Skip to main content
SpringerLink
Log in

Associations between coronary/aortic 18F-sodium fluoride uptake and pro-atherosclerosis factors in patients with multivessel coronary artery disease

  • Original Article
  • Published:
Journal of Nuclear Cardiology Aims and scope

Abstract

Background

18F-NaF PET/CT is a novel approach to detect and quantify microcalcification in atherosclerosis. We aimed to explore the underlying systematic vascular osteogenesis in the coronary artery and aorta in patients with multivessel coronary artery disease (CAD).

Methods

Patients with multivessel CAD prospectively underwent 18F-NaF PET/CT. The coronary microcalcification activity (CMA) and aortic microcalcification activity (AMA) were calculated based on both the volume and intensity of 18F-NaF PET activity. Peri-coronary adipose tissue (PCAT) density was measured in adipose tissue surrounding the coronary arteries and the 18F-NaF tissue-to-blood ratio (TBR) was measured in the coronary arteries.

Results

100 patients with multivessel CAD were prospectively recruited. The CMA was significantly associated with the AMA (r = 0.70; P < .001). After multivariable adjustment, the CMA was associated with the AMA (Beta = 0.445 per SD increase; P < .001). The coronary TBR was also significantly associated with the PCAT density (r = 0.56; P < .001). The PCAT density was independently associated with the coronary TBR after adjusting confounding factors.

Conclusions

Coronary 18F-NaF uptake was significantly associated with the PCAT density. There was a significant relationship between the coronary and the aortic 18F-NaF uptake. It might indicate an underlying systematic vascular osteogenesis in patients with multivessel CAD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

Abbreviations

18F-NaF:

18F-sodium fluoride

CAD:

Coronary artery disease

CT:

Computed tomography

LAD:

Left anterior descending

LCX:

Left circumflex

PCAT:

Peri-coronary adipose tissue

PET:

Positron emission tomography

RCA:

Right coronary artery

SUV:

Standardized uptake value

TBR:

Tissue-to-background ratio

References

  1. Libby P, Pasterkamp G, Crea F, Jang IK. Reassessing the mechanisms of acute coronary syndromes. Circ Res 2019;124:150‐60.

    Article  CAS  Google Scholar 

  2. Ferraro RA, van Rosendael AR, Lu Y, Andreini D, Al-Mallah MH, Cademartiri F. Non-obstructive high-risk plaques increase the risk of future culprit lesions comparable to obstructive plaques without high-risk features: The ICONIC study. Eur Heart J Cardiovasc Imaging 2020;21:973‐80.

    Article  Google Scholar 

  3. Radcliff K, Tang TB, Lim J, Zhang Z, Abedin M, Demer LL, et al. Insulin-like growth factor-I regulates proliferation and osteoblastic differentiation of calcifying vascular cells via extracellular signal-regulated protein kinase and phosphatidylinositol 3-kinase pathways. Circ Res 2005;96:398‐400.

    Article  CAS  Google Scholar 

  4. Irkle A, Vesey AT, Lewis DY, Skepper JN, Bird JL, Dweck MR, et al. Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography. Nat Commun 2015;6:7495.

    Article  Google Scholar 

  5. Hoshino T, Sissani L, Labreuche J, Ducrocq G, Lavallee PC, Meseguer E, et al. Prevalence of systemic atherosclerosis burdens and overlapping stroke etiologies and their associations with long-term vascular prognosis in stroke with intracranial atherosclerotic disease. JAMA Neurol 2018;75:203‐11.

    Article  Google Scholar 

  6. Høilund-Carlsen PF, Sturek M, Alavi A, Gerke O. Atherosclerosis imaging with 18F-sodium fluoride PET: State-of-the-art review. Eur J Nucl Med Mol Imaging 2020;47:1538‐51.

    Article  Google Scholar 

  7. Li L, Li X, Jia Y, Fan J, Wang H, Fan C, et al. Sodium-fluoride PET-CT for the non-invasive evaluation of coronary plaques in symptomatic patients with coronary artery disease: A cross-correlation study with intravascular ultrasound. Eur J Nucl Med Mol Imaging 2018;45:2181‐9.

    Article  CAS  Google Scholar 

  8. Fletcher AJ, Lembo M, Kwiecinski J, Syed MBJ, Nash J, Tzolos E, et al. Quantifying microcalcification activity in the thoracic aorta. J Nucl Cardiol 2021. https://doi.org/10.1007/s12350-020-02458-w.

