Winter 2012 - National Lipid Association

Official Publication of the National Lipid Association 

LipidSpin 

Theme 

New and Novel Targets: 

Controversies and Therapies for 

Atherosclerosis and Lipid Disorders 

Also in this issue: 

Utilizing Clinical Lipid Specialists in the Patient-Centered Medical Home 

Deceivingly Elevated HDL-C—Mounting Risk Factors Overpower Presumed Protection 

This issue sponsored by the Southwest Lipid Association 

Volume 10 Issue 1 Winter 2012 

visit www.lipid.org

2012 

MAY 31–JUNE 3 

Scottsdale 

National Lipid Association 

Annual Scientific Sessions 

JW MARRIOTT – CAMELBACK INN | SCOTTSDALE, AZ | MAY 31–JUNE 3, 2012 

www.lipid.org/sessions 

Masters Summit on Emerging LDL Therapies 

Point/Counterpoint Debate Session on Omega-3 

Fatty Acids: Is it EPA or EPA and DHA? 

Special Session on Atherosclerotic Plaque 

featuring World-renowned Experts 

Interact with Thought Leaders at a Special Meet 

the Experts Roundtable Breakfast Session 

Call for Abstracts 

Young Investigator Awards 

Sponsored by LipoScience, Inc. 

Evidence-based, Clinically-relevant Sessions on 

Gender Issues in CAD, Metabolic Syndrome, Diet, 

Adherence and much more! 

Practical Breakout Sessions and Workshops 

Satellite Dinner Symposia 

Pre-Conference Professional Development Courses: 

May 30–31, 2012 

Submit your research for presentation as a poster during the 2012 NLA Scienti�c Sessions in Scottsdale, AZ. The deadline for 

poster abstract submissions is April 2, 2012. All accepted poster abstracts will be published in the May/June 2012 issue of the 

Journal of Clinical Lipidology. 

Lead presenters with accepted abstracts who are Young Investigators (in training students, residents and fellows or members in 

practice for < 5 years) will have the chance to compete for the NLA’s enhanced Young Investigator Award o�ering a $1,000 cash 

prize and certi�cate to �rst place and $500 cash prizes to second and third place. 

Visit www.lipid.org/abstracts for complete information.

In This Issue: Winter 2012 

Editors 

JAMES A. UNDERBERG, MD, MS, FACPM, FACP, FNLA* 

Preventive CV Medicine, Lipidology and Hypertension 

Clinical Assistant Professor of Medicine 

NYU Medical School and Center for CV Prevention 

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 

MEGAN SEERY 


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, Suite1000 

Jacksonville, FL 32216 

Phone: 904-998-0854 | Fax: 904-998-0855 

Copyright ©2012 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. 

*indicates ABCL Diplomate status 

(Volume 10, Issue 1) 

2 From the NLA President 

Many Exciting Opportunities Ahead 

—Penny Kris-Etherton, PhD, RD, CLS, FNLA 

3 From the SWLA President 

Small but Strong Regional 

Membership 

—James M. Falko, MD, FNLA* 

4 Editor’s Corner 

The Changing Face of Lipidology 

—Robert A. Wild, MD, PhD, MPH, FNLA* 

6 Clinical Feature 

Optimizing CETP Inhibition: Insights 

from Genetic and Mechanistic 

Studies 

—Patrick S. Dib, MS 

10 EBM Tools for Practice 

To Treat or Not to Treat? 

— Joseph L. Lillo, DO 

12 Specialty Matters 

Should PCOS Be Called Syndrome 

XX? 

— Steven A. Foley, MD 

14 Practical Pearls 

Utilizing Clinical Lipid Specialists in 

the Patient-Centered Medical Home 

—Randy W. Burden, PharmD, MDiv, PhC, FNLA* 

—Darcie Robran-Marquez, MD, MBA 

17 Lipid Luminations 

Male Hypogonadism, the Metabolic 

Syndrome and Cardiovascular 

Disease—An Update for Clinical 

Lipidologists 

—Vasudevan A. Raghavan, MBBS, MD, MRCP* 

—Glenn R. Cunningham, MD 

Look for the NLA Community logo to discuss 

articles online at www.lipid.org 

21 Case Study 

Deceivingly Elevated HDL-C— 

Mounting Risk Factors Overpower 

Presumed Protection 

—Thomas J. Bartlett, MD 

23 Chapter Update 

Low HDL-C in Childhood and 

Adolescence 

—Piers R. Blackett, MB, ChB, FAAP, FNLA* 

—Stephen R. Daniels, MD, PhD, FAAP, FNLA 

27 Guest Editorial 

29 Member Spotlight 

—Judith A. Collins, NP, MSN, CLS 

30 Member Update 

31 News and Notes 

32 Education and Meeting Update 

33 Foundation Update 

34 Events Calendar 

35 The Last Word 

—David T. Nash, MD, FNLA* 

37 References 

41 Patient Tear Sheet 

1

From the NLA President: 

Many Exciting Opportunities Ahead 

PEnny Kris-EthErton, PhD, rD, CLs, FnLA 

National Lipid Association President 

Distinguished Professor of Nutrition 

Penn State University 

University Park, PA 

Discuss this article at www.lipid.org 

Go to “Topics/Lipid Spin Winter 2012” 

and look for “From the NLA President.” 

There continue to be many new and ongoing 

activities that benefit NLA members. From 

January 27 to 29, 2012, the NLA held an 

Educational Planning Retreat in Las Vegas, 

Nevada. The focus of the meeting was to 

plan educational programs to meet the needs 

of members. Topics addressed included 

educational standards for CME/CE credits, 

core curriculum to be developed that 

covers topics important to NLA members, 

performance measures (i.e., competencies 

and certification), and options for delivering 

CME/CE programs. Chapter Presidents will 

play a key role in planning and coordinating 

Chapter-sponsored educational programs. 

There are many opportunities for NLA 

members to be involved in educational 

programs that advance the mission of NLA 

and serve our members. Please contact your 

Chapter President if you are interested in 

becoming involved with NLA educational 

programs. 

I am happy to share that our international 

initiative is moving forward under the 

leadership of Michael Davidson, MD, 

FnLA*, and Peter toth, MD, PhD, 

FnLA*. NLA leadership will meet with 

counterparts in Australia at the International 

Symposium on Atherosclerosis that will be 

held from March 25–29 in Sydney, Australia. 

The NLA is sponsoring a reception at the 

ISA meeting on March 26. Please e-mail 

Deborah Walker at dwalker@lipid.org if 

you wish to attend. 

I also am excited to share that the NLA 

recently became a member of Sharecare, 

which is an interactive website designed 

to simplify a consumer’s search for quality 

healthcare information. This partnership will 

expand the visibility of the NLA and provide 

a platform that enables our members to 

share their expertise. 

Based on many comments from members at 

the 2011 Annual Scientific Sessions in New 

York City, we have created a new Advocacy 

Committee. All NLA Chapter Presidents are 

members as well as some NLA Executive 

Committee members. This committee is in 

the early stages of planning its mission and 

scope of work. Much remains to be done to 

define the scope of this Committee and how 

it will function. Nonetheless, the Advocacy 

Committee, chaired by terry Jacobson, 

MD, FnLA*, will serve the interests of our 

members and also the patients we serve. You 

will be pleased to know that the staff liaison 

for this Committee is Brian hart, Esq. His 

legal expertise will be of great benefit to this 

Committee in executing our work plan. 

The other new committee that is making 

great strides is the Practice Management 

Committee which is chaired by ralph La 

Forge, Msc, CLs, FnLA, and Kaye-Eileen 

Willard, MD*. The over-arching goal of 

this committee is to define best practices in 

Clinical Lipidology. Subcommittees that have 

been established for which we are seeking 

NLA members include: Literature Search; 

Coding and Reimbursement; Cardiometabolic 

Risk Reduction Clinical Manual; Trends 

Survey; and Health Quality Survey. For more 

information about these committees, as well 

as to volunteer to serve, please contact Brian 

Hart at bhart@lipid.org. 

The NLA 2012 Annual Scientific Sessions 

will be held in Scottsdale, Arizona, from 

May 31–June 3. The meeting will be very 

informative and the sessions will provide 

exciting updates about aspects of Clinical 

Lipidology. There are many fabulous speakers 

who have confirmed their participation. We 

look forward to seeing you in Scottsdale. n 

*Indicates Diplomate, American Board of Clinical 

Lipidology 

2 LipidSpin

I am happy to have our members review 

and read this issue of Lipid Spin, which is a 

product of our Southwest Lipid Association 

(SWLA) membership. What’s great about 

this issue is the fact that I put out a memo 

to ask SWLA members to volunteer their 

time, skill and talents to contribute to 

this issue. We received an overwhelming 

response despite the fact that we are the 

smallest of all the regions in membership. 

Our low membership numbers reflect the 

small population in the Western states but 

because of our region’s talents, we are 

highly committed to foster the practice of 

lipidology and to produce this issue of Lipid 

Spin. 

The theme of this edition is “New and Novel 

Targets: Controversies and Therapies for 

Atherosclerosis and Lipid Disorders.” I am 

most grateful to Patrick Dib, Ms; Joseph 

Lillo, Do*; steven Foley, MD; randy 

Burden, PharmD, CLs, FnLA; Darcie 

robran-Marquez, MD, MBA; Vasudevan 

raghavan, MD, MrCP*; Glenn 

Cunningham, MD; 

thomas Bartlett, MD; David nash, MD, 

FnLA*; Piers Blackett, MD, FnLA*; 

stephen Daniels, MD, FnLA; and Kris 

Vijayaraghavan, MD, FnLA*, for their 

contributions to this issue. 

From the SWLA President: 

Small but Strong Regional Membership 

I am pleased that Judith Collins, nP, CLs, 

is the featured member for this issue’s 

Member Spotlight. 

As President of SWLA, I want to urge 

you to attend the 2012 Annual Scientific 

Sessions in Scottsdale, Arizona. The 

meeting, sponsored by our SWLA Chapter, 

will take place at an exciting venue and will 

feature a new component—the Program 

Committee will select individuals to give 

oral presentations based on their abstract 

submissions. The oral presentations should 

be balanced and of great interest to the 

membership. 

As a member of the NLA since its infancy, 

I have found our group to be unique in its 

collegiality and having no other equal since 

lipidology reaches a multitude of clinical 

and scientific disciplines in medicine. I urge 

all of you to network with others who may 

benefit as I do by being a member of our 

association. n 

*Indicates Diplomate, American Board of Clinical 

Lipidology 

JAMEs M. FALKo, MD, FnLA 

Southwest Lipid Association President 

Professor of Medicine 

University of Colorado 

Denver, CO 

Diplomate, American Board of Clinical Lipidology 



and look for “From the SWLA President.” 

Official Publication of the National Lipid Association 3

Editor’s Corner: 

The Changing Face of Lipidology 



and look for “Editor’s Corner.” 

roBErt A. WiLD, MD, PhD, MPh, FnLA 

Clinical Epidemiology and Biostatistics and 

Clinical Lipidology Professor 




Returning from our recent education 

retreat in Las Vegas, Nevada, I reflected on 

the energizing experience of a combined 

effort of a group of people with different 

talents, backgrounds, and skill sets, all 

sharing a common purpose. Truly, the 

whole was much more than the sum of 

its parts: synergy was taking place. The 

obvious takeaway from this meeting is 

what the NLA is and what lipidologists 

offer is changing. Our specialty is rapidly 

evolving, keeping pace with an explosion 

of information and new tools to enhance 

our knowledge and skill sets. This age of 

communication brings new technology at 

a rate that can be challenging to integrate, 

but has the potential to revolutionize 

and enrich the way we communicate 

not just socially, but in our research and 

patient care. Integrating new practices 

and standards of care will be faster 

and easier than ever, thanks to instant 

communications available at our fingertips. 

There are a myriad of NLA educational 

offerings on the radar: HDL science, 

emerging LDL therapies, continuing our 

FH awareness efforts, and reaching out to 

primary care practitioners. We are busy 

revamping the core curriculum, broadening 

the scope while sharpening the focus on 

background information as a foundation 

for accessing foreground information. 

The enhanced core curriculum will offer 

greater integration of specialties as parts 

of a comprehensive care team. Our efforts 

will highlight the importance of risk 

prevention, from before conception to the 

challenges of senescence. 

Our Annual Scientific Sessions, hosted in 

2012 by the Southwest chapter, promises 

to cater to the full spectrum, with offerings 

for basic scientists, researchers, clinicians, 

teachers and all members of the healthcare 

team. This annual meeting will give us an 

early glimpse of the future of the NLA. 

Our goal is to embrace and showcase all 

disciplines. 

There are exciting developments on the 

horizon, so stay tuned. 

This issue of Lipid Spin focuses on 

“New and Novel Targets: Controversies, 

and Therapies for Atherosclerosis and 

Lipid Disorders.” We’re excited by the 

increasing diversity of submissions from 

an array of professionals, and we hope 

you enjoy it; it is a springboard for things 

to come. Read this issue with the goal of 

enhancing your background information, 

on which to build foreground information. 

We will refer often to this “background” 

concept. We need to know all about 

why things occur, of course, but we also 

want to know how best to deal with 

whatever problems we encounter using 

the best evidence available. We hope 

that as you improve your knowledge in 

both arenas that you never forget that 1) 

your experience, 2) your understanding 

of your patients’ needs and values, 3) 

the resources available to you, and 4) 

the organizational context must all be 

integrated to make the best clinical 

decisions. n 


Editors’ Note: This letter is in response 

to the Winter 2011 issue of Lipid 

Spin, which focused on the theme of 

“Nonpharmacologic and Complementary 

Approaches to Lipid Management.” The 

views expressed are those of the author. 

Because the now >10 year old National 

Cholesterol Education Program Expert 

Panel (NCEP ATP III) recommends 

phytosterol enriched functional foods 

as part of an optimal dietary prevention 

strategy, many health professionals— 

such as the authors of the Winter 

2011 issue of the Lipid Spin—may 

recommend sterol products. I would 

like to counter that, in spite of these 

products reducing cholesterol levels, 

perhaps the recommendations should be 

reevaluated and that unless sterol levels 

are monitored only stanol products should 

be recommended. 

Sterols are ubiquitous and found naturally 

in many foods such as vegetables, nuts, 

seeds, vegetable oils, and fruits. The 

average American ingests about 200 to 

400 mg/day. Because they compete with 

cholesterol for inclusion in biliary micelles 

they reduce intestinal absorption of 

cholesterol and ultimately, by upregulating 

LDL receptors in inducing clearance of 

LDLs, they are associated with reduced 

LDL blood levels. The amounts that 

occur naturally in foods are not usually a 

concern. Consuming sterols at 10-20 times 

the amount we get in foods naturally from 

a variety of foods to which sterol esters 

have been added as well as supplements 

for prostate health and cholesterol 

management might create variable degrees 

of phytosterolemia in persons who for one 

reason or another are hyperabsorbers of 

sterols. 

While phytosterols do lower LDL 

cholesterol about 10-15%, they have 

the potential to elevate sitosterol and 

campesterol levels in individuals who have 

increased sterol absorption. 1,2 Several 

studies have suggested cholesterol and 

noncholesterol sterol hyperabsorption 

is a CV risk factor. 3-5 In our practice 

we have found that individuals taking 

statins, menopausal women, diabetics 

and at times those with the apoE 3/4 or 

E 4/4 phenotype tend to hyperabsorb. 

