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Is Cholesterol-Lowering Therapy Worthwhile in the Elderly?
Research still in progress will
clarify the issues, but a major panel
of experts cites enough existing
evidence to suggest that older adults
can benefit as much from aggressive
antihyperlipidemia therapy as can the
general population.
By W. Richey Neuman, MD,
and Caroline Milne, MD
Dr. Neuman is assistant professor of
medicine at the University of
Pennsylvania School of Medicine. Dr.
Milne is a general medicine fellow at
the University of Pennsylvania School
of Medicine and the Philadelphia
Veterans Administration Hospital.
Coronary heart disease (CHD) is
the leading cause of death in older
adults in the United States,
accounting for more than half of all
deaths in patients older than 65. The
incidence and prevalence of CHD is
highest among men and women in this
age group, in whom 80% of all CHD
deaths occur. Several well-recognized
risk factors contribute to the
development of CHD, including
hypertension, smoking, and diabetes.
In the last decade, however,
cholesterol has emerged as an
independent risk factor for the
development of CHD in the elderly
population.
Data from recent clinical
trials have shown that elderly
patients who undergo treatment for
hyperlipidemia are at decreased risk
for CHD-related disability and death.
In addition, lipid-lowering agents,
particularly HMG-CoA reductase
inhibitors, known as statins, have
been shown to be effective and well
tolerated by patients older than 65.
For these reasons, the National
Cholesterol Education Program Expert
Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol
in Adults (NCEP/ATP-III) recommends
screening for and treating
hyperlipidemia in elderly patients.
In this review we will discuss
the medical evidence and clinical
rationale supporting the evaluation
and treatment of hyperlipidemia in
elderly patients. We will then review
screening recommendations and
treatment guidelines regarding diet,
exercise, and medical therapy.
EPIDEMIOLOGY OF CHD IN THE
ELDERLY
The burden of atherosclerotic
disease among the elderly is high:
two thirds to three quarters of
people older than 65 have either
subclinical or clinical CHD. In 1993,
the NCEP/ATP-II declared age to be an
independent risk factor for CHD. In
fact, they concluded, age alone
raises the risk for CHD in men aged
45 or older and in women aged 55 and
older. The other risk factors they
found to be related to CHD include
hyperlipidemia, hypertension,
diabetes mellitus, current cigarette
smoking, and a family history of
premature CHD-that is, a CHD event
occurring before the age of 55 in a
father or first-degree male relative
or before the age of 65 in a mother
or first-degree female relative. The
NCEP/ATP-II also pointed out that
patients who have an elevated
high-density lipoprotein (HDL) level
are at a reduced risk for the
development of CHD.
The debate about the role of
serum cholesterol in the development
of coronary artery disease (CAD) in
the elderly is still ongoing.
Lipoprotein metabolism undergoes
several hormone-mediated and
liver-related changes that occur with
aging. As a result, low-density
lipoprotein (LDL) levels
progressively increase after puberty
in men and women (although more
slowly in women), and total and LDL
cholesterol levels gradually decline
after 50 years in men and 60 years in
women.
Although those age-related
metabolic changes have been
documented and understood, some
studies that have addressed increased
total serum cholesterol or LDL as a
possible risk factor for CHD have
failed to show a link between that
phenomenon and an increased relative
risk among the elderly population.
Other prospective studies, however,
have demonstrated that link. The
differing conclusions are thought to
be due to the methods used by the
investigators in those studies to
express risk.
In studies reporting negative
findings, researchers usually use a
relative risk ratio to describe
differences in risk between groups.
Given the high frequency of CHD in
the elderly, however, attributable
risk (the difference in absolute risk
between groups with high and low
cholesterol levels) is thought to be
a more appropriate method of
expressing CHD risk related to high
serum cholesterol in this population.
When analyzed this way, as Grundy and
colleagues discovered, attributable
risk does reveal the high impact of
elevated serum cholesterol among the
adult population older than 65
(Archives of Internal Medicine, vol.
159, p. 1670, 1999). Thus, this
population has a high absolute risk
for CHD, and a significant portion of
that risk can be attributed to
elevated serum cholesterol. This
conclusion usually applies to the
elderly population aged 65 to 85;
limited data are available for
patients older than 85.
PATHOPHYSIOLOGY OF CHD
The formation of cholesterol
plaques is a process that begins in
puberty and continues throughout
life. A high serum cholesterol
concentration causes cholesterol
deposits to form in blood vessel
walls, leading to plaque formation. A
significant component of plaque
formation is thought to involve an
inflammatory reaction in which immune
system cells and modulators process
cholesterol in the arterial wall. An
excessive serum cholesterol
concentration promotes increased
activity of this inflammatory
component, which in turn produces a
plaque that is vulnerable to rupture.
