Physical
Exam (Current)
Height: 70
in
Weight: 210 lb
Body mass index: 30 kg/m2
Waist circumference: 38
in
Blood pressure: 122/82
mm Hg
Pulse: 74 bpm (regular)
Cardiovascular: No bruits
Heart: RRR without murmurs
Abdomen: no bruits
Extremities: no edema
Medications
Doxazosin mesylate 4 mg qd
Lisinopril 5 mg qd
Simvastatin 20 mg qd
Multivitamin 1 qd
Vitamin E 400 units qd
Fiber capsules 88 mg
2 capsules qd
Omega-3 capsules 1,000 mg
1 capsule qd
Cholestin™
(policosanol) 15 mg
2 capsules qd
Garlique®
(garlic/allium sativum)
400 mg 1 capsule qd
Soy milk 8 oz per day
Soy health bar 1 per day
10-15 nuts per day
Laboratory Values
Baseline (1 yr ago)/Today
TC: 298/233 (mg/dL)
TG: 298/218 (mg/dL)
LDL-C: 195/145 (mg/dL)
HDL-C: 43/45 (mg/dL)
Non–HDL-C: 255/188 (mg/dL)
Fasting glucose: 96/98 (mg/dL)
HbA1c:
6.8/6.9 (%)
AST: 33/34
CPK: <100/<100
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| Related
information on this website: |
|
 In
the Slide Library section:
HPS:
Effects of Antioxidant Vitamins on Vascular Events
by Year
HPS:
Effects of Antioxidant Vitamins on Vascular Events
by LDL-C
In
the Current Literature section:
MRC/BHF
Heart Protection Study of Antioxidant Vitamin Supplementation
in 20,536 High-Risk Individuals: A Randomised Placebo-Controlled
Trial.
Collins R, Armitage J, Parish S, Sleight P, Peto R,
writing for the Heart Protection Study Collaborative
Group. Lancet. 2002;360:23-33.
Antioxidant
Vitamins and the Risk of Carotid Atherosclerosis—The
Perth Carotid Ultrasound Disease Assessment Study
(CUDAS).
McQuillan BM, Hung J, Beilby JP, Nidorf M, Thompson
PL. J Am Coll Cardiol. 2001;38:1788-1794.
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Middle-Aged Male Prefers a “Natural” Treatment
Plan
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James
M. McKenney, PharmD |
The following case was provided by James M. McKenney, PharmD,
Professor Emeritus, Virginia Commonwealth University, and
President, National Clinical Research, Richmond, Virginia
Disclosure Information for Dr McKenney: Speaker Honorarium:
AstraZeneca, KOS, Merck, Novartis (Reliant), Pfizer, Sankyo;
Grant Support: AstraZeneca, GlaxoSmithKline, Genaissance,
KOS, Merck, Novartis, Sankyo, Schering Plough, Pfizer, TAP;
Consultant: AstraZeneca, KOS, Pfizer.
A 55-year-old male, a PhD employed by a local liberal arts university
as a Civil War historian, presents with hypertension, benign
prostatic hyperplasia, and hypercholesterolemia. He has no clinical
evidence of coronary heart disease (CHD). His CHD risk factors
include family history (father died of a myocardial infarction
[MI] at age 47 years; grandfather died suddenly at age 50 years),
sex (male >45 years), and hypertension (which is being treated).
He does not smoke and does not have diabetes. Thus, the National
Cholesterol Education Program Adult Treatment Panel III (ATP
III) recommends an LDL-C goal of <130 mg/dL and a non–HDL-C
goal of <160 mg/dL. His 10-year estimated CHD risk is 12%.
He states that he follows a low-saturated-fat diet and walks
3 miles briskly 5 to 6 days each week.
Discussion
Our patient (we will call him Professor) fits a profile that
is very familiar to today’s health professionals: people
who are taking several herbal and dietary supplements each
day to address common health problems. Professor is worried
about his very strong family history of CHD-related deaths
and has spent many hours of study identifying ways to reduce
his risk. He is articulate about many issues relevant to his
case and is convinced that his “natural” treatment
plan is a good one. He tries to eat properly (he follows an
ATP III Therapeutic Lifestyle Change [TLC] diet) and to exercise
regularly. He is overweight, but fit. He wishes to augment
these initiatives with natural therapies because they are
“better and safer.” In fact, Professor admits
that he recently abandoned statin therapy and replaced it
with his “natural” regimen. His pharmacist’s
records indicate that Professor has received about 160 days
of simvastatin doses since it was first prescribed 1 year
ago, but none in the past 90 days. He is unaware of the clinical
trials supporting today’s prescriptive therapies for
CHD risk reduction, and states a preference to avoid “drugs”
to treat medical problems. However, he is open to an informed
discussion on how he can best reduce his risk of CHD.