Could such phytosterolemia, not to the 

levels seen with genetic phytosterolemia, 

result in uncertain consequences such 

as increased risk of CV events? The 

Special Turku Coronary Risk Factor 

Intervention Project or STRIP study 

showed that children who had double the 

usual sterol intake increased blood levels 

by around 50%. 6 Despite reduction of 

LDL, risk of heart disease may increase. 

Likewise studies of patients on statins 

have demonstrated increased levels of 

phytosterols in carotid plaque. 7,8 

The clinical trials to-date with sterol esters 

have used LDL and total cholesterol as 

endpoints, not cardiovascular events. If we 

reduce cholesterol levels with phytosterol 

supplementation but increase blood levels 

of phytosterols, then it is theoretically 

possible that we could increase the risk 

Letter to the Editors: 

of heart disease. Indeed, 2011 European 

Guidelines state such supplementation 

needs to be monitored. 9 

Stanols, unlike sterols, are not absorbed. 

Yet in the U.S. the only available source 

is sitostanol (Benecol) margarine and 

chews. I find recommending the margarine 

product for daily use in the amount of 3-4 

tablespoons disingenuous based on what 

we know about trans fats. The other form 

of obtaining stanols are Benecol smart 

chews (not to be confused by Corowise 

Cardio Chews, which contain sterols), 

which are currently available only from 

online sellers, and may be rejected by 

those who find the sweet taste—12g sugar 

and 80 calories in the recommended four 

servings/day—objectionable. 

Bottom line: Check baseline sterol levels 

and again periodically after therapies. 

Unless one has phytosterolemia or 

significant hyperabsorption, do not stop 

eating plants, as the amount of sterols is 

not likely a concern. Stop supplements 

with added phytosterols as well as the 

many highly processed foods with added 

sterols. 

—Margaret Pfeiffer, MS, RD, CD, CLS 

Personal Health Coach 

Health Diagnostic Laboratory, Inc. 

Advanced Lipidology 

Delafield, WI 

References listed on page 38. 


Clinical Feature: 

Optimizing CETP Inhibition: Insights from Genetic and Mechanistic 

Studies 



and look for “Clinical Feature.” 

PAtriCK s. DiB, Ms 

Doctoral Research Assistant 

Department of Pharmaceutical Sciences 



Several cross-sectional and prospective 

epidemiological studies have shown that 

HDL-C is a strong, independent, and 

inverse predictor of CVD. Data from the 

Framingham Heart Study, Lipid Research 

Clinic, Prevalence Mortality Follow-up 

Study, Lipid Research Clinic Primary 

Prevention Trial, and the Multiple Risk 

Factor Intervention Trial estimate that 

a 1mg/dL (0.02 mmol/l) rise in HDL-C 

reduces CVD mortality by 2-3%. 1 

HDL-C exerts its anti-atherogenic effects 

by augmenting the reverse cholesterol 

transport (RCT) pathway. Specifically, 

HDL-C modulates the RCT pathway 

through ApoA-1, the major lipoprotein 

(70%) of HDL-C. 2 After maturation 

through minor lipidation, ApoA-1 removes 

cholesterol and phospholipids from cell 

membranes as well as atherosclerotic 

lesions and transports them to the liver 

for elimination. 2 

Not only does HDL-C produce its 

anti-atherogenic effects via RCT, but 

HDL-C has non-RCT anti-atherogenic 

effects. HDL-C independently improves 

endothelial function and has been shown 

to exert vasodilatory effects and reverse 

thrombogenic surfaces of endothelial 

cells by increasing nitric oxide (NO) and 

prostacyclin production, tPA synthesis, 

and inhibiting thromboxane A2 and 

PAI-1 expression. 2 Additionally, HDL-C 

reduces the inflammatory and immune 

response in vascular cells by inhibiting 

the upstream proinflammatory mediator, 

sphingosine kinase which in turn lowers 

the risk of atherosclerotic lesions by 

decreasing nuclear factor kappa-B 

(NF-kB), vascular adhesion molecule-1 

(VCAM-1) and intercellular adhesion 

molecule-1 (ICAM-1). 2 

CEtP and hDL-C 

Several novel pharmaceutical treatments 

have been in development to raise HDL- 

C. The interest in developing these 

novel drugs stem from findings of the 

NCEP ATP III and other research that 

implicate low HDL-C as a categorical 

risk factor for CVD. Another major 

reason for developing new drugs is the 

inadequacy of current treatments (statins, 

fibrates, niacin) to raise HDL-C to achieve 

improved clinical outcomes. Of these 

new pharmaceutical therapies, CETP 

inhibition has been on the forefront of 

the pharmaceutical quest to increase 

HDL-C. In particular, inhibition of CETP 

has been shown to substantially increase 

HDL-C (up to 150%), which suggests a 

potential emergence of a new drug family 

in dyslipidemia management. 3 

CETP is a hydrophobic glycoprotein with 

an Mr of 70000-74000 and consists of 

476 amino acid residues. The human 

CETP gene is located in chromosome 16 

(16q12-16q21) and spans over 25 kb, 

consisting of 16 exons and 15 introns. 4 

Studies have shown that CETP serves as 

a shuttle to facilitate the stoichiometric 

1:1 bidirectional transfer of triglycerides 

(TG) for cholesteryl ester between ApoB 

containing lipoproteins and HDL-C. 4 

Consequently, the effects of lipoproteins 

transfer in HDL results in a reduction 

of cholesteryl ester and increase in TG. 

Therefore, the role of CETP appears to 


have an important effect on regulating 

HDL-C as well as modulating HDL-C 

particle size and consequently the antiatherogenic 

properties of HDL-C. 4 

Research on Japanese populations with 

hyperalphalipoproteinemia (elevated HDL- 

C) deficient in CETP coupled with the 

well-established strong inverse relationship 

between HDL-C and CVD initiated the 

interest in the development of CETP 

inhibitor drugs. Further augmenting 

the interest in CETP inhibitors are the 

results of genome-wide association studies 

which suggest that CETP alleles are the 

most significant determinant of HDL-C 

levels than any other loci in the genome. 5 

Unfortunately, the failure of torcetrapib 

to reduce mortality despite significant 

elevations in HDL-C has led to controversy 

regarding the efficacy of CETP inhibitors. 

However, further examination of the 

torcetrapib trials have suggested off-target 

mechanisms that might have contributed 

to the increased paradoxical observations 

in mortality rates. 6 Although off-target 

effects could have largely contributed to 

the failure of torcetrapib, the torcetrapib 

trials were a clear indication for the need 

to further examine the biological and 

pathophysiological role of CETP in CVD 

development. 

With the lessons learned from the 

torcetrapib trials and the several 

mechanistic and genome-wide association 

studies conducted since then, a potential 

answer to the CETP enigma lies in the 

careful dissection of data on: 

1. Metabolic environment and its 

effects on CETP function 

2. Magnitude of CETP inhibition and 

lipoprotein Metabolism: Genetic 

and Mechanistic Findings 

3. Quality (structure, composition) of 

lipoproteins as a consequence of 

CETP inhibition 

Effects of Metabolic Profile on 

CEtP Function 

The metabolic environment appears to 

modulate CETP activity. In a prospective 

study, elevated CETP levels were 

shown to be associated with increased 

risk of future CVD in individuals with 

hypertriglyceridemia (>1.9 mmol/l). 7 

Whereas in a nested case controll study, 

elevated CETP was associated with 

reduced CVD risk in individuals with 

low TG levels. 8 Therefore, triglyceride 

levels appear to play a crucial role in 

identifying the pro-atherogenic or antiatherogenic 

effects of CETP. Not only that, 

but hepatic lipase activity also appears to 

influence CVD risk. In particular, reduced 

In particular, 

inhibition of CETP 

has been shown to 

substantially increase 

HDL-C (up to 150%), 

which suggests a 

potential emergence 

of a new drug family 

in dyslipidemia 

management. 

hepatic lipase activity, despite low CETP 

and elevated HDL-C, is associated with 

an increased risk for atherosclerosis. 9 

Hepatic lipase plays an important role in 

producing functional, very small HDL-C 

and converting TG-rich atherogenic LDL-II 

to LDL-III. Additionally this explains the 

different lipoprotein profiles in men and 

women since they appear to be modulated 

by sex steroid hormones. 10 

Effects of CEtP Gene Variants on 

hDL-C and CVD 

The Honolulu Heart Program suggest that 

male heterozygotes for CETP deficiency 

with mild or moderately elevated HDL-C 

levels (1.0–1.6 mmol/l) had no increased 

risk of CVD compared to men with or 

without CETP deficiency but with largely 

elevated levels of HDL-C (>1.6 mmol/l). 11 

Also, supporting this are the results from 

a cross-sectional study in a Japanese 

population with very high HDL-C levels, 

as well as those with mild-to-moderate 

HDL-C elevation. Both groups are 

protected against CVD regardless of CETP 

status. 12 Whereas in the Omagari region 

in Japan, CETP deficiency did not increase 

longetivity and if accompanied by reduced 

HL there was an increase in CVD risk. 9 

Inconsistent findings from epidemiological 

studies suggest that the role of CETP 

inhibition in development of CVD is 

complex. In turn, this has sparked a debate 

whether CETP is “anti”-atherogenic or 

“pro”-atherogenic. In a unique Japanese 

population, CETP deficient homozygous 

families are resistant to atherosclerosis. 13 

On the other hand, CETP gene variants 

such as (D442G) are associated with 

increased LDL particle size and thus, 

CETP appears to be pro-atherogenic. 14 

Another variant with inconsistent findings 

is the TaqIB variant particularly the B1B1 

genotype which has been associated 

with higher CETP activity and lower 

HDL-C. 14 On the other hand, findings 

from the Framingham Offspring Study, 

Veterans Affair HDL-C Intervention 

Trial and in the WOSCOPS trial have 

shown that the B2 allele was associated 

with a reduced risk of coronary heart 

disease in men. 11 The Atherogene Study 

suggested that the A allele of the CETP 

-629 promoter polymorphism was found 

to be associated with decreased mortality 

from cardiovascular events. 15 Further 

complicating the interpretation of data 

was the lack of association between 


TaqIB genotype and CVD in the Coronary 

and Recurrent Events Study and in the 

Physicians’ Health Study. 16 

Despite the very large elevations in HDL- 

C, there are excessive inconsistencies 

to determine the role of reduced CETP 

activity in lowering CVD risk. Therefore, 

a possible explanation is that CETP is not 

only limited to HDL-C biology but rather 

extends to other biological processes 

implicated in CVD development. Indeed, 

it has been demonstrated that CETP 

inhibition not only increases HDL-C 

Nascent 

HDL 

Figure 1. Goal of CETP inhibitor therapy. 

HDL3 

Homotypic Transfer 

CE CE 

CETP 

CE 

but also modulates LDL structure and 

metabolism. 17 Therefore, when studying 

CETP inhibition, it is imperative to not 

only examine quantitative traits (i.e., 

HDL-C, LDL-C etc.) as surrogate markers 

for drug targeting but also it is important 

to examine the biological pathways that 

produce these changes in lipoprotein 

levels. Subsequently, this approach can 

help determine the efficacy of treatment. 

Upon examination of the biological 

pathways, it is then feasible to assess the 

quality of these surrogate markers (i.e., 

TG 

Heterotypic Transfer 

VLDL/LDL 

HDL-C functionality). Thus, to determine 

CETP inhibition efficacy, it is essential 

to examine the mechanistic changes in 

lipoprotein metabolism/dynamics. 

CEtP Biological role in Lipoprotein 

Metabolism and CVD 

As mentioned previously CETP acts a 

lipid shuttle between several lipoproteins 

and HDL-C via 2 major exchange events. 

The heterotypic transfer involves transfer 

cholesteryl ester (CE) in exchange for 

triglyceride (TG) from HDL to LDL and 

VLDL , whereas homotypic exchange 

HDL2b 

involves the transfer of cholesteryl ester, 

to produce functional HDL-C, from HDL3 

to HDL2 generating larger, lower density 

HDL and preβ-HDL. 18 

Interestingly, partial CETP inhibition 

appears to have differential, not equal, 

effects on these exchange events 

which is dependenton the magnitude 

of inhibition. 17 Partial CETP inhibition 

tends to block the pro-atherogenic 

heterotypic cholesteryl ester transfer 

between HDL and LDL/VLDL without 

disrupting the homotypic anti-atherogenic 

intra-HDL transfer. This is in contrast 

to CETP deficiency or complete CETP 

inhibition which blocks both lipid transfer 

mechanisms. In turn, this results in the 

formation of dysfunctional apoE enriched 

HDL-C which extends into the size range 

of LDL-C. 18 Dysfunctional ApoE-enriched 

HDL-C is ineffective in preventing 

cholesterol accumulation in macrophages 

and facilitating cholesterol efflux from 

cholesterol-loaded macrophages. 19 Also, 

ApoE-enriched HDL is a ligand for the 

LDL receptor, unlike control HDL. 20 

Additionally, LDL from CETP-deficient 

subjects is small and polydisperse, has low 

affinity for the LDL receptor, cholesteryl 

oleate enriched, and more susceptible to 

oxidation than control LDL and ultimately 

more atherogenic. 21,22 

In contrast to complete inhibition, lower 

levels of CETP inhibition differentially 

affect pro-atherogenic heterotypic lipid 

transfer. In vitro studies have shown 

that at ~25% inhibition, the transfer 

effects were almost exclusively blocking 

heterotypic transfer whereas homotypic 

transfer was minimally affected. 17 Further 

reductions in CETP activity produced a 

magnitude dependent diminishment of this 

preferential effect. 17 

Supporting these findings are the differing 

effects of complete CETP inhibitors and 

dalcetrapib, a selective CETP inhibitor 

(also considered a CETP modulator). 23 In 

fact, unlike torcetrapib and anacetrapib, 

dalcetrapib not only reduces atherogenic 

ApoB LDL but also significantly increased 

macrophage to feces RCT in a hamster 

RCT model. 18 Torcetrapib was found to 

have negligible effects on macrophage to 

feces RCT in humans and the hamster RCT 

model. 18 

8 LipidSpin 

RCT

tying it All Up: Lessons from 

Mechanistic and Genetic studies 

Adding more credibility to the mechanistic 

studies are the results from the metaanalysis 

of 92 genetic studies which 

have data on CETP phenotypes and lipid 

levels from 1970 to 2008. The findings 

of this meta-analysis suggest that 3 CETP 

genotypes: 1) carriers of the TaqIB (A 

allele), or 2) the I405V (G allele), or 

3) the −629C>A (A allele) variant are 

associated with moderate inhibition of 

CETP activity. 5 Additionally, these carriers 

have modestly higher levels of HDL-C and 

ApoA-I and exhibit inverse, albeit weakly, 

associations with CVD. 5 The modest 

inhibition of the genetic variants appear 

to be in parallel with the mechanistic 

data suggesting that partial inhibition 

maintains anti-atherogenic effects of CETP 

while blocking pro-atherogenic lipid flux. 

Also, the magnitude of per-allele risk 

reductions was in line with associations 

observed between HDL-C levels and CVD 

in prospective studies. 5 Thus, clinically, 

it appears that gene variants that exhibit 

modest inhibition of CETP confer an antiatherogenic 

lipid profile. Although very 

promising, it is necessary to replicate 

these findings in larger more ethnically 

diverse populations to confirm the benefits 

of partial inhibition demonstrated in 

mechanistic studies. 

