiovascular Risk in Asians
and Pacific Islanders
Beatriz Rodriguez, MD, PhD
Keawe’aimoku Kaholokula, PhD
Nathan Wong, PhD
Latha Palaniappan, MD, MPH
See you in Maui!
Visit www.lipid.org/springclu to register now.
To book your room, call 800-888-6100 and ask for the
National Lipid Association room rate.
Get the NLA room rate starting at $235/night plus tax if you
book your room by February 11, 2014.
Delta Airlines discount code: NMGR6
WALDORF ASTORIA GRAND WAILEA HOTEL
WAILEA, MAUI, HAWAII
CME Credit provided by the National Lipid Association
This activity has been approved for AMA PRA Category 1 Credit™
This activity is eligible for CDR credit
CE credit provided by Postgraduate Institute for Medicine
This activity is eligible for ACPE and ANCC credit
See final activity program for specific details
Debate: Is it time to Stop using
Fibrates Combined with Statins?
Jocelyne R. Benatar, MD, MBChB
Eliot Brinton, MD, FNLA
CVD Reduction Through Fish Oils,
Diet and Supplements
Kathleen Wyne, MD, PhD, FNLA
Terry Jacobson, MD, FNLA
Forrest Batz, PharmD
Geeta Sikand, RD, FNLA
In This Issue: Winter 2013/2014 (Volume 12, Issue 1)
Editors
JAMES A. UNDERBERG, MD, MS, FACPM, FACP, FNLA*
President, Northeast Lipid Association
Clinical Assistant Professor of Medicine
NYU School of Medicine & NYU Center for Prevention of
Cardiovascular Disease
Director Bellevue Hospital Lipid Clinic
New York, NY
ROBERT A. WILD, MD, PhD, MPH, FNLA*
Clinical Epidemiology and Biostatistics and
Clinical Lipidology Professor
Oklahoma University Health Sciences Center
Oklahoma City, OK
Managing Editor
EMILY T. PARKER, MA
National Lipid Association
Executive Director
CHRISTOPHER R. SEYMOUR, MBA
Contributing Editor
KEVIN C. MAKI, PhD, CLS, FNLA
Associate Editor for Patient Education
VANESSA L. MILNE, MS, NP, CLS
Cardiac Vascular Nurse and Family Nurse Practitioner
Bellevue Hospital Lipid Clinic
New York, NY
Lipid Spin is published quarterly by the
6816 Southpoint Parkway, Suite 1000
Jacksonville, FL 32216
Phone: 904-998-0854 | Fax: 904-998-0855
Copyright ©2013 by the NLA.
All rights reserved.
Visit us on the web at www.lipid.org.
The National Lipid Association makes every effort to
provide accurate information in the Lipid Spin at the
time of publication; however, circumstances may alter
certain details, such as dates or locations of events.
Any changes will be denoted as soon as possible.
The NLA invites members and guest authors to
provide scientific and medical opinion, which do not
necessarily reflect the policy of the Association.
2 From the NLA President
My First Six Months
—Matthew K. Ito, PharmD, CLS, FNLA
3 From the NELA President
Time Flies When You Are Having
Fun
— James A. Underberg, MD, MS, FACPM, FACP,
FNLA*
4 Letter from the Lipid Spin Editors
Let’s Not Confuse Health Care Costs
and Health
—Edward Goldenberg, MD, FACC, FNLA*
5 Clinical Feature
New Pharmacologic Approaches to
Obesity
—Kenneth A. Kellick, PharmD, CLS, FNLA
9 Guest Editorial
Look for the NLA Community logo to discuss
articles online at www.lipid.org
20 Practical Pearls
Can Smartphones Help our Patients
Lose Weight?
—Ruchi Prasad, MD
—Dean G. Karalis, MD, FACC, FNLA*
22 Case Study
Childhood Adiposopathy Unmasks
Type III Hyperlipoproteinemia
—Daniel Soffer, MD, FNLA*
—Danielle Duffy, MD
—Fran Burke, MS, RD
— Joyce Ross, MSN, CRNP/CCS, FPCNA, CLS, FNLA
Atherosclerosis in the Indian
Population
25 Chapter Update:
12 EBM Tools for Practice
—Linda C. Hemphill, MD, FACC, FNLA*
—Vinay R. Hosmane, MD, MPH, FASE, FACC
—Vivek K. Reddy, MD
Weight Management: EvidenceBased Nutrition Strategies
—Wahida Karmally, Dr.PH, RD, CDE, CLS, FNLA
15 Lipid Luminations
PREDIMED Commentary
—Eugenia Gianos, MD*
—Joaquin Carral, MD
17 Specialty Corner
—Edward Goldenberg, MD, FACC, FNLA*
— Jaya Bathina, MD
NELA’s Past and Vision for the
Future
27 Member Spotlight:
David M. Capuzzi, MD, PhD, FNLA,
FACP, FACE*
28 Education, News and Notes
29 Foundation Update
30 References
32 Events Calendar
33 Provider Tear Sheet
*indicates ABCL Diplomate status
1
From the NLA President: My First Six Months
Matthew K. Ito, PharmD, CLS, FNLA
National Lipid Association President
Professor of Pharmacy Practice
Oregon State University/Oregon Health and Science University
Portland, OR
Diplomate, Accreditation Council for Clinical Lipidology
Discuss this article at
www.lipid.org/lipidspin
It has been a busy—and rewarding—six
months since I took over as President of the
NLA. It is extremely gratifying to see so many
projects that were discussed in the Board’s
Strategic Plan taking shape.
In our efforts to streamline processes and
refine our organizational structure, we
created three Councils, each managed by a
Board officer. Every Council has a number
of Committees that fall under it, and the
Committee Chairs now have a better process
for funneling ideas and initiatives up to the
Council Chair, where it is heard directly by a
Board officer.
In the education arena I have several
improvements and accomplishments to
share with you. First, we have adopted a
core curriculum for education that reflects
initiatives across the entire NLA. The NLA’s
Core Curriculum in Clinical Lipidology serves
as a guide for development of educational
activities tailored to health care professionals
at all stages of their careers. The NLA SelfAssessment Programs have been completely
revised and updated as of September. Revising
the SAP was a very time-consuming task, and
I want to thank Dr. Carl Orringer for leading
that effort. With the help of Associate Editors,
Dr. Terry Jacobson, Dr. James Underberg,
Dr. Vera Bittner, and Dr. Eliot Brinton, the
2
new edition of the NLA-SAP is the most
comprehensive training tool to date. We had
a very successful Clinical Lipid Update in
Baltimore, MD hosted by the Northeast and
Southeast regional chapters. The conference,
Clinical Tools for the Practicing Lipidologist:
Recent Advances in Genetics, Lifestyle and
Pharmacy, was attended by approximately
220 people. The Spring Clinical Lipid Update
(March 13-16 in Maui, HI) is in its final
planning stages and is looking to be the best
international meeting the NLA has ever
hosted. And, of course, the Annual Scientific
Sessions are approaching quickly. The 2014
Sessions will be held May 1-4 in Orlando, FL
with a focus on familial hypercholesterolemia
(FH).
The NLA has taken a very proactive role in
offering guidance and recommendations
for recently released guidelines. The
International Atherosclerosis Society
(IAS) released guidelines on The Global
Management of Dyslipidemia, which were
endorsed by the NLA. In addition, the NLA
is actively involved in collaborating with
the American College of Cardiology (ACC)
and the American Heart Association (AHA)
on improvements to the recently released
2013 Blood Cholesterol Guideline. While
the NLA did not endorse this new Guideline,
we are hopeful that we can provide positive
input and recommendations as the ACC
and AHA continue to revise and modify the
Guideline. After careful review, the NLA
did endorse three Guidelines released by
the ACC/AHA: Management of Overweight
and Obese Adults; Lifestyle Management to
Reduce Cardiovascular Risk; and Assessment
of Cardiovascular Risk. Links to all of these
Guidelines can be found at www.lipid.org.
As you will read in the Foundation of the
NLA Update, in mid-September several
NLA members attended the FH Summit in
Annapolis, MD hosted by the FH Foundation.
At the Summit, the FH Foundation
announced the launch of its FH patient
registry, and I was honored to be a guest
speaker at the opening session to share my
personal experience with FH and a call to
action for more research in non-invasive
assessment of subclinical atherosclerosis in
asymptomatic patients with FH.
Dr. Anne Goldberg and I were invited to
attend the LDL: Address the Risk Think
Tank organized by the ACC. Representatives
from medical specialty societies and other
stakeholder groups were invited for an
interactive discussion about:
1. Guidelines: What is their treatment target,
how were they developed, and what will be
their role in the future?
2. Gaps in Care: How do they occur?
3. Special Populations: What are the issues?
It was insightful meeting and will be used by
the ACC moving forward on development of
practical guidance for lipid management.
I value your input and participation both at
the national and regional level.
I hope to see you at one of our upcoming
meetings. I wish you and your families a
Happy New Year. n
LipidSpin
From the NELA President:
Time Flies When You Are Having Fun
JAMES A. UNDERBERG, MD, MS, FACPM, FACP, FNLA
President, Northeast Lipid Association
Clinical Assistant Professor of Medicine
NYU School of Medicine & NYU Center for Prevention
of Cardiovascular Disease
Director Bellevue Hospital Lipid Clinic
New York, NY
Diplomate, American Board of Clinical Lipidology
It is with great pride and excitement
that I compose this chapter message.
Conveniently, this issue of Lipid Spin falls
midway through my year as President of
NELA, and therefore provides a perfect
opportunity to update you on where we
are, and where we are going.
The summer months were a time of
planning, both for our NELA/SELA CLU
in Baltimore in mid-September and for
our community outreach project in early
September. I am pleased to say that both
were great successes. The Baltimore
meeting, focusing on “The Genetics of
Lipid Disorders” was one of the most
well-attended Clinical Lipid Updates.
The combination of speakers and venue
provided a wonderful opportunity for
attendees to re-energize and connect after
the summer months. The NELA Board
was able to have a face-to-face meeting
and discuss our upcoming plans for the
remainder of the year.
Just prior to the Baltimore meeting we
held our first NELA community outreach
event in New York City at the “NY
Yankees Fan Fest” held at the Intrepid Air
and Space Museum in Manhattan. This
event was co-sponsored by NELA and
the Foundation of the NLA. Many thanks
to Merle Myerson, MD and NLA staff
members Judi Span and Emily Parker for
helping to coordinate this event, along
with the numerous NELA members who
traveled from throughout the Northeast
region to participate in this event. We
participated in a cholesterol screening and
awareness program, while also promoting
FH awareness. It was wonderful seeing one
another on a warm, sunny New York day.
Next time we will make sure we are not
next door to the free ice cream booth!
Most recently NELA endorsed and helped
promote the NY Lipid Forum, held at
Roosevelt Hospital in New York City.
Similar events have been held in other
NELA cities, including the Philadelphia
Lipid Group (Dan Soffer, MD, FNLA), and
in Boston. Despite the inclement weather
and the proximity to the Thanksgiving
holiday, almost 100 attendees showed
up to listen to NELA members Robert
Rosenson, MD, Don Smith, MD, FNLA,
and Joyce Ross, MSN, CRNP, FNLA
discuss several interesting and timely
subjects. Expected debate ensued with
a lively question-and-answer session. It
was great to see current and new NELA
members attending. Once again, thanks to
Dr. Merle Myerson for spearheading this
program. We look forward to endorsing it
again next year!
and even CME programs can all serve
as opportunities to meet, engage and
enlist more NELA members. Our new
membership committee, co-chaired by Ken
Kellick, PharmD, FNLA and Spencer Kroll,
MD, PhD, FNLA is working on additional
ways to increase our numbers. Many
thanks to all who have helped make this
a great 2013, including our wonderful
executive committee, our great Board of
Directors and all of the members who have
volunteered and helped out this year. I
look forward to an exciting 2014, and hope
to see many of you at our Annual Scientific
Sessions in Orlando this May. n
My hope for the first half of 2014 is to
continue these types of activities in many
of our other NELA locations. Local gettogethers, community outreach projects
3
Letter From the Lipid Spin Editors: Let’s Not Confuse Health Care Cost and Health
EDWARD GOLDENBERG, MD, FACC, FNLA
Medical Director of Cardiovascular Prevention and Employee Wellness
Christiana Care Health System
Chairman, Million Hearts Initiative Delaware
Newark, DE
Let’s not confuse health care cost and health.
