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Short-term changes in arterial inflammation predict long-term changes in atherosclerosis progression

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

It remains unclear whether changes in arterial wall inflammation are associated with subsequent changes in the rate of structural progression of atherosclerosis.

Methods

In this sub-study of the dal-PLAQUE clinical trial, multi-modal imaging was performed using 18-fludeoxyglucose (FDG) positron emission tomography (PET, at 0 and 6 months) and magnetic resonance imaging (MRI, at 0 and 24 months). The primary objective was to determine whether increasing FDG uptake at 6 months predicted atherosclerosis progression on MRI at 2 years. Arterial inflammation was measured by the carotid FDG target-to-background ratio (TBR), and atherosclerotic plaque progression was defined as the percentage change in carotid mean wall area (MWA) and mean wall thickness (MWT) on MRI between baseline and 24 months.

Results

A total of 42 participants were included in this sub-study. The mean age of the population was 62.5 years, and 12 (28.6 %) were women. In participants with (vs. without) any increase in arterial inflammation over 6 months, the long-term changes in both MWT (% change MWT: 17.49 % vs. 1.74 %, p = 0.038) and MWA (% change MWA: 25.50 % vs. 3.59 %, p = 0.027) were significantly greater. Results remained significant after adjusting for clinical and biochemical covariates. Individuals with no increase in arterial inflammation over 6 months had no significant structural progression of atherosclerosis over 24 months as measured by MWT (p = 0.616) or MWA (p = 0.373).

Conclusions

Short-term changes in arterial inflammation are associated with long-term structural atherosclerosis progression. These data support the concept that therapies that reduce arterial inflammation may attenuate or halt progression of atherosclerosis.

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Author information

Authors and Affiliations

  1. Cardiology Division and Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Suite 400-165 Cambridge St, Boston, MA, 02114, USA

    Philip Joseph, Amorina Ishai & Ahmed Tawakol

  2. Population Health Research Institute, Department of Medicine, and Department of Radiology, McMaster University, Hamilton, ON, Canada

    Philip Joseph

  3. Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY, USA

    Venkatesh Mani & Zahi A. Fayad

  4. The Medicines Company, Parsippany, NJ, USA

    David Kallend

  5. Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK

    James H. F. Rudd

  6. Translational and Molecular Imaging Institute and Department of Radiology, Icahn School of Medicine at Mount Sinai School of Medicine, Hess CSM Building Floor TMII, Rm S1-104, 1470 Madison Avenue, New York, NY, 10029, USA

    Zahi A. Fayad

Authors
  1. Philip Joseph
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  2. Amorina Ishai
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  3. Venkatesh Mani
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  4. David Kallend
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  5. James H. F. Rudd
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  6. Zahi A. Fayad
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  7. Ahmed Tawakol
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Corresponding authors

Correspondence to Zahi A. Fayad or Ahmed Tawakol.

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Funding

This study was funded by F. Hoffmann-La Roche Ltd. Dr. Joseph is supported in part by a McMaster University Early Career Investigator award. Dr. Rudd is supported in part by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation and the Wellcome Trust.

Conflict of interest

P. Joseph, A. Ishai and V. Mani declare that they have no conflict of interest. D. Kallend was previously employed by and received share options from F. Hoffmann-La Roche Ltd. J. Rudd has received speaking honoraria from Roche. Z. Fayad has received research grants from Roche, GlaxoSmithKline, Merck, VBL Therapeutics, Novartis, Bristol-Myers Squibb and Via Pharmaceuticals, and speaking honoraria from Roche. A. Tawakol has received research grants from Merck, BMS, Takeda, Genentech, GlaxoSmithKline and VBL, and honoraria from Roche, BMS and Novartis.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Philip Joseph and Amorina Ishai are co-primary authors.

Zahi A. Fayad and Ahmed Tawakol are co-senior authors.

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Joseph, P., Ishai, A., Mani, V. et al. Short-term changes in arterial inflammation predict long-term changes in atherosclerosis progression. Eur J Nucl Med Mol Imaging 44, 141–150 (2017). https://doi.org/10.1007/s00259-016-3524-0

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  • DOI: https://doi.org/10.1007/s00259-016-3524-0

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