Side Effects of Anabolic Steroids - National Lipid Association

28 Pages·2009·1.75 MB·English

The Official Publication of the National Lipid Association Volume 7 • Issue 3 • Summer 2009
Lipid
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THE
Spin
Clinical Feature:
Side Effects of Anabolic Steroids

—Negah Rassouli, MD
—Don H. Catlin, MD
—Fred H. Faas, MD
connect • collaborate • contribute
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In this issue
• MWLA 2009 Preview • Case Studies and Practical Pearls on Diabetes • CVD Risk Assessment
From the
President
in this issue...
4 Clinical Feature VERA BITTNER, MD, MSPH
Striking Lipoprotein Changes NLA President
and Liver Toxicity Induced by Over- Professor of Medicine
the-Counter Androgen Division of Cardiovascular Disease
Supplements Superdrol and University of Alabama at Birmingham
Birmingham, AL
Orastan-E
Diplomate, American Board of Clinical Lipidology
—Negah Rassouli, MD

—Don H. Catlin, MD
—Fred H. Faas, MD
NLA –-2010: Where are we going?
7 Case Studies
A mammogram leads to discovery
of arterial stenosis, and Type 2 Professional Education Programs
diabetes mellitus causes lipid- As has been the case throughout the existence of the NLA, professional education
lowering complications
remains the major focus of the organization. We will continue to offer both the Lipid
—Thomas Dayspring, MD
Management Training Course and the Masters Course in conjunction with regional
and national meetings. Under the leadership of Dr. Mary McGowan,who leads the
13 Practical Pearls
LMTC effort, and Drs. Michael Davidson and Peter Toth, who lead the Masters Effort,
Residual Risk Reduction in Insulin
Resistant Patients the curriculum for both courses is being reviewed continuously and slides and other
—Gregory S. Pokrywka, MD course materials are being updated on an ongoing basis to stay current with the
rapidly evolving literature. The NLA Self-Assessment Programs (now available on the
16 Lipid Luminations
Web), the Clinical Lipid Management Self-Assessment Programs, CME meetings on a
Treatment Induced HDL-C Change
variety of topics, and the Virtual Lipid Clinic round out the teaching portfolio.
Is Not Associated with
Cardiovascular Benefit in
Meta-regression Analysis Past symposia in conjunction with AHA and ACC meetings have been very well
—Ronald Goldberg, MD received. At AHA 2009, NLA will present a symposium in close collaboration with
the American Society of Hypertension and the American Society of Preventive
18 News and Notes from the NLA
Cardiology which will address hot topics in dyslipidemia , hypertension, diabetes
and obesity management. You won’t want to miss this event—be sure to mark
20 Physicians Quality Reporting
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Initiative
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21 Meeting Calendar Publications
The Lipid Spin has greatly thrived under Drs. Maria Lopez-Virella’s and Ron
22 Foundation of the National
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Lipid Association
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How to apply for grants
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28 NLA Community Goes Online
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2
Lipid Spin
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Editors
Journal of Clinical Lipidology, first. James A. Underberg, MD
Clinical Assistant Professor of
Medicine
International Initiative NYU School of Medicine
New York, NY
Dr. Virgil Brown and the administrative staff have been hard at work on the
Diplomate, American Board of
international outreach program. We now have an official name for this effort: Clinical Lipidology
the International Federation of Clinical Lipidology. The major goal of this
Robert A. Wild, MD, PhD, MPH
worldwide federation of independent clinical lipidology associations
Professor of Reproductive Endocrinology
will be to share ideas and programs designed to improve professional services and Gynecology
Oklahoma University Health Sciences
in the area of Clinical Lipidology. As a first step, we are developing plans to run Center
Oklahoma City, OK
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Diplomate, American Board of
Clinical Lipidology leadership. This will require additional funding and finding Clinical Lipidology
partners willing to join us with financial support is critical to the success of this
Co-editors
exciting initiative.