Health care cost is the amount of money spent
predominantly for the diagnosis and treatment
of people with an acute illness or a chronic
disease. The cost is related to the number of
encounters and the cost per encounter. It is
estimated that one third of health care costs
are related to unnecessary care. The Affordable
Care Act is aimed at improving the efficiency
of the system, providing higher quality of care
at a lower cost and ultimately eliminating
unnecessary care. This plan may achieve the
immediate goal of decreasing cost but it will
be ineffective in controlling cost in the long
term. The epidemic of obesity will result in
an increased number of people with chronic
diseases who will require cost effective care.
According to the 2011 America’s Health
Rankings, Delaware is the 30th healthiest
state in the United States. The basis of health
is not the effectiveness in caring for the sick
but the prevention of people at risk from the
development of chronic disease. The factors
that contribute to the development of chronic
4
disease include individual behaviors such as
the prevalence of smoking, binge drinking
and obesity. There are community and
environmental factors such as the incidence
of violent crime, the number of children
who graduate high school, the quality of air,
the number of children in poverty and the
prevalence of infectious diseases. There are
public and health policies such as lack of health
insurance, and availability of immunization.
The last is clinical care, which includes
prenatal care, preventable hospitalizations and
the availability of primary care physicians.
To achieve health and decrease the number of
people who will require health care requires a
co-operative effort on the part of clinical care,
the development of public policy focused on
improving health, and improving community
and environment factors. Ultimately, health is
the responsibility of the individual.
At the end of the 19th century and the
beginning of the 20th century an alliance of
public health, labor, and social and housing
reformers were able to remove garbage from
the water and address unfair labor practices.
Hibbert Hill in his 1916 book The New
Public Health noted “The old public health
was concerned with the environment; the
new is concerned with the individual.” The
recent New York City ban on the size of
sugar containing beverages was a challenge to
corporate and industrial practices that place
profit above public health. This was reversed
because the New York City Board of Health
is an administrative agency, which can do
only what is authorized by the legislature.
Physicians deal with one patient at a time, but
legislatures set the standards for community
health and the path to follow to achieve health.
Dr. Frieden, the director of the Centers for
Disease Control and Prevention, addressed in
the May 16, 2013 issue of the New England
Journal of Medicine Government’s Role in
Protecting Health and Safety. “Government
has a responsibility to implement effective
public health measures that increase
information available to the public and decision
makers, protect people from harm, promote
health, and create environments that support
healthy behaviors. Opponents of public health
action often fail to acknowledge the degree
to which individual actions are influenced
by marketing, promotion, and other external
factors.”
Have we, citizens, legislators, and elected
officials effectively partnered to legislate,
educate and encourage individuals to choose a
path toward health and not chronic disease? n
LipidSpin
Clinical Feature:
New Pharmacologic Approaches to Obesity
KENNETH A. KELLICK, PharmD, CLS, FNLA
Clinical Pharmacy Coordinator, VA Western
New York Healthcare System
Buffalo, NY
Changed lifestyles and diet have been
associated with the current obesity
epidemic. Pharmacologic interventions
date back to the Greco-Roman era when
laxatives coupled with exercise and other
modalities to facilitate weight loss were
prescribed or used. Many still remember
the use of the following medications:
thyroid hormone, amphetamines, digitalis,
diuretics and dinitrophenol. These were
early 20th century options. Phentermine
was approved in 1959 by the U.S. Food
and Drug Administration (FDA) as an
adjunct to diet. Its mechanism of action
appears to be related to stimulation of the
hypothalamus to release norepinephrine
resulting in reduced appetite while
increasing at-rest energy expenditure.
While phentermine was still on the market
and although riddled with side effects such
as insomnia and irritability, new players
emerged.
Fenfluramine (3-trifluoromethyl-Nethylamphetamine) is a drug that was
part of the fen-phen anti-obesity regimen,
the other component was phentermine.
Fenfluramine was introduced on the U.S.
market in 1973. Dexfenfluramine was
introduced 20 years later as a “reduced
side effects” fenfluramine. Fenfluramine
and dexfenfluramine likely upregulated
5HT2B receptors as their weight-loss
mechanism.
Patients were only to be on the “fenphen” combination for 12 weeks. Late
in 1997 there were reports of significant
valvulopathy in patients who had been
on the medications for more than six
months. These led to the withdrawal of
fenfluramine and dexfenfluramine but not
phentermine.
Orlistat entered the market in 1999 as
the prescription medication Xenical®. The
action mechanism is to inhibit gastric and
pancreatic lipases and when taken with a
meal containing fat. This concept renders
the medication less effective for patients
on a low-fat, low-carbohydrate diet. While
the weight loss was modest, the orlistat
in the Prevention of Diabetes in Obese
Subjects (XENDOS) study showed patients
taking orlistat lost an average of 2.7 kg
more in 1 year compared to placebo.2
Common adverse reactions with orlistat
include oily spotting, flatus with discharge,
fecal urgency, fatty/oily stool, oily
evacuation, increased defecation and fecal
incontinence. Monitoring of renal function
because of increases in oxalate levels also
is recommended.3
In 2007, the FDA approved over-thecounter orlistat under the brand name
Alli. It is available as a 60mg capsule
– the prescription dose is 120mg – and
is administered the same way as the
prescription version. Because of its
interference with absorption of fat from
the gastrointestinal tract, the absorption
of fat-soluble vitamins (A, D, E and K) may
be impaired. Consequently patients should
take a daily multivitamin supplement
containing these vitamins when using this
agent.
While it would appear that a non-absorbed
agent would be totally safe, the FDA in
2010 added information about reported
cases of liver injury tied to orlistat.4,5 The
5
Drug
(DEA Class)
{AWP}
Length
MOA,
of
Metabolism
Treatment
Phenterimine
(Class IV)
{$15/day}
12wks
Orlistat
Alli®
Xenical®
(No DEA
sched.)
{$2-5/day}
ADRs
Dose and
Administration
Warnings
Drug Interax
Sympathomimetic Palpitations
~Amphetamine
BP, HR,
Satiety
Insomnia
--70-80% renal
Some hepatic
Unstable
cardiovascular
disease,
uncontrolled
BP, Glaucoma,
Alcohol abuse,
Pregnancy
(Category X)
Effects of CNS 15-37.5mg
stimulators
once daily in
Effect of
the morning.
guanethidine
Serotonin
Syndrome
with MAO
inhibitors.
12wks
(if loss
of 5%
TBW)
No real
length
of
therapy
if
effective
Gastrointestinal
lipase inhibitor
Cholestasis
Chronic
malabsorption
syndrome,
Pregnancy
(Category X)
Decreased
absorption of
fat soluble
vitamins,
cyclosporine,
vitamin K and
levothyroxine.
Take
interacting
drugs 3-4
hours apart
from orlistat
One 60 or
120mg
capsule three
times a day
with meals
containing fat.
Lorcaserin
Belviq®
(Class IV)
{$24/day}
12
weeks if
5%
weight
loss
achieved
Serotonin 2c
agonist
Dizziness
Fatigue
Headache
Nausea
Dry mouth
Constipation
Hyperprolac
tinemia
Bradycardia
Possible
serotonergic
syndrome,
caution if
signs of
valvulopathy,
memory
disturbances,
caution using
heavy
machinery,
euphoria,
disorientation,
monitor blood
glucose,
watch for
priapism
(Pregnancy
Category X)
Caution with
MAO
inhibitors,
triptans,
SNRIs,
bupropion,
dextromet
horphan, and
bupropion
10mg BID
Phentermine/
Topiramate
Qysmia®
(Class IV)
{$17-25/day}
Discontinue
if 3%
weight
loss not
achieved
in 12
weeks,
limited
data
beyond
24 weeks
Phenterminesympthominetic
increased satiety.
Topiramate
augments the
activity gammaaminobutyrate,
modulates
voltage-gated ion
channels, inhibits
AMPA/kainite
excitatory
glutamate
receptors, or
inhibition of
carbonic
anhydrase
resulting in
increased satiety.
Parasthesias,
dizziness,
dysgeusia,
insomnia,
constipation,
and dry
mouth
Tachycardia,
sucidal
ideations,
acute myopia
and secondary
angle closure
glaucoma,
mood or sleep
disturbance,
disturbance in
attention or
memory
(caution in
vehicles),
metabolic
acidosis,
elevated Cr,
changes in
glucose level.
Taper off over
1 week to
avoid
seizures.
Increased
bleeding with
oral
contraceptives.
Avoid
concomitant
alcoholo.
May
potentiate
hypokalemia
with diuretics.
One 3.75 /23
mg ER tablet
daily for 14
days, then
increase to
7.5 mg/46 mg
daily.
Oily rectal
discharge,
flatus, fecal
incontenence,
increased
defacation,
reports of
hepatotoxicity
Table 1. Weight Loss Medications
package insert notes some success when
tested with adolescent patients ages 12-16.
Additional studies show that weight regain
remains less with orlistat compared to a
6
formulations. It appears to reduce appetite
through augmentation of adrenergic
nerve transmission, both peripherally and
centrally. Similar to amphetamines, it is
classified as a Schedule IV drug with very
low abuse potential. The FDA’s labeled
indications say it should be used for a
few weeks (no>3mos) along with diet,
exercise and behavioral modification for
the management of obesity.7 To avoid
insomnia, the medication should be taken
in the morning. While not FDA approved,
some continue treatment beyond 12
weeks.
Two new obesity medications recently
were approved by the FDA. Lorcaserin
(Belviq®) and phentermine-topiramate
(Qsymia®). These were approved for
use in patients as an adjunct to diet and
exercise for chronic weight management
in adult patients with an initial body mass
index (BMI) of 30 kg/m2 or more (obese)
or 27 kg/m2 or more (overweight) in the
presence of at least one weight-related
comorbid condition (e.g., hypertension,
dyslipidemia, type 2 diabetes).8,9 With new
action mechanisms, these modalities are
the first recent additions to obesity therapy
in many years.
Lorcaserin is a selective agonist of 5-HT2C
receptors that are mainly in the brain –
in areas of the cortex, choroid plexus,
hippocampus, cerebellum, amygdala,
thalamus and hypothalamus. The activated
proopiomelanocortin (POMC) cell region
of the hypothalamus is believed to trigger
proopiomelanocortin production and
promote satiety.10 Lorcaserin’s selectivity
for the 5-HT2C receptor is significantly less
than for the 5-HT2A and 5-HT2B receptors.
Lorcaserin’s exact action mechanism to
decrease food consumption and promote
satiety is not fully known.11
placebo.6
As previously noted, phentermine
remains on the market in various generic
The approved dose is 10mg twice daily
with no regard to administration with
meals. The medication is administered
LipidSpin
in mild to moderate renal impairment
(CrCl 30-50ml/min) without altering dose.
There is limited data in patients with
Child-Pugh Class C hepatic impairment
or in patients with CrCl <30ml/min, so
caution is advised. Side effects including
headache, sinusitis and upper respiratory
tract infection are mild and well tolerated.
Lorcaserin is in pregnancy Category X.8,11
Three pivotal trials demonstrated lorcaserin
efficacy, the first being a 52-week trial of
the 10mg-twice-daily and 10mg-once-daily
doses versus placebo. The criterion for
success was 5% weight loss from baseline.
More weight loss (47.2%) was noted with
the twice-daily group versus the oncedaily (40.2%) or placebo (25%) groups.
