Synthetic 'Good' Cholesterol Helps Clear Arteries
Small Study Indicates the Possibility That Drug Therapy Could Reverse
By Rob Stein
Washington Post Staff Writer
Wednesday, November 5, 2003.
A synthetic form of "good" cholesterol has been shown to quickly shrink
blockages clogging coronary arteries,
offering for the first time the possibility of a drug that could actually
rapidly reverse heart disease, researchers
In a small, preliminary study, the laboratory-made substance, which mimics
a type of cholesterol discovered in a
group of surprisingly healthy villagers in rural Italy, significantly
reduced in just six weeks the amount of plaque
narrowing the arteries of patients who had suffered heart attacks or had
Because the approach attacks the underlying source of many heart attacks,
the results could mark a milestone in
the search for new ways to treat the nation's No. 1 killer, researchers
"For the first time, we've shown that you can reverse coronary disease
with drug therapy in a matter of weeks,"
said Steven E. Nissen, a cardiologist at the Cleveland Clinic who
coordinated the nationwide study. "We really
have, for the first time, the opportunity to attack this disease at its
fundamental basis. It's a paradigm shift. It's
opening a new door."
While drugs that lower cholesterol and blood pressure can cut the risk of
developing heart disease, and aspirin
protects against heart attacks, one of the Holy Grails of modern medicine
has been to find a way to reverse the
deadly process once it has begun. The results of the new study suggest
that synthetic HDL may finally offer such a
Nissen and other researchers cautioned that the study involved only 47
patients, and further studies are needed to
confirm the findings, fully evaluate the drug's safety and determine
whether the treatment actually cuts the risk of
heart attacks and strokes.
"It's extremely preliminary," said Susan K. Bennett, clinical director of
the George Washington University Hospital
Women's Heart Program, speaking on behalf of the American Heart
Association. "But it is very intriguing."
Regardless of whether this particular drug eventually offers a practical,
effective treatment, other experts said the
study has opened up an entirely new way to approach treating
atherosclerosis, known commonly as hardening of
"This is the first true test of the concept that specifically targeting
HDL, the good cholesterol, can impact plaque
and atherosclerosis in humans," said Daniel J. Rader, director of
preventive cardiology at the University of
Pennsylvania, who wrote an editorial accompanying the study in today's
Journal of the American Medical
Scientists have long known that there are two forms of cholesterol: One is
low-density lipoprotein (LDL), which is the "bad" cholesterol because
it accumulates inside artery walls, causing the vessels to narrow and
setting the stage for heart attacks and strokes. The other is high-density
lipoprotein (HDL), called the good cholesterol because it protects against
heart disease, primarily by lowering LDL levels.
About 30 years ago, researchers discovered a group of about 40 people
living in the rural northern Italian town of Limone sul Garda who had a
surprisingly low rate of heart disease despite their extremely low HDL
levels. Scientists determined that their HDL was slightly unusual, raising
the possibility that it provided powerful protection against heart
Esperion Therapeutics Inc. of Ann Arbor, Mich., developed a genetically
engineered form of this version of HDL, dubbed ApoA-I Milano, and
showed that it reduced plaque inside the arteries of laboratory animals.
The company then asked Nissen to test it in people.
In the study, Nissen and colleagues at 10 centers around the country gave
weekly infusions of either the synthetic HDL or an inert placebo to
heart disease patients for five weeks. The plaques clogging the walls of
their arteries were carefully measured before and after the treatment
using an extremely precise ultrasound technique.
Compared with those who received the placebo, the patients who received
the synthetic HDL experienced about a 4 percent reduction in the
plaques lining their arteries, a reduction 10 times as great as anything
scientists had tried previously, the researchers found.
"When the statisticians delivered the data to me, I fell off my chair,"
Nissen said in a telephone interview. "We've run across something that can
literally clear out the plaque in just a few weeks. That's unprecedented."
Rader agreed. "I don't think anyone thought you could induce regression in
six weeks -- that's the single most surprising thing about this study,"
The only other thing that may reduce plaque inside arteries is long-term
use of anti-cholesterol drugs such as statins. Some research has also
suggested people who strictly adhere to the high-fiber, low-fat,
vegetarian Dean Ornish diet can also somewhat reverse their heart disease.
the amount of plaque reduction in those cases was just a fraction of what
patients taking the synthetic HDL experienced, and it took many
It remains unclear how this form of HDL works, but it may be especially
adept at transporting LDL out of the blood and back into the liver,
where it is harmlessly processed.
Rader noted that there could be nothing particularly special about the
synthetic HDL. It could be that it is the only one that has been tested
way because it is a form of HDL that can be patented. Other companies are
trying to develop different ways of using HDL to fight heart
disease, such as drugs that boost the body's own production of HDL.
In the meantime, Esperion plans to conduct a follow-up study that will
involve thousands of patients who would be followed for a year to
determine whether the treatment reduces the risk for heart attacks and the
need for angioplasties and bypass surgery to restore blood flow to
the heart muscle.
"This is a landmark study in our mind that validated the whole HDL
hypothesis -- that it is something that could change the way medicine is
practiced," said Roger Newton, Esperion's president and chief executive.
B) 2003 The Washington