Conclusion 

In conclusion, the aforementioned 

findings although preliminary, potentially 

explain the CETP enigma and why many 

CETP deficient individuals have an 

increase in CVD risk despite significantly 

elevated HDL-C levels. Therefore, it is 

possible that the increased risk of CVD 

is largely explained by the disruption of 

the homotypic exchange pathways that 

produce functional HDL-C 

which results in pro-atherogenic 

effects. Providing more evidence to this 

hypothesis are the findings pertaining 

to non-selective CETP inhibitors such 

as torcetrapib which appear to have 

negligible effects on macrophage to 

Clinically, it appears 

that gene variants 

that exhibit modest 

inhibition of CETP 

confer an antiatherogenic 

lipid 

profile. 

feces RCT despite significantly raising 

HDL-C levels. Additionally, dalcetrapib (a 

selective CETP inhibitor) appears to exert 

the anti-atherogenic effects of CETP by 

preferentially blocking the pro-atherogenic 

lipid transfer pathway while maintaining 

the anti-atherogenic functional HDL-C 

producing pathway. This might offer a 

potential explanation why CETP gene 

variants that result in modest inhibition 

result in decreased CVD risk. You know 

what they say, everything in moderation! 

n 

Disclosure statement: Mr. Dib has no relevant 

disclosures. 



EBM Tools for Practice: 

To Treat or Not to Treat? 

JosEPh L. LiLLo, Do 

Assistant Professor, Affiliate Faculty 

Midwestern University 

Arizona College of Osteopathic Medicine 

Glendale, AZ 

Clinical Lipidologist in Private Practice 

Scottsdale, AZ 



and look for “EBM Tools for Practice.” 

Evidence-Based Medicine, or EBM, has 

become the apparent gold standard in the 

daily practice of clinical medicine. In my 

practice, I try to apply EBM principles into 

my decision-making process. However, in 

my 32 years of practice, as I have watched 

EBM develop, I have noted two issues. 

First, should we always accept EBM at face 

value? Second, if we have no EBM to guide 

us, are we to become victims of clinical 

inertia? 

I believe we need to evaluate the 

validity of the data used to generate 

recommendations. We need to question 

not only the design and methods of 

data collection and analysis but, most 

importantly, how does the analysis reach 

the conclusion. The purpose of this article 

is not to attempt a complete review of data 

analysis, but to make sure we pause to ask 

the right questions. Third party payors are 

certainly beginning to embrace EBM. Their 

ability to pick and choose what they refer 

to as EBM may help influence how we are 

reimbursed. 

I think we all need to revisit some basic 

data analysis to understand the difference 

between absolute and relative risk. We 

need to think about study population 

size. We need to understand confidence 

intervals. We need to ask for numbers 

needed to treat and harm. We need to 

read the inclusion and exclusion criterion 

to help determine study bias. Data often 

presented by pharma may report relative 

risk reduction. RRR might tell us how 

effective the intervention was compared 

to another intervention or placebo, but 

it seldom tells the whole story of how 

clinically beneficial an intervention actually 

was. Of more importance to us is the 

effect size. Here is where clinical judgment 

must be applied as we consider the data 

to help us determine how we plan to treat 

the patient in front of us. 

A recent simple example is data published 

regarding the consumption of alcoholic 

beverages in females as a risk factor for 

breast cancer. The national media used 

a relative risk of a 15% increase in breast 

cancer in women who drink alcohol. A 

more fair statement might have been to 

explain that since the baseline lifetime risk 

of breast cancer is about 10%, the real risk 

in this study is about 11.5%. This closer 

look suggests that the data in this study 

is not quite as “newsworthy” when put in 

this context. 

What if no data exists for a given disease 

state that the patient on our exam table 

suffers from? Do we not consider an 

intervention because no EBM exists? 

I believe we must return to basics. A 

thorough history and physical interpreted 

through our knowledge of physiology, 

clinical experience, peer reviewed 

literature, the mechanism of action of 

the intervention, and the guidance of 

recognized experts (the lowest form 

of evidence) might help us with this 

individual patient. I find that a much better 

option than trying to make the patient fit 

into a flow sheet paradigm that doesn’t 

exactly match the clinical situation. 

I find it somewhat frustrating that many 

use EBM, or lack thereof, as an excuse 


to stay rooted in old clinical patterns, not 

moving forward. I get the same comment 

every time I do a lipid presentation to 

a group of providers and try to mention 

looking beyond LDL-C to Apo B or LDL-P. 

I hear that advanced testing has no 

outcome data, and is therefore useless. 

I can understand this attitude from a 

third party payor’s perspective because of 

economic and population concerns. I do 

not understand this from clinicians. This 

I find it somewhat 

frustrating that many 

use EBM, or lack 

thereof, as an excuse 

to stay rooted in old 

clinical patterns, not 

moving forward. 

often comes from the same cardiologist 

who embraces ATP III as the gold standard, 

but yet still places raising HDL-C as a 

first priority. I also wonder where is 

the EBM for his/her favorite three-drug 

combination to treat hypertension? I 

would wager that same cardiologist 

treats hypertension because of the 

general knowledge that lowering blood 

pressure is a good thing. He/she probably 

chooses agents based upon physiologic 

principles, and mechanism of action of 

those agents. I am going to continue to 

ask that clinician to apply the same clinical 

judgment to both assessing and treating 

hyperlipoproteinemia. 

I will use one of my patients as a brief 

example of what I am emphasizing. An 

asymptomatic 54-year-old male was seen 

for a routine physical. His family history 

was positive for father with hypertension 

and CHF. The patient had 3 of 5 metabolic 

syndrome parameters. Labs revealed: blood 

pressure 138/88, waist circumference 

41 inches, glucose of 89, TC 163, LDL-C 

99, HDL-C 28, non HDL-cholesterol 135, 

Trig 128, 10 year FRS of 10%. He was at 

primary ATP III goal and no therapy was 

indicated by guidelines. NMR revealed 

an LDL-P of 2026 (90th percentile in 

Framingham database). This led me 

personally to order an echocardiogram that 

became a stress echo which demonstrated 

a small inferior wall infarct. Now my 

therapy became much more intensive. 

My view is that enough data exists in 

our own Journal of Clinical Lipidology to 

support advanced testing. The September/ 

October 2011 issue of our Journal 

has an elite panel of experts providing 

recommendations for advanced testing. 1 

Please be sure to read and save that 

opinion statement. 

No less than seven national or international 

organizations also recommend advanced 

testing (EBM). What are we waiting for? 

Will EBM help me reduce my patient’s 

risk? Will my clinical acumen help me 

to help my patient prevent his/her next 

event? Medicine ultimately is the artful 

application of judgment to science, which 

should result in therapeutic wisdom. I 

suggest we give our patients the benefit of 

the best medicine we can offer. EBM alone 

may not be enough. n 

Disclosure statement: Dr. Lillo has received honoraria 

related to speaking from Abbott Laboratories, Merck 

& Co., Kowa Pharmaceuticals and Eli Lilly & Co. Dr. 

Lillo has received consulting fees from Sanofi-Aventis. 

Dr. Lillo has received research grants from Forest 

Laboratories, Pfizer Inc., Eli Lilly & Co., and Furiex. 


Editors’ note: 

We read with interest the opinion 

article by Dr. Lillo. It contains a useful 

review of some terms that can help us 

understand how to interpret literature. 

We would suggest that the best 

approach is to seek out best evidence 

when available. Practicing based on best 

evidence has never been, nor will it ever 

be, blindly unidimensional based only on 

guidelines or current literature. 

It encompasses finding best evidence, 

understanding patient values and 

integrating clinical experience to arrive 

at best clinical choices. We always need 

to find out if what we read is internally 

valid and generalizable to our individual 

situation. Most of the problems and 

clinical decisions we have to deal with 

involve making clinical choices when 

there is no real best evidence. 

Remember: “It ain’t so much what we 

don’t know that gets us into trouble as 

what we do know that just ain’t so.” 

—Variously attributed to Will Rogers 

and Mark Twain 

“All scientific work is incomplete— 

whether it be observational or 

experimental. All scientific work is liable 

to be upset by advancing knowledge. 

That does not confer upon us a freedom 

to ignore the knowledge we already 

have, or to postpone the action it 

appears to demand at a given time.” 

—Sir Austin Bradford Hill 


Specialty Matters: 

Should PCOS Be Called Syndrome XX? 

stEVEn A. FoLEy, MD 

Advanced Gynecology/Institute for Sustained Health 

Colorado Springs, CO 

PCOS, such as infertility, type 2 diabetes 

and hirsuitism, was in excess of $4 billion 

a year. 2 

PCOS is associated with an increased 

incidence of diabetes, insulin resistance 

and cardiovascular disease. 5 

Syndrome XX was first described in 

2003 by Drs. Dunaif and Sam1 This is a major issue, affecting from 

6–10% of women 

, who 

suggested this name for patients with 

type 2 diabetes, dyslipidemia, visceral 

adiposity, hypertension, anovulation and 

hyperandrogenemia. These symptoms 

also are found in patients with polycystic 

ovarian syndrome (PCOS), so some argue 

that Syndrome XX would be a better name 

for this condition. 

Many treat PCOS simply as a gynecological 

condition, but the high risk of developing 

diabetes and cardiovascular disease makes 

it more accurate to recognize it as a 

metabolic condition. Another reason to 

discuss PCOS is its economic burden. Dr. 

Azziz showed in 2005 that the cost of 

caring for the complications of untreated 

3 in the reproductive age 

group. It affects between 7 million and 

10 million women, making it one of the 

most common endocrine conditions. It is 

a condition that needs to be recognized 

and treated early. PCOS may show 

symptoms as early as premenarche. The 

most common symptoms are excessive 

weight gain, abnormal periods and 

hirsuitism. Another common presentation 

is infertility. It is important to note that 

as many as 50% of patients with infertility 

have PCOS. While the gynecologic issues 

are well recognized, the metabolic issues 

often are unrecognized or ignored. Darkos 

et al. 4 Wang et al. showed an increased incidence 

of diabetes and dyslipidemia independent 

of body mass index (BMI). 

showed in 2005 that these patients 

have an 11-fold increase in the prevalence 

of metabolic syndrome compared to agematched 

controls. The standard definition 

of increased waist circumference, elevated 

triglyderides, low high-density lipoprotein 

cholesterol (HDL-C), glucose intolerance 

and hypertension was used. 

6 Discuss this article at www.lipid.org 


and look for “Specialty Matters.” If you have a patient, 

regardless of weight, 

who has irregular 

periods, then the 

primary consideration 

should be PCOS. 

It is important 

to remember that 20% of PCOS patients 

are lean. These patients should have lipid 

and glucose screening as part of their 

diagnostic workup. PCOS is a metabolic 

condition with significant long-term risk 

for patients. The American Association of 

Clinical Endocrinologists (AACE) position 

statement on metabolic syndrome and 


cardiovascular consequences of PCOS 

states that “80% of women with irregular 

periods have PCOS.” If you have a patient, 

regardless of weight, who has irregular 

periods, then the primary consideration 

should be PCOS. 

Making the diagnosis of PCOS is difficult 

because of indistinct definitions. 

The Rotterdam criteria 7 set in 2004 stated 

that two out of three of the following 

criteria were needed for a diagnosis: 

a) oligo or anovulation (represented by 

irregular periods), 

b) clinical and/or biochemical evidence 

of hyperandrogenism and/or, 

c) ultrasound confirmation of polycystic 

ovaries with the exclusion of other 

etiologies. 7 

The most important tool for diagnosing 

PCOS is the patient’s history. Recent 

studies have shown that certain laboratory 

studies also are helpful in the diagnosis 

of PCOS. Metabolic parameters must be 

evaluated. We routinely obtain a vertical 

auto profile (VAP) cholesterol test and 

advanced lipoprotein testing, as well as 

hemoglobin A1C (HgbA1C) and highsensitivity 

C-reactive protein (hs-CRP) 

tests. We also check homocysteine and the 

Lp-PLA2. 

Ultrasound evaluation of the ovaries 

assists in diagnosis. A carotid intimamedia 

thickness (CIMT) check also can be 

helpful, especially as patients get older. 

PCOS is associated with abnormal glucose 

levels in as many as 30% of patients. 5 It 

also is associated with obesity in at least 

40% of cases. It has been shown that as 

many as 70% of patients have abnormal 

lipids, including the insulin-resistance triad 

of elevated triglycerides, low HDL-2, and 

LDL pattern B. 9 

We find that advanced lipid testing often 

finds abnormalities. Women with PCOS 

may be more likely to have LDL pattern 

B. HDL-2 also has been shown to be 

disproportionately low in PCOS patients 10 , 

even though total HDL may be normal. 

Some of the emerging markers, such as hs- 

CRP, may be elevated and might prove to 

be useful for monitoring interventions. 

Other effects of PCOS have been well 

documented. Talbott showed that CIMT in 

PCOS patients is not significantly different 

from controls until the patient reaches 

age 40 11 , suggesting that recognizing this 

disease and treating it at a younger age 

may well prevent future disease. 

Current treatment of PCOS at our clinic, 

the Institute for Sustained Health, focuses 

on the treatment of insulin resistance. The 

diabetes prevention program has shown 

powerful effects in treating high-risk 

patients, such as those with PCOS, and 

preventing the development of diabetes. 12 

To effectively manage this condition. A 

team approach is needed to address the 

different aspects of treatment. 

The most common medication used to 

treat insulin resistance is metformin. 

There have been several studies of 

patients treated with this drug that 

showed improvement in metabolic 

syndrome through weight reduction, 

more regulated periods, and improvement 

of other parameters, such as lipids. 13,14 

Thiazolidinediones (TZD’s) have been 

shown to improve insulin resistance and 

decrease HgbA1C, but they generally result 

in weight gain. This is not a result that 

most patients want. Phentermine also is a 

medicine that may have some short-term 

utility. Elevating norepinephrine in the 

hypothalamus helps to lower the patient’s 

metabolic set point and enhances the 

weight loss. 15 

Nutritional counseling for these patients 

is critical. If patients begin taking 

metformin without adequate nutritional 

counseling, then they may have significant 

gastrointestinal issues and stop taking 

the medication. This is because one 

mechanism of metformin is preventing 

the absorption of carbohydrates. When 

carbohydrates are not absorbed, they will 

cause stomach upset, nausea and diarrhea. 

A low-carbohydrate diet with increased 

protein intake has been shown to be 

helpful in treating insulin resistance and 

decreasing triglycerides. 16 

We have found a defined nutritional 

plan to be very effective in producing 

sustained weight loss in our patients. The 

recommendation in our clinic is 50 grams 

of carbohydrate and 100 grams of protein 

daily. These patients must have ongoing 

support for this life change; unless they 

are able to significantly lower carbohydrate 

intake and increase protein intake, they 

will not be successful. There are adjuvant 

treatments that also help, but only when 

used in addition to the treatment of insulin 

resistance through dietary changes and 

medication. We also encourage exercise as 

a key part of achieving total health. n 

Disclosure statement: Dr. Foley has no relevant 

disclosures. 



