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You Want Statins With That? |
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It’s summertime and the eating is easy. As you throw more
red meat on the grill, you know that little pill will keep
your cholesterol down. But could it also stop Alzheimer’s?
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July 14 issue — Jim
Moviel never met an egg roll he didn’t like. His list of
favorite foods also includes garlic chicken wings smothered in
blue-cheese dressing, and mashed potatoes made with real butter
and whole milk.
INDEED, THE 45-YEAR-OLD computer-services manager from
Chicago is drawn to saturated fat like a 6-foot-1, 260-pound
moth to a flame. So it wasn’t exactly a surprise when Moviel
found out a few years ago that he had a total cholesterol level
of 290, a full 50 points beyond the American Heart Association’s
threshold for high risk. For six months, Moviel tried to lower
his cholesterol through diet and exercise alone. But even though
Moviel says he “did everything the right way,” his level dropped
just 27 points, to 263. Lifestyle changes just didn’t get the
job done, which is true for a lot of people with high
cholesterol.
“I needed more than exercise and a boneless, skinless
chicken breast,” he says. His doctor prescribed Lipitor, one of
the class of powerful cholesterol-lowering drugs known as
statins. Within three months Moviel’s cholesterol was 180. Last
month it was just 140. Though Moviel has become an avid cyclist,
he continues to indulge his weakness for heart-stopping entrees
and was recently diagnosed with type 2 diabetes. He knows he
should try harder to eat right (his goal is to lose 30 pounds
this year), but he also knows he doesn’t have to worry about
cholesterol as long as he takes that little pill every day.
“It’s ‘better living through chemistry’,” he says. Or, perhaps
more to the point, longer living.
TARGETING LDL
Welcome to the age of statins. If you
aren’t taking a cholesterol-lowering drug yourself, chances are
you know someone who is. And it’s not necessarily an overweight,
out-of-shape sports fan in his 50s who ventures off the couch
only in search of chips and beer. An estimated 12 million to 15
million American adults of every age and description—from Gen-Xers
to their octogenarian grandparents—depend on America’s most
popular prescription drugs to scour their bloodstreams of LDL
cholesterol, the waxy goo that can block arteries and cause
heart attacks and strokes. And, according to federal health
guidelines, 21 million more Americans should be taking
statins to help ward off cardiovascular disease. Statins have
become so critical in the war against cholesterol that a leading
statin researcher compares them to the ultimate miracle med.
Says Dr. Rory Collins of Oxford University: “Statins are the new
aspirin.”
His bold words could be an understatement. Promising new
research is underway to investigate statins as a treatment for a
number of other disorders, including Alzheimer’s disease,
multiple sclerosis, osteoporosis and even cancer. “I’m very,
very hopeful,” says Alzheimer’s researcher Dr. Larry Sparks of
Sun Health Research Institute in Sun City, Ariz., who is nearing
the end of a yearlong clinical trial of statins.
High cholesterol was first recognized as a major risk
factor for heart disease—more than 40 years ago, but no one
really started worrying about it until the 1980s, when tests for
it became common. The concern took on a new urgency in May 2001,
when the National Institutes of Health (NIH) issued aggressive
new cholesterol guidelines that nearly tripled overnight the
number of people in the United States who should be using
statins, from 13 million to 36 million. According to an
independent analysis of the NIH guidelines, the number of people
under 45 who ought to be on cholesterol-lowering drugs jumped
201 percent, to 12 million, while the pool of drug candidates 65
and older increased 131 percent, to 10 million. Then, six months
after the NIH bombshell, Collins and his team released the
world’s largest randomized study of statins (they followed
20,000 patients for up to eight years), which showed that
cholesterol-lowering drugs reduced the risk of heart attack and
stroke by at least one quarter for those at highest risk.
BILLIONS AND BILLIONS
That was supersize news in the land of the double
bacon-cheeseburger, and statin sales jumped a whopping 32.5
percent in the two years ending March 2003. Of course, the
billions of dollars the drugmakers spent marketing and
advertising statins ($1.4 billion in 2002) certainly helped.
Last year alone, sales reached $12.5 billion as doctors wrote
more than 118 million statin prescriptions, according to IMS
Health.
Critics of drug therapy say the NIH guidelines and
Collins’s study are flawed by an implicit assumption that people
can’t or won’t change their behavior. They say statins can
reinforce bad habits and actually serve as a disincentive to get
up and move. “Most people can accomplish comparable reductions
in LDL [the bad cholesterol] by diet and lifestyle alone, if the
changes are comprehensive enough,” says Dr. Dean Ornish, head of
the Preventive Medicine Research Institute in Sausalito, Calif.
