Using modified magnetic resonance imaging techniques,
researchers at Johns Hopkins have been able to detect the
early benefits of a cholesterol-lowering medication much
sooner than before.
The researchers applied MRI to measure the success of
simvastatin (Zocor), a widely used form of so-called statin
therapy, in reducing plaque formation in patients with
hardened and clogged arteries, or atherosclerosis.
Reductions in plaque levels were detected within six months
after therapy began. Traditionally, MRI has been unable to
show results until one or two years after the onset of
treatment.
The Johns Hopkins findings, published in the journal
Circulation online Oct. 11, should make it easier
for physicians to monitor how well initial
cholesterol-lowering therapy works for patients, especially
those with advanced-stage cardiovascular disease in need of
quick results.
The research also linked the early benefits of statins
to their lipid-lowering actions, not to anti-inflammatory
properties as some earlier studies suggested.
"Our study increases the likelihood that MRI could
eventually be used as a predictive technology for
determining which patients should be placed on statin
therapy for atherosclerosis," said the study's lead author,
cardiologist Joao Lima, associate professor of
medicine and
radiology at the Johns Hopkins School of Medicine.
"Heart disease, especially atherosclerosis, is still
the leading cause of death in the United States," Lima
said. "While it has been proven that patients can benefit
from even a short period of statin therapy, as early as 16
weeks, our abilities to harness modern technology for
monitoring this condition — and tracking the
effectiveness of our treatments — have not kept pace
until now."
Cholesterol-lowering medications, which decrease
lipid/fat levels in the blood, have been shown to reduce
plaque formation by as much as 30 percent to 40 percent,
and death rates by as much as 30 percent. Increased plaque
formation is part of atherosclerosis and consists of the
buildup of fatty deposits — hardened by calcium
particles — along the inside walls of arteries,
making work more difficult for the body's blood vessels.
During the three-year study, the Johns Hopkins team
measured plaque levels in 29 patients on a
cholesterol-lowering therapy for significant
atherosclerosis. Using a standard MRI scanner, the
researchers took two measurements of plaque formation.
First, they measured calcium deposits at the start of
therapy, to establish a baseline reading of plaque volume.
Then, after six months, they took another reading to gauge
if statin therapy and reduced levels of blood lipids were
correlated to reduced plaque volume.
To improve upon standard imaging techniques, the Johns
Hopkins team amplified picture taking by placing a series
of extra coil rings around the chest of each patient (the
main electromagnetic coil ring gives MRI its distinct
doughnut shape). To amplify the signal, or image, received
by MRI, each patient swallowed an antenna, inserted through
the nose and placed in the esophagus, or "food pipe," next
to and directly in line with many of the main arteries,
including the biggest artery on top of the heart, the
aorta. Six different MRI images, each taken at a different
angle, were required to calculate plaque volume levels in
each artery.
After six months of therapy with simvastatin (20-80 mg
daily), plaque volume levels were significantly reduced by
9 percent, on average, from 3.3 cm3 to 2.9 cm3. The
researchers were unable to determine how these results
improved long-term survivability for patients. However, it
is already known that cholesterol-lowering therapies can
benefit patient outcomes as early as 16 weeks after therapy
starts.
"Like a permanent scar, calcium deposits in plaque are
a key indicator of how much atherosclerosis a patient has
at one point in time," Lima said. "Our results show the
benefits of statins much earlier than before, and how we
can use MRI to more closely monitor the progress of
patients under therapy, because we really want to shrink
those plaques and rapidly improve the condition of the
patient. Eventually, it may be possible to use MRI
measurements of plaque volume levels as a predictor to
selecting the best statin therapy for treating a patient
with atherosclerosis."
Study results also helped resolve a long-standing
dispute in cardiology about whether or not the early
benefits of statin therapy are due to their abilities to
lower blood lipid levels or if they were merely the
short-term effect of a statin's anti-inflammatory
properties. What the researchers found was that LDL
cholesterol levels, a key blood lipid indicator to lower in
treating heart disease, were lowest in patients with the
greatest amount of plaque reduction.
"The direct correlation was proof that, indeed, the
early benefits of statin therapy resulted from its
lipid-lowering properties," Lima said.
According to the latest statistics from the American
Heart Association, in 2001 more than 72,100 deaths were
directly related to atherosclerosis, and it causes many
more deaths from heart attack and stroke. Overall,
atherosclerosis accounts for nearly three-fourths of all
deaths from cardiovascular disease.
This study was funded by the Donald W. Reynolds Johns
Hopkins Cardiovascular Center and the National Institutes
of Health, with further assistance from Merck, the maker of
simvastatin. The research was part of two larger ongoing
clinical trials that compare the efficacy of low- and
high-dose statin therapies, and the effects of niacin on
plaque formation.
Other investigators in this research, conducted solely
at Johns Hopkins, were Milind Desai, Henning Steen, William
Warren, Sandeep Gautam and Shenghan Lai.