A technique utilizing ultra-small super-paramagnetic iron oxide (USPIO)-enhanced MRI can detect macrophage activity, a sign of inflammation, and allows clinicians to individualize their treatment for atherosclerosis and improve outcomes, according to a study presented this week at the 2008 American College of Cardiology (ACC) Scientific Sessions in Chicago.
Treatment options for people with diseased coronary or carotid arteries have traditionally been based on the degree of stenosis of the vessel. However, research has revealed that stenosis is but one piece of the atherosclerosis puzzle and that other factors, including inflammation, also play a role.
“The real star of this study is this new way of imaging, which allows you to zero in on what is actually going on in these arteries,” said Jonathan H. Gillard, MD, who presented the results of the study. “Once you know this, then you can individualize therapy accordingly.”
Gillard, an academic neuroradiologist at Cambridge University in England, said the investigation was conducted as a randomized double-blind study to determine the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on macrophage activity in carotid atherosclerotic plaques using serial USPIO-enhanced T2-weighted MRI.
According to the researchers, preliminary studies indicated that MRI can identify active macrophage infiltration in human carotid atheroma in vivo and hence may be a surrogate marker of inflammation, a risk factor for vulnerable plaque. Their hypothesis was that treatment with 80 mg of atorvastatin would demonstrate quantifiable changes in USPIO-enhanced MRI defined inflammation within the first three months of therapy.
A cohort of 47 patients with carotid stenosis greater than 40 percent on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomized in a balanced, double blind manner to either 10 mg or 80 mg atorvastatin daily for 12 weeks.
The researchers stated that baseline statin therapy was equivalent to 10 mg of atorvastatin or less. Their primary endpoint was a change from baseline in signal intensity on USPIO-enhanced MRI in carotid plaque at six and 12 weeks.
From the original cohort, 20 patients completed 12 weeks of treatment in each group. The team found a significant reduction from baseline in USPIO-defined inflammation in the 80-mg group at both six weeks and at 12 weeks; no difference was observed with the low-dose regime.
The scientists demonstrated that aggressive lipid-lowering therapy over a three-month period is associated with significant reduction in USPIO-defined inflammation. Gillard, noted that as validation continues, USPIO-enhanced MRI methodology may be a useful imaging biomarker for the assessment of therapeutic response to anti-inflammatory interventions in patients with carotid atherosclerotic lesions.
“This study tells us that if you randomize patients who have inflammation of the carotid artery to a high dose of atorvastatin, you substantially reduce the amount of inflammation and risk of stroke, whereas low dose atorvastatin does not reduce risk,” he stated. “And thanks to this imaging technique, we can now figure out which patients need the aggressive treatment before we begin our therapy. This novel use of MRI can allow us to give better targeted care to the individual patient. This is personalized medicine.”