Dropout rates approximated half of the
study population. Side effects were mild, as
previously noted.12
Similarly, in another trial, 47.5% of those
in the lorcaserin-twice-daily group achieved
targeted results as compared to 20.3%
of those in the placebo group.13 In the
BLOOM-DM diabetes trial more patients
lost ≥5% body weight with lorcaserin daily
(44.7%) compared to twice daily (37.5%)
or placebo (16.1%).14 Vavlulopathies at one
year occurred in 2.4% of patients assigned
to lorcaserin and 2% of those in the placebo
group. In the Behavioral Modification
and Lorcaserin Second Study for Obesity
Management (BLOSSOM) study, 12%
developed valvular regurgitation in the
twice-daily group and 11% in the once-daily
cohort. There were minimal improvements
in serum lipids with lorcaserin. After two
years of exposure to lorcaserin, the rate
of valvulopathy was 2.6%; it was 2.7% in
the placebo arm.12,13,14 The FDA originally
delayed approval in 2010 because of
concerns about tumors in rats receiving
high doses of lorcaserin. With subsequent
studies, the FDA approved the medication
in 2012.15,16
The combination of phenterminetopiramate also was recently approved by
the FDA. Unlike lorcaserin, this product
is governed by a Risk Evaluation and
Mitigation Strategy (REMS) program. The
mechanism of phentermine was previously
discussed and, while the exact mechanism
is unclear, topiramate increases satiety and
suppresses appetite. Possible mechanisms
include increasing the activity of the
neurotransmitter gamma-aminobutyrate,
modulation of voltage-gated ion channels,
inhibition of alpha-amino-3-hydroxyl-4isoxazole-propionic acid/kainite excitatory
glutamate receptors, or inhibition of
carbonic anhydrase.
Doses start at 3.75mg/23mg (phentermine/
topiramate) for 14 days then increase
to the 7.5mg/46mg dose. If a 3% loss in
total body weight is not reached by Week
12, then the medication is discontinued.
Doses can be increased to the maximum
15mg/92mg dose, but the drug should
be discontinued if a 5% weight loss is not
achieved after 12 weeks on the maximum
dose. To avoid seizure, the drug should be
slowly discontinued (taken every other day)
for a week.
Adverse events such as tachycardia,
paresthesia, dizziness, dysgeusia,
insomnia, constipation and dry mouth
are infrequent. Phetermine/topiramate is
in pregnancy Category X. In the EQUIP
study, a significant difference in weight
loss was noted with the 3.75mg/23mg
and 15mg/92/mg doses compared to the
placebo. Patients receiving the maximal
dose showed significant improvements in
fasting glucose, triglycerides, high-density
lipoprotein (HDL) cholesterol and lowdensity lipoprotein (LDL) cholesterol. In
the large CONQUER study, between 60%
and 70% (low dose versus high dose) of
patients achieved the target of at least
5% weight loss from baseline.12,13,14 While
attractive as moderate weight loss drugs,
costs and lack of insurance coverage for
these agents (Table 1) may limit their use.
Other medications that are currently under
investigation include a fixed combination
of naltrexone, bupropion and liraglutide.
Table 1 provides a summary of the
common current weight-loss medications.
Full drug information on each of these
available medications is available from the
manufacturers.
Popular OTC medications for weight loss
include green tea, green coffee, conjugated
linoleic acid, guarcia, guarana chromium
and bitter orange, among others. While
interactions are possible, they usually
concentrate around those items with
stimulant activities and other stimulant
medications, including monoamine oxidase
(MAO) antidepressants. Items such as
green coffee extract, green tea extract
and bitter orange may have moderate
interactions with stimulant drugs.
OTC diet supplements containing ephedra
were removed from the market by the
FDA in 2004. Ephedra was a non-selective
alpha and beta receptor stimulant. Adverse
reaction reports linked ephedra to serious
side effects, including hypertension,
myocardial infarction (MI), seizure, stroke,
psychosis and other illness.20
There has been a long time desire for
pharmacotherapy options to enhance
weight loss not achieved by diet and
exercise alone. The currently available
medications offer a variety of choices
for the clinicians – whether pediatric,
adult or geriatric – to offer their patients.
The agent of choice should be closely
monitored for effects and adverse
reactions. n
Disclosure statement: Dr. Kellick has no disclosures to
report.
References are listed on page 30.
7
Updated and Revised
September 2013
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1 The Science of Lipidology: Lipid Metabolism, Pathogenesis of
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and Management of Patients at Risk
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Guest Editorial:
Atherosclerosis in the Indian Population
VINAY R. HOSMANE, MD, MPH, FASE, FACC Hosmane Cardiology Newark, DE VIVEK K. REDDY, MD Inpatient Consultants, The Hospitalist Company Director of Post-Acute Cardiology Newark, DE
Upon hearing the words “Atherosclerosis
and Indians,” the following key points and
definitions come to mind: 1. South Asia comprises Bangladesh,
India, Nepal, Pakistan and Sri Lanka.
Indians comprise 85% of this group
in the U.S.1 Often, these groups are
investigated together in large studies. 2. The Coronary Artery Disease in
Asians Indians (CADI) research project:
Groundbreaking research begun in
the 1990s is a must read for anyone
treating Indians. CADI has provided
understanding of the development of
premature, malignant cardiovascular
disease at younger ages than
Caucasians.2
3. The Indian Paradox: Described as
both 1) a higher prevalence of coronary
artery disease (CAD) despite lower
cholesterol, and 2) Indian vegetarians
and non-vegetarians having the same
lipoprotein levels and CAD rates in
contrast to Western vegetarians, who
have favorable lipids and lower disease
rates.3,4
4. Metabolic Syndrome: 32.7%
prevalence in U.S. Indians5 who
also suffer a higher prevalence of
hypertension, diabetes mellitus, obesity
and hyperlipidemia at a younger age
compared to non-Indians. 5. The Need for better risk
stratification: “If you are a male from
the Indian subcontinent, over age
30 and have a parent with coronary
disease, then you should take a
statin.” – Dr. Robert A. Vogel in 2005
at the American College of Physicians,
Delaware Chapter seventh annual
Lower Shore Symposium). Research
has shown that the Framingham
risk assessment and traditional lipid
panel do not account for the disease
prevalence and aid in risk reduction. India’s population is more than 1.2
billion. More than 2.8 million Indians
live in the U.S., 70% more than in
2000. Despite having increased risk
(40%-400%) of developing and dying
of coronary disease than the general
population, this group is generally
poorly understood by clinicians.
9
Coronary Artery Disease in Asian Indians
(CADI) Research Foundation A non-profit organization dedicated to reducing
the ravages of heart disease around the globe,
with special focus on Asian Indians. A great
repository of facts and links to articles. The CADI demonstrated a three- or
fourfold higher rate of heart disease among
U.S.-Indian physicians and family members
compared to U.S. physicians.3,6 A higher
diabetes rate, ranging between 17% and
26%, was found. It also demonstrated
the role of lipoprotein(a) in early CAD7,8,9
and that non-high-density lipoprotein
(HDL) cholesterol explains most of the
otherwise unexplained heart disease
among South Asians.8 Indians have
higher rates of myocardial infarctions and
death at a lower BMI and lower waist
circumference, occurring at a younger age,
even among non-smoking vegetarians who
exercise.10,11,12,13,14,15 TABLE 1. Useful Clinical Resources for the Care of South Asian Patients
Interestingly, Indians have higher coronary
artery calcium scores at younger ages and
lower hypertension prevalence compared
to other ethnicities.16 CAD onset is from
5 to 10 years earlier compared to other
ethnicities, averaging around age 53 for a
first myocardial infarction.17 South Asians
present later during acute myocardial
infarction and are more likely to have
an anterior infarct. Significant left main,
multi-vessel and distal disease, despite
presenting younger than their Caucasian
counterparts, is noted.18 abdominal region compared to the uniform
obesity found in the West. Compared with
Europeans, South Asians have increased
abdominal visceral fat and greater insulin
resistance at similar levels of BMI, which
suggests that reliance on BMI alone may
underestimate true risk in South Asians.
Waist circumference may be a better tool
to assess the harmful effects of obesity.20
Diabetic prevalence also is high, around
6% or 7% for those considered to have a
normal weight; it’s a rate that increases to
between 19% and 33% for the obese.21
The risk for CAD in the South Asian
community can be accounted for by nine
modifiable risk factors: ApolipoproteinB/
ApolipoproteinA-I (ApoB/ApoA-I) ratio,
smoking, hypertension, diabetes,
waist-hip ratio, psychosocial factors,
moderate/high intensity exercise, alcohol
consumption and consumption of fruits
and vegetables. They account for 85.8%
of attributable risk, similar to other
populations.19 Tobacco use is generally
lower, though this is rapidly increasing
with economic expansion. Along with central obesity, South Asians
have lipid profile characteristics, elevated
levels of triglycerides, low HDL Cholesterol
and perhaps only mildly elevated LDL
Cholesterol. LDL particle size tends to be
smaller, They have lower HDL Cholesterol
levels and tend to be concentrated with
more small, HDL particles and lower levels
of HDL2b, which can be associated with
reverse cholesterol transport.20 Metabolic syndrome prevalence in U.S.
Asian Indians is high, more than 32%.5
Most tend to accumulate obesity in the
10
http://www.cadiresearch.org American Association of Physicians of
Indian Origin – Indian Foods: AAPI’s Guide to
Nutrition, Health and Diabetes, 2nd Ed.
http://aapiusa.org/resources/nutrition.aspx Society for Heart Attack Prevention and
Eradication (SHAPE) Guidelines http://www.shapesociety.org/about-shape/
shape-your-heart 2010 ACCF/AHA Guideline for Assessment of
Cardiovascular Risk in Asymptomatic Adults J Am Coll Cardiol. 2010;56(25):2182-2199.
Physical activity is less common in
South Asians. Daily, moderate-intensity
exercise is associated with a more than
50% risk reduction for coronary heart
disease (CHD). It improves insulin
sensitivity, HDL cholesterol, hypertension,
Guide for healthcare professionals with
descriptions of the dietary characteristics of
different regions of India and the context from
which the ethnic foods and eating habits have
evolved. Recipe book for patients with HTN,
DM, obesity and hyperlipidemia. A clinical screening protocol that builds on
risk-factor detection to identify cardiovascular
disease.
The American College of Cardiology
Foundation and American Heart Association
Task Force Guidelines
endothelial function, diabetes and central
obesity.19 Walking 12 miles a week can
significantly reduce LDL-particle number,
despite LDL-C and total cholesterol
remaining unchanged.22 Cultural biases and goals often hinder
physical activity in the Indian community.
Immigrants have skilled but sedentary
jobs. Children are encouraged to seek
academic excellence, leaving little time for
physical activity. One immigrant-physician
mentioned that participation in sports was
considered a “low-class” activity in India.
That same bias permeates to children. They
are involved in sedentary activities such
as extra tutoring and music along with
the ubiquitous electronics. Sports are not
encouraged for fear that they may interfere
with academics. An hour after physical
inactivity, lipoprotein lipase is suppressed
in skeletal muscle, which can contribute to
hypertriglyceridemia.23 Clinicians need to be better versed in the
diverse diet of the subcontinent. As Indian
physicians, even we, the authors, admit
we are not experts. Our South Indian diet
differs from that of other regions and from
mainstream Indian restaurants. Anecdotal
patient reports suggest that many U.S.-
LipidSpin
based dietitians are not well versed
in South Asian diets. We’ve generally
relied on dietitians of Indian origin, but
find a shortage of availability. The AAPI
(American Association of Physicians of
Indian Origin) has spent a considerable
effort in producing “Indian Foods: AAPI’s
Guide to Nutrition, Health and Diabetes,
2nd Ed.,” a worthwhile resource for those
treating patients from the Subcontinent
(http://aapiusa.org/resources/nutrition.
aspx). Non-Indian vegetarians outside India
enjoy better health compared to meateaters. Decreased dyslipidemia, obesity,
hypertension, diabetes, CAD and cancer
result in an increased life-expectancy of
3 to 6 years.3 Indian vegetarians do not
appreciate the same benefits. They have
similar rates of dyslipidemia and CAD
as non-vegetarians, likely because of a
“contaminated vegetarianism”. 3 Despite
nearly half of Indians being vegetarians,
low amount of fruits and vegetables are
consumed. Increased fruit and vegetable
servings decrease CHD risk, which has
been validated in India.24 An Indian
vegetarian diet constitutes grains, breads
and legumes but vegetables often are
subjected to prolonged cooking, removing
much of their protective benefits. Deepfrying vegetables in high-saturated-fat
palm and coconut oils is a common
practice. Also, many sweets and curries
contain saturated fats, trans-fats and
refined sugars. Liberal amounts of butter,
ghee/clarified butter, cheese, ice cream
and yogurt increase LDL Cholesterol
levels 3 times as much as they raise HDL
Cholesterol levels. Many physicians do not understand the
risk associated with the combination
of low HDL-C and elevated TG’s, often
coupled with insulin resistance. We
feel this information needs to be shared
with physicians in a manner similar to
the familial hypercholesterolemia (FH)
campaign. These patients’ cardiovascular
disease risk is often underappreciated; they
also often don’t make it to lipidologists
until it’s too late. CAD onset in Indians
doesn’t occur as early as in FH patients
but does occur earlier than Caucasians.
