Using modified magnetic resonance imaging (MRI) 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 Hopkins findings, to be 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 and cardiologist João Lima, M.D., associate professor of medicine and radiology at The Johns Hopkins University School of Medicine.
"Heart disease, especially atherosclerosis, is still the leading cause of death in the United States," added Lima. "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 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 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 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 different angles, 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," said Lima. "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," said Lima.
According to the latest statistics from the American Heart Association, in 2001, there were more than 72,100 deaths 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 Inc., 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, M.D.; Henning Steen, M.D.; William Warren, M.D.; Sandeep Gautam, M.D.; and Shenghan Lai, M.D., Ph.D.
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