In a 1998 study, Ornish reported a 40 percent reduction in LDL
after one year among a group of patients with heart disease who
followed a rigorous program, including 30 minutes of moderate
exercise daily, and a low-fat, vegetarian diet. (Statins have
been shown to reduce LDL by 25 to 60 percent.) Ornish also notes
that taking pills isn’t necessarily easy, citing one study that
found 65 percent of statin users stopped taking their medicines
after a year. Dr. Donald Fedder of the University of
Maryland-Baltimore, who wrote an analysis of the new NIH
guidelines in which he expressed some concern about
overprescribing statins, says physicians need to present their
patients with all the options. “You’ve got to give the
intelligent patient a [chance],” says Fedder. “I wouldn’t want
to be on the Ornish diet because I’m a carnivore. But if you
follow his diet you will not have to take any pills.”
DIFFICULT CHANGES
While
the doctors in the front lines of the war against heart disease
agree that lifestyle changes should be the cornerstone of
cholesterol-lowering therapy, they also say their
fast-food-loving patients simply aren’t up to the task. “There
is a great deal of truth in what Ornish is doing,” says Dr.
Sidney Smith, professor of medicine at the University of North
Carolina-Chapel Hill and former president of the American Heart
Association. “The problem is that the changes needed are
frequently very difficult. For some it’s an inability to break
habits, but for many the reality is it’s just not palatable.”
That’s certainly true for statin user and self-styled
gourmand Paul Braverman. “As a weak man without willpower or
self-motivation, it’s a lot easier for me to take the pill than
to eat the damn veggie burger, which I’m not particularly keen
on,” says Braverman. When the 40-year-old New Yorker had his
cholesterol checked for the first time in October 2001, it was
293. The doctor told Braverman, a reporter for The American
Lawyer, that he didn’t think he’d ever get his cholesterol down
without a statin, and immediately put him on 10mg of Lipitor
daily. Braverman did not resist. “We’re in the 21st century,
right?” he says. “Medical science should have progressed to the
point where there’s a pill for everything.” By April 2002,
Braverman’s total cholesterol was down to 209—much better, but
not ideal. His doctor increased his dosage to 20mg. Braverman, 5
feet 7, 180 pounds, hasn’t had his cholesterol checked since,
but he’s not worried. He exercises regularly, but he also likes
to cook, and he hasn’t changed his diet at all. “There’s nothing
I’d rather do than go to a fancy French restaurant and have a
big, blowout dinner,” he says.
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How Statins Work
Statins lower cholesterol in two ways. First, they block
an enzyme that the body needs for cholesterol production.
Second, they boost the liver's ability to remove LDL from
blood.
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Liver Function:
The liver has receptors on its surface that grab harmful
cholesterol (LDL) and clear it from the bloodstream.
This helps keep blood LDL at safe, healthy levels.
Impaired Function: The receptors can malfunction,
losing their ability to clear LDL from the blood.
Cholesterol can then build up, damaging arteries and
leading to heart disease.
Statins in action: Statins work by increasing LDL-receptor
production in the liver. The extra receptors help remove
excess blood cholesterol, bringing it down to safer
levels.
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The rising popularity of statins, first introduced in
1987, has been accompanied by twin epidemics of obesity, which
jumped a mind-boggling 61 percent in the 1990s, and diabetes,
which climbed 49 percent over the same period. Both conditions
are preventable, and their rise is due in large part to what
might be called couch-potato syndrome. Although experts
recommend at least 30 minutes of exercise daily, fewer than half
of U.S. adults (more than 60 percent of whom are overweight or
obese) get any regular exercise at all.
A ONE-TWO PUNCH
While statins help control high cholesterol, that’s just
one of the many risk factors for heart attack. Others—including
high blood pressure, smoking and obesity—are not affected by
statins. “So you have an enormously greater benefit if you fix
the obesity, if you exercise, if you eat the low-saturated-fat
and low-cholesterol diet” in addition to using the drugs,
Cleeman says. “It’s a one-two punch: lifestyle and drugs.”
Indeed, the same revised NIH guidelines that increased the
number of potential statin users to 36 million also recommended
diet changes for 65 million Americans.
Though it has developed a rather ugly reputation,
cholesterol is essential for the formation of cell membranes and
hormones. Our bodies make all the cholesterol we need; it’s
synthesized in the liver. The problem is, the food we eat,
especially the saturated fat in it, can elevate LDL. There is
also a genetic condition in which the body makes too much LDL.
