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Intensification of Statin Therapy Results in a Rapid Reduction in Atherosclerotic Inflammation: Results of a Multi-Center FDG-PET/CT Feasibility Study
Study Questions:
Does high-dose statin treatment result in greater reductions in plaque inflammation than low-dose statins, as measured by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)?
Methods:
Adults with risk factors (diabetes or central obesity) or with established atherosclerosis (coronary, carotid, cerebral, and peripheral), who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, and 4 and 12 weeks after randomization, and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment.
Results:
There was no difference between groups for the following: mean age was 60 years, 76% were male, 37% had diabetes, 41% clinical coronary artery disease, 59% were on low-dose prestudy statins, and mean low-density lipoprotein cholesterol was 106 and high-density lipoprotein cholesterol was 46 mg/dl. Sixty-seven subjects completed the study. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction [95% CI]: 14.42% [8.7%, 19.8%]; p < 0.001), but not atorvastatin 10 mg (% reduction [95% CI]: 4.2% [-2.3%, 10.4%]; p > 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% [2.2%, 18.3%]; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p < 0.05) and 80 mg (12.5% reduction, p < 0.001). Changes in TBR did not correlate with lipid profile changes.
Conclusions:
Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis.
Perspective:
HMG-CoA reductase inhibitors (statins) reduce atherothrombotic events in coronary artery disease and persons at risk. The benefit is accompanied by substantial reductions in circulating markers of inflammation, and the benefit occurs early in the course of treatment. There appears to be a correlation of benefit with dose as well as on-treatment low-density lipoprotein cholesterol and high-sensitivity C-reactive protein. The findings in this novel and elegant study help explain the clinical trial results, albeit not the mechanism, that occur in persons with relatively normal lipids.
Keywords: Obesity, Abdominal, Inflammation, Feasibility Studies, Coronary Artery Disease, Atherosclerosis, Plaque, Atherosclerotic, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Risk Factors, Heptanoic Acids, Multimodal Imaging, Pyrroles, Cholesterol, C-Reactive Protein, Diabetes Mellitus
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