Statin
Trials
Readers of this newsletter are undoubtedly familiar
with the body of evidence supporting cholesterol-reduction
therapy, including the six major statin trials—4S, WOSCOPS,
CARE, AFCAPS/TexCAPS, LIPID, HPS.1-6
Together, these trials demonstrated that statin therapy reduces
by about one third nearly every clinical manifestation of
atherosclerosis, including MIs, CHD deaths, revascularization
procedures, strokes, and total mortality. HPS has extended
our understanding of the power of statin therapy by demonstrating
a substantial risk reduction in: patients with CHD or a CHD
risk equivalent (ie, peripheral vascular disease, cerebrovascular
accident, or diabetes); patients up to age 80 years; women;
and even those with baseline LDL-C levels below 100 mg/dL.6
Additionally, these trials demonstrate that statin therapy
is remarkably safe. Serious adverse events are rare; when
they do occur, they are almost always reversible upon withdrawal
of the statin therapy.
Dietary
Adjuncts
Professor is not likely to alter his dietary adjunctive therapy
without an informed discussion of the scientific evidence,
or the lack thereof, supporting it. Following is a brief review
of these data for each of the therapies he is pursuing.
Vitamin E.
Since LDL-C must be oxidized to be taken up
by macrophage cells and to participate in atherogenesis, it
has been hypothesized that an antioxidant, such as vitamin
E, could protect against coronary disease. Supporting this
position are several large epidemiologic trials that report
less occurrence of CHD in people who took vitamin E than in
patients who did not. In recent years, however, a number of
well-designed, randomized clinical trials involving nearly
100,000 subjects have failed to demonstrate a significant
change in CHD risk with vitamin E. This is true whether study
subjects had CHD or not, whether vitamin E was used alone
or in combination with other antioxidants, and regardless
of the vitamin E dose used. Further, vitamin E supplementation
has not been shown to affect the occurrence of other health
issues, including any form of cancer. Professor should be
discouraged from taking vitamin E supplementation.
Garlic.
Garlic (Allium sativum) was used as early as 3000
BC to improve the “fluidity of the blood and strengthen
the heart.” In the early part of the last century, researchers
recognized that patients who ate onions and garlic had lower
cholesterol levels. In recent years, garlic products have
been widely promoted for cholesterol lowering, including the
brand Professor is taking. Fortunately, many randomized clinical
trials are available to objectively determine just how useful
garlic is for cholesterol lowering. Results are mixed. A recent
analysis of 13 trials involving nearly 800 patients concluded
that the reduction in total cholesterol was a modest 5.8%.7
Most of these studies tested dried-powder preparations providing
about 900 mg of garlic daily and 1.3% of alliin/dose, the
equivalent of 2.7 g of fresh garlic (about 1 clove/d). The
cholesterol-lowering effect appears to be dose-related, but—at
the high doses needed to produce greater cholesterol lowering—unpleasant
side effects are more likely to occur, including garlic odor
and gastrointestinal upset and bleeding. Given Professor’s
need for substantial cholesterol lowering, it seems impractical
for him to continue to use garlic.
Omega-3 Fatty
Acids. Cold-water fish (eg, mackerel, herring,
halibut, salmon) provide an excellent source of omega-3 polyunsaturated
fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA). These are reported to lower TG levels and blood
pressure (very slightly), reduce platelet aggregation, and
improve endothelial dysfunction. The TG reduction is dose-related:
Only marginal 3% to 5% reductions occur with doses of 1,000
mg/d, but reductions of 25% to 35% are commonly associated
with doses of 5 g to 12 g per day. The effect on LDL-C is
variable and generally insignificant. The greatest benefit
of fish-oil supplements, however, is an antiarrhythmic effect
that may lower the risk of sudden death. A recent analysis
of nine studies involving 13,168 patients receiving supplements
containing EPA in doses of 0.3 to 6.0 g/d and DHA in doses
of 0.6 to 3.7 g/d for an average of 20 months showed that
the occurrence of nonfatal MIs was not significantly lowered,
but that sudden death and total mortality was. (See Table
1.) This suggests that Professor may well benefit from
fish-oil therapy.
Soy.
Soybeans provide a source of soy protein and isoflavones (phytoestrogen),
which together have a cholesterol-lowering effect. Cholesterol
levels may be reduced by simply substituting soy protein for
animal protein in hyperlipidemic patients, but soy may also
lower cholesterol by increasing thyroxine levels, increasing
bile-acid excretion, and/or increasing the removal of cholesterol
from the circulation. A recent analysis of 38 randomized clinical
trials involving 564 subjects who received a mean dose of
47 g/d reported a 13% average reduction in LDL-C.8
(See Table 2.) The cholesterol-lowering effect was only
3% to 4% when baseline total cholesterol levels were less
than 250 mg/dL, but 20% when levels were over 335 mg/dL. The
reduction in total cholesterol was 9, 17, and 26 mg/dL with
the daily intake of 25 g, 50 g, and 75 g of soy, respectively.
These data support Professor’s use of soy in his diet,
although the cholesterol reduction is likely to be modest.
Policosanol.