Notably, approximately 60% of
all acute myocardial infarctions (MIs)
occur in patients whose coronary
artery stenosis measures 50% or less,
a finding that shows the impact and
danger of unstable plaques on
CHD-related morbidity and mortality.
In animal studies, researchers have
observed that a reduced cholesterol
concentration attenuates the
mechanism of plaque instability,
which in turn reduces the number of
proinflammatory cells in plaques.
This effect in animals is thought to
mirror the mechanism in humans and is
buttressed by data from human studies
in which patients with CHD who
reduced their C-reactive protein
levels through statin therapy
suffered fewer adverse events. There
is no reason to believe that the
pathophysiology of CHD in elderly
patients differs from that in younger
ones.
[Karl Note: Dr. Garry F. Gordon, the founder
of the intravenous chelation group of doctors discovered that oral chelation is,
in fact, better than IV chelation. The Group of IV doctors is called ACAM
-- the American College of Advancement in Medicine. That group refused to
allow its own founder, Dr. Gordon, to present his many studies on the
effectiveness of oral EDTA to the group. So, Garry quit that group and for
many years has been perfecting and lecturing about the advantages of the oral
chelation approach.
Garry has now become very famous, all over the
world, as a distinguished physician who solves medical problems with natural
alternatives to drugs. I have a very large web section devoted exclusively
to Garry F. Gordon --
HERE.
One of the features of the Gordon Web Site is a
selection of recorded lectures, mostly by Dr. Gordon, but also others.
Some of these lectures you can actually download from my site, at no cost.
Others can be purchased from Dr. Gordon's organization.
These lectures are mostly aimed at the medical
doctor, but if you take the time to listen several times and look up the words
you don't understand, you can get a great deal of fascinating information from
them. For each of these lectures, as I listen to them, I have some notes
on a separate page. You can listen to the lectures, yourself, and you can
also review my notes from having listened to those lectures.
In several lectures Dr. Gordon describes the huge
importance of "inflammation" as a important factor in heart disease - in this
sense he is agreeing with Dr. Furster. But, while Dr. Furster and others
like him find new data about heart disease and cancer, they also are driven by
the drug company money in their studies, and can only be expected to also
discover some new drug that will handle the newly discovered health problem.
What Dr. Gordon does is look over these new studies,
but then apply his vast knowledge of natural remedies to find products that are
NOT drugs, but do as well as or better than drugs in handling the problem.
In many cases it is not so simple as to say, "Just use the herb, Cat's Claw for
inflammation." There are good companies out there, not drug companies,
doing their research with vitamins and herbs. In this case Garry found a
very specially refined version of Cat's Claw that is far, far better at reducing
C Reactive Protein levels.
Thus, you can read about new discoveries, such as C
Reactive Protein, and in hundreds of places you will find some new drug being
touted as the remedy.
Check out my web about Garry F. Gordon and you may
well find a natural alternative. There is more information on this natural
alternative to a drug for handling C Reactive Protein.
CLICK
HERE for my lecture notes on that.
Other pages where I describe this C Reactive Protein
are HERE:
Vulnerable Plaque -- The New Kid On The Block!
... During the inflammatory process,
a substance-C-reactive protein-is
produced in the blood. By measuring blood levels of C-reactive
...
www.chelationtherapyonline.com/articles/p204.htm
- 56k -
Cached -
Similar pages
Heart-Disease Sleuths Identify Prime Suspect: Inflammation
of ...
... They checked samples from 543
doctors who they knew eventually had heart attacks
or strokes, to see what their levels of C-reactive
protein had been about ...
www.chelationtherapyonline.com/articles/p195.htm
- 71k -
Cached -
Similar pages
Nanobacteria -- The New Thing In Heart Disease
... Most of the commonly known
medical “markers of inflammation” (C Reactive
Protein,
MMP's, MPO, Interleukins, etc.) are found to be elevated in
response to ...
www.chelationtherapyonline.com/articles/p54.htm
-
Similar pages
ORAL CHELATION – THE OTHER SIDE OF THE STORY by Dr. Garry F.
...
... inflammatory therapy to deal with
the newly recognized molecular risk factors such
as fibrinogen, ultra sensitive C-reactive
protein, Intracellular Adhesion ...
www.chelationtherapyonline.com/anatomy/p63.htm
- 51k -
Cached -
Similar pages
EFFECT OF LIFESTYLE CHANGES ON
HYPERLIPIDEMIA
Physicians are often frustrated
by the results of diet modification
for lowering serum cholesterol
concentration. Current trial data
reported in the literature reflect
the limited gains from this approach.
