NEW ORLEANS, Nov. 13 – For the first time in humans, researchers have used magnetic resonance imaging (MRI) to show that a cholesterol-lowering drug removes the fat build-up from atherosclerotic lesions, stabilizing the plaque that is most likely to cause a heart attack or a stroke. The work was presented today at the American Heart Association’s Scientific Sessions 2000.
“This is the first study which, by direct visualization, shows that cholesterol lowering by statin drugs reduces the amount of lipids deposited in artery walls,” say lead authors Roberto Corti, M.D., a research fellow, and Juan Jose Badimon, Ph.D., director, both of The Cardiovascular Biology Research Laboratory at The Cardiovascular Institute, Mount Sinai Hospital in New York.
Statin drugs, like the simvastatin that was used in this study, are very effective at lowering blood cholesterol. High cholesterol levels are associated with plaque buildup on artery walls and an increased risk of heart disease.
“The major implications of this report are that MRI may detect patients at risk for cardiovascular disease, help identify the most appropriate treatment for individual patients and, most importantly, monitor the effectiveness of treatment,” says Corti.
In large clinical trials, statins have been associated with 30 percent to 35 percent reductions in heart attacks, unstable angina and strokes. However, their mode of action has been unclear. One hypothesis is that statins may reduce the fat content of plaques, making them more stable. Until now, this hypothesis could not be tested by conventional imaging techniques, such as angiography, which does not show the artery wall, notes Corti.
Refinements in MRI technology now allow visualization of the artery wall as well as the artery cavity. “The painless, non-invasive procedure could someday make imaging the arteries as easy and routine as getting a mammogram,” says co-author Valentin Fuster, M.D., Ph.D., who heads the Cardiovascular Institute at Mount Sinai School of Medicine and developed the technology with scientist Zahi Fayad, Ph.D., director of cardiovascular MRI research there.
The Mount Sinai group has identified important details about atherosclerotic plaque including finding that all plaques are not created equal: cholesterol-rich plaques are the most likely to rupture and cause heart attacks and strokes.
Plaque does not cause problems as long as it stays in the artery wall. When plaque ruptures, the body tries to repair the damage by forming blood clots, which can cause heart attacks or strokes by blocking the blood vessels, researchers say.
The plaque that is most likely to rupture, known as vulnerable plaque, has several common characteristics. Its core contains lipids and scavenger cells called macrophages that damage the vessel wall. It also has a large amount of the chemical that stimulates the formation of blood clots.
The researchers, who have enrolled 50 people so far in the ongoing study, reported on preliminary results based on the first patients who had been followed for 12 months. They recruited patients with total cholesterol between 200 and 240 milligrams/deciliter and atherosclerotic lesions. They were randomly assigned to receive daily simvastatin doses of either 20 or 80 milligrams.
The researchers imaged more than 600 segments of the subjects’ aortas and carotid arteries at baseline and after six and 12 months of treatment with simvastatin. Blood is pumped out of the heart and travels through the aorta and the carotid arteries to reach the brain. Plaques that rupture in those arteries cause strokes just as plaque ruptures in arteries feeding the heart cause heart attacks.
Even though significant reductions in the low-density lipoprotein cholesterol (LDL) and total cholesterol levels were observed six weeks after statin administration, it took 12 months for changes to appear in the artery wall.
“Although the diameter of the artery cavity did not change, the vessel wall area shrank by 8 to 10 percent, indicating that the plaque had regressed,” Corti reports. “These are not people with heart attacks and they do not have particularly high blood cholesterol,” he says. “They are the kind of people doctors see and have to make decisions about each day.”
Fuster says these findings might make it possible to someday detect blood vessel disease much earlier in the disease process, before a patient shows symptoms or signs of disease. “Patients who already have severe disease, have many of these plaques,” he says. “The problem is in patients who are developing disease and you don’t have any idea if these plaques are present. Before you have a heart attack or manifestations of disease it would be worthwhile to know what your arteries look like – just like using a chest X-ray or mammogram – for prevention.”
Collaborators include; Stephen Worthley, M.D.; Gerard Helft, M.D.; James Chesebro, M.D.; Jesse Weinberger, M.D.; and Donald Smith, M.D., with the assistance of Stella Palencia, R.N.
NR00-1207 (SS2000/Corti)