A higher prevalence of disease starts at a
younger age than in Caucasians and the
fact that severe insulin resistance can be
seen in the absence of visceral fat in lean,
young South Asian patients25 argues for
earlier screening. Metabolic Syndrome
factors must be documented in each Indian
patient as a standard.
“If you are a male
from the Indian
subcontinent, over
age 30 and have a
parent with coronary
disease, then
you should take a
statin.”
Reducing adiposity should affect
dyslipidemia and insulin resistance in
a beneficial way, leading to decreased
vascular events.26 We applaud AAPI for
targeting childhood obesity with its “Be Fit
Be Cool” national program and its recent
partnership with the American Heart
Association (AHA) in promoting awareness. are necessary. More population-specific
research studies are needed. Identification
of Asian subgroups on such items as death
certificates and hospital demographics can
aid studies.
Randomized, controlled prospective
data on this population is not available
but we need to do a better job of
identifying these at-risk patients earlier.
The traditional Framingham Risk Score
appears to be inadequate and alternate
risk score calculators [QRISK score (http://
www.qrisk.org) or Reynolds Risk Score
(http://www.reynoldsriskscore.org)]
may be superior (Shah, 2010). The
Society for Heart Attack and Eradication
(SHAPE) guidelines are an option; they
advocate assessment of biomarkers in
all intermediate risk patients, a position
not yet endorsed by NLA. ACC/AHA
Guideline for Assessment of Cardiovascular
Risk in Asymptomatic Adults (2010)
lists a few diagnostic tests as Class IIa
recommendations. As an organization,
we collectively need not only to educate
the Indian/South Asian population but
also our colleagues to recognize this
group as a unique population that has
early events that often are not identified
using traditional risk assessment tools or
diagnostic tests. “It is health that is the real wealth and not
pieces of gold and silver.”
– Mahatma Gandhi n
Disclosure statement: Dr. Hosmane and Dr. Reddy have
no disclosures to report.
Continued efforts are needed to increase
awareness and primary prevention for
this at-risk group. A higher incidence
of CAD in expatriate South Asians
compared to the native cohorts has been
observed.27 Collaborative efforts between
the National Lipid Association (NLA),
national organizations and the community
11
EBM Tools for Practice:
Weight Management: Evidence-Based Nutrition Strategies
WAHIDA KARMALLY, Dr.PH, RD, CDE, CLS, FNLA
Associate Research Scientist
Director of Nutrition
Irving Institute for Clinical and Translational Research
Columbia University
New York, NY
Introduction:
Obesity is a complex multifactoral chronic
disease that develops from an interaction
between genetics and the environment.
The development of obesity involves the
integration of social, behavioral, cultural,
physiological, metabolic and genetic
factors. Treatment of obesity should
be based on a comprehensive weightmanagement program to produce weight
loss, prevent further weight gain and
maintain weight loss over a prolonged
period. Overweight is currently defined as
a body mass index (BMI) of 25 to 29.9 and
obesity as a BMI of >30. But BMI may not
correspond to the same degree of fatness
in different populations, and health risk
may differ for different populations.
Obesity is associated with increased
12
morbidity and mortality. Scientific
evidence supports the effectiveness of
weight loss in the reduction of risk factors
for diabetes and cardiovascular disease
among people who are overweight or
obese.
National evidence-based guidelines
recommend diet therapy as an integral
component of a comprehensive weightmanagement program. Based on the
client’s treatment plan and comorbid
conditions, other nutrition practice
guidelines – such as hypertension, type 2
diabetes mellitus, childhood overweight
and nutrition care in bariatric surgery
– may be needed to provide optimal
treatment.
Strategies for Weight Loss and
Maintenance include:
• Dietary therapy
•
Physical activity
•
Behavior therapy
•
“Combined” therapy
•
Pharmacotherapy
•
Weight-loss surgery
Evidence-based nutrition recommendations
are developed through the use of
systematically reviewed scientific evidence
in making food and nutrition practice
decisions by integrating the best available
evidence with professional expertise and
client values to improve outcomes.
The Academy of Nutrition and Dietetics
Evidence Analysis Library (EAL) provides
a series of evidence-based guidelines
describing the treatment of obesity. Each
recommendation is rated according to the
strength of the supporting evidence (Table
1) and based on the benefits versus harms
of implementing the recommendation.
Strong evidence is available for the
following recommendations:
• Medical Nutrition Therapy (MNT)
for weight loss should last at least
6 months or until weight-loss goals
are achieved, with implementation
of a weight-maintenance program
LipidSpin
Strong
A Strong recommendation means the workgroup believes
Practitioners should follow
the benefits of the recommended approach clearly exceed
a Strong recommendation
the harms (or the harms clearly exceed the benefits in the
unless a clear and
case of a strong negative recommendation), and that the
compelling rationale for
quality of the supporting evidence is excellent/good (grade
an alternative approach is
I or II).* In some clearly identified circumstances, strong
present.
recommendations may be made based on lesser evidence
and should result in a weight loss of
1 to 2 pounds per week.
•
Total caloric intake should be
distributed throughout the day,
with the consumption of 4 or 5
meals/snacks per day, including
breakfast. Consumption of greater
energy intake during the day may be
preferable to evening consumption.
•
For people who have difficulty with
self-selection and/or portion control,
meal replacements (e.g., liquid
meals, meal bars, calorie-controlled
packaged meals) may be used as
part of the diet component of a
comprehensive weight-management
program. Substituting one or two
daily meals or snacks with meal
replacements is a successful weightloss and weight-maintenance
strategy
•
A low glycemic index diet is not
recommended for weight loss or
weight maintenance as part of a
program, because it has not been
shown to be effective in these areas.
•
Physical activity should be part of a
program.
•
Behavior therapy in addition to
diet and physical activity leads to
additional weight loss. Continued
behavioral interventions may be
necessary to prevent a return to
baseline weight.
when high-quality evidence is impossible to obtain and the
anticipated benefits strongly outweigh the harms.
Fair
A Fair recommendation means the workgroup believes the
benefits exceed the harms (or the harms clearly exceed the
benefits in the case of a negative recommendation), but the
quality of evidence is not as strong (grade II or III).* In some
clearly identified circumstances, recommendations may be
made based on lesser evidence when high-quality evidence
is impossible to obtain and the anticipated benefits outweigh
the harms.
Weak
A Weak recommendation means the quality of evidence that
exists is suspect or that well-done studies (grade I, II or III)*
show little clear advantage to one approach versus another.
Consensus
A Consensus recommendation means Expert opinion (grade
IV) supports the guideline recommendation even though
the available scientific evidence did not present consistent
results or controlled trials were lacking.
Table 1. Statement Rating and Definitions.
rate RMR. If possible, RMR
should be measured (e.g., indirect
calorimetry). If RMR cannot be
measured, then the Mifflin-St. Jeor
equation using actual weight is
the most accurate for estimating
RMR for overweight and obese
individuals.
after that time. A greater frequency
of contacts between the patient
and practitioner may lead to
more successful weight loss and
maintenance.
•
•
Individualized goals of weight-loss
therapy should be to reduce body
weight at an optimal rate of 1 to
2 pounds per week for the first 6
months and to achieve an initial
weight-loss goal of up to 10% from
baseline. These goals are realistic,
achievable and sustainable.
Estimated energy needs should
be based on resting metabolic
•
An individualized reduced-calorie
diet is the basis of the dietary
component of a comprehensive
weigh-management program.
Reducing dietary fat and/or
carbohydrates is a practical way to
create a caloric deficit of 500- 1,000
kcals below estimated energy needs
Fair evidence is available for the following
recommendations:
• Portion control should be included
as part of a comprehensive weightmanagement program. Portion
control at meals and snacks results
in reduced energy intake and weight
loss.
13
•
Having patients focus on reducing
carbohydrates rather than reducing
calories and/or fat may be a shortterm strategy for some individuals.
Research indicates that focusing
on reducing carbohydrate intake
(<35% of kcals from carbohydrates)
results in reduced energy intake.
Consumption of a low-carbohydrate
diet is associated with a greater
weight and fat loss than traditional
reduced-calorie diets during the first
six months, but these differences
are not significant after one year.
Behavior therapy
in addition to diet
and physical activity
leads to additional
weight loss.
The key to achieving and maintaining a
healthy weight is about a lifestyle that
includes enjoyable and healthful foods,
regular physical activity and balancing the
number of calories you consume with the
number of calories your body uses. n
Patient referred to
Dietitian for MNT
Screen for:
- Eating disorder
- Pregnancy
- Receiving chemotherapy
Screen for
appropriateness of
weight management
No
Weight
Management
Appropriate?
Yes
Assess measures
of adiposity
- BMI
- Waist circumference
BMI ≥ 25
or
WC > 102cm (males)
WC > 88cm (females)
Treat for primary
nutritional problem or
refer back to primary
health professional
No
Brief weight
maintenance education
Yes
Access Risk Factors
-smoking
-hypertension (SBP ≥ 140 mmHg, DBP ≥ 90 mmHg
High LDL-C (>4.13 mmol/L)
Low HDL-C (<0.90 mmol/L)
Diabetes
Age (M>45 yrs, F>55 yrs)
Previous cardiovascular event
Family history of premature cardiovascular disease
Recommend Weight
Management Treatment
Patient
motivated to
lose weight?
No
Yes
Commence
Treatment
Weight-Management Screening Algorithm.
© 2006. Academy of Nutrition and Dietetics. Reprinted
with permission.
Disclosure statement: Dr. Karmally has received
honoraria from the American Pistachio Growers and
the Sesame Workshop.
14
LipidSpin
Lipid Luminations: PREDIMED Commentary
EUGENIA GIANOS, MD
Director, Preventive Cardiology Fellowship
New York University Medical Center
New York, NY
JOAQUIN CARRAL, MD
Preventive Cardiology Fellow
New York University Medical Center
New York, NY
The recently published PREDIMED trial
is a landmark study assessing the efficacy
of a dietary intervention in the primary
prevention of cardiovascular disease. The
authors used a parallel group design and
randomized subjects from multiple centers
in Spain. Subjects were men ages 55 to
80 and women ages 60 to 80, with either
diabetes or three or more risk factors for
coronary artery disease, without diagnosed
coronary heart disease at baseline.
The subjects were randomized to one
of three groups: a Mediterranean diet
supplemented with nuts, a Mediterranean
diet supplemented with extra virgin olive
oil, or a control diet. The primary outcome
was a composite of myocardial infarction,
stroke or death from cardiovascular causes.
There were 288 primary outcome events
in 7,447 subjects, driven primarily by the
rate of stroke. The trial was terminated
early (median follow-up of 4.8 years)
when an interim analysis showed a
statistically significant difference between
groups with a hazard ratio of 0.7 for both
Mediterranean diets compared to the
control diet.1,2,3
The authors of this trial are to be
commended. To date, randomized,
controlled outcomes data on dietary
interventions are sparse and limited
to secondary-prevention populations.
The study was well-powered to show
a difference in outcomes among the
groups and sought to differentiate benefit
obtained from individual components of
the Mediterranean diet, including nuts
and olive oil. The hazard ratio of 0.7
from a lifestyle intervention is extremely
impressive, although it is difficult to know
where that benefit was derived.