Lynn Cofer-Chase, MSN, RN, FAHA
Research Coordinator
Winfield, IL
Stay tuned—more details on this are to come in future issues of the Lipid Spin. Clinical Lipid Specialist
Peter P. Toth, MD, PhD, FAAFP, FICA,
Lipidologists in Training – We Want You to Get Involved! FAHA, FACC
Director of Preventive Cardiology
In-Training Members have been added to 3 of the 5 regional boards and will be
Sterling Rock Falls Clinic, Ltd
added shortly to the remaining 2 chapters. The regional and national meetings Sterling, IL
Clinical Associate Professor
provide an excellent forum to
Southern Illinois University
present your research data at School of Medicine
Vera Bittner, MD, MSPH
Springfield, IL
the poster competition, get up
Dr. Vera Bittner was elected to serve as Diplomate, American Board of Clinical
to date and in depth education Lipidology
President of the National Lipid Association
on a variety of clinical lipidology NLA Staff Editor
at the NLA 2009 Annual Scientific Sessions
Daniel Sosnoski
topics, and to network with
held in Miami Beach, FL, April 30–May 3, 2009. National Lipid Association
experienced clinical lipidologists
She is Professor of Medicine in the Division NLA Executive Director
in practice and in academic
Christopher R. Seymour, MBA
of Cardiovascular Disease, Department
settings. Most of you are already National Lipid Association
of Medicine, University of Alabama at
familiar with the potential of
The Lipid Spin is published quarterly by
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org and you’ll find that the NLA head of Preventive Cardiology, director 6816 Southpoint Parkway, Suite1000
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Phone: [phone] • Fax: [phone]
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Visit us on the web at:
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www.lipid.org
always contact Karen Kent at the
is a past president of the Southeast Lipid
NLA if you need assistance in
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is confident that Dr. Bittner will have a major
available to you ([email protected]).
role in leading the organization to accomplish
its goals in the coming year.
continued on page 24
3
Clinical Feature
S
N
EI Striking Lipoprotein IntroductIon
T
Androgenic Anabolic Steroids (AAS) have been associated
O Changes and Liver
R with a wide range of adverse effects. Some of these
P
Toxicity Induced by Over- products can be easily obtained over the internet,
O
P where they are marketed as “dietary supplements” and
The-Counter Androgen
LI “pro hormones.” Consumers are not always aware of the
O
Supplements potential side effects.1
P
A
Here, we report various side effects of two over-the-
counter (OTC) bodybuilding supplements, Superdrol
Negah Rassouli, MD (methasteron) and Orastan-E (prostanozol), in a young,
Kaiser Permanente of Georgia, previously healthy individual.
Atlanta, GA
case PresentatIon
A 28 year-old previously healthy white male presented
with a two-week history of nausea, jaundice, pruritis
and dark urine. Two months prior to the onset of his
Don H. Catlin, MD
symptoms, he had started using the OTC bodybuilding
Anti-doping Research Inc.
supplements Superdrol (methasteron) and Orastan-E
Los Angeles, CA
(prostanozol) at daily doses of 40 mg and 50 mg,
respectively. Further history revealed that in the few
weeks prior to admission, he had noticed decreased
sexual desire and difficulty in maintaining an erection. He
Fred H. Faas, MD
had been smoking one pack of cigarettes daily for 10 years
Division of Endocrinology
but he denied using alcohol or illicit drugs. Family history
Department of Medicine was negative for liver disease or lipid abnormalities. On
