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Carotid plaque composition by CT angiography in asymptomatic subjects: a head-to-head comparison to ultrasound

  • Computed Tomography
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Abstract

Objectives

To describe carotid plaque composition by computed tomography angiography (CTA) in asymptomatic subjects and to compare this to carotid plaque assessment by ultrasound, coronary plaques by coronary CTA, and inflammatory biomarkers in plasma.

Methods

Middle-aged asymptomatic men, n = 43, without known cardiovascular disease and diabetes were included. Plaques in coronary and carotid arteries were evaluated using CTA. Total plaque volumes and plaque composition were assessed by a validated plaque analysis software. The 60% centile cut point was used to divide the population into low or high carotid total plaque volumes. The occurrence of carotid plaques and intima-media thickness (IMT) was estimated by ultrasound.

Results

Carotid plaque by ultrasound was undiagnosed in 13 of 28 participants (46%) compared to CTA. Participants having carotid plaques by ultrasound had significantly higher absolute volumes of all CTA-defined carotid plaque subtypes and a higher fraction of calcified plaque. A high carotid total plaque volume was independently associated with age (adjusted odds ratio (OR) 1.41 [95% confidence interval (CI) 1.14–1.74], p = 0.001), IMT (adjusted OR 2.26 [95% CI 1.10–4.65], p = 0.03), and D-dimer (adjusted OR 8.86 [95% CI 1.26–62.37], p = 0.03). All coronary plaque features were significantly higher in participants with a high carotid total plaque volume.

Conclusion

The occurrence of carotid plaques in asymptomatic individuals is underestimated by ultrasound compared to plaque assessment by CTA. Carotid plaque composition by CTA is different in individuals with and without carotid plaques by ultrasound.

Key Points

• The occurrence of carotid plaques by ultrasound was underestimated in 46% of participants who had plaques by carotid CTA.

• Participants with carotid plaques by ultrasound had higher volumes of all plaque subtypes and a higher calcified plaque component as determined by carotid CTA compared to participants without carotid plaques by ultrasound.

• A high carotid total plaque volume was independently associated with age, intima-media thickness, and D-dimer.

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Abbreviations

Ag:

Agatston score

BMI:

Body mass index

CAC:

Coronary artery calcification

CRP:

C-reactive protein

CT:

Computed tomography

CTA:

Computed tomography angiography

CVD:

Cardiovascular disease

HDL:

High-density lipoprotein

IMT:

Intima-media thickness

IQR:

Interquartile range

LDL:

Low-density lipoprotein

LD-NCP vol.:

Low-density non-calcified plaque volume

MRI:

Magnetic resonance imaging

NCP vol.:

Non-calcified plaque volume

SD:

Standard deviation

TPV:

Total plaque volume

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Acknowledgments

We express our gratitude to the study participants in the current study and the dedicated staffs at the Departments of Cardiology, Radiology, and Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark and at the Unit for Thrombosis Research, University of Southern Denmark, Esbjerg, Denmark. The authors thank Martin W. Kusk, Department of Radiology, University Hospital of Southern Denmark, Esbjerg, Denmark, for the valuable help with designing the CTA protocols and assistance provided during collection of the CTA data.

Funding

This work was supported by Cardiac Research Fund, University Hospital of Southern Denmark, Esbjerg; Institute of Regional Health Research: Centre South West Jutland, University Hospital of Southern Denmark, Esbjerg; Institute of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark; Edith and Vagn Hedegaard Jensen Foundation, Esbjerg; Karola Jørgensens Research Foundation, Esbjerg; and A. P. Møller Foundation, Copenhagen; all Denmark.