The most recent study of
lipid-lowering diet therapy is the
Diet and Exercise for Elevated Risk
trial, which enrolled men and
postmenopausal women who had average
HDL cholesterol and moderately
elevated LDL cholesterol levels and
no known heart disease. Patients
randomly assigned to an American
Heart Association (AHA) Step 2 diet
alone (which limits daily cholesterol
intake to 200 mg, total fat to less
than 30% fat, and saturated fat to 7%
or less) were successful in losing
weight, but they did not
significantly reduce their total or
LDL cholesterol levels, nor did their
HDL cholesterol levels change (New
England Journal of Medicine, vol.
339, p. 12, 1998). Results from the
Lifestyle Heart Trial, however, did
show a significant decrease (37.4%)
in serum LDL among patients who
followed a very low-fat, whole-food
vegetarian diet high in complex
sugars and low in simple sugars
(Lancet, vol. 336, p. 129, 1990).
The results of many
epidemiologic studies have shown that
the incidence of CHD is higher among
sedentary people than among those who
are physically active. Most studies
have revealed that exercise of low to
moderate intensity can produce a
modest increase in HDL cholesterol
concentration and a slight decrease
in total and LDL cholesterol levels.
The Diet and Exercise for Elevated
Risk trial showed that the greatest
benefits are seen from modifications
in diet and exercise together.
Subjects in this study showed a
significant reduction in their total
and LDL cholesterol levels at one
year when compared with control
subjects; however, no increase in HDL
cholesterol levels was observed.
Nevertheless, it is clear that
although exercise alone has only a
minimal effect on a patient's lipid
profile, regular exercise and optimal
physical fitness significantly reduce
the risk of death from cardiovascular
or other causes. Research has shown
that men who maintain adequate
physical fitness are less likely than
others to die from cardiovascular or
other causes. Moreover, as the
results of one study show, risk can
be reduced by as much as 44% among
men who improve their physical health
status from "unfit" to "fit" after
following a fitness program for five
years.
PHARMACOLOGIC THERAPY
The drugs most often
administered in clinical trials
involving pharmacologic
lipid-lowering therapy for elderly
patients are statin agents, because
they are effective and well tolerated
by such patients. They are also known
to be safe: In the major trials
conducted so far, including those
discussed below, no significant
adverse events were observed among
patient groups of any age after five
years of therapy, and other studies
have reported similar findings.
Efficacy and cost-effectiveness.
Statins have been shown to be
effective in lowering LDL and total
cholesterol levels in elderly
patients. In one study of 142
subjects 64 to 90 years old, Santinga
and colleagues found that 16 weeks of
pravastatin therapy lowered LDL and
total cholesterol levels 31% and 22%,
respectively (American Journal of
Medicine, vol. 96, p. 509, 1994). In
the Scandinavian Simvastatin Survival
Study (4S), simvastatin therapy
lowered LDL and total cholesterol
levels by 36% and 26%, respectively,
in 1021 subjects older than 65
(Lancet, vol. 344, p. 1383, 1994).
The lipid-lowering role of niacin,
fibric acid derivatives, and bile
acid sequestrants is less clear in
the elderly population, since these
agents have not been studied as
extensively in older populations.
Statin therapy has also proved
to be a cost-effective method of
preventing the occurrence of a second
CHD-related cardiac event in elderly
patients. For the monthly cost of
statin therapy with various agents,
see table below. As expressed in cost
per year of life gained, values range
from $3800 to $13,300 for patients
aged 70, which are within the range
of acceptable therapeutic costs in
the United States, according to
Johannesson and colleagues (New
England Journal of Medicine, vol.
336, p. 332, 1997). In preventing a
first CHD-related coronary event, the
cost-effectiveness of statin therapy
depends on the patient's overall risk
for CHD; costs range from $35,166 per
year gained for 70-year-old men at
high risk to $75,725 for women of the
same age at low risk. The optimal CHD
risk profile for cost-effective
prevention of a first cardiac event
in the elderly has yet to be
determined.
Preventing a first cardiac event.
The practice of administering
antihyperlipidemia therapy to elderly
patients to prevent a first
CHD-related cardiac event is not
supported as well as that for
preventing a second event. To date no
large trials focusing on this
population have shown elderly
patients to derive clear benefit from
the treatment. However, the results
of two large studies that have
included older patients do show
clearly that cholesterol-lowering
agents can reduce the risk for
coronary events and death.