University of Arkansas for Medical physical examination, he had an athletic appearance
Sciences with excoriations throughout the skin. The sclerae were
Central Arkansas Veterans icteric. There was mild right upper quadrant abdominal
Healthcare System tenderness. The liver was not enlarged. Laboratory
studies (Table 1) revealed an elevated bilirubin and mild
elevation of serum transaminases. Extensive work up for
Correspondence:
the etiology of his jaundice was negative. While prior to
Fred H Faas MD
using the supplements his lipid profile was normal, at
Central Arkansas Veterans Healthcare System
presentation in September 2005, the total cholesterol was
4300 West 7th St., Mail Slot 111J
Little Rock, AR, United States, 72205
501-257-5766
E-mail: [email protected]
Testosterone
Superdrol (Methasteron)
Prostanozol Stanozol
Figure 1: Chemical structures of testosterone, methasteron,
4
stanozolol and Prostanozol
S
N
439 mg/dL, triglycerides 342 Table 1: Patient laboratory results EI
mg/dL, high-density lipoprotein 4/25/05 9/22/05 9/25/05 10/24/05 11/7/05 12/28/05 T
O
cholesterol (HDL-C) 9 mg/dL, and
R
direct low-density lipoprotein AST (SGOT) U/L (15-37) 86 104 112 113 30 P
O
cholesterol (LDL-C) 354 mg/ ALT (SGPT) U/L (11-63) 134 140 139 166 35
P
dL. Three days later, the HDL-C Alkaline Phosphatase U/L (31-126) 114 121 215 160 81 I
L
reached a nadir of 4 mg/dL. His GGT U/L (5-60) 57 62 16 O
serum testosterone, follicle- Total b ilirubin mg/dl (0.1-1 ) 7.4 8.4 7.6 3.5 0.8 P
A
stimulating hormone (FSH) and Direct bilirubin mg/dl (0.1-1) 4.7 5.3 3.8 1.5
luteinizing hormone (LH) levels HDL cholesterol mg/dl (30-70) 39 9 4 5 39
LDL cholesterol mg/dl (0-100) 171 354 355 311 168
were also low. The jaundice,
Triglyceride mg/dl (35-200) 217 342 288 230 133
hypogonadism and lipid profiles
Cholesterol mg/dl (135-200) 231 439 423 332 200
abnormalities were attributed
Testosterone ng/ml (1.7-7.4) 0.2 4.1
to his AAS abuse. Several weeks
FSH mIU/ML (1.8-9) 1.3 3.2
after discontinuation of AAS, the
LH mIU/ml (2-12) 1.3 5.1
serum testosterone returned
to normal. Nevertheless, his AST= aspartate aminotransferase; SGOT= serum glutamic oxaloacetic transaminase; ALT= alanine
aminotransferase; SGPT = serum glutamic pyruvate transaminase; GGT= gamma-glutamyl transferase;
libido, pruritis and liver function HDL-C= High-Density Lipoprotein Cholesterol; LDL-C=Low-Density Lipoprotein Cholesterol; FSH=
tests remained abnormal and Follicle-stimulating hormone; LH= Luteinizing hormone
serum lipids were only slightly derived from testosterone) are shown in Figure 1.
improved. A liver biopsy was performed showing pure
canalicular cholestasis consistent with an adverse drug Various side effects have been reported with the
reaction. Three months later, the lipid profile returned to use of AAS. A review by Glazer showed that AAS
baseline with an HDL-C of 39 mg/dL and LDL-C of 168 mg/ decreased HDL-C levels (40–70%), while it increased
dL. Liver function tests also normalized. After recovery, the LDL-C concentration by an average of 36% (11%–
patient provided the investigators with samples of the two 100%).4 The responsible mechanism is not fully
supplements. These were analyzed by one of the authors
understood; however, it is suggested that oral forms of
(D.C.). Superdrol contained methasteron and Orastan-E
17 α-alkylated steroids stimulate hepatic triglyceride
contained 3 peaks on Liquid Chromatography-Mass lipase, which reduces serum HDL-C.4-7 The effect of
Spectrometry (LC/MS) analysis, each with a molecular
AAS on serum LDL-C levels is variable, with reports of
weight corresponding to that of prostanozol. Further increase, decrease and no change in LDL-C levels.4,5,7-10
studies are needed to establish the exact molecular
identity of each peak.
