title: Relationships among regional arterial inflammation, calcification, risk factors, and biomarkers: a prospective fluorodeoxyglucose positron-emission tomography/computed tomography imaging study.
abstract: 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. We explored how atherosclerotic plaque inflammation varies across arterial territories and how it relates to arterial calcification. We also tested 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.
  
  
  RESULTS
  Forty-one subjects underwent vascular PET/computed tomography imaging with FDG. All had either vascular disease or multiple risk factors. Forty subjects underwent carotid imaging, 27 subjects underwent aortic, 24 subjects iliac, and 13 subjects femoral imaging. Thirty-three subjects had a panel of biomarkers analyzed. We found strong associations between FDG uptake in neighboring arteries (left versus right carotid, r=0.91, P<0.001; ascending aorta versus aortic arch, r=0.88, P<0.001). Calcification and inflammation rarely overlapped within arteries (carotid artery FDG uptake versus 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
  <0.01) and in males versus females (target-to-
  
  
  BACKGROUND
  <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 target-to-
  
  
  BACKGROUND
  =0.53, P=0.01; carotid target-to-
  
  
  BACKGROUND
  =0.50, P=0.01). Nonsignificant 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.
authors.affiliation: Imaging Science Laboratories, Mount Sinai School of Medicine, New York, NY, USA. jhfr2@cam.ac.uk
authors.forename: James H F
authors.initials: JH
authors.lastname: Rudd
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Myers
authors.forename: Sameer
authors.initials: S
authors.lastname: Bansilal
authors.forename: Josef
authors.initials: J
authors.lastname: Machac
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.forename: Michael E
authors.initials: ME
authors.lastname: Farkouh
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
mesh_terms: D000368:Aged; D000792:Angiography; D001158:Arteries / Q000000981:diagnostic imaging; D050197:Atherosclerosis / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood*; D002114:Calcinosis / Q000175:diagnosis*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007249:Inflammation / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012307:Risk Factors; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18