Policosanol is a mixture of aliphatic alcohols, which are
isolated from sugar-cane wax and beeswax. More than 60 randomized
trials involving about 4,000 patients have been conducted
with this product. The average LDL-C reduction with 10 mg/d
is reported to be between 20% and 25%, and the reduction with
20 mg/d is between 27% and 32%.9-11
(See Table 3.) Only one published study10
addresses doses above this level. The LDL-C reduction with
a daily 10-mg dose of policosanol has been shown to be similar
to the reduction achieved with simvastatin 10 mg, pravastatin
10 mg, and lovastatin 20 mg daily.9
HDL-C levels generally increased 8% to 18% with 10 mg to 20
mg per day; the effect on triglycerides varies and is unpredictable.
There is no information about the drug’s pharmacokinetics,
teratogenic or carcinogenic effects, or propensity to interact
with other drugs. Published studies generally report good
tolerance and few side effects.9-11
A 2-year placebo-controlled, randomized clinical trial has
demonstrated a significant improvement in initial and absolute
walking time in patients with peripheral vascular disease.12
Professor should be made to understand that more research
must be done on this drug.
Fiber.
Fiber intake of 25 g to 35 g per day is recommended by the
US Department of Agriculture. If supplements are used for
cholesterol reduction, the preferred form is water-soluble
(viscous) fiber from oat, pectin, psyllium, and guar gum.
Supplements have been reported to reduce cholesterol levels
to over 20%; much of this variance is probably due to the
small number of patients and failure to control the diet during
the study. For example, LDL-C reductions of over 10% with
psyllium were routinely reported until it was studied in patients
who were on an American Heart Association Step I diet, when
reductions of about 5% were achieved. A recent analysis of
67 randomized clinical trials involving 2,990 patients who
received an average of 9.5 g of supplemental fiber per day
showed reductions from all fiber sources of 1 mg/dL to 2 mg/dL
per gram consumed.13 The
reduction achieved is related to the fiber dose as well as
the baseline cholesterol level. High doses are associated
with the gastrointestinal symptoms of diarrhea, rectal gas,
and loose stools. For Professor, fiber supplementation is
appropriate, though in higher doses than he currently takes.
Assessment
Professor has three CHD risk factors. Because of his strong
family history but only a modest 10-year estimated CHD risk,
some authorities would pursue additional evaluations, such
as Lp(a), hs-CRP, homocysteine, and/or particle composition
and size determinations, as well as ankle-brachial index,
carotid IMT, and ultrafast CT evaluations for atherosclerosis
to better clarify his risk. However, even without these additional
evaluations, ATP III recommends that he be treated aggressively
to achieve an LDL-C goal <130 mg/dL (although his strong
family history may warrant an even lower LDL-C goal). Professor
is not currently at his LDL-C or non–HDL-C goals. He
should be encouraged to continue pursuing those dietary supplement
steps that are supported by well-designed studies—preferably
as part of a lipid-lowering, low-saturated-fat diet. One can
make an argument that he may need to increase the dose of
his fiber, soy, and omega-3 fatty-acid intake to maximize
their lipid-lowering effects. However, if he still cannot
reach his LDL-C goal, he should be strongly advised to reconsider
statin therapy given its strong clinical-trial evidence for
CHD risk reduction. Not only will this help him reach his
LDL-C goal, but it will provide other positive effects to
reduce his CHD risk.
Additional
tables pertaining to this article are available by clicking
on this link.
References*
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| 1. |
Scandinavian
Simvastatin Survival Study Group. Lancet.
1995;345:1274-1275. |
| 2. |
Shepherd
J, Cobbe SM, et al. N Engl J Med. 1995;333:1301-1307. |
| 3. |
Sacks
FM, Pfeffer MA, et al. N Engl J Med.
1996;335:1001-1009. |
| 4. |
AFCAPS/TexCAPS
Research Group. JAMA. 1998;279:1615-1622. |
| 5. |
The
Long-Term Intervention With Pravastatin In Ischaemic
Disease (LIPID) Study Group. N Engl J Med.
1998;339:1349-1357. |
| 6. |
Heart
Protection Study Collaborative Group. Lancet.
2002;360:7-22. |
| 7. |
Stevinson
C, Pittler MH, et al. Ann Intern Med.
2000;133:420-429. |
| 8. |
Anderson
JW, Johnstone BM, et al. N Engl J Med.
1995;333:276-282. |
| 9. |
Gouni-Berthold
I, Berthold HK. Am Heart J. 2002;143:356-365. |
| 10. |
Castano
G, Mas R, et al. Int J Clin Pharmacol Res.
2001;21:43-57. |
| 11. |
Castano
G, Mas R, et al. Drugs R D. 2002;3:159-172. |
| 12. |
Castano
G, Mas R, et al. Angiology. 2001;52:115-125. |
| 13. |
Brown
L, Rosner B, et al. Am J Clin Nutr. 1999;69:30-42. |
*For
complete listing of references, please click here.
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