Relevant to the present report, in one study of male
weight lifters, oral administration of stanozolol
dIscussIon led to a 29% increase in LDL-C and a 35% increase
New “designer steroids” such as prostanozol and
in apoprotein B levels, whereas intramuscular
methasteron have been available in nutritional
testosterone treatment caused a 16% decrease in
supplements markets over the Internet for the last few serum LDL-C.7 Our patient presented with an 87%
years and are being advertised as products with “minimal
decrease in HDL-C and a 110% increase in LDL-C
side effects.”2 While both of these products are on the
levels. These alterations in lipid profiles are more
2008 prohibited list by the World Anti-Doping Agency dramatic than any previously reported with AAS use.11
(WADA),3 their legal status is not clear. According to the
It has been suggested that the magnitude of AAS-
Anabolic Steroid Control Act (ASCA) of 2004, the sale of
induced lipoprotein changes are dose dependent
anabolic steroid as nutritional supplements is prohibited and are more severe in poly-drug regimens.8 This may
in the US; however, these products are not on the list of
explain the striking changes in the lipoprotein profile
banned steroids.1 For reference, the chemical structures
in our patient. Complete recovery from AAS induced
of Superdrol and Prostanozol with their relation to
lipoprotein changes is more dependent on duration
testosterone and stanozolol (synthetic anabolic steroid rather than the dosage of AAS.11 Fortunately, in our
5
Clinical Feature
S
N
I patient despite 8 weeks’ use of AAS, the side effects were
E
T reversible and the lipid profile returned to baseline after
O references
discontinuation of AAS.
R
P
O 1. Hans Geyer, Maria Kristina Parr, Karsten Koehler, Ute Mareck,
Chronic cholestatic liver disease is associated with an
P Wilhelm Schänzer, Mario Thevis. Nutritional supplements
I increased serum LDL-C and often high HDL-C.12 In our cross-contaminated and faked with doping substances. J
L
Mass Spectrum. 2008;43:892-902.
O case, the liver biopsy showed canalicular cholestasis,
P
but liver obstructive enzymes were only mildly elevated 2. http://www.netnutri.com/ (Accessed April 14, 2008)
A
and the HDL-C was very low, suggesting the lipoprotein
3. http://www.wada-ama.org/en/prohibitedlist.ch2. (Accessed
changes were due to the AAS. Although methasteron April 14, 2008)
has been reported to cause cholestatic jaundice, its
4. Glazer G. Atherogenic effects of anabolic steroids on serum
effect on lipid profile was not reported.13 lipid levels. Arch Intern Med. 1991;151:1925-1933.

5. Kouri EM, Pope HG, Oliva PS. Changes in lipoprotein-
In about 60% of AAS users, decrease in libido occurs
lipid levels in normal men following administration of
after using anabolic androgens,14 which is typically increasing doses of testosterone cypionate. Clin.J.Sport Med.
1996;6:152-157.
reversible. The exact time needed for full recovery is
unknown and varies based on the dose and duration 6. Schleich F, Legros JJ. Effects of androgen substitution on
lipid profile in the adult and aging hypogonadal male.
of AAS use.15 Full recovery may take from 4–5 months
Eur.J.Endocrinol. 2004;151:415-424.
to more than a year.11 Testosterone levels in our
patient returned to the baseline in 4 months after 7. Thompson PD, Cullinane EM, Sady SP et al. Contrasting
effects of testosterone and stanozolol on serum lipoprotein
discontinuation of AAS.
levels. JAMA. 1989;261:1165-1168.
8. Hartgens F, Rietjens G, Keizer HA et al. Effects of androgenic-
According to a recent position statement from the
anabolic steroids on apolipoproteins and lipoprotein (a).
Endocrine Society,16 the dangers of AAS, including those Br.J.Sports Med. 2004;38:253-259.
advertised as “designer steroids,” should be publicized.
9. Jockenhovel F, Bullmann C, Schubert M et al. Influence of
The manufacturing and distribution of all hormones and various modes of androgen substitution on serum lipids and
pro-hormones, including sales via the Internet, need lipoproteins in hypogonadal men. Metabolism. 1999;48:590-
596.
to be regulated. Given the continuous development
of so-called “designer drugs,” high quality laboratory 10. Whitsel EA, Boyko EJ, Matsumoto AM et al. Intramuscular
testosterone esters and plasma lipids in hypogonadal men:
methodologies for the measurement of these products
a meta-analysis. Am J Med. 2001;111:261-269.
are essential, otherwise detecting the presence of these
11. Hartgens F, Kuipers H. Effects of androgenic-anabolic
substances would be extremely difficult.
steroids in athletes. Sports Med. 2004;34:513-554.
conclusIons 12. Longo M, Crosignani A, Podda M. Hyperlipidemia in Chronic
Cholestatic Liver Disease. Curr Treat Options Gastroenterol.