Author information

Authors and Affiliations

  1. Department of Cardiology, University Hospital of Southern Denmark, Esbjerg, Denmark

    Ramshanker Ramanathan, Ida S. Bjerrum & Niels Peter R. Sand

  2. Department of Regional Health Research, University of Southern Denmark, Odense, Denmark

    Ramshanker Ramanathan, Ida S. Bjerrum & Niels Peter R. Sand

  3. Department of Clinical Biochemistry, University Hospital of Southern Denmark, Esbjerg, Denmark

    Ramshanker Ramanathan, Johannes J. Sidelmann & Jørgen B. Gram

  4. Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Esbjerg, Denmark

    Ramshanker Ramanathan, Johannes J. Sidelmann & Jørgen B. Gram

  5. Cedars-Sinai Medical Center, Biomedical Imaging Research Institute, Los Angeles, CA, 90048, USA

    Damini Dey & Markus Goeller

  6. Department of Cardiology, Skejby University Hospital, Aarhus, Denmark

    Bjarne L. Nørgaard

  7. Department of Radiology, University Hospital of Southern Denmark, Esbjerg, Denmark

    Ronald Antulov

  8. Department of Cardiology, Odense University Hospital, Odense, Denmark

    Axel C. P. Diederichsen

Authors
  1. Ramshanker Ramanathan
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  2. Damini Dey
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  3. Bjarne L. Nørgaard
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  4. Markus Goeller
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  5. Ida S. Bjerrum
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  6. Ronald Antulov
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  7. Axel C. P. Diederichsen
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  8. Johannes J. Sidelmann
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  9. Jørgen B. Gram
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  10. Niels Peter R. Sand
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Corresponding author

Correspondence to Ramshanker Ramanathan.

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Guarantor

The scientific guarantor of this publication is Dr. Niels Peter R. Sand, PhD, Department of Cardiology, University Hospital of Southern Denmark, Esbjerg, and Department of Regional Health Research, University of Southern Denmark, Denmark.

Conflict of interest

The authors of this manuscript declare relationships with the following companies: Dr. Bjarne L. Nørgaard has received research grant from Siemens, Edwards Lifesciences and Heartflow. Dr. Damini Dey is a patent-holder of Autoplaque research software and receives royalties from Cedars-Sinai Medical Center, Los Angeles, CA, USA. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Statistics and biometry

Ramshanker Ramanathan and Damini Dey performed the statistical analyses. Statistician Pia V. Larsen, Department of Public Health, University of Southern Denmark, Odense, provided statistical advice.

Informed consent

Written informed consent was obtained from all individual participants included in the study. All procedures performed in the study were conducted in accordance with the ethical standards of the Regional Scientific Ethics Committee for Southern Denmark and with the ethical guidelines of the 1975 Declaration of Helsinki and its later amendments.

Ethical approval

The study protocol was approved by the Regional Scientific Ethics Committee for Southern Denmark, reference number: S20080140 and S20130169 (45023).

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in the following papers: [1–9]. The study subjects recruited in the current study were part of the Danish Risk Score Study (the DanRisk study) conducted in 2009/2010 with follow-up examinations performed in 2015. The DanRisk study was a multicenter study involving four regional centers (Odense, Esbjerg, Vejle, and Svendborg).

The current study is based on follow-up examinations on asymptomatic male study subjects from one study center, Esbjerg, who were free of cardiovascular disease (CVD), diabetes, and any medication at baseline. The current study differs from the other studies by examining the carotid plaque composition by computed tomography angiography (CTA) and by comparing these findings with carotid plaque by ultrasound. In addition, this is the first study from DanRisk focusing on CTA.

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[5] S.Z. Diederichsen, M.H. Gronhoj, H. Mickley, O. Gerke, F.H. Steffensen, J. Lambrechtsen, N.P. Ronnow Sand, L.M. Rasmussen, M.H. Olsen, A. Diederichsen, CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers, JACC. Cardiovascular imaging 10(8) (2017) 858–866.

[6] J. Lambrechtsen, O. Gerke, K. Egstrup, N.P. Sand, B.L. Norgaard, H. Petersen, H. Mickley, A.C. Diederichsen, The relation between coronary artery calcification in asymptomatic subjects and both traditional risk factors and living in the city centre: a DanRisk substudy, Journal of internal medicine 271(5) (2012) 444–50.

[7] M.H. Sorensen, O. Gerke, J. Eugen-Olsen, H. Munkholm, J. Lambrechtsen, N.P. Sand, H. Mickley, L.M. Rasmussen, M.H. Olsen, A. Diederichsen, Soluble urokinase plasminogen activator receptor is in contrast to high-sensitive C-reactive-protein associated with coronary artery calcifications in healthy middle-aged subjects, Atherosclerosis 237(1) (2014) 60–6.

[8] M.Z. Diederichsen, S.Z. Diederichsen, H. Mickley, F.H. Steffensen, J. Lambrechtsen, N.P.R. Sand, K.L. Christensen, M.H. Olsen, A. Diederichsen, M.H. Gronhoj, Prognostic value of suPAR and hs-CRP on cardiovascular disease, Atherosclerosis 271 (2018) 245–251.

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Ramanathan, R., Dey, D., Nørgaard, B.L. et al. Carotid plaque composition by CT angiography in asymptomatic subjects: a head-to-head comparison to ultrasound. Eur Radiol 29, 5920–5931 (2019). https://doi.org/10.1007/s00330-019-06086-y

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