MRI Offers Powerful Research Tool for Assessing Lipid-Lowering Therapy

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MRI scans might give researchers a powerful new tool for monitoring the effectiveness of lipid therapies for coronary or carotid artery disease, a new study shows.

Led by Dr. Xue-Qiao Zhao, of the University of Washington, Seattle, the researchers sought to determine if cholesterol-lowering drugs deplete plaque lipid content. Zhao told the Hub by e-mail that they used MRI as a tool to make direct assessment of the plaque tissue composition during treatment. The study appears in the October issue of the Journal of the American College of Cardiology: Cardiovascular Imaging.

The CPC Study (Carotid Plaque Composition by MRI During Lipid-Lowering), co-authored by Loyola University Health System cardiologist Dr. Binh An P. Phan, was a randomized, double blind, and partial placebo-controlled study.

The three-fold objective was to test two hypotheses regarding the effects of lowering LDL cholesterol and raising HDL cholesterol with medications. Specifically the research team wanted to know if intensive lipid therapy would deplete plaque lipid content. In addition, they also wanted to know how two strategies for lowering LDL cholesterol and raising HDL cholesterol compared in terms of plaque depletion.

"In the future, MRI scans may become important and powerful tools to see how medication therapy is working inside arteries," Phan said. "However, our study is just the first step. Additional studies will be needed."

In the study, conducted at the University of Washington where Phan was completing a cardiovascular clinical and research fellowship, 123 patients were randomly assigned to receive one of three cholesterol treatments:

After three years of intensive lipid therapy, the 33 patients with measurable carotid plaques had a significant reduction in the cholesterol within the plaque. The volume of cholesterol dropped from an average of 60.4 cubic millimeters to 37.4 cubic millimeters, and the percentage of plaque volume consisting of cholesterol dropped from 14.2 percent to 7.4 percent.

Among the 123 subjects enrolled in the study, mean age was 55 years, mean body mass index was 30 kg/m2, 73 percent were male, 43 percent had a family history of premature cardiovascular disease, 37 percent had a previous myocardial infarction, 80 percent had clinically established coronary artery disease. In addition, 52 percent had hypertension and 12 percent had diabetes.

Over the three years of the study, MRI scans were done on patients' carotid arteries, rather than on their coronary arteries. The researchers noted that they used the carotid arteries because they are closer to the surface of the body and easier to image. They do not move as much as the coronary arteries of a beating heart.

All subjects were followed up monthly for the first 6 months and then bimonthly for the remaining 30 months of the 36-month protocol. A total of 21 visits per subject was conducted for this study. At these visits, subjects underwent questioning about side effects and symptomatic state as well as a targeted cardiovascular examination. The carotid MRI scans were obtained at baseline, and at one, two, and three years.

There were 33 subjects with measurable lipid-rich necrotic core (LRNC), or the buildup of lipid behind the plaque formation that could be measured by MRI at baseline who completed three-year follow-up scans with acceptable image quality for comparison. Six subjects were excluded because of poor image quality. Another 81 subjects had no measurable LRNC at baseline and were excluded from the analysis. Finally, three subjects with LRNC at baseline did not complete three-year follow-up scans and were excluded.

The researchers said that because there were only 33 patients in the final analysis, they were unable to make statistically significant comparisons of the differing effects of the treatment strategies. They will continue enrolling patients and they hope to investigate fully the differential treatment effect.

“These findings suggest a potential mechanism for plaque stabilization associated with intensive lipid therapy,” the authors concluded. “Furthermore, these results highlight the importance of selection of subjects with a LRNC in future trials examining the effect of therapy on plaque regression.”

By Michael O’Leary, contributing writer, Health Imaging Hub