AAS use may result in various adverse effects. This report 2001;4:111-114.
demonstrates the importance of public knowledge
13. Shah N, Zacharias I, Khettry U, et al. Methasteron-associated
about their potential effects, especially since these
cholestatic liver injury. Clinicopathologic findings in 5 cases:
products may be advertised as nutrient supplements. Clin Gastroenterol and Hepatol. 2008;6:255-258.
The magnitude of lipoprotein changes was unique in
14. O’Sullivan AJ, Kennedy MC, Casey JH et al. Anabolic-
our case. androgenic steroids. Medical assessment of present, past
and potential users. Med J Aust. 2000;173:323-327.
dIsclosure 15. Jarow JP, Lipshultz LI. Anabolic steroid-induced
The authors have no conflicts of interest to disclose. hypogonadotropic hypogonadism. Am.J.Sports Med.
1990;18:429-431.
acknowledgements 16. The Endocrine Society position statement on steroid abuse.
June 2008.
The authors wish to thank Ashkan Emadi, MD, PhD,
Johns Hopkins University, Baltimore, Maryland, for the
preparation of Figure 1.
6
From the Files
THOMAS DAYSPRING, MD, FACP She was started on Crestor (rosuvastatin) 10 mg and Zetia
Clinical Assistant Professor of Medicine (ezetimibe) 10 mg daily. Soon thereafter, while out with
S
New Jersey Medical School her husband, she developed chest pain and dyspnea. They E
I
Director, North Jersey Institute of D
went to the hospital and the EKG was abnormal, so an
Menopausal Lipidology U
Wayne, NJ angiogram was done and 2 stents were placed because of 90 T
S
Diplomate, American Board of percent stenosis of 2 vessels. She was advised to return for
E
Clinical Lipidology
re-evaluation but 6 days later the chest pain, dyspnea, and S
A
clammy skin made her return and 3 additional stents were
C
placed. She is now doing well.
This article focuses on actual lipid disorders from actual
patients, and how one clinical lipidologist evaluates the

available clinical and laboratory data and then arrives at
Discussion:
a therapeutic solution. Dr Dayspring has been in practice
First let’s discuss this case as to the workup and treatment
33 years and lectures extensively through the country on
before the Acute Coronary Syndrome (ACS) occurred. At her
lipids and lipoprotein disorders.
age, and with a lack of 2 major CV risk factors, she would
not have qualified for Framingham Risk Scoring (FRS) using
2001 NCEP guidelines.1 The five major coronary heart disease
Case 1—A routine Ob/Gyn exam leads to
(CHD) risk factors are age (55 in women, 45 in men), low high-
complications:
density lipoprotein cholesterol (HDL-C), cigarette smoking,
I received the following case from a gynecologist
family history of premature CVD, and hypertension. This
who is quite adept at cardiovascular disease (CVD)
patient has only the low HDL-C. Thus, the FRS would classify
risk recognition and management. The patient is an
her as low risk, but it is well recognized that FRS can leave
asymptomatic 48 year old, thin, perimenopausal,
a lot to be desired in women.2 The low-density lipoprotein
normotensive, non-smoking, Caucasian female whom
cholesterol (LDL-C) goal of therapy for low-risk patients is 160
was seen for a routine annual gynecological exam.
mg/dL and therapeutic lifestyle therapies would be advised.
Interestingly, her normal mammogram was reported as
However, an aggressive reading of the 2004 NCEP interim
showing some arterial calcifications. She was advised
report could be interpreted as also having an optional goal
to have a thorough cardiac evaluation despite the
of trying to achieve an LDL-C of 130 mg/dL in this woman.3
absence of any family history of premature CVD. Her
To achieve that goal, lifestyle would still be the preferred
lipid evaluation was:
therapeutic option with drug therapy as a secondary strategy.