    Article  Google Scholar 

  9. Kitagawa T, Yamamoto H, Nakamoto Y, Sasaki K, Toshimitsu S, Tatsugami F, et al. Predictive Value of 18F-Sodium Fluoride Positron Emission Tomography in Detecting High-Risk Coronary Artery Disease in Combination With Computed Tomography. J Am Heart Assoc 2018;7:e010224.

    Article  CAS  Google Scholar 

  10. Kwiecinski J, Tzolos E, Meah M, Cadet S, Adamson PD, Grodecki K, et al. Machine-learning with 18F-sodium fluoride PET and quantitative plaque analysis on CT angiography for the future risk of myocardial infarction. J Nucl Med 2021;63:158.

    Article  Google Scholar 

  11. Bettencourt N, Toschke AM, Leite D, Rocha J, Carvalho M, Sampaio F, et al. Epicardial adipose tissue is an independent predictor of coronary atherosclerotic burden. Int J Cardiol 2012;158:26‐32.

    Article  CAS  Google Scholar 

  12. Yamashita K, Yamamoto MH, Igawa W, Ono M, Kido T, Ebara S, et al. Association of epicardial adipose tissue volume and total coronary plaque burden in patients with coronary artery disease. Int Heart J 2018;59:1219‐26.

    Article  CAS  Google Scholar 

  13. Kitagawa T, Nakamoto Y, Fujii Y, Sasaki K, Tatsugami F, Awai K, et al. Relationship between coronary arterial 18F-sodium fluoride uptake and epicardial adipose tissue analyzed using computed tomography. Eur J Nucl Med Mol Imaging 2020;47:1746‐56.

    Article  CAS  Google Scholar 

  14. Kwiecinski J, Dey D, Cadet S, Lee SE, Otaki Y, Huynh PT, et al. Peri-coronary adipose tissue density is associated with 18F-sodium fluoride coronary uptake in stable patients with high-risk plaques. JACC Cardiovasc Imaging 2019;12:2000‐10.

    Article  Google Scholar 

  15. Kwiecinski J, Berman DS, Lee SE, Dey D, Cadet S, Lassen ML, et al. Three-hour delayed imaging improves assessment of coronary 18F-sodium fluoride PET. J Nucl Med 2019;60:530‐5.

    Article  Google Scholar 

  16. Kwiecinski J, Cadet S, Daghem M, Lassen ML, Dey D, Dweck MR, et al. Whole-vessel coronary 18F-sodium fluoride PET for assessment of the global coronary microcalcification burden. Eur J Nucl Med Mol Imaging 2020;47:1736‐45.

    Article  CAS  Google Scholar 

  17. Commandeur F, Goeller M, Betancur J, Cadet S, Doris M, Chen X, et al. Deep learning for quantification of epicardial and thoracic adipose tissue from non-contrast CT. IEEE Trans Med Imaging 2018;37:1835‐46.

    Article  Google Scholar 

  18. Scheidt M, Wesolowski M, Salazar D, Garbis N. A 3-dimensional comparison of hand and power reamers in accuracy of glenoid retroversion correction. J Shoulder Elbow Surg 2020;29:609‐16.

    Article  Google Scholar 

  19. Antonopoulos AS, Sanna F, Sabharwal N, Thomas S, Oikonomou EK, Herdman L, et al. Detecting human coronary inflammation by imaging perivascular fat. Sci Transl Med 2017. https://doi.org/10.1126/scitranslmed.aal2658.

    Article  Google Scholar 

  20. Nakahara T, Strauss HW. From inflammation to calcification in atherosclerosis. Eur J Nucl Med Mol Imaging 2017;44:858‐60.

    Article  Google Scholar 

  21. Hutcheson JD, Maldonado N, Aikawa E. Small entities with large impact: microcalcifications and atherosclerotic plaque vulnerability. Curr Opin Lipidol 2014;25:327‐32.

    Article  CAS  Google Scholar 

  22. Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res 2014;114:1852‐66.

    Article  CAS  Google Scholar 

  23. Calais F, Eriksson Ostman M, Hedberg P, Rosenblad A, Leppert J, Frobert O. Incremental prognostic value of coronary and systemic atherosclerosis after myocardial infarction. Int J Cardiol 2018;261:6‐11.

    Article  Google Scholar 

  24. Gallino A, Aboyans V, Diehm C, Cosentino F, Stricker H, Falk E, et al. Non-coronary atherosclerosis. Eur Heart J 2014;35:1112‐9.

    Article  Google Scholar 

  25. Kwiecinski J, Tzolos E, Adamson PD, Cadet S, Moss AJ, Joshi N, et al. Coronary 18F-sodium fluoride uptake predicts outcomes in patients with coronary artery disease. J Am Coll Cardiol 2020;75:3061‐74.