A careful analysis of the food-frequency
questionnaires completed by patients
listing the composition of the three dietary
groups shows a great deal of overlap,
making it unclear whether there was a true
control group. The intervention groups
consumed only slightly more legumes,
fish and sofrito (minced tomato, garlic
and onion simmered with olive oil), and
less butter, cream or margarine than
the control group. In addition, although
the control group was planned to be a
low-fat diet, it included 37% fat, with
no difference in saturated fat, making
it very similar to the overall fat content
in the intervention groups4. Given the
diet structure actually followed, it seems
as though it is only the presence versus
absence of sofrito, olive oil and/or nuts
that makes up the dietary difference across
15
the three groups. It also is difficult to know
whether the results of this trial, which
were noted in the setting of nuts and oil
being given to patients as gifts, would have
been replicated in a population that was
expected to purchase and consume these
foods in large quantities.
Aside from the different dietary patterns
between groups, there was far less
counseling provided to the control group.
Patients in the Mediterranean diet groups
received two individual motivational
interviews and one educational group
session every three months throughout
the trial. Patients in the control group
only received these sessions after the
third year, when it was recognized as a
limitation. The less frequent contact with
the dietitian during the first three years of
the trial may have been the reason for the
higher dropout rates and lower compliance
with dietary recommendations noted in
Although there are limitations to the trial,
the potential benefits of a diet based on
hard clinical outcomes evaluated in a
prospective randomized study design is
tremendous.5 Understanding the individual
components of diet that improve health is
a challenging task, but there appears to be
ample evidence to recommend a balanced
Mediterranean diet to our patients at risk
for cardiovascular disease. n
the control group. In addition, the sessions
may have had other psychological benefits
that could have independently contributed
to the change in outcomes noted.
The potential benefits
of a diet based
on hard clinical
outcomes evaluated
in a prospective
randomized study
design is tremendous.
Disclosure statement: Dr. Gianos has no disclosures to
report. Dr. Carral has no disclosures to report.
Editor’s Note:
The authors were cautious that this is in a
Mediterranean country for persons at high
CVD risk and limitation of generalization
needs to be considered.
The PREDIMED trial is the first
randomized controlled trial to assess the
use of a Mediterranean diet in primary
prevention of cardiovascular disease.
The editor of this article, Dr. Wild, thanks
the Lipid Luminations authors for turning
the article around on a short deadline.
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16
LipidSpin
Specialty Corner:
EDWARD GOLDENBERG, MD, FACC, FNLA
Medical Director of Cardiovascular Prevention and Employee Wellness
Newark, DE
JAYA BATHINA, MD
Cardiology Fellow
Newark, DE
Multicellular organisms depend on two
central mechanisms for their survival: the
ability to store energy to prevent starvation
and the ability to fight infection. Adipocytes
in higher organisms are reminiscent of the
integrated function seen in lower organisms
such as the fat body of the Drosophila
melanogaster that comprises adipose tissue
(AT), liver and immunologic cells in one
unit Human adipose tissue is composed
of energy-storage adipocytes as well as
connective tissue matrix, vascular tissue
and neural tissue. Non-adipose cells (that
constitute the stromal vascular fraction
include fibroblasts, pre-adipocytes and
endothelial cells; leukocytes, macrophages
and lymphocytes)are responsible for the
chronic inflammatory response seen with
obesity.1
Energy balance is an integrated system
under the regulation of the hypothalamus.
Total energy expenditure (TEE) is
composed of resting energy expenditure
(70% of TEE), energy expended in physical
activity (20% of TEE); and the Thermic
Effect of Food, (10% of TEE). Adipose tissue
is the largest storage body of energy. The
average 70kg man has 13,000 grams of
adipose tissue supplying an energy source
of 120,000 kcal from the triglycerides
stored in his adipocytes. Lipogenesis from
glucose makes only a limited contribution
to triglycerides stored in adipocytes.
Chylomicrons from the diet and very lowdensity lipoproteins (VLDL) from the liver
are the major sources of triglycerides for
lipogenesis in the adipocyte. Lipoprotein
lipase (LPL), which is manufactured in
the adipocyte, hydrolyzes circulating
triglycerides, releasing free fatty acids
(FFAs) that are taken up by the adipocyte.
Insulin and cortisol stimulate LPL activity.
Lipolysis is regulated by insulin (which
inhibits), and cathecolamines (which
stimulate) hepatic sensitive lipase (HSL) to
release FFAs from the triglycerides which
are stored in adipocytes. The released
FFAs, which escape immediate oxidation,
are restored as triglycerides in adipose
tissue, muscle or liver to provide energy
during periods of famine. VLDL produced
by the liver is sequentially converted to
low-density lipoprotein (LDL) by LPL on
endothelial cells. This releases FFAs
from triglycerides to provide energy to
peripheral tissues. LDL recirculates to the
liver and, in times of excess, diffuses into
the intima. This serves as a nidus for foam
cell formation ultimately developing into
an atherosclerotic plaque. In contrast to
17
Hypothalamic control of energy
homeostasis stems from the ability of
the hypothalamic neurons to orchestrate
behavioral and autonomic responses. The
hypothalamus receives sensory inputs
from the environment, from afferent vagal
neurons from the gut and from several
hormones such as leptin* coming from the
adipocyte and ghrelin coming from the
stomach. This finely balanced system can be
adversely influenced by learned behavior,
emotions and personal gratification.3
Subcutaneous fat (SCAT) accumulation is
the normal physiologic buffer for excess
energy intake. When the ability to generate
new adipocytes is impaired, because of
either genetic predisposition or stresses,
fat begins to spill over from the SCAT and
accumulates in areas outside subcutaneous
tissue. These areas include visceral
adipocytes (VAT), epicardial, perivascular
and myocardial cell sites. Hypertrophic
adipocytes and VAT are dysfunctional and
they exhibit abnormal physiology. Besides
energy storage, the adipocyte produces
a laundry list of hormones, cytokines,
extracellular matrix proteins, complement
factors, enzymes, plasminogen activator
inhibitor-1 and acute- phase response
proteins.4
Adipose tissue resident inflammatory
immune cells exert a wide range of
functions. They can be divided into two
groups: 1) Immune cells that drive AT
inflammation and insulin resistance, and
2) immune cells that protect against these
pathologies. The first group consists of M1
*Leptin’s primary role is to serve as a metabolic signal of
energy sufficiency. Several other endocrine effects of leptin
include regulation of immune function, hematopoiesis,
angiogenesis and bone development.
18
macrophages, mast cells, B-2 cells, CD8+
T cells, and Th 1 CD4+ T cells. These cells
induce the polarization of M1 macrophages
and drive what is referred to as a T
helper 1 (Th1) response, necessary for an
efficient immune response against bacteria.
The second group compromises M2
macrophages, eosinophils and regulatory
T cells, which produce IL-10, IL-4 or IL-13
and drive what is referred to as a T helper
2 (Th2) response. This is instrumental
metabolism and immunity that seems
to help explain some of the metabolic
dysfunction seen with obesity.5 Bacterial
infections stimulate a Th1 response
creating an acute bioenergetics demand
because macrophages and T cells utilize
circulating nutrients for an effective
response to clear the bacteria. The Th1activated immune response promotes
inflammation and insulin resistance.
This leads to mobilization of nutrients
Hypoxemia, ER stress
the tight negative feedback regulation of
insulin secretion by glucose levels, insulin
and cathecolamines concentrations are
not under negative feedback regulated by
lipolysis or FFA levels.2
Adipocyte Expansion
adipocyte
Adipocyte
Excess Energy
Inflammatory
Cytokines
Apoptotic
Th 1 activation
M1
Macrophage
Recruitment
B Cell
M1 Polarization
Pro-inflammatory Milieu
IL-B,IL-6,IL-8,TNFα,NO,IFNY
T Cell
Lymphocyte
Recruitment
Th1 Polarization
Insulin Resistance
Figure 1. The pathogenesis of obesity related insulin resistance and viseral fat inflammation.
for an efficient immune response against
parasites. Taken together, an antibacterial
Th1 response in AT is associated with
inflammation and insulin resistance, while a
Th2 immune cell response offers protection
against parasites and in adipose tissue is
anti-inflammatory and promotes insulin
sensitivity.1
Chawla and co-workers proposed a
model to explain the link between
via gluconeogenesis, hyperglycemia and
lipolysis. However, the bioenergetics for
controlling parasitic infections requires
the opposite response of bacterial
infections. Deprivation of circulating
nutrients is necessary to prevent the
parasitic consumption of host nutrients
and slows down parasite growth. The Th2
response in AT prevents inflammation
and insulin resistance and preserves host
nutrient requirements. The “energy-on-
** Adiponectin is the most abundant secretory protein produced by adipocytes. There is an inverse
relationship between both insulin resistance and inflammation and adiponectin levels. Adiponectin levels
decrease in non-human primates before the onset of obesity and insulin resistance, and suggesting that
hypoadiponectinemia may contribute to the pathogenesis of these conditions.
LipidSpin
demand model” presents the Th1 and Th2
responses in AT as an adaptive strategy,
allowing the body to tailor the necessary
energy for the different immune responses
against bacteria and parasites.1
The lean adipocyte secretes IL-4, IL13, IL-10 and adiponectin** which
can promote a Th 2 response of insulin
sensitivity, suppressed inflammation and
energy preservation. The hypertrophic
adipocyte in visceral adipose tissue
develops hypoxemia, oxidative stress, and
endoplasmic reticulum stress. This leads to
adipocyte dysfunction, inflammation and
insulin resistance. The release of TNFα
(Tumor Necrosis Factor alpha) from the
adipocyte results in adipocyte apoptosis,
which in turn promotes recruitment
of lymphocytes (adaptive immunity)
and macrophages (innate immunity)
that surround the necrotic debris and
forms crown-like structures (CLS). The
lymphocytes (Th1CD4+T cells and CD8+
T cells) release IFN-γ(interferon gamma),
which polarizes macrophages to a proinflammatory M1 phenotype. Saturated
fatty acids and cholesterol crystals from
the local environment, and gut derived
lipopolysaccharides trigger TLR4 ( toll like
receptor) and NLrp (Nod like receptor)3
inflammasome activation, which further
promotes macrophage pro inflammatory
cytokine release including IL-1β, IL-6,
TNF-α and IL-18 all contributing to insulin
resistance. B-2 lymphocytes respond to
T-dependent antigens and influence other
T lymphocytes and produce pathogenic
IgG, further stimulating M1 macrophages6
(Please refer to figure 2).
VLDL manufactured in the liver along with
chylomicrons manufactured in the gut
provide energy to peripheral tissues by LPL
release of FFA from triglycerides. During
times of excess energy, triglycerides are
stored in SCAT for release during periods of
famine to provide energy to the peripheral
tissues. This efficient system designed
Figure 2.
Permission received to reproduce figure.
Adipose tissue - resident immune cells: key players in immunometabolism. Trends in Endocrinology and Metabolism. August 2012.
to handle the cycle of feast and famine
in past times is dysfunctional in modern
times of easy access to food. This leads
to the development of chronic disease. It
is useful to remember that except during
sleep, it would be unusual to go more than
4 hours without eating. Spillover of energy
storage from the SCAT to the VAT leads
to dysfunctional hypertrophic adipocytes
that release inflammatory cytokines, which
contribute to the development of insulin
resistance. An immune system designed
to combat bacterial infection (Th1) is
constantly activated by inflammatory
cytokines released from hypertrophic
adipocytes and apoptotic adipocytes in
VAT. The state of persistent inflammation
contributes to the development of vascular
and other chronic disease (Please refer to
Figure 1).
The Adipocyte and lipoproteins are
essential to maintain energy homeostasis
during times of feast and famine. However,
in present society there is only feast and
no famine. This excess of energy which
needs to be stored in the adipocyte leads
to insulin resistance and chronic VAT
inflammation. n
Disclosure statement: Dr. Goldenberg has received
speaker honoraria from Amarin, Abbott Laboratories,
GlaxoSmithKline and Merck & Co., Inc. Dr. Bathina has
no disclosures to report.
