Scientists Begin to Question Benefit of 'Good' Cholesterol

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March 15, 2004

 

Scientists Begin to Question Benefit of 'Good' Cholesterol

 

NY TIMES

By GINA KOLATA

 

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.

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