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Predictors of change in carotid atherosclerotic plaque inflammation and burden as measured by 18-FDG-PET and MRI, respectively, in the dal-PLAQUE study

  • Venkatesh Mani
  • Mark Woodward
  • Daniel Samber
  • Jan Bucerius
  • Ahmed Tawakol
  • David Kallend
  • James H. F. Rudd
  • Markus Abt
  • Zahi A. Fayad
Original Paper

Abstract

Baseline predictors of response to treatment of patients with coronary heart disease (CHD) with respect to vascular inflammation and atherosclerotic plaque burden are poorly understood. From post hoc analysis of the dal-PLAQUE study (NCT00655473), 18F-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) imaging and carotid black blood magnetic resonance imaging (MRI) were used to track changes in these vascular parameters. Baseline demographics, imaging, and biomarkers were collected/measured in 130 patients with CHD or CHD risk-equivalents, and imaging follow-up at 6 months (PET) and 24 months (MRI) was performed. Using stepwise linear regression, predictors of change in carotid plaque inflammation by PET [target-to-background ratio (TBR), n = 92] and plaque burden by MRI [wall area (WA) and total vessel area (TVA), n = 89] were determined. Variables with p < 0.05 in multivariable models were considered independently significant. Interleukin-6, systolic blood pressure and standard deviation of wall thickness (WT) at baseline were independently positively associated with 18-FDG uptake (mean of maximum [MeanMax] TBR change over 6 months). Mean of mean TBR, phospholipase A2, apolipoprotein A-I, and high-sensitivity C-reactive protein at baseline were independently negatively associated with MeanMax TBR change over 6 months. Mean WT and plasminogen activator inhibitor-1 (PAI-1) activity at baseline, and age, were independently associated with change in WA over 24 months. For TVA changes; mean WA and PAI-1 activity at baseline, age, and female gender were independent predictors. These findings may help determine patients most suitable for clinical trials employing plaque inflammation or burden changes as endpoints.

Keywords

Fluorodeoxyglucose-positron emission tomography Inflammation Magnetic resonance imaging Plaque burden 

Notes

Acknowledgments

The authors thank Michael E. Farkouh and Valentin Fuster for their review and feedback of the manuscript. This study was funded by F. Hoffmann-La Roche Ltd. Editorial assistance was provided by Prime Healthcare during the preparation of this report, and funded by F. Hoffmann-La Roche Ltd. All opinions expressed are those of the authors.

Conflict of interest

V.M., J.B. and D.S. indicate they have nothing to disclose. M.W. discloses that he has received honoraria from Roche. A.T. discloses that he has received honoraria from Roche, BMS and Novartis, and research grants from Merck, BMS, Genentech, GSK and VBL. D.K. was an employee of F. Hoffman-La Roche Ltd at the time the study was performed. M.A. is an employee of F. Hoffman-La Roche Ltd and receives share options. J.H.F.R. discloses that he has received honoraria from Roche and is part-supported by the National Institute for Health Research Cambridge Biomedical Research Centre. Z.A.F. discloses that he has received research grants from Roche, GlaxoSmithKline, Merck, VBL Therapeutics, Novartis, Bristol-Myers Squibb, and Via Pharmaceuticals and honoraria from Roche.

Supplementary material

10554_2014_370_MOESM1_ESM.pdf (2.1 mb)
Supplementary material 1 (PDF 2196 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Venkatesh Mani
    • 1
    • 2
  • Mark Woodward
    • 3
  • Daniel Samber
    • 1
    • 2
  • Jan Bucerius
    • 1
    • 2
    • 4
  • Ahmed Tawakol
    • 5
  • David Kallend
    • 6
  • James H. F. Rudd
    • 7
  • Markus Abt
    • 6
  • Zahi A. Fayad
    • 1
    • 2
    • 8
  1. 1.Translational and Molecular Imaging InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Department of RadiologyIcahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.George InstituteUniversity of SydneySydneyAustralia
  4. 4.Department of Nuclear Medicine, Cardiovascular Research Institute Maastricht (CARIM)Maastricht University Medical CenterMaastrichtThe Netherlands
  5. 5.Harvard Medical SchoolMassachusetts General HospitalBostonUSA
  6. 6.F. Hoffmann-La Roche LtdBaselSwitzerland
  7. 7.Division of Cardiovascular MedicineUniversity of CambridgeCambridgeUK
  8. 8.Cardiovascular InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA

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