19
Practical Pearls:
Can Smartphones Help Our Patients Lose Weight?
RUCHI PRASAD, MD
University of Pennsylvania Health System
Department of Medicine and Cardiology
Pennsylvania Hospital
Philadelphia, PA
DEAN G. KARALIS, MD, FACC, FNLA
University of Pennsylvania Health System
Department of Medicine and Cardiology
Pennsylvania Hospital
Clinical Professor of Medicine
University of Pennsylvania
Philadelphia, PA
Your 9 a.m. appointment walks in. He’s an
overweight executive who tells you that
he has been trying to lose weight, but he
does not have the time to go to the gym or
prepare healthy meals. But sitting in front
of you during the office visit, he fields two
phone calls, fires off three text messages
to colleagues and pulls up his calendar
to schedule a follow-up appointment.
This type of behavior is not uncommon.
Smartphones are revolutionizing the way
we live our lives. The question is, can
we use the smartphone to change our
lifestyle?
20
It is estimated that, on average, users
check their smartphones every six and
a half minutes and each person has
approximately 41 applications (apps) on
their phone.1 There are smartphone apps
for absolutely everything. Whether it’s for
social networking, productivity or to play
games, you can be assured that out of the
more than 900,000 apps available,2 there
is something for everyone. The medical
world also has caught on with upwards
of 20,000 medical apps available online.3
Since the smartphone has become an
inherent part of our lives, clinicians should
make use of this fact and encourage their
overweight patients to use specific apps
targeted at weight loss. Just remember
that not every app is effective and it can be
difficult to comb through the multitude of
apps to find just the right one. (We suggest
avoiding the application that recommends
keeping your phone on vibrate to shake
away your abdominal fat.)
The New York Daily News4 and Forbes5
have recently reviewed a number of
weight-loss apps, coming up with what
they consider to be the top apps out there.
(Table 1). Topping both of their lists – and
the recipient of the United States Surgeon
General’s Healthy Apps Challenge – is
an app called “Lose It.” Lose It works by
calculating the daily calorie intake needed
to achieve your goal weight (Figure 1). It
then helps you keep track of your daily
calorie consumption and estimates the
nutritional value of a given food item by
scanning the barcode. It also works by
connecting you with other people who
are trying to lose weight, for support,
encouragement and advice. Probably the
best part about this app is that it’s free.
Other weight-loss apps making both lists
include “Fooducate.” also on the Surgeon
General’s best apps list6 (Figure 2), and
“MyFitnessPal.” Both count calories and
LipidSpin
On Both the New York Daily News & Forbes Lists
Only on the New York Daily News List
Only on the Forbes List
Lose It *
iTrackBites
Locavore
MyFitnessPal
Fitocracy
CSPI Chemical Cuisine
Fooducate **
Nike Training Club
Endomondo
Eat This, Not That! The Game
Table 1. List of the Top Weight-Loss Apps Appearing on the New York Daily News and Forbes Lists
allow you to scan the barcode or search
for food to give you a health grade for that
particular item. Whether at the grocery
store or at a chain restaurant, these apps
enable you to make healthy choices on the
go. MyFitnessPal has the added benefit of
allowing you to track calories that you have
burned through exercise.
* denotes recipient of United States Surgeon General’s award for top app.
**denotes placement on USSG’s list of top apps.
in this field is still in its infancy, but a
recent pilot randomized control trial has
looked into compliance with smartphone
apps for weight loss as compared to
website or paper diary-based tools.7
Although the number of trial participants
was small, they found better adherence for
smartphone apps compared to other
Reused with permission from Fooducate
Figure 2. Example of smartphone screenshot
from the Fooducate app.
Reused with permission from Lose It
Figure 1. Example of smartphone screenshots from the Lose It app.
Not all apps target calorie counting as
the primary method for weight loss.
“Endomondo.” featured on both the New
York Daily News and Forbes lists, allows
you to use your smartphone as a personal
trainer to keep track of your sports
activities and workouts. It also incorporates
a social aspect in that is enables the user to
share encouraging messages with friends
and invite others to participate in sport
challenges with them.
The important question is whether these
apps really help you lose weight. Research
more conventional weight-loss tools, and
participants using a smartphone app lost
a mean weight of 10.2 pounds over the
course of the 6-month trial.
It also can be difficult to determine
what makes a good app. According to
a recent study in Telemedicine Journal
and e-Health, there are five essential
elements to a successful technology-based
weight-loss tool.8 It must allow for selfmonitoring, have social support, have
an integrated counselor feedback and
communication tool, incorporate the use
of a structured program and allow for the
tailoring of the program to the individual.
As clinicians, it’s important to stay up
to date on new resources available to
our patients. Admittedly, given the wide
variety of weight-loss apps available, it
can be difficult to determine the best app
to recommend, and what works for one
patient may not work for another. There
are, however, excellent options available
and patients should be encouraged to try
a few weight-loss apps to find the one that
works best for them. Perhaps, the next
time your patient picks up his smartphone,
it will be to help lose weight and stay
healthy. n
Disclosure statement: Dr. Karalis has received speaker
honoraria from GlaxoSmithKline. Dr. Prasad has no
disclosures to report.
21
Case Study:
Childhood Adiposopathy Unmasks Type III Hyperlipoproteinemia
DANIEL SOFFER, MD, FNLA
Perelman School of Medicine
Philadelphia, PA
FRAN BURKE, MS, RD
Philadelphia, PA
DANIELLE DUFFY, MD
Jefferson Medical College
Philadelphia, PA
JOYCE ROSS, MSN, CRNP/CCS,
FPCNA, CLS, FNLA
Philadelphia, PA
Diplomate, Accreditation Council for
Clinical Lipidology
We report the case of a young girl
who presented with classic type III
hyperlipoproteinemia to emphasize the
importance of clarifying the lipid diagnoses,
to illustrate the key features of this
uncommon condition, and to demonstrate
the potency of non-pharmacologic therapy in
improving both lipoprotein parameters and
body morphology.
Case Presentation
JF was referred to our preventive cardiology
clinic by a dermatologist at neighboring
Children’s Hospital of Philadelphia. On
presentation, she was a previously healthy
9-year-old who developed a progressive
22
rash, prompting a biopsy and subsequent
lipid profile. The rash was characterized by
eruptive xanthomas on her torso, buttocks,
popliteal and antecubital fossae, as well
as orange creases on her palms. Biopsy
confirmed the presence of xanthoma, and
laboratory analysis demonstrated severe
combined hyperlipidemia (Table 1, 3/26/09).
Lipid levels had started to improve with a
very restrictive diet prior to her presentation
in our clinic. (Table 1, 5/22/2009). Of
note, she attended clinic with her mother
and maternal grandmother, both of whom
expressed feeling terribly guilty about
“causing” the girl’s problem and then having
to restrict her diet differently from that of
her friends.. JF’s diet consisted of mostly
high-fat, processed foods and more than 1
liter of soda daily. The family was counseled
on a “heart healthy” diet that limits total and
saturated fat as well as refined sugars and
starches. She was advised to choose whole
grain starches, to increase her daily servings
of fruits and vegetables, and to eliminate
sugar-sweetened beverages.
A clinical diagnosis of type III
hyperlipoproteinemia was made, despite
the uncharacteristic age of presentation.
Given the physical exam findings and lipid
testing, evaluation for a “second hit” was
undertaken. Directly measured very lowdensity lipoprotein cholesterol (VLDL-C):
triglyceride ratio was well more than 0.3,
and apolipoprotein E2/E2 phenotype was
later documented, confirming the diagnosis.
However, no obvious second hit could be
found other than her highly processed/
junk food diet. There was no precipitous
weight gain, change in diet/activity level,
kidney/liver dysfunction or thyroid disorder.
She had normal glycemic control and no
evidence of other endocrine disorders. She
had not reached menarche, and she had
normal features of maturation. However, at
the time of her first evaluation, she was at
or above the 95th percentile for body mass
index (BMI) for her age. She also was above
LipidSpin
Parameter
3/26/2009
5/22/2009 Ultra LP
Height
4’9”
Weight (lbs)
99
BMI (kg/m2) [ percentile for age]
21.42 [>95 %]
Glucose/insulin (mg/dL)
75/2.5
8/6/2009 Standard LP
Subsequent ranges-to
present
4’9”
5’5”
93
114
20.1 [>90 %]
th
th
19.0 [>50th %]
Sodium/potassium/HCO /chloride
Normal
Creatinine (mg/dL)
0.7
AST/ALT (U/L)
88/30
74/18
TSH/free T4
5.1/1.35
3.5
Total cholesterol (mg/dL)
393
217
205
150-197
Triglycerides (mg/dL)
533
179
141
89-141
HDL-c (mg/dL)
44
46
49
58-64
LDL-c (mg/dL)
Not calculated
28 (direct)
128 (calculated)
74-130 (calculated)
nonHDL-c (mg/dL)
349
171
156
3
VLDL-c (mg/dL)
143
VLDL-c/TG ratio
0.8
54-75/14-30
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density
lipoprotein cholesterol; LP, lipoprotein profile; TG, triglyceride; TSH, thyroid stimulating hormone; VLDL-C, very-low-density lipoprotein cholesterol.
Table 1. JF’s lipid and other metabolic parameters.
the 95th percentile for height for her age,
although abdominal adiposity was noted by
several clinicians.
JF returned to our clinic after 3 months with
a weight loss of 7 pounds and continued
improvements in her lipid profile (Table 1,
8/6/2009). Over time, she has had gradual
improvements in body morphology and
lipid parameters with continued dietary
counseling from our dietitian (author Fran
Burke, MS, RD). Now 13, JF has been
able to maintain normal lipid levels with
fairly minimal restriction and without
pharmacotherapy (Table 1, Overall, her
cardiometabolic status has improved,
though we have counseled the family about
the expected challenges as she enters her
adolescent years and begins to exert her
independence.
Discussion
Type III hyperlipoproteinemia, also known as
dysbetalipoproteinemia or remnant removal
disease, is a rare disorder (prevalence
~1/10,000) characterized by significant
increases in cholesteryl-ester-enriched VLDL,
intermediate density lipoprotein (IDL) and
chylomicron remnants, with relatively low
levels of low-density lipoprotein (LDL). The
diagnosis should be suspected when there
are high levels of both total cholesterol (TC)
and triglycerides (TG), typically >300 mg/
dL. Directly measured VLDL-C: TG ratio
should exceed 0.3 (normal <0.15). In
addition, direct LDL-C will be significantly
lower than calculated LDL-C because of
generalized assumptions about VLDL built
into the Friedewald formula that do not hold
in this condition.
The disorder usually is caused by a pairing
of variant apoE alleles that affect normal
catabolism of TG-rich lipoproteins.
There are three common alleles in the
population, with a frequency of ε3 > e4
> ε2; the most common apoE phenotype
is E3/E3. The E2/E2 combination is
most commonly associated with type III
hyperlipoproteinemia. The E2/E2 phenotype
leads to an apoE that has a lower affinity for
the triglyceride-rich lipoprotein receptors,
which results in the accumulation of partially
catabolized cholesteryl-ester-enriched
remnant particles. In addition, there is
enhanced clearance of LDL particles. This
background apoE phenotype is felt to be
necessary, but not sufficient, to manifest
type III, and a second hit is considered
necessary to trigger the clinical presentation.
The second hit generally results in increased
production of TG-rich lipoproteins, which
then overwhelm the catabolic mechanisms.
Weight gain, hypothyroidism, pregnancy,
diabetes and particular medications are
common triggers (Table 2). Accumulation
of highly atherogenic remnant particles
predisposes a patient to the development of
atherosclerosis, and these individuals have
a higher-than-expected risk of developing
atherosclerotic cardiovascular disease,
especially peripheral arterial disease.
Dermatologic manifestations are not
uncommon and often herald the condition.