The AHA women’s guidelines suggest an LDL-C of < 100 mg/
TC = 207 mg/dL
dL for all women to be achieved with lifestyle and medication
HDL-C = 39 mg/dL
if the risk so dictates.4
LDL -C =146 mg/dL

Triglycerides = 146 mg/dL
Since CVD can present as sudden death, especially in women
VLDL-C = 29 mg/dL
who often have atypical symptoms that do not suggest CHD,
Lp(a) = 139 mg/dL
one may not get a second clinical opportunity. Therefore it

is critical that we make correct risk assessments on the initial
An NMR LipoProfile was also performed and the
encounter. In today’s insulin-resistant climate, we certainly
gynecologist found the results to be astounding:
have to look way beyond the LDL-C value. So, let’s take a real

close look at the lipid profile. The very low (for a woman)
Total LDL-P = 2043 nmol/L (extremely high > 95th
HDL-C of 39 mg/dL is a major risk factor. Based on the initial
population percentile)
history, most providers would probably not have ordered
LDL size was small or Pattern B at 20.2 nm (small size is
lipoprotein (a), as it was deemed an emerging risk factor
< 20.6 nm)
by NCEP ATP-III. However, it was ordered and the elevated
7
From the Files continued
Lp(a) in a Caucasian woman is a risk factor if the level the clinician was correct and very wise to start aggressive
is very high (as in this case) and also associated with lipoprotein modification with lifestyle and drugs (statin
S
E elevated LDL-C.5 The TC/HDL-C is 5.3 (N < 4.0). The and ezetimibe) in such a patient. Despite the perfect FRS,
I
D non-HDL-C, calculated as total cholesterol (TC) minus there were plenty of indicators that identified this woman
U
HDL-C, is 168 mg/dL (elevated according to AHA as high risk.
T
S
women’s guidelines, but non-applicable in this case

E
S according to NCEP as the triglycerides (TG) are not > With an LDL-P > 2000 nmol/L, the most potent statin
A
200 mg/dL. Both the TC/HDL-C ratio and non HDL-C (rosuvastatin) with ezetimibe was a good choice
C
level are surrogates of elevated apoB (the potentially to get rapid lowering of apoB (atherogenic LDL
atherogenic lipoproteins). The TG/HDL-C ratio is 3.7, a particles). Multiple studies reveal that you get as much
level highly associated with predominately small LDL (approximately 20%) apoB reduction by adding ezetimibe
particles. Almost all drug naïve patients with small LDL to the starting dose of any statin than you do by using
particles have elevated apoB or LDL-P. Thus, a careful higher doses of the statin (and most statin side effects are
analysis of the lipid profile in this woman is certainly dose related). The ezetimibe will also negate the usual
suggestive of too many LDL particles (high apoB)
with the predominant size likely being small. Finally,
although guidelines do not yet recognize breast arterial
calcification as a CHD risk equivalent, there is data that
it is linked to systemic atherosclerosis.6
The NMR lipoprotein analysis clearly demonstrates
significant worry. Using population cutpoints from
studies like Framingham Offspring7 and MESA (Multi-
Ethnic Study of Atherosclerosis), an LDL-P > 1600
nmol/L is considered high (75–80 % of patients will
have lower levels) and > 2000 is very high (90% of
patients have lower levels). One might think this
is another case where lipoprotein quantification
outperforms lipid concentrations in predicting risk,
however an LDL-C of 146 mg/dL is also in the 70th–80th
percentile Framingham population cutpoint. The major
factors determining apoB (LDL particle) entry into the
arterial intima is particle concentration and endothelial
function/integrity. LDL size per se is not a major factor
influencing arterial entry as all LDL particles (large
or small) and even larger remnant lipoproteins, if reflexive statin-induced hyperabsorption of sterols. The
present in elevated concentrations, can penetrate the high Lp(a) does not alter the choice of statin/ezetimibe
endothelium. Putting it all together (before the acute therapy as NCEP suggests the proper way to reduce risk
coronary syndrome): We had a perimenopausal woman in persons with elevated Lp(a) is to normalize LDL-C.1
without obvious historical risk factors who had (1) a Aspirin and blood pressure (BP) control were also clearly
very worrisome lipid profile, (2) a terrible lipoprotein indicated at the time of presentation. Believing her to be
profile, (3) arterial calcium seen on mammography and high risk, I would have also prescribed omega-3 fatty acids
who was (4) probably an insulin resistant metabolic at 1000 mg dosage as AHA/ACC recommends for high-risk
syndrome patient (low HDL-C, TG nearly 150 mg/dL patients with CHD.8 Unfortunately, this woman almost
and increased numbers of small LDL particles). I believe died due to severe coronary artery disease (CAD) and
8
multiple unstable plaques, and she is now a very high risk fatty acid (FA) esters to the regimen might help and
patient. Although the woman received proper treatment thus further lower LDL-P. If needed to get to goal, in
S
by her gynecologist, would any additional studies have this case where the TG were < 200 mg/dL, I’d go with E
I
D
provided clues that she was on the brink of an event or extended-release niacin (Niaspan). There is positive
U
acute coronary syndrome (ACS)? The answer is probably lipid-modulating data using statin/ezetimibe/extended- T
S
yes and of course it is always so easy to do this with the release niacin.10 In the HDL Atherosclerosis Study (HATS)

E
retrospectoscope: They are: (1) If you determine someone study, slow-niacin (and additional IR niacin in some) S
A
added to a statin in high-risk patients demonstrated
C
Because she is now in the very
dramatic angiographic and very positive outcome data.