Practical Pearls: 

Utilizing Clinical Lipid Specialists in the Patient-Centered Medical Home 

rAnDy W. BUrDEn, PharmD, MDiv, PhC, CLs, BC-ADM, CDE, FnLA 

Captain, U.S. Public Health Service (ret.) 

Presbyterian Medical Group 

Belen, NM 

DArCiE roBrAn-MArQUEZ, MD, MBA 

Medical Director, Primary and Urgent Care Service Line 

Presbyterian Medical Group 

Albuquerque, NM 



and look for “Practical Pearls.” 

According to the Medical Home Position 

Statement published by the Association 

of American Medical Colleges (AAMC), 

“the medical home is a concept or model 

of care delivery that includes an ongoing 

relationship between a provider and 

patient, around-the-clock access to medical 

consultation, respect for the patient/ 

family’s cultural and religious beliefs, and 

a comprehensive approach to care and 

coordination of care through providers and 

community services...in most cases, the 

provider of primary or principal care is a 

healthcare team guided by a generalist.” 1 

In a recent editorial in the Archives of 

Internal Medicine, Dr. Patrick O’Malley 

suggests that healthcare providers with 

disease-specific expertise, in collaboration 

with primary care providers, will enhance 

goal-directed care and be a central 

component of the patient-centered 

medical home (PCMH). He says, “The 

most important elements of collaborative 

care are the establishment of explicit goals 

and the persistent systematic follow-up to 

achieve these goals.” 2 

To provide goal-directed care, clinical staff 

need to be trained to a level of expertise 

that would be adequate to manage 

efficiently and effectively specific clinical 

entities. For example, the PCMH could 

utilize allied healthcare providers in a 

collaborative, team-based model to help 

manage patients with lipoprotein disorders. 

For those needing additional training, the 

National Lipid Association offers different 

levels of courses, from basic to advanced 

lipid management, at conferences and 

through webinars and on-demand modules. 

Allied healthcare providers also could 

seek certification from the Accreditation 

Council of Clinical Lipidology as a Clinical 

Lipid Specialist (CLS) to “validate their 

competency in clinical lipidology.” 3 

In addition to disease-specific training 

and certification, for the healthcare team 

to be fully operative and deliver efficient 

care, each member of the team should 

be functioning at “the maximum of their 

licensure, skill-set, and abilities...given 

both authority and responsibility for 

performing those tasks.” 4 

the Journey 

Presbyterian Healthcare Services (PHS) 

cares for around a half-million patients 


in New Mexico through 70 Presbyterian 

Medical Group (PMG) clinics throughout 

the state. The PCMH journey for PHS 

started in 2009 with a pilot program at 

a single site. PMG since has spread this 

initiative to include 10 primary care clinics 

and around 70 primary care providers. 

PMG has received National Committee 

for Quality Assurance (NCQA) 5 Level 3 

accreditation for ten central New Mexico 

primary care sites. 

One of the more rural PMG sites is the 

clinic in Belen, NM, in Valencia County. 

The Belen clinical staff consists of a multidisciplinary 

team of five primary care 

providers (PCP)—two physicians (internal 

medicine and family medicine) and three 

nurse practitioners—a social worker, two 

nurse care managers, a registered dietitian 

(RD)/certified diabetes educator (CDE) who 

is working toward obtaining certification 

as a CLS, and a CLS pharmacist clinician 

(PhC) specializing in chronic disease 

management. The advanced practice PhC 

license for pharmacists is unique to New 

Mexico and is regulated by both pharmacy 

and medical boards. PhCs practice as 

providers with prescriptive authority based 

on a scope of practice delineated by their 

supervising physician(s). 

With this team in place, the first significant 

step to establishing the PCMH was 

implementing the electronic medical 

record (EMR). The EMR helped to facilitate 

referrals and communication between 

primary care providers and the PhC and RD 

disease management specialists, most often 

dealing with patients having metabolic 

syndrome or some component of it. 

While they were implementing the EMR, 

a decision was made to focus on three 

key areas for interventions in the Belen 

patient population, one being low-density 

lipoprotein cholesterol (LDL-C) goal 

attainment in diabetics. The EMR helped 

to identify these patients through a disease 

registry, which gave the ability to generate 

patient- and provider-specific reports by 

disease state. In this case, reports could be 

generated to list all diabetic patients with 

an LDL-C > 100 mg/dL for evaluation and 

intervention by the PCP, PhC or nurse care 

manager. 

The process of 

becoming an 

accredited PCMH 

has helped PCPs 

more fully utilize 

the Clinical Lipid 

Specialist in 

managing patients. 

Nurse care managers have been integral to 

the process, helping the PCP to generate 

EMR referrals to the PhC or the RD for 

management of specific clinical entities. At 

times when PCP access is limited, the care 

managers also direct patients to see the 

PhC to bridge the care gap until they are 

seen by their PCP. This allows the PhC to 

see the patient for immediate or overdue 

chronic care issues and discuss with the 

patient the possibility of being referred 

for long-term management of lipoprotein 

disorders—or other chronic diseases—if 

not at therapeutic goal. If the patient is 

amenable, then a note saying as much will 

be sent by the PhC through the EMR to 

the PCP for review and referral for disease 

management. 

The PCMH also lends itself to patient 

group visits that have shown to be helpful 

in chronic disease management. At PMG 

PCMH clinics, group visits have been 

successful and encompassed tobacco 

cessation and diabetes management. As the 

Belen clinic moves toward offering group 

visits, it is likely that lipid and/or metabolic 

syndrome management through this venue 

will evolve and utilize the clinical lipid 

specialist. 

The process of becoming an accredited 

PCMH has helped PCPs more fully utilize 

the clinical lipid specialist in managing 

patients with complicated lipoprotein 

disorders and has allowed the whole 

team to plan and implement the care of 

each patient in a more comprehensive 

manner. The PCMH also has helped to 

facilitate the functioning of the members 

of the healthcare team at the level of 

their training and abilities, delegating the 

responsibility for a higher level of care. 

Through the use of the PCMH model, 

PMG has been able to improve the quality 

of care for diabetic patients, resulting in 

better patient outcomes and lower overall 

costs. n 

Disclosure Statement: Dr. Burden has no relevant 

disclosures. Dr. Robran-Marquez has no relevant 

disclosures. 



2011 Update 

Now Available 

National Lipid Association Self-Assessment Program 

Assess and Maintain Your Clinical Knowledge of 

the Complete Clinical Lipidology Curriculum. 

The National Lipid Association now offers the 2011 Update of the NLA-SAP series — 

a one-of-a-kind comprehensive, clinical problem-solving program and self-assessment 

exam. Designed for physicians, physician assistants, nurses, pharmacists, and 

dietitians managing patients with dyslipidemia, the NLA-SAP serves as an invaluable 

resource to ensure mastery of this critical content and to prepare you for certification, 

maintenance of certification, and/or state licensure. 

The four-volume NLA-SAP series provides over 750 multiple-choice questions with 

robust, evidence-based critiques: 

• Volume I Basic Lipid and Lipoprotein Metabolism, Diagnosis and 

Treatment of Dyslipidemia 

• Volume II Management of Cardiometabolic Risk, Biomarkers of 

Atherosclerosis, Epidemiology and Statistics, Clinical Trials 

• Volume III Complex Case Management and Advanced Pharmacology 

• Volume IV Vascular Biology, Advanced Lipid Metabolism and Lipoprotein 

Biochemistry 

Each Volume of the NLA-SAP consists of a board exam-style Question Book and a 

separate, referenced Critique Book, providing comprehensive explanations for the 

correct answers. 

Benefits of Participation in the NLA-SAP 

• Earn 32-40 hours of CME credit at the completion of each Volume of the NLA-SAP 

• Strengthen areas of weakness identified in your confidential score reports 

• Reinforce positive areas of knowledge and understanding 

• Identify further study materials through supporting references 

• Prepare for high stakes exams or licensure 

• Complete the NLA-SAP anywhere — no travel costs or time away from your 

patients and family 

Place your order now at www.lipid.org/SAP 

Sponsored by the National Lipid Association. 

This activity has been approved for AMA PRA Category 1 Credit. 

CE credit provided by AKH Inc, Advancing Knowledge in Heathcare. 

This activity is eligible for ACPE, ANCC and CDR credit; see final CE activity announcement for specific details. CDR provider #AN008. 

Full accreditation information and details regarding order fulfillment available at www.lipid.org/SAP 

Questions: Call the NLA office at 904.998-0854

Lipid Luminations: 

Male Hypogonadism, the Metabolic Syndrome and Cardiovascular 

Disease—An Update for Clinical Lipidologists 

Case: A 48-year-old male rancher-farmer 

is referred for evaluation of a mixed 

hyperlipidemia. He also complains of easy 

fatigability and tiredness, low libido and 

erectile dysfunction (ED). He is not on any 

medications. He is 5 feet 5 inches tall and 

weighs 223 pounds [body mass index =37.1 

kg/m2]. His waist circumference is 44 inches 

(109.2 cm). His blood pressure is 135/80 

mm Hg. Laboratory values revealed a fasting 

glucose of 101 mg/dL, serum total cholesterol 

(TC) of 219 mg/dL, high-density lipoprotein 

cholesterol (HDL-C) of 37 mg/dL, 

triglyceride (TG) of 228 mg/dL and lowdensity 

lipoprotein cholesterol (LDL-C) of 

138 mg/dL. An androgen profile reveals 

the following: total testosterone (total T) of 

200ng/dL (lab normal reference range 230- 

1000 ng/dL). He fulfills the criteria [4/5] for 

metabolic syndrome (METS). 

What are the diagnostic, prognostic 

and therapeutic issues in a man with 

symptomatic testosterone deficiency 

associated with the metabolic syndrome? 

VAsUDEVAn A. rAGhAVAn, MBBs, MD, MrCP 

Director, Cardiometabolic & Lipid Clinic Services 

Scott & White/Texas A&M Health Sciences Center 

Temple, TX 


GLEnn r. CUnninGhAM, MD 

Professor of Medicine and Molecular and Cellular Biology 

Baylor College of Medicine and St. Luke’s Episcopal Hospital 

Houston, TX 

introduction 

Abdominal obesity is associated with 

insulin resistance, prediabetes and diabetes 

mellitus (DM) in those with and without an 

elevated body mass index (BMI). 1-5 Insulin 

resistance, hyperinsulinemia, dysglycemia, 

and release of certain cytokines by adipose 

tissue (adipokines) leads to endothelial 

dysfunction, an atherogenic lipid profile, 

hypertension and vascular inflammation, 

all of which may promote the development 

of atherosclerotic cardiovascular disease 

(ASCVD). 1,2,6 Patients with METS (see Box 1) 

are at increased risk for having or developing 

cardiovascular disease-related mortality. 

The various definitions, prevalence, clinical 

implications and treatment of METS have 

been reviewed elsewhere. 7 This review 

will focus on the relationship between low 

testosterone (low T), type 2 diabetes mellitus 

(T2DM), METS and cardiovascular disease 

(CVD). 

The diagnosis of androgen deficiency (AD) 

is based on low T levels and symptoms 



and look for “Lipid Luminations.” 

The presence of any three of the following five 

traits defines the metabolic syndrome: 

1. Abdominal obesity, defined as a waist 

circumference in men >102 cm (40 in) and 

in women >88 cm (35 in) 

2. Serum triglycerides ≥150 mg/dL (1.7 

mmol/L) or drug treatment for elevated 

triglycerides 

3. Serum HDL cholesterol

consistent with hypogonadism (see Box 2). 

Male hypogonadism refers to a decrease 

in sperm counts, low T, or both. For 

purposes of this article, we will restrict 

our discussion to the low T aspect of male 

hypogonadism. Low T levels can result from 

testicular disease (primary hypogonadism), 

pituitary or hypothalamic disease (secondary 

hypogonadism), or both. In primary 

hypogonadism, serum T concentrations are 

below normal and the serum luteinizing 

hormone (LH) concentrations are above 

normal. LH is an anterior pituitary hormone 

that is regulated by the hypothalamic 

hormone, gonadotropin-releasing hormone 

(GnRH), and sex steroids. In secondary 

hypogonadism, serum T is low and serum 

LH concentrations are either low or 

“inappropriately normal.” 

Conditions Associated with Decreased SHBG 

Concentrations 

Moderate obesity 1 

Nephrotic syndrome 1 

Hypothroidism 

Use of glucocorticoids, progestins, and 

androgenic steroids 

Acromegaly 

Diabetes mellitus 1 

Conditions Associated with Increased SHBG 

Concentrations 

Aging 1 

Hepatic cirrhosis and hepatitis 1 

Hyperthyroidism 

Use of anticonvulsants 1 

Use of estrogens 

HIV disease 

Box 2. Symptoms and Signs Suggestive of 

Androgen Deficiency. Adapted from “Metabolic 

and Cardiovascular Effects of Androgen Deprivation 

Therapy.” BJU Int. 2008;102(11):1,509-1,514. 

Laboratory Considerations 

Many factors influence serum T levels, 

and some can cause spuriously low levels. 

Testosterone is secreted in a diurnal manner 

with highest levels occurring in the early 

morning. Normal serum testosterone ranges 

are based on blood samples drawn before 10 

a.m. Values vary from day to day, even 

when time of day is held constant, so a 

minimum of two low levels is needed 

to confirm the diagnosis. Different 

methodologies give different T levels. Liquid 

chromatography coupled with tandem mass 

spectrometry (LC-MS/MS) is the preferred 

methodology. Platform assays usually are 

automated, but results vary with different 

platform assays. Radioimmunoassays (RIAs) 

can provide reliable measurements but are 

not used by most laboratories. The normal 

range for serum T in most laboratories 

is from around 300 to 1,000 ng/dL. The 

Centers for Disease Control and Prevention 

(CDC) has undertaken a project to require 

that a single gravimetric standard be used 

for harmonization of all laboratory assays. 

Approximately 97% of circulating T is bound 

to sex hormone-binding globulin (SHBG) 

and albumin. Changes in SHBG can affect 

total T levels but may or may not affect the 

bio-available or free T levels (see Box 3). 

When changes in SHBG are suspected, 

one should measure free or bio-available 

T. Measurement of serum-free T or 

bioavailable T can provide a more accurate 

assessment of a patient’s testosterone 

status. Serum-free T should be performed 

by equilibrium dialysis method only, and 

only in laboratories that specialize in 

endocrine testing (such labs are rare). 

Serum bioavailable T represents the 

fraction of serum T that is weakly bound 

to albumin, not precipitated by ammonium 

sulfate. When one employs accurate 

measurements of total t, shBG and 

albumin, it is possible to calculate the 

free and bioavailable t levels. the 

analog free t assay that is employed 

by many laboratories is not reliable 

when there are changes in shBG. 

T concentrations may be affected by 

illness—the so-called “sick-eugonadal” 

state analogous to non-thyroidal illness 

or “sick-euthyroid” state—and several 

medications, including opiates, fluconazole 

and glucocorticoids. Thus, one must couple 

symptoms that are consistent with T 

deficiency with appropriate T measurements 

to establish the diagnosis of hypogonadism. 

