Some Physicians Question
the Benefits of
Raising 'Good' Cholesterol

By GINA KOLATA

Published: March 15, 2004

For years, doctors have been saying that to prevent heart
disease, patients should pay attention to both the
so-called bad cholesterol, or L.D.L., and the good
cholesterol, or H.D.L. The good, they said, can counteract
the bad.

But now, some scientists say, new and continuing studies
have called into question whether high levels of the good
cholesterol are always good and, when they are beneficial,
how much.

While some heart experts are not ready to change their
treatment advice, others have concluded that H.D.L. should
play at most a minor role in deciding whether to prescribe
cholesterol-lowering drugs. In the meantime, doctors are
calling researchers and asking what to do about patients
with high H.D.L. levels, or what to do when their own
H.D.L. levels are high, and patients are left with
conflicting advice.

"There is so much confusion about this that it is
unbelievable," said Dr. Steven Nissen, a cardiologist at
the Cleveland Clinic.

The good cholesterol hypothesis comes from studies like the
Framingham Heart Study, which has followed thousands of
people in Framingham, Mass., for decades to see who
developed heart disease. The studies showed that if two
people had the same levels of the bad cholesterol, L.D.L.,
but different levels of the good cholesterol, H.D.L., the
one with more H.D.L. was less likely to have heart disease.


Researchers examining the biochemistry of the two molecules
learned that they have opposite roles. Both transport
cholesterol, the fatty substance used to make cell
membranes and some hormones, but they carry it in opposite
directions.

L.D.L. ferries cholesterol to coronary arteries, where it
imbeds and participates in the growth of plaque. H.D.L.
takes cholesterol away from arteries to the liver, where it
is disposed of.

So with epidemiological studies showing reduced heart
disease risk and science showing why, it would seem the
picture was clear: the more H.D.L. the better. One H.D.L.
molecule might even cancel one of L.D.L.

Too simplistic, says Dr. Daniel Rader, a cholesterol
researcher at the University of Pennsylvania School of
Medicine. "Yes, high H.D.L. is generally a good thing, but
it doesn't mean it is so powerful that it creates a total
immunity to heart disease," he said.

Dr. Rader and others say, for example, that there are
people who have high levels of H.D.L., but the H.D.L. does
not function properly. Instead of being protected from
heart disease, these patients may be particularly
vulnerable. A simple H.D.L. measurement does not reveal
whether a person's high level is good or bad.

Cholesterol researchers say that every clinic has patients
with high levels of H.D.L. who ended up with heart disease.
The average H.D.L. level for men is 40 to 50 milligrams per
deciliter of blood and for women 50 to 60. But, even when
H.D.L. levels are much higher, "the L.D.L. can overpower
the H.D.L.," said Dr. Christie Ballantyne of Baylor College
of Medicine.

Many are like 60-year-old Thomas E. Siko of Chagrin Falls,
Ohio, who thought he had nothing to worry about. Heart
disease runs in his family on both sides, but no doctor had
ever suggested cholesterol-lowering medication. His H.D.L.
level was high, at 72, and his L.D.L. only mildly elevated,
at 121. (National guidelines say that an L.D.L. level of
less than 100 is optimal; 100 to 129 is near or above
optimal, depending on other factors; and above 130 is
high.)

But last year, after being tested for what he thought was
indigestion, Mr. Siko ended up having bypass surgery. Now,
with a cholesterol-lowering statin, his L.D.L. level is
down to 72 while his H.D.L. is 70. He feels fine. "I run
four miles a day," Mr. Siko said.

Part of the confusion arises from an evolving view of the
immense importance of reducing L.D.L. levels. Two recent
studies, one announced last week, the other published the
week before, found that ultra-low levels of L.D.L., down to
the 60's or 70's, can protect heart patients from plaque
growth in their arteries and from heart attacks and deaths.
That raised questions among many doctors and patients of
whether their own L.D.L. levels really were optimal and
whether their good cholesterol really was canceling out the
bad.

Dr. Rader is leading a large study on genetic variations
causing high H.D.L. that is trying to sort the question
out. But for now he says, "I really don't feel that
treatment for high L.D.L. should be withheld just because
the H.D.L. level is high."

Instead, Dr. Rader puts high H.D.L. levels to the side and
looks at L.D.L. and other risk factors, like a family
history of heart disease. If L.D.L. levels and other risk
factors tell him to treat, he prescribes L.D.L.-lowering
medication. If he is undecided, he brings the high H.D.L.
levels back into the picture, allowing them to push him
toward or away from treatment.

Dr. Bryan Brewer, chief of the molecular disease branch of
the National Heart, Lung and Blood Institute, said no one
should ignore high levels of L.D.L. "If you have a high
L.D.L. level you should be concerned about it,
independently of your H.D.L. You are still at risk," he
said.

Dr. Nissen says he focuses on L.D.L. so much that he mostly
discounts H.D.L. in deciding whether to give
cholesterol-lowering drugs to patients with heart disease
or to those with high L.D.L. levels and other risk factors
like high blood pressure or a family history of heart
disease. He notes that statins are safe drugs that reduce
L.D.L. levels and that study after study has shown that
lowering L.D.L. prevents heart attacks and deaths.

He says that recent research bears him out. His study,
published this month in the Journal of the American Medical
Association, looked directly at the accumulation of plaque
in coronary arteries when heart patients took
cholesterol-lowering drugs. Their H.D.L. levels, he said,
played no role in plaque growth; the only thing that
mattered was what happened to L.D.L. When L.D.L. levels
dropped, plaque growth slowed. That means, Dr. Nissen
concludes, that the benefit of lowering L.D.L. is the same
whether H.D.L. levels are high or low.

Others have different views on how to weigh H.D.L. in
treatment decisions. Many, like Dr. Alan Garber, a
professor of internal medicine at Stanford, look at overall
risk. The starting place, he says, is assessing how likely
it is that people will have heart attacks, given everything
known about their L.D.L. and H.D.L. levels, their blood
pressure, their family history and whether they smoke or
have diabetes.

Dr. Garber said that with data from recent studies, it
looked increasingly safe to treat high L.D.L. levels and
ignore other factors. But, he said, "that's not the way I
would do it." One concern is that people who are otherwise
at low risk for heart disease would gain little by taking
drugs to reduce their L.D.L. levels but would spend years
paying for the drugs, which can cost $100 a month.

Dr. David Waters, of the University of California at San
Francisco, also looks at overall risk, but lets a high
H.D.L. level counteract one of the other predisposing
factors to heart disease in deciding who needs to take
drugs to lower L.D.L. levels.

With different doctors using such different reasoning,
doctors and patients say they can be frustrated and
confused about what to do.

Dr. Christopher Cannon of Brigham and Women's Hospital in
Boston needed advice for his mother. Her H.D.L. was above
100, which is very high, but her L.D.L. was 160, also high.
Last year, he called Dr. Rader, who said that because Dr.
Cannon's mother's only risk factor for heart disease was
her L.D.L., he did not advise treatment.

But now, new studies, including one reported last week by
Dr. Cannon and his colleagues, are indicating that people
might do much better with much lower levels of L.D.L. He
looked over his own data and said it showed people with
high H.D.L. levels got the same benefit from driving their
L.D.L. very low as people whose H.D.L. was low or normal.
So, he says, he will be calling Dr. Rader again. "It's time
for a reassessment," he said.

http://www.nytimes.com/2004/03/15/health/15HEAR.html?ex=1080362506&ei=1&en=ebea62e171d18790

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