high risk category, we must be There is little niacin outcome data in women, and a
perimenopausal woman is likely to be already dealing
very aggressive in normalizing the
with vasomotor symptoms which might limit its use.
treatable risk factors.
Many might consider niacin an especially good choice
because of the elevated Lp(a) and low HDL-C. However,
approaching age 50 is in a high-risk category, stress there are no prospective trials showing reducing
testing is indicated to rule out significant obstructive apoprotein (a) levels with any drug improves outcomes.
disease and to determine a functional capacity so a proper There were some interesting potential positive
exercise prescription can be advised. Had it been done, effects of estrogen in Heart and Estrogen/progestin
the stenotic lesions might have been discovered; (2) use Replacement Study (HERS) in women with elevated
of high-sensitivity C-reactive protein (hs-CRP) and/or Lp(a).11
Lipoprotein Associated Phospholipase A2 test (available as
the PLAC test) might have given us a better idea regarding Case 2—Diabetes presents a challenge:
vascular inflammation, plaque vulnerability and imminent The case discusses a frequent dilemma: Do all diabetic
risk. The PLAC test is stable and more specific (unlike CRP) patients need statins? I was asked about a 42-year-
for vascular events (including stroke which is always a old male who presented with a diagnosis of Type 2
higher worry in a woman than in a man). Cost can be a diabetes mellitus (T2DM), solitary kidney, hypertension
consideration on which inflammatory marker to order. I (controlled with verapamil 240 mg daily and valsartan
am not sure that CIMT testing would have told us anything [Diovan] 160 mg daily) and with a history of biopsy
more than did the mammograms, i.e., that atherosclerosis diagnosed NASH (nonalcoholic steatotic hepatitis) as
was present. well as microalbuminuria.