A. More specific symptoms and signs 

Incomplete or delayed sexual development, 

eunuchoidism 

Reduced sexual desire (libido) and activity 

Decreased spontaneous erections 

Loss of body (axillary and pubic) hair, reduced 

shaving 

Very small (especially >5 ml) or shrinking 

testes 

Inability to father children, low or zero sperm 

count 

Height loss, low trauma fracture, low bone 

mineral density 

Hot flushes, sweats 

B. Other less specific symptoms and signs 

Decreased energy, motivation, initiative, and 

self-confidence 

Feeling sad or blue, depressed mood, 

dysthmia 

Poor concentration and memory 

Sleep disturbance, increased speepiness 

Mild anemia (normochromic, normocytic, in 

the female range 

Reduced muscle bulk and strength 

Increased body fat, body mass index 

Diminished physical or work performance 

Box 3. Conditions Associated with Alterations in 

SHBG Concentrations. Adapted from “Testosterone 

Therapy in Men with Androgen Deficiency 

Syndromes: An Endocrine Society Clinical 

Practice Guideline.” J Clin Endocrinol Metab. 

2010;95(6):2,536-2,559. 

Low t, Cardiovascular and All-cause 

Mortality 

In a population-based cohort study 8 of 

3,637 community-dwelling men ages 70 to 

88 years, lower free-T (100 vs. 280 pmol/ 

liter), and higher SHBG and LH levels were 

associated with all-cause mortality. In causespecific 

analyses, lower free T (100 vs. 280 

pmol/liter) and higher LH levels predicted 

CVD mortality, while higher SHBG levels 

predicted non-CVD mortality. 

Another prospective, population-based 

study 9 of 794 men ages 50 to 91 years who 

had serum T measurements at baseline and 

were followed for mortality, showed that 

low T in older men was associated with 

increased risk of death during the next 

20 years, independent of multiple other 

risk factors and several pre-existing health 

conditions. During an average 11.8 years of 

follow-up, 538 deaths occurred. Men whose 

total T levels were in the lowest quartile 

(

than those with higher levels, independent 

of age, adiposity and lifestyle. Additional 

adjustment for health status markers, 

lipids, lipoproteins and blood pressure, 

glycemia, adipocytokines and estradiol 

levels had minimal effect on risks. The low 

T mortality association was independent of 

the presence of METS, T2DM and prevalent 

CVD, but was attenuated by adjustment for 

interleukin 6 (IL-6) and C-reactive protein. 

In cause-specific analyses, low T predicted 

increased risk of CVD and respiratory 

disease mortality but was not significantly 

related to cancer death. Results were similar 

for bioavailable T, except the hazard ratio 

for respiratory disease was not significant. 

Shores et al. 12 used a clinical database 

to identify men older than age 40 with 

repeated T levels obtained from October 1, 

1994, to December 31, 1999, and without 

prostate cancer. A low T level was defined 

as total T

diastolic blood pressure levels. HDL-C 

levels were significantly lower in the 

T-treated group than in the control group 

(0.49 mg/dL; 95% CI, 0.85 to 0.13). 18 The 

majority of these analyses were associated 

with significant heterogeneity. A major 

confounding factor in many of these studies 

is the effect of co-morbidities on serum 

lipid levels, especially since obesity and 

METS often are associated with atherogenic 

dyslipidemia. The effects of intramuscular 

testosterone (IM-T) therapy on serum lipid 

levels are inconsistent in various studies, 

with only a few reporting a decrease in 

HDL-C and TC levels. 19 In a meta-analysis 

by Isidori et al., 11 the authors collated data 

on 1,083 subjects, 625 of whom were 

randomized to T, 427 to placebo and 31 

to observation (control group). Weighted 

mean age was 64.5 years and mean 

serum T was 10.9 nmol/l (range 7.8-19) 

T treatment reduced TC by 0.23 mmol/l 

(CI: -0.37 to -0.10), especially in men with 

lower baseline T concentrations, with no 

change in LDL-C. A significant reduction 

in HDL-C was found only in studies with 

higher mean T-values at baseline (-0.085 

mmol/l, CI: -0.017 to -0.003). Sensitivity 

and meta-regression analysis revealed that 

the dose/type of T used, in particular the 

possibility of aromatization, explained the 

heterogeneity in findings observed on bone 

density and HDL-C.. 

treatment Considerations 

Updated evidence-based treatment 

guidelines have recently been published. 20 

T therapy is appropriate in symptomatic 

hypogonadal men and is aimed at 

inducing and maintaining secondary sex 

characteristics and improving libido, ED, 

overall sense of well-being and bone mineral 

density. Therapy is contraindicated in those 

with breast or prostate cancer. Urologic 

evaluation is necessary in patients with 

a palpable prostate nodule or induration 

or with serum prostate-specific antigen 

(PSA) levels greater than >4 ng/ml (or PSA 

>3 ng/ml in men at high risk of prostate 

cancer, such as African-Americans or men 

with first-degree relatives with prostate 

cancer). Likewise, T therapy is best avoided 

in patients with hematocrit above 50%, 

untreated severe obstructive sleep apnea, 

severe lower urinary tract symptoms 

(American Urological Association [AUA]/ 

International Prostate Symptom Score [IPSS] 

> 19) or uncontrolled or poorly controlled 

heart failure. Other means for increasing 

testosterone levels should be used in those 

men who desire fertility. 

Several T formulations exist, and choice 

depends on patient’s preference, 

consideration of pharmacokinetics, 

treatment burden and cost. T cypionate 

or enanthate (50-100 mg weekly, or 

100-200 mg biweekly) can be injected 

intramuscularly (IM); 4-15 mg of 

testosterone in a gel or solution or one or 

two 5 mg T patches can be applied every 

24 hours over the skin of the back, thigh 

or upper arm, away from pressure areas 

as directed; 30 mg bio-adhesive buccal 

T tablets can be applied to the buccal 

mucosa every 12 hours; or T pellets can be 

implanted subcutaneously at intervals of 3 

to 6 months. Oral testosterone undecanoate 

and injectable testosterone undecanoate 

are treatment options that are available 

outside the United States. Monitoring is 

essential, and mid-normal T levels should 

be sought, but supraphysiologic levels of 

serum T must be avoided. 19 Abnormal 

elevation in packed cell volume/hematocrit 

(> 54%) or significant suppression of 

HDL-C levels 11,20,21 also should be avoided. 

T therapy may be offered to treated sleep 

apnea patients. One usually ensures 

appropriate levels of testosterone during 

the first two months of treatment, and 

monitoring of the hematocrit, PSA and 

digital rectal examination are done at three 

and 12 months and then annually. It is not 

necessary to monitor prostate parameters in 

men under the age of 40. 

Conclusions 

The relationships among serum T, SHBG, 

obesity, METS and T2DM are complex. 

Obesity is accompanied by increased 

adipokines and a pro-inflammatory milieu. 

These factors adversely affect insulin 

sensitivity in fat, liver and muscle, and are 

associated with endothelial dysfunction, 

which eventually may lead to the 

development of METS, T2DM, ED and 

CVD. Many men with T2DM, especially 

those who are obese, have low serum total 

T and SHBG levels. Some studies of T 

treatment in men with METS and T2DM 

have shown improved insulin sensitivity and 

small improvement in glycemic control. 22 

However, findings from many of these 

studies are subject to confounding by 

various factors, including co-morbidities, 

changes in medications for diabetes, 

etc. There is an urgent need for large, 

randomized controlled trials in clearly 

defined patient populations. Stratifying 

study cohorts according to METS/T2DM 

status may help clarify the true effects of T 

therapy in these patient groups. At present, 

it is important for the clinician to recognize 

that low T and sexual dysfunction are 

common in patients with obesity, METS and 

T2DM, and that testosterone treatment may 

improve sexual function, body composition 

and insulin sensitivity in these patients. 

Note: To obtain testosterone in ng/dL, divide 

levels in nmol/l by 0.0347. To obtain total & 

HDL cholesterol in mg/dL, divide levels in 

mmol/L by 0.0259. n 

Authors’ Note: Dr. Cunningham is a member of 

The Endocrine Society Clinical Practice Guideline 

Committee on Testosterone Therapy. The online version 

of the guidelines can be accessed at www.endo-society. 

org/guidelines/final/upload/FINAL-Androgens-in-Men- 

Standalone.pdf. 

Disclosure Statement: Dr. Raghavan has no relevant 

disclosures. Dr. Cunningham has received consulting 

fees from Abbott Laboratories, Endo Pharmaceuticals, 

Repros Therapeutics and Ferring Pharmaceuticals. Dr. 

Cunningham has received honoraria related to speaking 

from Merck & Co. 



Case: Mr. CW is a thin, 64-year-old, 

healthy appearing Caucasian male, who 

is a new established care patient to my 

practice seen in August of this year. This 

patient has a history of hypertension, 

tobacco abuse since high school and 

recently trying to cut back, hyperlipidemia, 

and a remote history of prostate cancer 

treated with radiation seed implantation. 

His social history reveals a very active 

semi-retired attorney who is married 

with one son, tobacco use as above and 

1-2 mixed drinks 3-4 times a week. His 

family history is positive for a mother 

with diabetes, deceased at 88, father who 

had hypertension, deceased at 93 and 

three brothers who have hypertension 

and one with obesity. There is no first 

degree relative history of atherosclerotic 

cardiovascular disease , myocardial 

infarction or ischemic stroke. 

Further review of his last set of laboratory 

tests done in April 2010 revealed the 

following: 

Case Study: 

Deceivingly Elevated HDL-C—Mounting Risk Factors 

Overpower Presumed Protection 

thoMAs J. BArtLEtt, MD 

Medical Director 

Mountain View Medical Group Cardiovascular Prevention Clinic 

Colorado Springs, CO 

Electrolytes WNL 

Glucose 91 mg/dL TSH 

1.74 miu/l reference range 

(.4-4.50) 

AST/ALT 33/27 u/l reference range 

(17-49/12-50) 

Standard Lipid Panel 

Total Chol 258 mg/dL 

Triglyceride 56 mg/dL 

HDL-C 128 mg/dL 

LDL-C 119 mg/dL 

CBC WNL 

Many of us would make the assumption 

that this patient has low risk by virtue 

of his significantly elevated HDL, as 

evidenced by the “incredible” comment 

by his previous PCP. We have much data 

to validate this general rule, that there 

exists an inverse association between 

HDL-C and risk of coronary artery disease. 1 

We have also had recent data to suggest 

that while this holds true, HDL may also 

be dysfunctional. Having a high HDL-C 

or raising HDL-C with a medication may 

not always afford our patients a protective 



and look for “Case Study.” 

benefit against ASCVD. 2 There is much to 

be gained in our knowledge of HDL-C and 

each individual patient that we treat. 

I became concerned of this patient’s 

risk due to his mounting risk factors and 

continued tobacco abuse. His Framingham 

cardiac risk is calculated to be 20% ten 

year CHD risk, and given his risk factors 

to include male>45 y/o, tobacco abuse, 

hypertension and hyperlipidemia, he 

would be placed in the high risk for future 

CAD category in my book. After much 

discussion and convincing he agreed to 

have a cardiovascular prevention work-up 

done at my clinic. He was somewhat 

reluctant at first due to his history of being 

told by multiple PCP’s that his HDL would 


surely protect him from atherosclerotic 

cardiovascular disease risk. Standard 

protocol for this patient is an advanced 

lipid panel with lipoprotein testing. These 

tests were scheduled before his next visit 

in September 2011. Results are as follows: 

VAP Cholesterol Profile* 

Total Cholesterol 284 mg/dL 

Triglyceride 86 mg/dL 

LDL-C 145 mg/dL 

HDL-C 118 mg/dL 

Lp(a) 23 mg/dL reference 

(

There has been increasing realization that 

cardiovascular risk begins in childhood, 

coinciding with mounting evidence 

for pathological change and tracking 

of risk factors—including high-density 

lipoprotein cholesterol (HDL-C) 1 —to 

adulthood. Consequently, American 

Academy of Pediatrics and American 

Heart Association guidelines based on the 

available evidence have largely targeted 

low-density lipoprotein cholesterol (LDL- 

C), with additional recommendations 

on managing HDL-C and triglyceride as 

secondary targets. 2,3 However, low HDL-C 

consistently has had a high prevalence 

relative to the other metabolic syndrome 

criteria 4 and, over the past two decades, 

the metabolic syndrome has unfortunately 

been increasingly recognized in 

adolescents. The following case illustrates 

a fairly common presentation and clinical 

course in which an adolescent presents 

with risk factors including low HDL-C. 

Chapter Update: 

Low HDL-C in Childhood and Adolescence 

PiErs r. BLACKEtt, MB, ChB, FAAP, FnLA 

University of Oklahoma Health Sciences Center 



stEPhEn r. DAniELs, MD, PhD, FAAP, FnLA 

University of Colorado School of Medicine 

Children’s Hospital Colorado 

Aurora, CO 

Case: A 14-year-old Hispanic boy 

presented for evaluation of risk factors 

associated with obesity. His body mass 

index (BMI) was 40.2, blood pressure 

(BP) 132/84, P92. The family history was 

positive for type 2 diabetes in his father 

and paternal grandmother. His maternal 

grandfather had a heart attack at age 57. 

His father smokes one pack of cigarettes 

a day. The teen’s physical examination 

revealed mild acanthosis nigricans around 

the neck and on the elbows. Laboratory 

testing: glucose 96 mg/dL; lipid profile: 

triglyceride 156, cholesterol 148, HDL-C 

23, calculated LDL-C 94 and non HDL-C 

125 mg/dL. The initial assessment was that 

he is insulin-resistant with risk for type 

2 diabetes and associated cardiovascular 

disease. He was referred to a dietitian for 

instruction to exercise for more than 30 

minutes a day (walking with family and 

football with friends). At the six-month 

follow-up, his BMI had increased to 42. 



and look for “Chapter Update.” 

A repeat lipid profile showed triglyceride 

172, cholesterol 152, HDL-C 22, LDL-C 

96, non HDL-C 130 mg/dL, fasting glucose 

95 mg/dL and glycated hemoglobin 

(HbA1c) 5.9%. The lifestyle treatment 

plan was continued. Four months later, 

he presented with polyuria and polydipsia, 

and random glucose was 182 mg/dL 

with HbA1c 7.1%. He was treated with 

500mg of metformin twice daily (bid) with 

intensive revision of lifestyle measures. 

After three months, the lipid profile 

showed triglyceride 148, cholesterol 154, 

HDL-C 24, LDL-C 100 and non HDL-C 130 

mg/dL. His BMI has decreased to 36 and 

his HbA1c is 6.4 %. 


Commentary 

This boy’s clinical course characterizes 

an initial presentation with the metabolic 

syndrome and progression to type 2 

diabetes. HDL-C was low at the onset and 

was only moderately responsive to lifestyle 

therapy. Unfortunately, the presentation is 

consistent with the worldwide trend for a 

classic sequence of events in adolescents, 

particularly in predisposed populations. 

In the National Health and Nutrition 

Examination Survey (NHANES) conducted 

from 2001 to 2006, the metabolic 

syndrome prevalence was highest in 

Hispanic youths (11.2%) at ages 12 to 19, 

followed by non-Hispanic whites (8.9%) 

and lowest in African-Americans (4.0%), 

in part attributed to their higher HDL-C. 4 

Pooled data from the Australian Childhood 

Determinants of Adult Health Study, the 

Cardiovascular Risk in Young Finns Study 

and the United States Bogalusa Heart 

Study have provided combined longitudinal 

data on lipoprotein levels, including HDL- 

C, that tracks to levels in adulthood and 

predicts carotid intima-media thickness, 

particularly when they are obese 5 , and 

consequently have strengthened the 

case for early detection and lifestyle 

intervention with the goal of reversing the 

risk factors. 