    Article  CAS  Google Scholar 

  26. McGill HC Jr, McMahan CA, Zieske AW, Sloop GD, Walcott JV, Troxclair DA, et al. Associations of coronary heart disease risk factors with the intermediate lesion of atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol 2000;20:1998‐2004.

    Article  Google Scholar 

  27. Komatsu S, Yutani C, Ohara T, Takahashi S, Takewa M, Hirayama A, et al. Angioscopic evaluation of spontaneously ruptured aortic plaques. J Am Coll Cardiol 2018;71:2893‐902.

    Article  Google Scholar 

  28. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 2003;108:2460‐6.

    Article  Google Scholar 

  29. Margaritis M, Antonopoulos AS, Digby J, Lee R, Reilly S, Coutinho P, et al. Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels. Circulation 2013;127:2209‐21.

    Article  CAS  Google Scholar 

  30. Ng AC, Goo SY, Roche N, van der Geest RJ, Wang WY. Epicardial adipose tissue volume and left ventricular myocardial function using 3-dimensional speckle tracking echocardiography. Can J Cardiol 2016;32:1485‐92.

    Article  Google Scholar 

  31. Mancio J, Barros AS, Conceicao G, Pessoa-Amorim G, Santa C, Bartosch C, et al. Epicardial adipose tissue volume and annexin A2/fetuin-A signalling are linked to coronary calcification in advanced coronary artery disease: Computed tomography and proteomic biomarkers from the EPICHEART study. Atherosclerosis 2020;292:75‐83.

    Article  CAS  Google Scholar 

  32. Tzolos E, Dweck MR. 18F-NaF for imaging microcalcification activity in the cardiovascular system. Arterioscler Thromb Vasc Biol 2020;2020:Atvbaha120313785.

    Google Scholar 

  33. Doris MK, Meah MN, Moss AJ, Andrews JPM, Bing R, Gillen R, et al. Coronary 18F-fluoride uptake and progression of coronary artery calcification. Circ Cardiovasc Imaging 2020;13:e011438.

    Article  Google Scholar 

  34. Ishiwata Y, Kaneta T, Nawata S, Hino-Shishikura A, Yoshida K, Inoue T. Quantification of temporal changes in calcium score in active atherosclerotic plaque in major vessels by 18F-sodium fluoride PET/CT. Eur J Nucl Med Mol Imaging 2017;44:1529‐37.

    Article  CAS  Google Scholar 

  35. Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016;37:267‐315.

    Article  CAS  Google Scholar 

  36. Joshi NV, Vesey AT, Williams MC, Shah AS, Calvert PA, Craighead FH, et al. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet 2014;383:705‐13.

    Article  Google Scholar 

Download references

Acknowledgements

We are extremely grateful to Dr. Wei Yu and Dr. Lei Xu, Department of Radiology, Beijing Anzhen Hospital, Capital Medical University Beijing, for her advice on improving the manuscript.

Disclosures

The authors have no relevant conflicts of interest to declare.

Author information

Author notes

  1. Wanwan Wen and Mingxin Gao have contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Molecular Imaging Lab, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

    Wanwan Wen MD, Mingkai Yun PhD, Jingjing Meng MD, Ziwei Zhu MD, Xiaoli Zhang MD, PhD & Xiang Li PhD

  2. Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

    Mingxin Gao MD, Wenyuan Yu MD & Yang Yu MD, PhD

  3. Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna General Hospital, Medical University of Vienna, Vienna, Austria

    Marcus Hacker MD & Xiang Li PhD

Authors
  1. Wanwan Wen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mingxin Gao MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mingkai Yun PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jingjing Meng MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ziwei Zhu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenyuan Yu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marcus Hacker MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yang Yu MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiaoli Zhang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xiang Li PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaoli Zhang MD, PhD.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The authors of this article have provided a PowerPoint file, available for download at SpringerLink, which summarizes the contents of the paper and is free for re-use at meetings and presentations. Search for the article DOI on SpringerLink.com.

All editorial decisions for this article, including selection of reviewers and the final decision, were made by guest editor Rob deKemp, PhD.

Funding: We thank the Key Medical Specialty Program of Sailing Plans organized by Beijing Municipal Administration of Hospitals (grant numbers: ZYLX202110) for supporting this research.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 642 kb)

Supplementary file2 (PPTX 4200 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wen, W., Gao, M., Yun, M. et al. Associations between coronary/aortic 18F-sodium fluoride uptake and pro-atherosclerosis factors in patients with multivessel coronary artery disease. J. Nucl. Cardiol. 29, 3352–3365 (2022). https://doi.org/10.1007/s12350-022-02958-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12350-022-02958-x

Keywords

Search

Navigation