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Carotid artery molecular calcification assessed by [18F]fluoride PET/CT: correlation with cardiovascular and thromboembolic risk factors

  • Nuclear Medicine
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

There is growing evidence that sodium fluoride ([18F]fluoride) PET/CT can detect active arterial calcifications at the molecular stage. We investigated the relationship between arterial mineralization in the left common carotid artery (LCC) assessed by [18F]fluoride PET/CT and cardiovascular/thromboembolic risk.

Methods

In total, 128 subjects (mean age 48 ± 14 years, 51% males) were included. [18F]fluoride uptake in the LCC was quantitatively assessed by measuring the blood-pool-corrected maximum standardized uptake value (SUVmax) on each axial slice. Average SUVmax (aSUVmax) was calculated over all slices and correlated with 10-year risk of cardiovascular events estimated by the Framingham model, CHA2DS2-VASc score, and level of physical activity (LPA).

Results

The aSUVmax was significantly higher in patients with increased risk of cardiovascular (one-way ANOVA, p < 0.01) and thromboembolic (one-way ANOVA, p < 0.01) events, and it was significantly lower in patients with greater LPA (one-way ANOVA, p = 0.02). On multivariable linear regression analysis, age ( = 0.07, 95% CI 0.05 – 0.10, p < 0.01), body mass index ( = 0.02, 95% CI 0.01 – 0.03, p < 0.01), arterial hypertension ( = 0.15, 95% CI 0.08 – 0.23, p < 0.01), and LPA ( = −0.10, 95% CI −0.19 to −0.02, p=0.02) were independent associations of aSUVmax.

Conclusions

Carotid [18F]fluoride uptake is significantly increased in patients with unfavorable cardiovascular and thromboembolic risk profiles. [18F]fluoride PET/CT could become a valuable tool to estimate subjects’ risk of future cardiovascular events although still major trials are needed to further evaluate the associations found in this study and their potential clinical usefulness.

Key Points

• Sodium fluoride ([ 18 F]fluoride) PET/CT imaging identifies patients with early-stage atherosclerosis.

• Carotid [ 18 F]fluoride uptake is significantly higher in patients with increased risk of cardiovascular and thromboembolic events and inversely correlated with the level of physical activity.

• Early detection of arterial mineralization at a molecular level could help guide clinical decisions in the context of cardiovascular risk assessment.

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Abbreviations

[18F]FDG:

Fluorodeoxyglucose

[18F]fluoride:

Sodium fluoride

aSUVmax:

Averaged maximal standardized uptake value

CAMONA:

Cardiovascular Molecular Calcification Assessed by 18F-NaF PET/CT

CHA2DS2-VASc:

Congestive heart failure, Hypertension, Age ( > 65 = 1 point, > 75 = 2 points), Diabetes, previous Stroke/transient ischemic attack (2 points)-vascular disease

CT:

Computed tomography

CVD:

Cardiovascular disease

FRS:

Framingham Risk Score

HTN:

Hypertension

LCC:

Left common carotid artery

LPA:

Level of physical activity

PET:

Positron emission tomography

ROI:

Region of interest

SUVmax:

Maximum standardized uptake value

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Acknowledgements

We thank the staff and participants of the CAMONA research study for their contributions.

Funding

This study has received funding from the Jørgen and Gisela Thrane’s Philanthropic Research Foundation, Broager, Denmark.

Author information

Authors and Affiliations

  1. Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA, 19104, USA

    Simon A. Castro, Hwan Lee, Emily C. Hancin, Austin J. Borja, Oswaldo Acosta, Thomas J. Werner & Abass Alavi

  2. Cardiac Electrophysiology, Cardiovascular Medicine Division, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    Simon A. Castro & Daniele Muser

  3. Quinnipiac University, St Vincent’s Medical Center, Bridgeport, CT, USA

    Simon A. Castro & Hwan Lee

  4. Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA

    Emily C. Hancin

  5. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Austin J. Borja

  6. Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark

    Anders Thomassen, Caius Constantinescu & Poul Flemming Høilund-Carlsen

  7. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Anders Thomassen, Caius Constantinescu & Poul Flemming Høilund-Carlsen

Authors
  1. Simon A. Castro
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Corresponding author

Correspondence to Abass Alavi.

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Guarantor

The scientific guarantor of this publication is Dr. Abass Alavi (abass.alavi@pennmedicine.upenn.edu).

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

Oke Gerke (Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark; Research Unit of Clinical Physiology and Nuclear Medicine, Department of Clinical Research, University of Southern Denmark, Odense, Denmark) kindly provided statistical advice for this manuscript.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained. The CAMONA study was approved by the Danish National Committee on Biomedical Research Ethics, registered at ClinicalTrials.gov (NCT01274749) and conducted from 2012 to 2016 in accordance with the Declaration of Helsinki.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in Castro S, Muser D, Acosta-Montenegro O, et al Common carotid artery molecular calcification assessed by 18F-NaF PET/CT is associated with increased cardiovascular disease risk: results from the CAMONA study. J Nucl Med 2017;58:34–34. (Abstract accepted to 2017 Society of Nuclear Medicine and Molecular Imaging conference).

Methodology

• retrospective

• case-control study

• performed at one institution

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Poul Flemming Høilund-Carlsen and Abass Alavi are co-last authors.

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Castro, S.A., Muser, D., Lee, H. et al. Carotid artery molecular calcification assessed by [18F]fluoride PET/CT: correlation with cardiovascular and thromboembolic risk factors. Eur Radiol 31, 8050–8059 (2021). https://doi.org/10.1007/s00330-021-07917-7

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