It can be assumed that the patient’s 

obesity contributed to the low HDL-C. 

Although his triglyceride of 156 mg/dL 

does not appear high, the Lipid Research 

Clinic’s 90 th percentile for 14-year-old boys 

is 112 mg/dL. Triglyceride values often can 

be well above 150 mg/dL and, therefore, 

can play a significant role in HDL-C 

lowering via enhanced cholesteryl ester 

transfer protein (CETP)-mediated delivery 

of triglyceride to HDL. A significant 

number of cases with low HDL-C may 

be non-obese and without the metabolic 

syndrome, as seen in the NHANES study. 4 

Such cases may present with persistently 

low HDL-C and could be associated with 

a genetic disorder of HDL metabolism. 

Monogenic or multi-genic causes can be 

operative 6 and could be an explanation for 

persistently low levels despite treatment. 

The C230 allele for the ABCA1 transporter 

is selective for Native American and 

Hispanic populations and could accentuate 

the HDL-C-lowering effect of obesity by 

compromising cholesterol efflux and both 

cardiovascular and diabetes risk. 7 The allele 

was found in 29 of 36 Native American 

groups, but not in European, Asian or 

African individuals. Human embryonic 

kidney cells expressing the C230 allele 

showed a 27% cholesterol efflux reduction 

(p< 0.001), confirming that this variant 

has a functional effect in vitro. 

Effective lifestyle 

education requires 

an individualized 

approach. 

HDL-C is low in adolescents when they 

become obese and insulin resistant, as 

observed in the nationally representative 

NHANES population 4 , and the declines 

with increasing BMI tend to be worse in 

adolescent boys than in girls, most likely 

because of the action of testosterone on 

hepatic triglyceride lipase. 8 Low HDL-C 

levels in youths with type 2 diabetes 

are attributable to persistent insulin 

resistance 9 which, in our case, began 

before diabetes onset and continued 

during the transition from obesity to 

diabetes, as suggested by the presence of 

acanthosis nigricans. The onset of diabetes 

is likely to have worsened the HDL status, 

because glycosylation and oxidation 

of apolipoprotein A-1 (apo A-1), and 

formation of advanced glycosylation endproducts 

impair HDL’s cardio-protective 

and anti-atherogenic properties, including 

the ability to promote cholesterol efflux, 

stabilize ABCA1 and inhibit the expression 

of adhesion molecules. 10 

Low and dysfunctional HDL has additional 

implications for populations at risk for 

type 2 diabetes, because there is mounting 

epidemiological 11 and in vitro experimental 

data 12 to support a role for HDL as the 

limiting factor in promoting cholesterol 

efflux from the β-cell and reducing the 

intracellular cholesterol load. The resulting 

intracellular cholesterol accumulation is 

found to compromise insulin secretion. 12 

Interestingly, other cell systems—such 

as fat and muscle cells—are under 

investigation for a similar interaction with 

HDL. This actively investigated area is 

supported by the finding that first-phase 

insulin secretion is decreased in Tangier 

heterozygotes because of their one 

defective ABCA1 allele, compromising 

cholesterol efflux from their β-cells. 13 If 

the hypothesis is true, then it supports 

aggressive targeting of low or dysfunctional 

HDL for the primary prevention of 

type 2 diabetes. There also is support 

for preserving HDL’s important antiinflammatory 

and anti-oxidative functions 

in the long term, beginning in childhood. 

The latter consideration becomes even 

more important in cases with elevated 

LDL-C or non-HDL-C. 

Using lifestyle as the cornerstone of 

treatment can result in effective weight 

management and, generally, as triglycerides 

fall, HDL-C increases. A meta-analysis of 

randomized controlled trials showed that 

aerobic exercise decreases triglycerides 

in obese and overweight children and 

adolescents, but there was only a trend for 

increases in HDL-C. 14 This is consistent 

with the moderate HDL-C elevation 

achieved in our case. Nevertheless, the 

cornerstone of management for low HDL-C 

in youths is lifestyle. 15 This requires 

a comprehensive dietary and exercise 

prescription, preferably with sensitivity 

to motivational and behavioral needs, 


including smoking-cessation counseling. 

Smoking strongly affects HDL-C and 

related outcomes in longitudinal studies 

such as the Young Finns study, in which 

smoking was identified as an unhealthy 

lifestyle occurring between youth and 

adulthood and affecting high-risk blood 

lipid and lipoprotein levels, including a low 

HDL-C in adulthood. 16 Effective lifestyle 

education requires an individualized 

approach with sensitivity to age, gender, 

ethnic background, family support and 

participation, and close attention to all 

three pillars—diet, exercise and behavior 

—of successful intervention, ideally with 

support personnel for each modality 

delivered as a team approach in a multidisciplinary 

clinic setting. 

We have observed obesity-related HDL 

lowering to occur at ages 5 to 9 years 8 , 

suggesting that the onset of obesity and 

associated risk factors may occur even 

earlier, particularly in Native American 

and Hispanic populations. This includes 

babies exposed to the effects of diabetes 

during pregnancy. Thus, there is an 

increasingly good rationale for early and 

universal childhood screening for risk 

factors, including a lipid profile followed 

by early intervention, but this presents 

as a significant educational challenge for 

pediatricians and their support personnel. 

HDL largely remains a residual risk factor 

in adults and is not yet regarded as a 

target for primary intervention. Thus, 

as in adults, there is no indication to 

target HDL-C with pharmaceutical agents 

as a primary target. Since “state of the 

art” approaches for increasing HDL-C in 

adults have largely been in the context 

of lowering residual risk after statin 

treatment, primary prevention by raising 

HDL-C with pharmaceutical agents has 

not yet had strong indication. However, 

when cases present with low HDL-C, 

it should be a signal to monitor LDL-C 

more closely and treat LDL-C to target, 

if indicated. Those of us who encounter 

cases with low HDL-C that is associated 

with apparent strong gene-environment 

Strive for Excellence 

Demonstrate Your Expertise by Achieving 

Certification as a Clinical Lipid Specialist 

interaction are watching with interest the 

developments of novel and potentially 

benign HDL-raising therapies. 17 Treatment 

of lipid targets with a statin, fibrate or 

extended release (ER) niacin 3 in childhood 

should be guideline-based and primarily 

directed at recommended dyslipidemic 

targets such as LDL-C and non-HDL-C, and 

preferably according to an ethics-approved 

protocol. New guidelines predicted to 

be announced this year may increase 

emphasis on HDL-C as a secondary target. 

In the case described, the LDL-C goal of 

100mg/dL was achieved and good diabetes 

control was attained. Although the HDL-C 

remains low, lifestyle remains the main 

therapy, with no indication for further 

pharmaceutical intervention. n 

Disclosure Statement: Dr. Blackett has no relevant 

disclosures. Dr. Daniels has received honoraria for 

serving on the Data and Safety Monitoring Boards of 

Merck & Co. and QLT Inc. 

Accreditation Council for Clinical Lipidology 

The ACCL Offers Two Pathways to Recognition: 

I. The Clinical Lipid Specialist (CLS) Certification Program is open to allied 

health professionals with advanced knowledge, experience and/or 

interest in specializing in lipid management. 

II. The Basic Competency in Clinical Lipidology (BCCL) Exam is a 

competency assessment and credentialing pathway open to any 

healthcare professional with basic involvement in the lipid field. 

"I joined a multidisciplinary team focused on chronic 

disease management as the lipid specialist and gained a Select a pathway that matches your professional goals. ACCL exams will 

new level of respect from my teammates. Clinicians consult evaluate and validate the specialized knowledge and training required to 

me for the best lipid management tactics and I have 

increased job security as I am the only registered dietitian 

certi�ed as a Clinical Lipid Specialist in my state.” 

practice in the dynamic and multifaceted field of lipid management. 

Learn more at 

Julie Bolick, RD, MS, CD, CLS 

The Official Publication of the National Lipid Association 

Salt Lake City, Utah 

www.lipidspecialist.org 27 

Phone: 904.309.6250

NATIONAL 

LIPID ASSOCIATION 

2002–2012 

Please join us in celebrating 

the 10th Anniversary of the National Lipid Association at a 

Dinner and Gala Event 

Honoring the Past Presidents 

Saturday, June 2, at six o’clock in the evening 

JW Marriott Camelback Inn 

Scottsdale, Arizona 

RSVP at www.lipid.org/sessions 

Past Presidents of the NLA will be honored at this special event, which is set to include 

live music, dancing, and anecdotes to guide us through the NLA’s storied history, from the 

organizations that predated the NLA, to incorporation in 2002, and on to today’s active 

regional chapters. The night will be marked with good food, drink, and great company as 

we take a look back on nearly 15 years of advances in Clinical Lipidology. 

Proceeds from this special gala event will benefit the Foundation of the NLA. 

Tables may be reserved for $2,500. Individual tickets cost $225 per person. 

To purchase a table or individual tickets, please visit www.lipid.org/sessions 

and prepare to toast the achievements of the NLA’s past Presidents and look 

toward the future at this distinctive 10th Anniversary event. 

A portion of your table or ticket purchase will be deductible for tax purposes. Please check with your tax advisor.

South Asians are people from India, 

Pakistan, Bangladesh, Sri Lanka or Nepal. 

They comprise 25% of the global population, 

yet they contribute 60% of the global 

cardiovascular disease burden. There are 

approximately 4 million South Asians living 

in North America, 2.84 million of whom 

are living in the United States. Prevalent 

lipid abnormalities in South Asians are 

closely intertwined with prevalent insulin 

resistance, diabetes and coronary artery 

disease (CAD). As the prevalence of type 2 

diabetes increases worldwide, with the total 

number of people with diabetes projected 

to rise from 171 million in 2000 to 366 

million in 2030, the predicted increase 

in prevalence on the Indian subcontinent 

during this period is 151%. The increase 

in prevalence is concerning. South Asians 

have a prevalence of diabetes from two to 

four times higher than other native ethnic 

groups. 1 Population-based studies that 

have sampled South Asians from different 

countries have reported an age-standardized 

adult diabetes prevalence of 21% from the 

U.K., 12.8% from Singapore, 15.3% from 

Mauritius, 13.1% from Fiji, 9.8% from 

South Africa, 9.9% from Tanzania and 15.3% 

from Canada. 2-7 In the U.S., a few studies 

Guest Editorial: 

Lipid Abnormalities in South Asians 

KrishnAsWAMi ViJAyArAGhAVAn, MD, FnLA 

Scottsdale Cardiovascular Research Institute 



have estimated diabetes prevalence. In 

Atlanta, 18.3% of attendees at a temple 

self-reported that they had diabetes. Of 

South Asian adults in a national U.S. study, 

17.4% were found to have diabetes, based 

on self-reporting and fasting glucose levels. 

Prevalence was 29% based on a study that 

used oral glucose tolerance testing. In a 

recent large population-based study out of 

New York City, the prevalence of diabetes 

among foreign-born South Asians was nearly 

twice that of foreign-born Asians from 

other areas (13.6% vs. 7.4%, P = 0.001). In 

multivariable analyses, foreign-born South 

Asians with a normal body mass index 

(BMI) had nearly five times the diabetes 

prevalence of comparable U.S.-born non- 

Hispanic whites (14.1% vs. 2.9%, 

P < 0.001) and 2.5 times the prevalence of 

foreign-born Asians from other areas 

(P < 0.001). 8-10 

South Asians develop coronary artery 

disease (CAD) at a younger age, with higher 

risk of CAD-associated mortality. Numerous 

studies have demonstrated higher CAD rates 

among South Asians at all ages. Prevalence 

of CAD in rural South Asia is from 3% to 4%, 

while the CAD prevalence amongst urban 



and look for “Guest Editorial.” 

South Asians and South Asian immigrants 

to the West approaches 10%. The Coronary 

Artery Disease in Indians (CADI) study 

demonstrated a CAD prevalence of 10% 

among first-generation South Asian 

immigrants to the United States, compared 

to a 2.5% CAD prevalence among the 

general population in the Framingham 

study. 11 Coronary vascular disease (CVD) 

mortality data from multiple studies is 

three times higher. CAD-prevalence for 

South Asians younger than 40 years and 

older than 60 years is 1.5 times higher. 

A 1990 World Health Organization 

publication showed that the proportion 

of cardiovascular deaths occurring before 

age 70 was 26% in developing countries 

but 52% in India. Although the risk for 

microvascular complications among South 

Asians with diabetes tends to be similar 

to the risk in Caucasian populations, they 

have a significantly higher prevalence of 


cardiovascular disease—and presumed 

risk—manifesting at a younger age in nonobese 

individuals. 12-14 

While their total cholesterol and lowdensity 

lipoprotein cholesterol (LDL-C) 

levels may be similar to those of other 

ethnic groups, South Asians have unique 

lipid profiles: They have high triglyceride 

levels, high lipoprotein(a) levels, increased 

ratio of apolipoprotein B to apolipoprotein 

A-1 (apoB/apoA-1), smaller high-density 

lipoprotein (HDL) and LDL particle size, 

and lower levels of HDL. Lipoprotein(a) is 

now known as an emerging independent 

risk factor for the development of CAD, 

complementing traditional risks. Unlike 

other lipids, its levels are completely 

determined by genetics. South Asians have 

the second highest levels of lipoprotein(a) 

after African-Americans, and this may 

explain some of the increased CAD risk 

in this ethnic group. It is postulated that, 

because of the exponential effect of 

lipoprotein(a) on other CAD risk factors, 

South Asians have a higher CAD risk at 

any given level of LDL-C. This results in 

a significant underestimation of CAD risk 

in South Asians by the Framingham risk 

score. 15-17 

Increased CAD risk in younger South Asians 

can be explained by a higher prevalence of 

traditional risk factors. The INTERHEART 

study, an international case-control study 

examining risk factors for initial myocardial 

infarction (MI) in 52 countries—including 

12,000 cases of initial MI and 14,000 

controls—demonstrated that more than 

90% of global MI risk can be attributed 

to nine modifiable risk factors—smoking, 

diabetes mellitus (DM), lipids, central 

obesity, hypertension, diet, physical activity, 

alcohol consumption and psychosocial 

factors). This was true for all populations, 

including South Asians. However, South 

Asians presented with initial MI at an earlier 

age, an average of 53 years versus 58 years). 

Protective factors—moderate daily alcohol 

consumption, regular physical activity, 

daily intake of fruits and vegetables—were 

significantly lower among South Asians and 

deleterious factors such as diabetes and an 

elevated apoB/apoA-1 ratio were significantly 

higher. When compared to other risk 

factors, elevated apoB/apoA-1 ratio had the 

highest attributable risk. When compared to 

other ethnic groups, certain risk factors— 

apoB/apoA-1 ratio, low daily consumption 

of fruits and vegetables, a lack of regular 

exercise and a high waist-hip ratio—had 

higher attributable risk in South Asians: 

Overall obesity rates, by BMI standards, 

were lower in South Asians. 18 However, 

central obesity rates are significantly higher 

and associated with insulin resistance, 

metabolic syndrome and a two- to threefold 

increase in CAD risk. Waist circumference 

or waist-hip ratios as a screening tool are 

more effective in identifying risk. The 

South Asian diet also predisposes a person 

toward developing dyslipidemia and, thus, 

increases CAD risk. The use of whole milk 

and clarified butter or ghee, deep frying, 

long cooking times and reuse of the same 

oil multiple times may be contributing to 

fatty acid oxidation and increased saturated 

and trans fat consumption, leading to 

insulin resistance and CAD. Regular physical 

exercise is rare in this population, including 

among women. 