Initial lipid panel:
On future follow up, what would one turn to if the
TC = 189 mg/dL
rosuvastatin (10–20 mg)/ezetimibe 10 mg tablet did
TG = 477 mg/dL
not normalize the lipid profile or LDL-P? I believe this
HDL-C = 30 mg/dL
woman with cardiometabolic risk needs to be followed
LDL-C = 64 mg/dL
with apoB or LDL-P, as per the recent ADA/ACC consensus
VLDL-C = 95 mg/dL
statement.9 Because she is now in the very high risk
non-HDL-C = 159 mg/dL
category, we must be very aggressive in normalizing
TC/HDL-C = 6.3
the treatable risk factors. Here are potential options (in
TG/HDL-C = 15.9
the order I would use them): I’d consider a therapy that
shifts LDL size as it is easier for upregulated LDL receptors
The provider started metformin with eventual
to recognize the apoB configuration on normal sized
titration to 1000 mg twice a day, ASA 81 mg daily and
rather than small LDL. Since neither statins nor ezetimibe
simvastatin/ezetimibe (Vytorin) 20/10. The very next
typically shift LDL size, adding extended-release niacin,
day, the liver function tests (LFTs) came back and were
a fibrate, or higher dose prescription strength Omega-3
significantly elevated (ALT 176, AST 110). The clinician
9
From the Files continued
discontinued Vytorin and emphasized the importance clinical trials, the focus must remain on achieving
S of therapeutic lifestyle and prescribed fenofibrate the recommended goals of therapy established by
E
I (TriCor) 145 mg daily, pioglitazone (Actos) 15 mg daily national guidelines.”12 Since then, JUPITER Trial data
D
and Omega-3 FA 1000 mg 3–4/day. Since then the 13 suggests reducing CRP levels might be important,
U
T patient has lost 30 pounds and the LFTs have come but it is speculative that lowering CRP is necessarily a
S
down (over 12 weeks) to normal values (AST 41, ALT pleiotropic rather than cholesterol-lowering effect of
E
S 51). His HgbA1c is now fine and microalbumin also statins. Ezetimibe, not known to have many pleiotropic
A
C returned to normal. The verapamil had to be stopped effects, significantly lowers CRP on top of that caused by
as the patient was having symptoms of pre-syncope statin therapy, likely by further lowering cholesterol. If
with a systolic BP in the 90–110s. one studies NCEP and ADA guidelines closely, they are
supportive of starting statin therapy in T2DM. Indeed,
After seeing the follow up lipid panel, the provider asks,
ADA guidelines advise that a T2DM > age 40 should start
“Can I even make an argument for prescribing a statin?”
a statin and get LDL-C <100 mg/dL. If the person has
CHD, statin therapy is advocated to reduce LDL-C < 70.14
TC = 182 mg/dL
NCEP 2004 addendum gives an option to start a statin in
HDL = 99 mg/dL
T2DM no matter what the baseline LDL-C and suggests
TG = 123 mg/dL
reducing it by 30–40%.3 Yet both ADA and NCEP remind
LDL-C = 58 mg/dL
us that in diabetics with CHD and an unremarkable LDL-C
VLDL-C = 25 mg/dL
that fibrates (gemfibrozil in VA HIT) reduce events. So is
non-HDL-C = 83
it considered the standard of care to use statins first line?
TC/HDL-C = 1.9
Or perhaps we should better ask: Is it not the standard of
care to start another drug first? In this case the LDL-C went
Discussion: from 64 to 58 (hardly a 30–40% drop). If the patient had an
The approach and management (with one exception) event, would one be questioned as to why no statin was
seems to be a fabulous therapeutic job. The exception prescribed?
is that there is a major P450 interaction between
Although there are no clinical trials providing evidence on
simvastatin and verapamil and you really should not
what drugs best reduce events in people with high-risk TG
use them both in a polypharmacy patient (if you do,
values, most guidelines, especially NCEP ATP-III, suggest
the dose of simvastatin should not exceed 20 mg).
A hydrophilic statin (pravastatin or the more potent
The focus must remain on
rosuvastatin) would have been a safer choice. With
achieving the recommended goals
respect to the provider’s inquiry as to whether a statin
is, required, most practitioners believe diabetics must of therapy established by national
be on a statin for their lipid and so-called non-lipid
guidelines.
or pleiotropic effects. Lipid and CV guru Michael
Davidson, MD, in an editorial about statin pleiotropy
a fibrate as the preferred first line therapy if the TG are >
reminded readers that, “The National Cholesterol
500 (this patient had 477). Although not mentioned when
Education Program Adult Treatment Panel III guidelines
ATP-III was published in 2001, prescription strength N-3 FA
do not recommend specific drugs to reduce CHD
(Lovaza) at doses of 4000 mg or higher also now have an
events but rather lipoprotein target goals based on
FDA indication when TG are > 500 mg/dL.
the weight of clinical evidence. Among clinicians the
pleiotropic benefits of statins have reached almost
The elevated aminases noted one day after starting statin/
mythical proportions. Although research and debate
ezetimibe were clearly not drug related but due to the
regarding this issue should continue, in the absence
hepatic steatosis. Package inserts with statins and fibrates
of evidence for benefits on events from randomized
state not to use them in cases of unexplained aminase
10