In the first of those two
trials, the West of Scotland Coronary
Prevention Study (WOSCOPS),
researchers enrolled 6595 men aged 45
to 64 years who had hyperlipidemia
and no history of MI and randomly
assigned them to receive 40 mg of
pravastatin or placebo. After an
average follow-up period of 4.9
years, patients who received
pravastatin had a lower serum
cholesterol level and their risk for
nonfatal MI and definite coronary
events was reduced by 31% (New
England Journal of Medicine, vol.
333, p. 1301, 1995). In addition,
fewer patients in that group required
coronary procedures, including
coronary angiography and coronary
revascularization procedures, and a
nonsignificant decrease in all-cause
mortality was also noted. In
comparing patients older than 55
years old with younger patients, the
investigators observed that the
relative risk reduction attributable
to pravastatin therapy was similar in
the two groups. In addition, none of
the patients who received pravastatin
reported significant adverse events.
The second major trial, the Air
Force/Texas Coronary Atherosclerosis
Prevention Study (AFCAPS/TexCAPS),
compared lovastatin therapy with
placebo among 6605 men and women who
did not have CHD and were aged 45 to
73 years, 21% of whom were older than
65 years. After an average follow-up
period of 5.2 years, the combined
number of fatal and nonfatal MIs,
episodes of unstable angina, and
sudden cardiac deaths among patients
receiving lovastatin was reduced by
37%, a finding that led the
investigators to stop the trial early
(JAMA, vol. 279, 1615, 1998). In
addition, a subgroup analysis showed
that men and women older than the
median ages of 57 and 62,
respectively, all benefited from
lovastatin therapy. All subjects,
regardless of age, tolerated the drug
well.
Preventing a second event.
The benefits of pharmacologic
antihyperlipidemia therapy for
preventing a second cardiac event in
elderly patients are well supported
in the literature. Three large trials
have been conducted, all employing
statin therapy, and the results
indicate the effectiveness of
cholesterol-lowering therapy and a
reduced incidence of related cardiac
events and death. The 4S trial
enrolled subjects who had documented
CHD (a history of MI or angina
pectoris) and hypercholesterolemia
and randomly assigned them to receive
20 mg of simvastatin or placebo. For
patients whose cholesterol
concentration was not reduced
sufficiently by this dose, 40 mg was
given.
After an average follow-up
period of 5.4 years, the risk of
death from all causes in patients
older than 65 who received
simvastatin was reduced by 34%. The
risk of death from CHD was reduced by
43%, as was the incidence of major
coronary events and nonfatal MI.
These findings were similar to or
better than those observed among
patients younger than 65. After the
study was extended two years (making
it the longest clinical trial of its
kind to date), the benefit of a much
lower mortality rate was still
observed among patients who continued
their simvastatin therapy. Among
patients older than 65, the risk of
death from CHD or all causes was
still 28% lower.
Two studies have investigated
the effects of pravastatin on cardiac
outcomes among patients who had
hyperlipidemia and a history of CHD.
In the Cholesterol and Recurrent
Events Trial (CARE), 4159 patients
who had a history of MI and moderate
hypercholesterolemia (mean LDL, 139
mg/dl) were assigned to receive 40 mg
of pravastatin a day or placebo.
After a five-year period, the
incidence of fatal coronary events or
nonfatal MI was 24% lower among the
patients taking pravastatin, who were
also significantly less likely to
require cardiac procedures (New
England Journal of Medicine, vol.
335, p. 1001, 1996). These benefits
were similar among patients younger
and older than 60 years. In addition,
the incidence of stroke among the
treatment group was reduced 31%.
In the second study, the
Long-Term Intervention with
Pravastatin in Ischaemic Disease
(LIPID) trial, researchers randomly
assigned 9014 patients, of whom 39%
were older than 65, to receive 40 mg
of pravastatin a day or placebo.
After a mean duration of 6.1 years,
the study was stopped early when the
mortality rate for each group
differed. Among patients of all ages
in the treatment group, the relative
risk of death from CHD was reduced by
24%, and overall mortality was
reduced by 22% as well. Also observed
were significant reductions in the
incidence of stroke, MI, coronary
artery bypass surgery and
angioplasty, and hospitalization for
unstable angina.