While cutaneous xanthomas are nonspecific,
23
Potential Second Hits
Weight gain
Excessive alcohol intake
Diabetes
Hypothyroidism and other endocrinopathy (eg Cushing syndrome)
Sex hormone fluctuations (e.g., menarche, menopause, pregnancy)
Medications (e.g., glucocorticoids, vitamin A analogues, androgens/estrogens,
protease inhibitors, anti-psychotics)
Table 2. Potential second hit inducing type III hyperlipoproteinemia
orange creases in the palms are considered
to be pathognomonic. In most cases, type III
does not present clinically until the end of
the second decade and tends to be present
in men earlier than women, often not until
after menopause in women.
Our patient had the classic physical exam
findings and lipid profile. Subsequent
ultracentrifugation with direct measurement
of LDL-C and VLDL-C confirmed the
lipid phenotype of remnant disease and,
ultimately, the E2/E2 genotype was
confirmed. There was a high suspicion for
this mutation in our patients and, given the
concern about uncovering apoE4 (a potent
risk factor for Alzheimer’s disease), family
counseling was undertaken prior to this
testing. In fact, the authors all agree that this
possibility is an important enough concern
that apoE genotyping should be reserved
to confirm a strong clinical suspicion for
type III hyperlipoproteinemia and not for
broader screening purposes. At our center,
our laboratory reports the findings as either
apoE2/E2 positive or negative, to avoid
providing information about E4 that is not
directly related to the present condition.
Treatment of type III entails identification
of the second hit and correction, if possible,
as well as dietary recommendations and
lipid-lowering medication. The medical
literature on type III consists mostly of
case series, and fibric acid derivatives have
been the most commonly tested therapy,
offering good results. Combination therapy
with statin drugs is reasonable after dietary
modification, even though the LDL-C levels
24
can be quite low, as with our patient. Other
treatment includes niacin or omega-3 fatty
acids in high doses. It should be noted that
the safety and efficacy of fibrates has not
been evaluated in children. Cardiovascular
risk should decrease with correction of the
hyperlipidemia and, as we saw in JF, the
cutaneous eruptions completely resolve,
including the orange palmar creases.
For our young female patient, the disorder
likely presented at a very early age
because of adiposopathy, or excess body
fat, and a nutrient-poor diet. Fortunately,
diet and lifestyle interventions can lead
to a dramatic improvement in type III
hyperlipoproteinemia, as seen in JF. If a
patient is overweight, weight loss should be
recommended. From a dietary standpoint,
calories derived from saturated fat should be
minimized; whole foods and unprocessed
diets are favored. Specific dietary
intervention for high TG can be complicated
by the distinction between excess
chylomicron versus VLDL remnant particles.
Certainly, type III can be the result of both
chylomicron and VLDL remnants, and the
relative response to diet and specific dietary
quality may have to take into account the
relative responsiveness to reduced fat versus
reduced calorie/simple carbohydrate for each
individual. In this case, the replacement of
heavily processed “junk” food with whole
foods, increased consumption of fresh fruits
and vegetables, lean cuts of meat, whole
grains and vegetable oils, all led to the
improvements seen.
significant abdominal adiposity. As a
result of the combination of an inherited
predisposition and unhealthy dietary
habits, she developed a very uncommon
hyperlipoproteinemia with potentially very
serious consequences and a disfiguring
skin reaction. Improvement in the quality
of her diet resulted in normalization of her
body morphology, improvement in the skin
manifestations and normalization of her lipid
parameters. She is not very verbal during our
office visits, so it is difficult to gauge how
committed she is as she enters adolescence.
It has been a struggle convincing her mother
that the entire family has to eat the same
diet as a critical step in improving the
family’s overall health, but also to normalize
the dietary intervention for JF. We have
counseled her mother that, in addition to all
of the normal struggles of adolescence, this
adds another layer of complexity and medical
need. We will continue to see JF regularly,
reinforcing the need for active engagement
in a healthy lifestyle and modeling of this
behavior by her mother. Hopefully, JF’s
rare condition can be controlled long-term
without the need for pharmacotherapy by
maintaining a healthy diet and normal body
weight. n
Disclosure statement: Dr. Soffer has received
honorarium from Aegerion, Potomac CME,
ACP Pier, and MD Consult. He has served
as a local subinvestigator for clinical trials for
Amgen, Sanofi, Regeneron and Novartis. Dr.
Duffy has received honoraria from Genzyme,
and research grants from Amgen and Forest
Laboratories. Ms. Burke has no disclosures
to report. Ms. Ross has received honoraria
from Abbott Laboratories, Genzyme, Kowa
Pharmaceuticals, AstraZeneca and Practice
Point.
JF is a very active young girl but had
LipidSpin
Chapter Update:
NELA’s Past and Vision for the Future
LINDA C. HEMPHILL, MD, FACC, FNLA
Instructor in Medicine
Harvard Medical School
Assistant Physician in Medicine
Massachusetts General Hospital
Boston, MA
“Strive not to be a success but rather to be of
value.” – Albert Einstein
The Northeast Lipid Association’s past
cannot be understood without discussing
the origins and rationale of the “mother
ship” – the National Lipid Association. In
1994, the “cholesterol hypothesis” became
evidence-based fact with the release of the
Scandinavian Simvastatin Survival Study
results at the American Heart Association
meetings in Dallas. For the first time it
was clear that real inroads could be made
against the No. 1 health hazard in the
U.S. – atherosclerosis – with its protean
manifestations of heart attack, stroke and
peripheral vascular disease. Following this
and ensuing statin trials, to quote Virgil
Brown, MD, FNLA, “The (American Heart
Association) is a wonderful organization
focusing on public health issues, research
and general recommendations. (But) it has
not reached the practicing cardiologist or
primary care physician regarding the details
of clinical lipidology. The clinical practice
of lipidology seemed to be lagging behind
the knowledge base from epidemiology and
clinical trials. As a result, many very practical
questions about evaluation and management
of lipid disorders were prevalent and
unanswered in the clinical arena in 1997...
Problems in lipoprotein metabolism and
clinical lipidology are so complex that this
field needs to be considered an important
specialty of medical practice but, at the
same time, reach every practicing health
professional.”
It was into that vacuum that the Southeast
Lipid Association stepped. The organizing
committee for SELA set out a vision and
set of principles that have remained as
this regional association subsequently
fostered a national one: “To enhance the
practice of lipid management in clinical
medicine.” A critical principle was to
engender a multidisciplinary team approach,
including all clinicians involved in lipid
management: nurses, registered dietitians,
pharmacologists, exercise physiologists and
physicians. It was this team concept of lipid
management that led to the establishment of
the regional chapters. Again to quote Brown:
“A region could have many different health
professionals who would want to go to
accessible meetings, perhaps together. We
felt that long-distance travel was a severe
detriment to this concept and, therefore,
recommended that there be regional
meetings.” In addition, “The key was to
bring the academic lipidologists (who were
doing the research) into contact with those
health professionals who were seeking to
improve their practice. This needed to be
done both nationally and regionally. Having
only national meetings reduces the
opportunities for this personal contact.”
In 2002, the NLA was officially incorporated
and, in 2004, the Midwest Lipid Association
was added. But how best to break into
New England? Brown “felt that the leader
organizing this effort in the Northeast
should be a highly informed clinician, active
in research and with a personality that had
both force and gentility. It was important
to have a person that was truly ‘likable’ and
that was not seen as highly competitive
for the limelight. We needed an academic
physician truly interested in making the
organization work without seeking credit for
its accomplishments. David Capuzzi, MD,
25
PhD fit the bill as an accomplished, unselfish
and conscientious physician who shared the
dream.”
And so it was, in late 2004, that Capuzzi,
along with co-chair Penny Kris-Etherton,
PhD, RD, contacted a group of clinical
lipidologists in the Northeast to plan the
inaugural scientific forum for NELA. True
to the core principle of multidisciplinary
involvement, the program committee
included two registered dietitians and a
doctor of pharmacy. Capuzzi and KrisEtherton were keenly aware that they had to
have an “impactful and memorable meeting;
it needed to be the foundation to help
grow a chapter of a national organization.”
Kris-Etherton recalls: “We wanted to make
a splash and I can remember David and I
concurring that we had to ‘invite everyone’
to speak!”
“Mapping the Future of Cardiovascular
Disease Prevention” was held Jan. 28-30,
26
2005, at the Westin New York at Times
Square. There were 167 attendees and it
was a huge success. The planning and the
meeting were “a lot of fun, to tell you the
truth,” Capuzzi said in his inimitable way.
NELA has continued to be a lot of fun as it
has grown from a membership of 68 to 609
members.
value to the education and motivation of
clinicians in the field of lipidology, thereby
benefitting the lives of their patients, we
also will continue to be a success. n
Commenting on the future, current
NELA President James Underberg, MD,
FNLA said, “Strengthening membership,
community outreach and more face-to-face
interactions throughout the year are steps
that will take us to the next level.” In fact,
the vision for our future can be summed
up in the word “community”: a mutually
supportive community of clinicians and
clinician-scientists, committed to best
practices in the care of patients with lipid
disorders.
To come back to the quote above, as we
continue to seek and find ways to be of
LipidSpin
Member Spotlight:
David M. Capuzzi, MD, PhD, FNLA, FACP, FACE
DAVID M. CAPUZZI, MD, PhD, FNLA, FACP, FACE
David Capuzzi, MD, PhD, FNLA currently
works with the cardiology group at the
Lankenau Medical Center (Main Line
Health) as an advisor to the cardiovascular
disease prevention program, where he
participates in clinical research and the
cardiology fellows training program.
Dr. Capuzzi values this opportunity to
educate other physicians and physicians in
training in the prevention of cardiovascular
disease, stroke, and related disorders.
He has always been interested in clinical
lipidology because early heart disease runs
in his family and he was aware of this at a
young age.
fellowship at The Johns Hopkins University
Hospital. His doctoral dissertation was on
biosynthesis of lipids, proteins and low
density lipoproteins by hepatocytes.
He says throughout his career he has
treated many patients and seen more
effective medicines develop, and has
always enjoyed the opportunity to teach
and guide other physicians so that they
effectively understand that the patients
they see have preventable occurrences of
heart disease and stroke.
In the past year, Dr. Capuzzi has retired
from clinical practice. While he still speaks
at different meetings and enjoys teaching,
he has many other interests.
He states that an important element of his
career is simply being able to help people
to regain or continue a healthy life.
Through the years he has built quite a train
collection, a hobby he started as a child.
He also enjoys outdoor activities such as
crabbing and fishing at the Jersey Shore.
Dr. Capuzzi says he remembers being a
medical student and seeing patients die of
heart attacks in their 40s and 50s that we
now know were preventable.
As is widely known, Dr. Capuzzi has
been involved with the NLA from the
very beginning and even chaired the first
meeting of the Northeast Lipid Association.
Dr. Capuzzi stresses the importance of
attending meetings and CME/CE sessions
for health care providers.
“There’s an adage, ‘a man is as old as his
arteries’,” Capuzzi said. “I have taught
trainees and patients how to manage lipid
disorders and what to do with lipoprotein
therapy. What we do early on prevents
premature cardiovascular disease.”
Dr. Capuzzi says he would like to see
scientific advances include a greater
understanding of the integrity of the artery
wall and its role in cardiovascular disease.
Dr. Capuzzi attended St. Joseph’s
University for his undergraduate degree
and Jefferson Medical College before
completing his doctorate, residency and
“I think there needs to be a greater
awareness in the field because it is so
important to prevent recurrence of a heart
attack, stroke, or blockage in the arteries.”
Capuzzi said.
“I think it is very important for physicians
and healthcare providers to participate
in educational activities to learn the very
latest in the field of managing lipoprotein
disorders,” Capuzzi said. “It’s better to
prevent the problem than correct it. At any
stage it is preventable. There are varying
degrees of training and experience but
you need education at every level because
you never know which one of various
healthcare providers will see something in
a patient that the others did not see.” n
27
Education and Meeting News and Notes
New Information for
Fellows-in-Training
The NLA is happy to announce a new
Fellows-in-Training section on lipid.org
listed under the Education tab. Trainees
can find information on how to join
the NLA as a complimentary member,
educational offerings including live, print
and online courses, Trainee Travel Grants
and much more.