South Asian migration to more affluent 

areas and from rural to urban living leads to 

significantly higher rates of CAD, pointing 

toward a genetic and environmental 

interaction. The susceptibility toward 

developing insulin resistance may be 

partially explained by the “fetal origins 

hypothesis,” which postulates that 

malnourished fetuses adapt to impaired 

nutrition by becoming relatively insulin 

resistant. However, this adaptation may 

persist into adult life, even when calories 

are abundant, thus leading to insulin 

resistance and adult-onset DM. 

While traditional risk factors account for 

the majority of CAD in South Asians, some 

novel risk factors also are under study, 

including smaller coronary artery diameter 19 , 

higher homocysteine levels and higher 

C-reactive protein (CRP) levels. CAD risk 

in South Asians may be increased by a 

prothrombotic milieu—higher levels of 

homocysteine, lipoprotein(a), plasminogen 

activator inhibitor-1, and smaller HDL and 

LDL particles—along with a more proinflammatory 

state with higher levels of 

high-sensitivity CRP, leptin, interleukin-6 

and tumor necrosis factor-alpha. 

Conclusion 

South Asians have higher rates, higher 

associated mortality, and earlier onset of 

CAD because of genetic predisposition, a 

more atherogenic dyslipidemia and at-risk 

for CVD lifestyle factors. South Asians 

have more traditional risk factors at an 

earlier age, higher Lp(a) levels, higher 

waist to hip ratios and elevated apoB/ 

apoA-1 ratios. The traditional risk factors 

should be screened for and modified in 

all populations, but especially so in South 

Asians, who have a higher prevalence of 

these risk factors at younger ages. It is not 

clear if the cut-off points for traditional 

risk factors should be any lower for South 

Asians. We recommend that all South 

Asians over the age of 30 have traditional 

risk-factor assessment. We suggest the 

measurement of lipid subfractions, including 

Lp(a), the waist-to-hip ratio, non-HDL-C, 

apo B and apo A1 levels. We also institute 

aggressive management, including weight 

loss and regular physical activity—to 

decrease central obesity and its associated 

atherosclerosis risk—as well as dietary 

modifications including decreased intake of 

saturated and trans fats, shorter vegetable 

cooking times and increased intake of raw 

vegetables. It is our hope that this will 

reduce the earlier-onset twin epidemic of 

diabetes and cardiovascular morbidity and 

mortality in South Asians. n 

Disclosure Statement: Dr. Vijayaraghavan has 

received honoraria related to speaking from Gilead 

Pharmaceuticals and Otsuka. Dr. Vijayaraghavan has 

served on the advisory board of Sanofi-Aventis. 



Over the past few decades, the Veterans 

Health Administration has updated its 

image—an experience that Judith Collins, 

NP, MSN, CLS, has experienced firsthand 

at the Denver Veterans Affairs Medical 

Center. 

“It’s a completely different culture here 

than it was 20 years ago,” she said. “We 

have one of the best electronic records 

system in the country, the veterans are 

so appreciative of the care they receive, 

and the staff feel that it is a real honor to 

work with those who gave so much to our 

country.” 

Collins transferred to the Denver site from 

the VA hospital in Ann Arbor, Michigan, 

in 2006, so she and her husband could 

pursue their dream of living near the 

Rocky Mountains. Today, they live in a 

log home not far from the Denver VA 

Medical Center, where Collins works with 

individuals admitted for congestive heart 

failure or who need post-intervention care, 

as well as with patients in the Peripheral 

Vascular Disease (PVD) Clinic. 

While Collins has long been involved in 

secondary prevention and follow-up, it was 

Member Spotlight: 

Helping Veterans Find a New “Lifestyle Path” 

JUDith A. CoLLins, Msn, APrn-BC, CVn-BC, CLs 

Cardiovascular Nurse Practitioner 

Denver Veterans Affairs Medical Center 

Denver, CO 

the opportunity to help launch a cardiology 

prevention clinic at the Ann Arbor VA 

hospital that really bolstered her into the 

field of lipidology. 

“The idea at the time was to help reduce 

the cardiac event rate with the veteran 

population. So we saw every patient after 

their intervention for ACS, heart attack, 

heart surgery or a stent,” she said. “Our 

program director, Dr. Mark Starling, had 

an amazing amount of foresight to really 

emphasize prevention and I became 

involved in developing lipid management 

and regional prevention guidelines.” 

Watching veterans change to a different 

“lifestyle path” after experiencing a cardiac 

event is the most important part of her job, 

she says, because these incidents trigger 

teachable moments in which Collins can 

answer their questions, explain rationale 

for treatment, and connect them with 

resources. 

Despite the many positive aspects of 

Collins’s job, there are some sad ones, too. 

Working with veterans who are homeless 

or have Post Traumatic Stress Disorder 

(PTSD) is challenging, she says, because 



and look for “Member Spotlight.” 

their priorities often are getting fed and 

having a place to sleep—not staying 

on their medications or thinking about 

prevention. 

“I’ve learned that you really have to 

take your cues from the patient to meet 

them where they are at that point in 

time,” she said. “Care needs to be really 

individualized.” 

Occasionally, Collins hears anecdotes 

about patients she treated long ago and 

that motivates her to keep focusing on 

secondary prevention and follow-up. 

“One man had a heart attack in the early 

1980s and we organized a support group 

called the Ann Arbor Heartbeats for 

patients like him,” she said. “He is in his 

upper 80’s now and has taken up ballroom 

dancing.” n 


Member Update 

Donald hunninghake, MD, passed away on his 

birthday, February 2, 2012 in Carlsbad, California, at 

the age of 78. A National Lipid Association member 

since 2004, Dr. Hunninghake was a modest man who 

never boasted of his many accomplishments. He will 

always be remembered by the many lives he touched 

and his contributions to the treatment of lipid disorders 

throughout the world. Dr. Hunninghake was instrumental 

in developing clinical trials of lifesaving lipid-lowering 

drugs. After receiving his medical degree from the 

University of Kansas in 1959, he went on to specialize in 

internal medicine, clinical pharmacology, and preventive 

cardiology. Dr. Hunninghake spent the majority of his 

career with the University of Minnesota Medical School 

as a professor in the departments of medicine and 

pharmacology. 

Interested in Pediatric Lipid Metabolism and Cardiac Risk Reduction? 

The Pediatric Atherosclerosis Prevention 

and Lipidology Group (PedAL), headed 

by sam Gidding, MD, of Nemours/ 

Alfred I. DuPont Hospital for Children 

in Wilmington, Deleware, is composed 

of practitioners and researchers working 

in the fields of lipid metabolism and 

cardiac risk reduction. PedAL’s mission 

is to advance the field of pediatric 

atherosclerosis prevention and lipidology. 

Core activities include development of 

new scientific data, provision of expert 

information/teaching on cardiovascular 

risk to pediatric practitioners, provision 

of a forum for management of rare lipid 

disorders, advocacy for cardiovascular risk 

reduction in youth with key stakeholders, 

and development of educational material 

for the general public. PedAL will work 

with investigators, experts in lipidology, 

educators and practitioners in pediatrics 

and its subspecialties to better understand 

the etiology, early pathophysiology, 

and potential reversability of 

atherosclerosis. Appropriate lifestyle and 

pharmacotherapeutic management of risk 

factors in children and adolescents will 

be championed. Goals will be promoted 

within important national organizations 

and with the general public. 

PedAL holds a monthly conference call 

to discuss present and future projects. 

Current work centers around FH advocacy, 

development of a Homozygous FH registry, 

and identification of research projects 

directed at evidence gaps noted in the 

Integrated CVD Risk Reduction Guideline 

for children published in Pediatrics in 

December of 2011. 

The monthly conference call also serves 

a forum for discussing complex pediatric 

lipid management cases. PedAL also has 

a number of long-term goals including: 

development of a roster of clinical sites to 

recruit patients for participation in clinical 

trials related to pediatric CVD prevention/ 

lipidology and identification of funding 

sources to support a broader organization 

linked to NLA and AHA. 

PedAL actively collaborates with NLA on 

scientific and advocacy projects related to 

premature CVD and pediatric aspects of 

lipidology. 

If you are interested in participating in the 

monthly conference call please contact 

either Ms. sharon Mapp at smapp@ 

nemours.org or samuel Gidding, MD, 

at sgidding@nemours.org. If you are 

interested in learning more about the 

Homozygous FH registry please contact 

Lisa hudgins, MD, from the Rogosin 

Institute/Weill-Cornell Medical College 

at lih2013@nyp.org. This repository is 

open to all children and adults nationwide 

who meet criteria for hoFH. The goal is to 

collect clinical and laboratory information 

in one database to better understand the 

natural history of cardiac disease and the 

response to specialized therapies, such as 

LDL-apheresis and liver transplant. This 

will greatly aid the development of specific 

protocols that seek to learn more about 

this disease and new therapies. 


nLA responds to U.s. FDA and Fsis 

The NLA Dietitian Task Force recently 

responded to the U.S. Food and Drug 

Administration (FDA) and the Food Safety 

and Inspection Service (FSIS) regarding 

sodium reduction. The NLA statement 

was submitted to the FDA and FSIS in 

late January and also is posted in the 

Clinical Guidance section on the NLA 

website. Please take a moment to read 

the statement and contact Brian hart at 

bhart@lipid.org with questions. 

nLA Goes to isA 2012 

The NLA has been invited to join the 

educational programming at the upcoming 

International Atherosclerosis Society 

program in Sydney, Australia. Penny- 

Kris Etherton, PhD, rD, CLs, FnLA, 

and Peter toth, MD, PhD, FnLA*, 

will be representing the NLA overseas. 

If you happen to be heading over to 

Sydney, please e-mail Deborah Walker at 

dwalker@lipid.org if you wish to join in 

an NLA-sponsored reception taking place 

on March 26 from 6 to 7 p.m. 

nLA-Endorsed Grand rounds on 

reducing residual risk and Managing 

Complex Dyslipidemia 

Select medical institutions are eligible to 

host an exciting new CME-certified inhospital 

grand rounds program endorsed 

by the NLA. This new program examines 

the importance of lipoprotein management 

for secondary prevention of major adverse 

cardiac events in post-ACS patients. 

Participants will learn to recognize residual 

risk associated with statin therapy to lower 

LDL, as well as the limitations of current 

therapies to increase HDL. Participants also 

will increase awareness of novel therapies 

to increase HDL and reduce CVD. For 

more information, please e-mail rachon 

Cottman at rcottman@potomacme.org. 

Fh Foundation international 

On November 28, an NLA partner 

organization, interChol , announced 

that it will focus specifically on Familial 

Hypercholesterolemia (FH), as reflected 

by changing its name to Fh Foundation 

international. The organization will seek 

to engage global partnerships to escalate 

awareness of FH in the public domain, the 

medical community and in government. FH 

Foundation International will orchestrate 

collaboration among these sectors to 

reduce the tragic costs of premature 

cardiac events and death in FH patients. 

For more information, please visit 

www.fh-foundation.org. 

UsAGE statin Adherence survey 

This May, results from the USAGE statin 

adherence survey will be presented at 

Annual Scientific Sessions. USAGE, which 

stands for Understanding Statin use in 

America and Gaps in Education, is the 

largest statin adherence survey with more 

than 10,100 respondents. The survey 

was conducted in partnership with the 

NLA, Kowa Pharmaceuticals and Eli Lilly 

& Co. NLA leaders in this effort included 

Consumer Affairs Committee Chair 

Jerome Cohen, MD, FnLA*, along with 

Eliot Brinton, MD, FnLA*, Matthew 

ito, PharmD, CLs, FnLA, and terry 

Jacobson, MD, FnLA*. The USAGE 

News and Notes 

public awareness campaign will launch in 

New York City on June 19. 

nLA 10 th Anniversary Gala 

Please make plans to attend an NLA 10 th 

Anniversary special event to benefit the 

Foundation during Annual Scientific 

Sessions in Scottsdale. The event will 

include dinner, dancing and the chance 

to mingle with past presidents of the 

organization. More information is available 

online at www.lipid.org/sessions. 

AhA Chairman’s Award 

Congratulations to stephen Daniels 

MD, PhD, FAhA, for being recognized 

with the Chairman’s Award during the 

American heart Association scientific 

sessions in november 2011. The 

purpose of the award is to identify 

and honor volunteers who have made 

contributions to further the AHA’s 

strategic goals in non-science areas. 

nLA staff Corner 

Allison Fellers recently 

joined the NLA staff as an 

Education Adminstrative 

Coordinator. She 

graduated from Augusta 

State University with a bachelor’s degree 

in psychology. 


Education and Meeting Update 

Call for Abstracts for 2012 Annual 

scientific sessions 

Submit your research 

2012 for presentation 

as a poster during 


the NLA Annual 

Scottsdale 

Scientific Sessions in 

Scottsdale, Arizona. 

The deadline for poster abstract 

submissions is April 2. All accepted 

poster abstracts will be published in 

the May/June 2012 issue of the Journal 

of Clinical Lipidology. In addition to 

posters being displayed at the meeting 

during the designated hours, selected 

abstracts will be identified for an oral 

presentation session on Saturday, June 

2. Visit www.lipid.org/abstracts for 

more information and to submit your 

poster. 

new! young investigator Award 

Program to Launch at 2012 Annual 

scientific sessions 

Lead presenters with accepted abstracts 

who are Young Investigators (in-training 

students, residents and Fellows or 

members in practice for

In 2012, we want to continue the 

important work that the Foundation 

began on its inaugural campaign, FH: It’s 

Relative—Know Your Family Cholesterol 

History, in 2011. We are partnering with 

the International Guidelines Center to 

produce a Familial Hypercholesterolemia 

(FH) pocket guide that will be useful 

to practitioners at many levels, with all 

proceeds to benefit the Foundation. 

We also recently expanded the reach of 

our public service announcement (PSA) 

to spread awareness of FH. Since mid- 

January, the PSA has been distributed 

throughout the United States, with a goal 

of 800 or more airings on cable television 

and more than four million viewer 

impressions. In addition, we will continue 

to enhance the patient-friendly website, 

www.LearnyourLipids.com, with useful 

information and resources related to FH 

and other topics of interest to patients and 

the community at-large. 

I also want to take this opportunity to 

thank you for your support of our first 

book project, 100 Questions & Answers 

About Managing Your Cholesterol, which 

was published in August 2011 and is 

available on the Jones & Bartlett Learning, 

Amazon, and Barnes & Noble websites. 

More than 1,200 copies of the book were 

sold in 2011, and 53 copies have been sold 

as of February 2012. All net royalties from 

the project will benefit the Foundation’s 

charitable and educational efforts. 

Also, please make plans to attend an NLA 

10 th Anniversary special event to benefit 

the Foundation during Annual Scientific 

Sessions in Scottsdale. The event will 

include dinner, dancing and the chance 

to mingle with past presidents of the 

organization. More information is available 

online at www.lipid.org/sessions. 

Looking ahead, we will have many 

opportunities for NLA members both to 

get involved with our charitable work 

and also to benefit from educational and 

professional development opportunities 

made available through the Foundation. 