Ample evidence shows that
lipid-lowering therapy decreases the
rate of disability and death from CHD
in older adults. This benefit is less
clear for elderly patients who do not
have established CHD, but because the
disease is strongly linked to
hyperlipidemia, these patients should
still undergo therapy and lifestyle
changes to prevent a first cardiac
event. In fact, in view of the
evidence, the NCEP/ATP-III panel
believes that statin therapy should
no longer be withheld from patients
simply because they are too old. The
panel recommends lipid-lowering
therapy not only for patients who
must control their risk profile but
also for men older than 65 and women
older than 75 who are likely to enjoy
a prolonged and healthy life. No age
limit applies to this recommendation.
Elderly patients who have multiple
medical problems or a poor prognosis
would probably benefit more from
attention to their functional status
than from prevention therapy. They
would not be good candidates for
lipid-lowering treatment.
INSTRUCTING AND MONITORING
PATIENTS WITH TYPE 1 DIABETES
The NECP/ATP-III guidelines for
determining risk profiles and
administering antihyperlipidemia
therapy apply to all patients,
including elderly ones (see tables
below). Older adults whose functional
status would benefit from preventive
antihyperlipidemia therapy should
undergo a screening evaluation based
on a fasting lipid panel or at least
serum total cholesterol and HDL
determinations. The first step for
all patients with hyperlipidemia is
what the NECP/ATP-III refers to as
therapeutic lifestyle changes (TLC),
which include a diet low in saturated
fat, weight reduction, and exercise.
Exercise.
The NCEP/ATP-III guidelines recommend
an aerobic exercise regimen for all
patients who have elevated
cholesterol levels and are physically
able to follow an individually
tailored program. Not only will
aerobic exercise lower a patient's
cholesterol levels but it will also
benefit his or her overall health.
Follow-up visits should be scheduled
every six weeks to monitor the
therapy's effectiveness.
Diet.
A weight reduction program is
recommended for obese patients, as is
a diet low in saturated fats for
patients who have hyperlipidemia. The
TLC dietary guidelines recommend that
less than 7% of total fat in the diet
should be saturated fat, which
equates to less than 200 mg a day. As
with the exercise program, patients'
progress should be monitored every
six weeks.
Pharmacologic therapy.
According to the NCEP/ATP-III
guidelines, the LDL cholesterol level
should be used to define a patient's
risk for CHD and determine the
appropriate therapy. Pharmacologic
therapy should be initiated when
exercise and dietary therapy fail. A
statin drug should be tried first,
since these agents have an excellent
safety and tolerability profile, but
if a patient's triglyceride level is
above 200 mg/dl or HDL level is less
than 40 mg/dl, niacin or a fibrate
might be a more appropriate first
choice.
A fasting lipid panel test and
liver-associated enzyme level
assessment should be performed before
patients begin treatment and at six
weeks afterward, at which time
medication doses can be adjusted.
Lipid and liver-associated enzyme
levels should then be monitored every
four to six weeks until a stable dose
is achieved, then biannually
thereafter. Less frequent monitoring
may be necessary, depending on the
specific statin agent used;
physicians should follow the
manufacturer recommendations.
SUGGESTED
READING
Blair SN, et
al.: Changes in physical fitness and
all-cause mortality. A prospective
study of healthy and unhealthy men.
JAMA 273:1093, 1995.
Carlsson CM, et
al.: Managing dyslipidemia in older
adults. J Am Geriatr Soc 47:1458,
1999.
Expert Panel on
Detection, Evaluation, and Treatment
of High Blood Cholesterol in Adults:
Summary of the Second Report of the
National Cholesterol Education
Program (NCEP) Expert Panel on
Detection, Evaluation, and Treatment
of High Blood Cholesterol in Adults
(Adult Treatment Panel II). JAMA
269:3015, 1993.
Hamilton VH, et
al.: The cost effectiveness of
HMG-CoA reductase inhibitors to
prevent coronary heart disease:
Estimating the benefits of increasing
HDL-C. JAMA 273:1032, 1995.
The Long Term
Intervention with Pravastatin in
Ischaemic Disease (LIPID) Study
Group: Prevention of cardiovascular
events and death with pravastatin in
patients with coronary heart disease
and a broad range of initial
cholesterol levels. N Engl J Med
339:1349, 1998.
Miettinen TA, et
al.: Cholesterol-lowering therapy in
women and elderly patients with
myocardial infarction or anginal
pectoris. Findings from the
Scandinavian Simvastatin Survival
Study (4S). Circulation 96:4211,
1997.
Ornish DM, et
al.: Can lifestyle changes reverse
coronary atherosclerosis? The
Lifestyle Heart Trial. Lancet
336:129, 1990.
Pedersen TR, et
al.: Follow-up study of patients
randomized in the Scandinavian
Simvastatin Survival Study (4S) of
cholesterol lowering. Am J Cardiol
86:257, 2000.
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