An excess of LDL cholesterol can accumulate in arteries that
feed the heart and brain and lead to a heart attack. HDL
cholesterol, the “good” kind, takes away excess cholesterol.
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Should You Be on Statins? The Guidelines
Diet and exercise can reduce cholesterol, but your doctor
may find that you need drugs, too. The decision is based
on your family medical history, your own health history
and your risk factors.
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Statins work by inhibiting an enzyme (HMG-CoA
reductase, a name only a scientist could love) in the liver,
thereby blocking production of cholesterol. This triggers a
vacuuming effect in which the liver sucks up the LDL cholesterol
in the bloodstream. Re—cent studies have found that statins also
reduce the level of C-reactive protein (CRP), a marker for
inflammation of blood vessels. Elevated levels of CRP have been
associated with increased risk of heart attack. In addition, a
new drug, Zetia, from Merck/Schering-Plough, inhibits the
absorption of cholesterol in the intestine; it’s used alone and
in combination with statins to lower cholesterol. Statins do
carry risks. The two main complications are liver problems,
which occur in about 1 percent of patients, and myopathy, a
painful muscle condition, which affects about one patient in a
thousand. (Quitting the drugs stops both side effects.)
Popular as statins are, it
could be that we ain’t seen nothin’ yet if they turn out to be
effective against Alzheimer’s disease, multiple sclerosis and
other disorders. Researchers are cautious, to say the least. “We
tell people not to take drugs for things that aren’t proven,”
says Dr. Robert Green, associate professor of neurology at
Boston University School of Medicine. But some of the early
results are intriguing. Green authored a study that showed a 39
percent reduction in Alzheimer’s risk in people who had been
taking statins at least six months.
DEFENDING YOUR BRAIN
Though not everyone agrees on the underlying causes of
Alzheimer’s, many believe that a protein called beta amyloid, or
A-beta, plays an important role. A-beta can form a plaque that
is always found in the brains of Alzheimer’s patients. Sparks
thinks that elevated cholesterol may “augment the production” of
A-beta plaque in the brain. “It may not be the only thing that
induces it,” he says, “but it certainly helps it along. And if I
can get rid of this agent that’s helping production of this
toxin, maybe I can slow down the disease.” Sparks is about to
complete a clinical trial involving 65 mild to moderate
Alzheimer’s patients. The patients on statins received 80mg of
Lipitor daily. (The research was funded in part by Pfizer,
Lipitor’s maker.)
The possibility that high cholesterol contributes to
Alzheimer’s disease is particularly frightening, considering the
fact that 42 million Americans have total cholesterol levels
over 240. “We’ve heard a lot about obesity and the coming
epidemic in diabetes,” says Harvard neurologist Rudy Tanzi, who
thinks other experimental cholesterol drugs may fight
Alzheimer’s better than statins. “I worry about the coming
epidemic of Alz-heimer’s, based on the clear molecular link of
cholesterol and A-beta production.”
Statins are also gettinga serious look as a possible
treatment for multiple sclerosis, which afflicts about 400,000
people in the United States. MS is an autoimmune disorder that
destroys myelin, the fatty sheath around nerve cells. This fall,
Dr. Scott Zamvil, a neurologist at the University of California,
San Francisco, will launch the first placebo-controlled clinical
study of MS patients taking statins. Because the object of the
study is to test the effectiveness of statins in suppressing the
development of the disease, the 152 subjects will be people who
have only had their very first attack of MS. The research is an
extension of work Zamvil and colleagues did on mice. That study,
published last fall in Nature, showed that statins reversed
paralysis in mice with MS and prevented relapse of the disease.
While it’s not known exactly how statins work against MS, Zamvil,
who has received a competitive research grant from Pfizer, says
the drugs prompt the cells that attack the nervous system in MS
to instead secrete molecules that protect it.
Statins also show potential for protecting against
aortic-valve disease, a hardening of the valve between the heart
and the aorta, and osteoporosis, the age-related deterioration
of bone that leads to fractures. And a Dutch study released last
month found that people who had been using statins for four
years or more had a 20 percent reduction in their cancer risk,
especially prostate and liver cancer. There are a few caveats,
however. It was only an association study based on analysis of
existing data, not a placebo-controlled clinical study, the gold
standard of medical research. And there have been other statin-cancer
studies with neutral or negative findings.
It will be years before we know whether statins will
work against these other conditions. But there’s little mystery
about their effectiveness in preventing heart disease. We may be
lazy and we may be fat and we may feel guilty about taking the
darn things. But we’re better off with them than without them.
With Anne Underwood, Joan Raymond, Arthur
Kimball-Stanley and Peter Bailey
© 2003 Newsweek, Inc. |
