Here is an article I found interesting.
ACC 2009 [American College of Cardiology annual meeting 2009]: MRI Study Shows Plaque Lipid Core Depletion With Intensive Lipid-Lowering Therapy
as reported on Heartwire — a professional news service of WebMD
April 7, 2009 (Orlando, Florida) — Intensive statin therapy in patients with coronary or carotid artery disease significantly depleted the lipid content of atherosclerotic plaques, a new study has shown. Plaque depletion, as measured by MRI, occurred in the first two years of treatment, slowing down in year three.
“Overall, intensive statin therapy, either as monotherapy or with additional drugs, like niacin, does change the lipid content of the artery and results in improved plaque lipid composition,” said lead investigator Dr Xue-Qiao Zhao (University of Washington, Seattle). “The biological changes we observed are consistent with what we’ve been learning from histology studies, as well as well as from animal models.”
Speaking with heartwire, Zhao said that despite confirming by MRI the hypothesis that treatment results in positive changes in plaque composition, MRI in this setting is still used primarily as a research tool and that further studies, which her group is performing, are needed.
“We need to see if the plaque changes measured by MR are clinical meaningful,” she said. “Otherwise, a clinician will be looking at changes in lipid content of plaque without knowing what it means. Does it mean the patient is going to be stable for the next five years, or does it have no correlation to events at all? This part of the puzzle is still missing, and until we have that information, I don’t think MRI can be utilized reliably in the clinical setting. The evidence just isn’t there yet.”
The results of the study, known as the Carotid Plaque Composition Study, were presented here last week during the i2 Summit at the American College of Cardiology 2009 Scientific Sessions.
The Lipid-Rich Necrotic Core
In an interview with heartwire, Zhao said that the observed reduction in cardiovascular events with lipid-lowering therapy is hypothesized to occur as a result of depletion of cholesterol esters from a vulnerable subgroup of lipid-, foam-, and macrophage-rich lesions. In these high-risk lesions, based on pathology studies, as well as animal models, improved mechanical strength (such as a strengthened fibrous cap), reduced inflammatory activity, and stabilized endothelial function are thought to be some of the positive changes that result from the depletion of these cholesterol esters.
“If you deplete the lipid content and increase the fibrous tissue, it makes sense that the plaque is going to be more stable,” said Zhao.
Recent advances in MRI have made it possible to identify lipid plaque composition and to measure changes in the lipid core that result from lipid-modifying therapies. With that in mind, the group performed, to their knowledge, one of the first in vivo studies of plaque composition in patients treated with intensive lipid-lowering therapy.
In this double-blind, partially placebo-controlled study, the researchers randomized 123 patients with coronary or carotid artery disease and elevated apolipoprotein B (apoB) levels–baseline LDL-cholesterol levels ranged from 100 to 190 mg/dL–to three treatment arms: atorvastatin 10 to 80 mg; atorvastatin and extended-release niacin 2 g; or atorvastatin, extended-release niacin, and colesevelam, a bile-acid-binding agent.
After one year, LDL-cholesterol and apoB levels were reduced approximately 50%. Triglyceride reductions ranged from 25% to 42% across the three treatment arms, while increases in HDL-cholesterol levels ranged from 12% to 29%. All subjects underwent high-resolution, multicontrast bilateral carotid MRI scans at baseline and annually for three years.
In terms of the primary end point, the change in the volume of the lipid-rich necrotic core (LRNC) in 33 patients with identifiable LRNC at baseline, treatment with the lipid-modifying therapies significantly reduced the lipid content of the carotid plaques. The depletion in lipid content was observed in different LRNC measurements, including the total volume of lipid content and lipid content expressed as a percentage of total wall volume, and occurred primarily in the first two years. The investigators did not measure the changes in lipid plaque content in the different treatment strategies but plan to perform that analysis when more patients complete the study.
Research Tool vs Clinical Utility
Commenting on the results of the study for heartwire, Dr Mario Garcia (Mount Sinai Medical School, New York) agreed with Zhao, noting that while MRI is primarily used as a research tool, it is occasionally used in patients to determine whether they have risk for coronary disease or should start medical therapy. Because of cost and the availability of other imaging modalities that have prognostic data, including coronary artery calcium score screening or carotid intima-media thickness (IMT), it is not used frequently in that setting, however. The main advantage with MRI over these other scans is the ability to characterize plaque composition.
“It is an ideal tool to determine in the short term if treatment is making a difference in a patient,” said Garcia.
He noted there is an ongoing debate about whether clinicians should be looking for vulnerable, high-risk plaques, as MRI scans can identify, or looking for vulnerable patients. “The reason is quite often that we see plaques that we think are vulnerable, but events end up occurring in different locations,” said Garcia. “We don’t really have evidence, even with invasive studies in the cath lab, that these so-called vulnerable plaques are the ones that are going to be rupturing in the near future. And then, we don’t know how to treat them. We treat the patient, and not the plaque.”
Zhao receives grant support from Pfizer, Abbott, Merck, Daiichi-Sankyo, Hoffman-La Roche, and KAWA Research. She is on the speaker’s bureau for Abbott. Garcia reports consulting fees or honoraria from BG Medicine, AstraZeneca, and Philips Medical Systems.
The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.