on January 26, 2009
Published online before print January 26, 2009, doi: 10.1161/CIRCIMAGING.108.811752
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Original Article |
The Relationships Between Regional Arterial Inflammation, Calcification, Risk Factors and Biomarkers – A Prospective FDG PET/CT Imaging Study
Mount Sinai School of Medicine, New York, New York
1 E-mail: jhfr2{at}cam.ac.uk
Background—Fluorodeoxyglucose positron emission tomography (FDG PET) imaging of atherosclerosis has been used to quantify plaque inflammation and to measure the effect of plaque stabilizing drugs. Here we explore how atherosclerotic plaque inflammation varies across arterial territories and how it relates to arterial calcification. We also test the hypotheses that the degree of local arterial inflammation measured by PET is correlated with the extent of systemic inflammation and presence of risk factors for vascular disease.
Methods and Results—Forty-one subjects underwent vascular PET/CT imaging with FDG. All had either vascular disease or multiple risk factors for it. Forty subjects underwent carotid imaging, twenty-seven underwent aortic, twenty-four iliac and thirteen femoral imaging. Thirty-three subjects had a panel of biomarkers analyzed. We found strong associations between FDG uptake in neighboring arteries (left vs. right carotid r=0.91, p<0.001, ascending aorta vs. aortic arch r=0.88, p<0.001). Calcification and inflammation rarely overlapped within arteries — carotid artery FDG uptake vs. calcium score r=-0.42, p=0.03). Carotid artery FDG uptake was greater in those with a history of coronary artery disease (target to background ratio (TBR) 1.83 vs. 1.61, p<0.01), and in males vs. females (TBR 1.83 vs. 1.63, p<0.05). Similar findings were also noted in the aorta and iliac arteries. Subjects with the highest levels of FDG uptake also had the greatest concentrations of inflammatory biomarkers: descending aorta TBR vs. matrix metalloproteinase 3 (MMP 3): r=0.53, p=0.01 and carotid TBR vs. MMP 9: r=0.50, p=0.01. Non-significant positive trends were seen between FDG uptake and levels of interleukin 18, fibrinogen and C-reactive protein. Finally, we found that the atheroprotective biomarker adiponectin was negatively correlated with the degree of arterial inflammation in the descending aorta: r=-0.49, p=0.03).
Conclusions—This study shows that FDG PET imaging can increase our knowledge of how atherosclerotic plaque inflammation relates to calcification, serum biomarkers and vascular risk factors. Plaque inflammation and calcification rarely overlap, supporting the theory that calcification represents a late, burnt-out stage of atherosclerosis. Inflammation in one arterial territory is associated with inflammation elsewhere, and the degree of local arterial inflammation is reflected in the blood levels of several circulating biomarkers. We suggest that FDG PET imaging could be used as a surrogate marker of both atherosclerotic disease activity and drug effectiveness. Prospective, event driven studies are now underway to determine the role of this technique in clinical risk prediction.
Key Words: atherosclerosis • imaging • inflammation • calcification • fluorodeoxyglucose • positron emission tomography
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