New Career Board Added to Lipid.org
Do you have open positions to advertise?
You can post available jobs on our career
board today. We invite you to review our
job postings to discover opportunities in
clinical lipidology and related fields. Are
you looking for a new job? Post your CV
here: lipid.org/practicetools/careers.
FH Tear Sheet Now Available for
Download
As a health care provider, you may
have suggested to a patient who has
been diagnosed with FH (Familial
Hypercholesterolemia), that they join
the FH Patient Registry at
thefhfoundation.org. To assist patients in
filling out the online patient registry, the
NLA has added an FH Patient Registry Tear
Sheet to the Practice Tool Kit page on the
website of the NLA. Download the tear
sheet here: lipid.org/sites/default/files/
fh_patient_tear_sheet.pdf.
Submit your Abstracts for NLA Annual
Scientific Sessions
The National Lipid Association is now
accepting abstracts for the Scientific
Sessions in Orlando, FL May 1 - 4, 2014.
28
This is your opportunity to submit your
science for inclusion in the NLA’s 2014
Poster Hall. The NLA Poster Hall will cover
a vast array of topics in 16 categories,
including clinical applications of
biomarkers, epidemiology of cardiovascular
disease, management of statin intolerance,
and imaging in atherosclerosis. All
accepted poster abstracts will also be
published in the 2014 Annual Scientific
Sessions edition of the Journal of Clinical
Lipidology. Visit lipid.org/abstracts to
submit online and for more information.
Submit your Chapter-Related News
Stories
Have you checked out the new chapter
pages at lipid.org? These individual pages
provide chapter news, discussion boards
and other chapter related information.
Send your chapter-related news items to
Lindsey Mitcham, Esq. (lmitcham@lipid.
org) and we will add it to the chapter page
after approval.
Health Information Technology Papers
now Available
The National Lipid Association along with
Save the Date for Spring Clinical Lipid
a panel of outside experts from various
Update
disciplines convened for a workshop in late
Save the date for breathtaking Maui! The
July to examine how health information
NLA Spring CLU is scheduled for March
technology (HIT) can be used to effectively
13-16, 2014 at the Grand Wailea Hotel
improve LDL-C goal attainment. The
in Maui, HI. Please check lipid.org/
workshop committee of experts included
springclu for the latest details.
participants from academic medical
centers, health care policy organizations,
Chapter Discussion Forums Now
large health care systems, as well as
Available
members from the HIT and pharmaceutical
Use our new chapter discussion forums
industries. The proceedings from the
to encourage interaction with fellow
workshop were developed into an article
members and colleagues.
printed in the November/December issue
of the Journal of Clinical Lipidology entitled
SWLA
lipid.org/forums/chapter- Use of health information technology (HIT)
discussion-swla
to improve statin adherence and low-density
SELA
lipid.org/forums/chapter- lipoprotein cholesterol goal attainment in
high-risk patients: Proceedings
discussion-sela
from a workshop.
MWLAlipid.org/forums/chapter-
discussion-mwla
NELA
lipid.org/forums/chapter-
discussion-nela
PLA
lipid.org/forums/chapter-
discussion-pla
LipidSpin
Foundation Update
ANNE C. GOLDBERG, MD, FNLA
President, Foundation of the National Lipid Association
Associate Professor of Medicine
Washington University School of Medicine
St. Louis, MO
I am pleased to give you an update
on several successful initiatives by
the Foundation of the National Lipid
Association in the past months.
As you know, in keeping with the
Foundation’s mission to educate clinicians
(as well as the lay public), the Foundation
of the NLA supported and sponsored a
public awareness campaign about familial
hypercholesterolemia (FH) that was
launched August 30, 2013, to coincide
with National Cholesterol Education
Month for September. You can still
download the “Are You the One?” poster/
supplement at learnyourlipids.com.
Several members of the Foundation of
the NLA, as well as other NLA members,
participated in the FH Foundation’s FH
Summit in Annapolis, just before the NLA’s
Fall CLU in Baltimore. The Foundation
of the NLA has created a tear sheet that
can be used by FH patients when they
are filling out the FH Foundation’s new
patient registry online. The tear sheet is
available on the NLA website and can be
downloaded by providers to give to their
FH patients to help provide them with
information that they need to know in
order to answer questions for the registry.
You may access this tear sheet directly
here: lipid.org/sites/default/files/fh_
patient_tear_sheet.pdf.
The Foundation hosted an event on
Saturday, Sept. 21 in conjunction with
the NLA Fall Clinical Lipid Update in
Baltimore, MD. The event in Baltimore,
which was a Food Tour of Fell’s Point
including a ferry ride across the Inner
Harbor, had 25 attendees and netted
approximately $600 for the Foundation.
as you enjoy traditional music, dance, food
and fun. This event will cost $150 per
person. You may register online at
lipid.org/springclu. n
We will hold another fabulous dinner event
at the Spring Clinical Lipid Update in Maui,
HI. Support the Foundation of the NLA at
a Hawaiian Luau, a traditional party filled
with Hawaiian foods, music and dance.
Sunset is the perfect time for a traditional
Hawaiian luau on the shores of Maui. Bring
your appetite since you’ll be feasting on
a magnificent spread of Hawaiian foods.
Then, settle down under the stars while
you listen to live music and watch skilled
performances of the hula. The Maui Luau
on a balmy evening under the stars will
transport you to the days of early Polynesia
29
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Elevated Lipoprotein(a) Levels in South Asians in North America.
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1. Schipper H, Prakken B, Kalkhovrn E, Boes M. Adipose tissue resident immune cells: key players in immunometabolism. Trends in
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4. Ibrahim M. Subcutaneous and visceral adipose tissue: structural and
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5. Chawla,A.et al(2011)Macrophage mediated inflammation in
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4. Ogden CL, Carroll MD, Curtin LR, Lamb MM and Flegal KM.
Prevalence of high body mass index in U.S. children and adolescents,
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6. Winer S, Winer D. Immunology and Cell Biology(2012);90:755-762
7. Winer S, Winer D. Immunology and Cell Biology(2012);90:755-762
8. Schipper H, Prakken B, Kalkhoven E, Boes M. Adipose tissue –
resident immune cells: key players in immunometabolism. Trends in
Endocrinology and Metabolism. 2012;23:407-415
Practical Pearls
1. How smartphones are on the verge of taking over the world.
New York Daily News [Internet]. March 22, 2013. http://www.
nydailynews.com/life-style/smartphones-world-article-1.1295927
Accessed Sept. 19, 2013.
2. Costello, S. How many apps are in the iPhone app store?
About.com [Internet]. June 2013. http://ipod.about.com/od/
iphonesoftwareterms/qt/apps-in-app-store.htm. Accessed Sept. 19,
2013.
3. Aungst, T. Apple app store still leads Android in total number of
medical apps. iMedicalApps [Internet]. July 12, 2013. http://www.
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Sept. 19, 2013.
31
NLA Events Calendar
2014 Scientific Meetings
2014 National Lipid Association
Clinical Lipid Update—Spring
Hosted by the Pacific Lipid Association and the Southwest Lipid Association
March 13–16, 2014
Grand Wailea Hotel, Maui, Hawaii
2014 National Lipid Association Scientific Sessions
Hosted by the Southeast Lipid Association
May 1–4, 2014
Hyatt Regency Grand Cypress Hotel, Orlando, Florida
Clinical
Lipid
Update
JW Marriott Hotel • Indianapolis, IN
August 22–24, 2014
2014 National Lipid Association
Clinical Lipid Update—Fall
Hosted by the Midwest Lipid Association and the Northeast Lipid Association
August 22–24, 2014
JW Marriott Hotel, Indianapolis, Indiana
For a list of additional scientific meetings visit lipid.org
Need Help Filling out the FH Patient Registry?
Your health care provider may have suggested you
Date of exam:
_____________ mm/dd/yyyy
join the FH Patient Registry. If you have been
Blood pressure:
Systolic: ________
Diastolic: ________
Exams and Labs:
Height:_________
Weight: _________
Total cholesterol: ________
LDL: ________
diagnosed with FH (familial hypercholesterolemia)
or suspect you may have it, it is important for you to
register at www.thefhfoundation.org. Click on
"Cascade FH Registry." The purpose of this registry is
to collect information that can help researchers and
Your Health Care Provider:
then lead to improved care and a longer and better
First Name: _______________________________________________________
life for people with FH. The FH Foundation and the
Last Name: ________________________________________________________
FH Patient Registry are not affiliated with the
Office Name: ______________________________________________________
Foundation of the National Lipid Association.
Street Address: ____________________________________________________
To assist you in filling out the online patient registry
City: ______________________________ State: ______ Zip code: _________
form, you will need the following information from
Telephone: ___________________________Fax: ________________________
your health care provider. Take this card to your
next appointment and ask your provider to help fill
in this information.
The Foundation of the National Lipid Association is pleased to
provide this simple worksheet to assist you in signing up for the FH
Patient Registry. For more information on FH or cholesterol issues, go
to www.learnyourlipids.com.
To register go to
www.thefhfoundation.org
32
LipidSpin
This information is intended for providers.
Authors: Vanessa Milne, NP, MS and Lisa Tully, MD
Summary of the International Atherosclerosis Position Paper:
Global Recommendations for the Management of Dyslipidemia
LDL Cholesterol and Non-HDL Cholesterol
• The IAS favors targeting non-HDL-C in addition to LDL-C as the primary target for lipid lowering therapy.
• Very low-density lipoprotein cholesterol (VLDL-C) promotes atherosclerosis and is therefore a potential
additional target for lipid lowering therapy.
• Non-HDL cholesterol is the sum of LDL-C and VLDL-C and represents cholesterol in all atherogenic lipoproteins.
• Non-HDL-C more accurately reflects the overall atherogenic burden especially in patients with
hypertriglyceridemia and has the advantage of accurate testing in the nonfasting setting.
Primary and Secondary Prevention Targets for LDL-C and Non-HDL-C
• For secondary prevention in patients with established CVD, the optimal level of LDL-C is <70 mg/dL and nonHDL-C <100 mg/dL.
• LDL-C <100 mg/dL and non-HDL-C <130 mg/dL are optimal levels for primary prevention of CVD especially in
high-risk populations.
• The IAS does not define specific treatment targets for all patients but rather emphasizes the importance of
optimal levels of atherogenic lipoproteins based on long-term risk.
Assessing Risk and Adjusting Intensity of Lipid-Lowering Therapy to Long Term Risk
• Assess long term or lifetime risk over short-term risk.
• Target the major risk factors of hypertension, diabetes, low HDL-C and tobacco use. Recalculate risk when a risk
factor no longer applies.
• Maximal lifestyle therapies are emphasized and recommended for anyone with a moderate or higher risk level
to age 80 yrs.
• Cholesterol lowering drug therapy is optional for those at moderate risk, should be considered for moderately
high risk and is indicated for those at high risk.
• For world populations the Lloyd-Jones/Framingham algorithm is recommended and risk should be recalibrated
with Framingham estimates.
• Diagnoses of Familial Hypercholesterolemia, DM with other risk factors and chronic kidney disease should make
an individual moderately high or high risk.
• CRP may be useful in patients of moderate risk and the Reynolds risk score includes CRP. Risk factors should be
aggressively targeted in someone with an elevated Lp(a).
Long Term Risk for ASCVD by age 80 (from age 50)
Long- Risk Category
Absolute Risk for ASCVD
Low
<15%
Moderate
15-30%
Moderately high
30-44%
High
≥ 45%
Table adapted from the full IAS report.
Full Report of the IAS Panel An International Atherosclerosis Society Position Paper: Global Recommendations for the Management of Dyslipidemia. 2013: 1-66.
http://www.athero.org/download/IASPPGuidelines_FullReport_20131011.pdf
Health Care Providers—access this tear sheet at www.learnyourlipids.com
6816 Southpoint Pkwy
Suite 1000
Jacksonville, Florida 32216

the Lipid Spin (Winter 2013-14)

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