Please think about ways in which you 

would like to get involved and support the 

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 




and look for “Foundation Update.” 

Foundation by volunteering, attending a 

benefit event or making a donation. As 

always, your support is much appreciated. 

Together, we are doing great things. n 


Events Calendar 

2012 nLA Meetings 

nLA 2012 Annual scientific sessions 

Hosted by the Southwest Lipid Association 

May 31–June 3, 2012 

JW Marriott 2012 

Camelback Inn 



Scottsdale 

nLA Clinical Lipid Update—Fall 

Hosted by the Southeast Lipid Association 

and the Northeast Lipid Association 

September 14–16, 2012 

Charlotte Westin 

Charlotte, NC 

CLINICAL LIPID UPDATE 

CHARLOTTE, NC • SEPT. 14–16, 2012 

2012 nLA Professional 

Development Courses 

hDL Master Class 

Masters in Lipidology Course 

Lipid Academy 


JW Marriott 


September 13–14, 2012 

Charlotte Westin 

Charlotte, NC 

it’s your nLA Community... 

Participate in the conversation online at 

www.lipid.org/topics. 

Excerpt from the “Statins Associated 

with Diabetes Risk” thread: 

“As lipid-centric clinicians our first response will probably be to staunchly 

defend statin therapy but I also think we need to consider statin riskbenefit 

and baseline pretreatment patient variables such as A1C, CRP, and 

fasting glucose—particularly with moderate CV risk patients and even 

more specifically in patients with pre-diabetes.” 

—Ralph La Forge, MSc, CLS, FNLA 

2012 Meetings 

PCnA 18th Annual symposium: 

“Cardiovascular risk reduction: 

Leading the Way in Prevention” 

April 12–14, 2012 

National Harbor, MD 

28th Annual sCAn symposium 

April 20–22, 2012 

Baltimore, MD 

First Annual AsPC southeastern 

Conference: 

“Cardiovascular Disease Prevention 

for Women” 

April 28, 2012 

Boca Raton, FL 

Ash Annual scientific Meeting & 

Exposition 2012 


New York, NY 

AACE 21st Annual Meeting 


Philadelphia, PA 

80th European Atherosclerosis 

society (EAs) Congress 


Milan, Italy 


Problem 

Within a decade, the United States’ annual 

expenditure on health care will exceed 

$4 trillion. This is between 20% and 25% 

of the gross domestic product. Medical 

care costs are growing at an unsustainable 

rate. If we adopt a national health service, 

millions of new patients will be in need 

and an already-stressed professional 

resource will be further burdened. Better 

adherence means better utilization of 

prescribed interventions. Non-adherence, 

in contrast, is a social, medical and 

financial loss. Many therapies have been 

shown to be cost-effective by reducing 

significant vascular events, including 

heart attack, stroke and possibly memory 

impairment. The patient and the health 

professional must both cooperate to help 

ease the issue of non-adherence. 

Definition 

Adherence is the extent to which patients 

take the medication prescribed. In a 

broader sense, adherence also includes 

dietary, behavioral and day-to-day activity 

changes aimed at reducing cardiovascular 

disease (CVD) risk as part of primary, 

secondary and tertiary prevention. 

Non-adherence can be intentional 

or unintentional. Intentional lack of 

adherence may be the result of a lack of 

knowledge, including ignorance of the 

risks of discontinuation; denial; adverse 

side effects; poor memory; poor attitude 

toward the doctor-prescribed drug 

therapy; inadequate funds to pay for the 

medication; or a desire to spend one’s 

resources elsewhere. 

In a recent study published in the Journal 

of the American Medical Association 

(JAMA), the investigators examined almost 

400,000 patients ages 65 years or more, 

who had been discharged from hospitals 

in Ontario, Canada. 1 Among those 

admitted to the intensive care unit (ICU) 

for an acute cardiovascular event, 15% 

had discontinued their prescribed statin 

medications when they were discharged. 

The Last Word: 

The Need to Do a Better Job 

DAViD t. nAsh, MD, FnLA 

Clinical Professor of Cardiology 

Syracuse Preventive Cardiology 

Upstate Medical University 

Syracuse, NY 




and look for “The Last Word.” 

Attempts to improve Adherence 

Many studies have been undertaken 

during the several decades since the 

magnitude of inadequate adherence was 

first understood. Many interventions have 

been tried, and most have met with limited 

success. These include: 

• Simplification of the regimen; 

medications that require only a single 

dose a day are usually easier to use 

• Change of ingestion times with a 

multiple drug regimen 

• Patient education and information, 

presented as written material or 

video 

• Intensification of patient care, 


including more frequent office visits, 

interim phone contacts or written 

reminders 

• Motivation through group meetings 

• Financial or motivational rewards 

Results of these efforts have been mixed, 

and there is a risk of bias in many of these 

studies. The results are varied among 

measures of adherence gathered from selfreporting, 

prescription refill rates, manual 

counting of pills and an electronic system 

that records each time a prescription pill 

bottle’s cap is removed. 

Adherence to statin Drugs 

Former U.S. Surgeon General C. Everett 

Koop, MD, once opined, “Drugs don’t 

work in patients who don’t take them.” 2 

It is clear that adherence to drug therapy 

drops off rapidly within the first six months 

and continues to decline more slowly 

thereafter. Patients with good adherence 

experienced a lower risk of cardiovascular 

events (CVE) than patients with lower 

adherence. 3 

In a Finnish study published by the British 

Journal of Clinical Pharmacology, the 

investigators examined the incidence 

of major coronary events (MCE)—a 

composite of acute myocardial infarction 

(AMI) and/or coronary revascularization— 

among diabetic patients in a nationwide 

database. 4 The investigators examined the 

data from approximately 60,000 statin 

initiators with diabetes, including 35,000 

with MCE and 20,000 controls. Patients 

with good adherence were compared 

with those with lower adherence rates. 

Good statin adherence was associated 

with a reduced incidence of MCE in those 

with prior coronary heart disease (CHD) 

or 0.84 (95% CI 0.74-0.95) and in those 

without CHD (OR 0.79 95% CI 0.66-94), 

respectively. The differences persisted 

during a five-year follow-up. Some 

physicians have labeled poor adherence 

as a hidden risk factor. 5 Not surprisingly, 

previous therapeutic history is related to 

adherence. 

A study of 13,100 Medicare patients 

hospitalized with coronary artery 

disease (CAD) from 1995 through 

2004 was published. Statin adherence 

was measured as the proportion of the 

number of days covered, with >80% 

considered fully adherent. 6 Adherences 

were compared in 3,700 patients treated 

with medical therapy, percutaneous 

coronary interventions (6,300) or coronary 

artery bypasses grafting (3,100). Overall, 

statin adherence increased slightly but 

significantly (p

21, 393 subjects who received a statin 

prescription between 1994 and 2003 

demonstrated that, while drug utilization 

indications showed an increase in statin 

use over the study period in terms of the 

number of patients prescribed, adherence 

to therapy remained low. There was a 50% 

discontinuation rate in the first year. 11 

In a demonstration of how fragile the 

motivation to adherence remains, a 

Denver study analyzed a cohort of 3,386 

patients receiving more than one refill 

of statin medication through an innercity 

healthcare system. After controlling 

for age, gender, race, copayments, 

comorbidites and insurance status, those 

who received a 60-day supply compared 

with a 30-day supply were more likely to 

be adherent to statin medication. (RR 1.41, 

95% CI 1.28-1.55, p

References 

Letter to the Editor references 

1. Sudhop T, Gottwald BM, and von Bergmann K. Serum plant sterols 

as a potential risk factor for coronary heart disease. Metabolism 

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2. Brown AJ and Jessup W. Oxysterols and atherosclerosis. 

Atherosclerosis 199;142:1-28. 

3. Miettinen TA and Gylling H. et al. Relation of non-cholesterol 

sterols to coronary risk factors and carotid intima-media thickness: 

the Cardiovascular Risk in Young Finns Study.Atherosclerosis 2010 

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4. Assmann, Gerd; Cullen, Paul; Erbey, John; Ramey, Dena R.; 

Kannenberg, Frank; Schulte, Helmut (2006). “Plasma sitosterol 

elevations are associated with an increased incidence of coronary 

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Prospective Cardiovascular Münster (PROCAM) study”. Nutrition, 

Metabolism and Cardiovascular Diseases16: 13–21 

5. Rajaratnam, Radhakrishnan A; Gylling, Helena; Miettinen, 

Tatu A (2000). “Independent association of serum squalene 

and noncholesterol sterols with coronary artery disease in 

postmenopausal women”. Journal of the American College of 

Cardiology35 (5): 1185–91. 

6. Special Turku Coronary Risk Factor Intervention Project. J Nutr. 

2001 Jul;131(7):1942-5. 

7. Miettinen TA and Gylling H. Synthesis and absorption markers of 

cholesterol in serum and lipoproteins during a large dose of statin 

treatment. Eur J Clin Invest 2003;33(11):976-982 

8. Miettinen TA and Gylling H. et al. Serum noncholesterol sterols 

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Med 2003;141:131-137. 

9. ESC/EAS Guidelines for the management of dyslipidaemias: the 

Task Force for the management of dyslipidaemias of the European 

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Society (EAS).Eur Heart J. 2011 Jul;32(14):1769-818. Epub 2011 

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Clinical Feature references 

1. Gordon D, Probstfield J, Garrison R, et al. High-density lipoprotein 

cholesterol and cardiovascular disease. Four prospective American 

studies. Circulation. January 1, 1989 1989;79(1):8-15. 

2. Peter P T. Novel Therapies for Increasing Serum Levels of HDL. 

Endocrinology & Metabolism Clinics of North America. 

2009;38(1):151-170. 

3. Masson D, Jiang X-C, Lagrost L, Tall AR. The role of plasma 

lipid transfer proteins in lipoprotein metabolism and 

atherogenesis. Journal of Lipid Research. April 1, 2009 

2009;50(Supplement):S201-S206. 

4. Neil J H. Chapter 2 - The Role of Cholesteryl Ester Transfer 

Protein (CETP) in HDL Metabolism. In: Tsugikazu K, ed. The HDL 

Handbook. Boston: Academic Press; 2010:17-33. 

5. Thompson A, Di Angelantonio E, Sarwar N, et al. Association of 

Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and 

Activity, Lipid Levels, and Coronary Risk. JAMA: The Journal of the 

American Medical Association. June 18, 2008 2008;299(23):2777- 

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What is HDL-C? 

HDL cholesterol (HDL-C) is the measure of the cholesterol carried in 

particles called high density lipoproteins (HDL). Apolipoprotein A-1 

is the main protein found on HDL. HDL is known as the “good” 

cholesterol and a protective lipoprotein fraction, because the high 

density lipoproteins usually carry harmful cholesterol molecules away 

from the vessel walls and return them to the liver where they are 

metabolized. This healthy process is called “reverse cholesterol 

transport.” Optimally HDL levels should be greater than 40 for 

males and greater than 50 for females. 

What health conditions require testing? 

The most common cause of low HDL-C is 

elevated triglycerides. A “lipid panel” (which 

includes HDL-C) may be recommended if you 

have markers of cardiovascular risk, such as 

elevated blood pressure, blood sugar or large 

waist circumference, or elevated levels of 

LDL-C, non-HDL, apoB and LDL-P (harmful 

lipoproteins when high). 

Your healthcare provider may also 

recommend a lipid panel if you have a family 

history of heart disease. Low HDL-C can be 

inherited. Gene defects can result in very low HDL 

which decreases protecting the blood vessel wall and leads 

to increased cardiovascular disease. 

Can low HDL-C be improved? 

Yes! There are several ways you can attempt to raise HDL-C: 

1. Exercise 

Raising the HDL-C can be achieved by exercise and weight 

management. Exercise and weight loss improves the way the 

hormone insulin works, resulting in improved fat metabolism. If 

this happens, HDL-C is likely to increase. Find an activity that you 

enjoy and set out to exercise most days of the week. Many people 

enjoy walking; attempt to work up to an hour of walking over the 

course of a day and ask a relative or friend to join you. 

2. Smoking Cessation 

Smoking lowers HDL-C and is a major risk factor for cardiovascular 

disease. Stop smoking! Consider the assistance of a skilled 

counselor to attain this goal. 

3. Diet 

Altering your intake of carbohydrates and fats may bene�cially 

a�ect your HDL-C. 

FOR YOUR PATIENTS 

HDL-C 

Name:_______________________________ Date:___________ Healthcare Provider:________________________________ 

LDL Goals:__________________________ Weight Loss Goals:______________________________ 

Activity/Exercise Goals:______________________________________________________________ 

Medications Recommended:_________________________________________________________ 

Provided by the National Lipid Association 

6816 Southpoint Pkwy., Ste. 1000 • Jacksonville, FL 32216 • www.learnyourlipids.com 

Carbohydrates 

HDL often increases when triglycerides in the blood are reduced 

Sugars and starches in the diet are sources for the three carbon 

back-bone for triglycerides, a fat that is made by the liver, released 

into the blood stream and, stored in your fat cells. Decrease the 

re�ned carbohydrates in your diet including white breads, pastas, 

desserts and soda. Select whole grains, fruits and vegetables, and 

legumes (such as dried beans, peas and lentils) as your main 

carbohydrates. These are absorbed less rapidly by the body and 

many contain soluble �ber, which can help lower cholesterol. Avoid 

sugary beverages, including soft drinks, fruit drinks and juices, 

sports and energy drinks, as well as sugar-sweetened 

teas and co�ees. Drink water as your main drink and 

add lemon or lime if you want to enhance the �avor. 

Fat 

Attempt to consume most of the fat in your diet in 

the form of unsaturated fats. Foods such as canola 

oil and other liquid vegetable oils, salmon, avocado 

and walnuts, as well as other nuts, seeds and 

peanuts contain unsaturated fats. Saturated fat, 

found in full-fat dairy (including butter), prime and 

rib meats and tropical oils (coconut and palm oil) 

should be avoided, because they increase LDL-C. Trans 

fats, found in many packaged foods and some fried foods, 

should be avoided because they increase LDL-C and lower HDL-C. 

Weight Control 

Achieving and maintaining a healthy body weight will increase HDL 

and achieve many other health bene�ts (ie, decrease triglycerides 

and LDL-C, among others). Fried foods should be avoided because 

they are high in calories and contribute to weight gain or prevent 

weight loss. Grain-based desserts and sugar sweetened beverages 

are two of the main sources of calories in the U.S. diet. Eliminating 

these extra calories can help with weight control to increase HDL-C. 

4. Medications 

Your doctor may recommend a medication to increase your HDL-C. 

The available medications usually lower the harmful lipids and 

simultaneously raise HDL-C. Some examples of these include 

Niacin, and groups of drugs called feno�brates and statins. There is 

no good evidence that raising HDL-C with medicines is bene�cial, so 

using medicines that lower LDL-C, non-HDL, apoB, or LDL-P is 

important. 

—Piers R. Blackett, MD, FNLA* 

—Stephen R. Daniels, MD, FNLA 

—Vanessa L. Milne, MS, RN, NP, CLS 

Healthcare Providers—access this tear sheet at www.learnyourlipids.com 

* Diplomate, American Board of Clinical Lipidology

6816 Southpoint Pkwy 

Suite 1000 

Jacksonville, Florida 32216

Winter 2012 - National Lipid Association

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