Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients with Established Cardiovascular Disease

Alexander J  Fletcher; Yong Yong Tew; Evangelos Tzolos; Shruti Joshi; Jakub Kaczynski; Jennifer Nash; Samuel Debono; Maria Lembo; Jacek Kwiecinski; Rong Bing; Maaz B J Syed; Mhairi Doris; Edwin J R  van Beek; Alistair J Moss; William Jenkins; Niki L  Walker; Nikhil V Joshi; Tania A Pawade; Philip D Adamson; William N Whiteley; Joanna M. Wardlaw; Piotr J Slomka; Michelle C Williams; David E Newby; Marc R Dweck

doi:10.1016/j.jcmg.2021.12.013

Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients with Established Cardiovascular Disease

Alexander J Fletcher , Yong Yong Tew, Evangelos Tzolos, Shruti Joshi, Jakub Kaczynski, Jennifer Nash, Samuel Debono, Maria Lembo, Jacek Kwiecinski, Rong Bing, Maaz B J Syed, Mhairi Doris, Edwin J R van Beek, Alistair J Moss, William Jenkins, Niki L Walker, Nikhil V Joshi, Tania A Pawade, Philip D Adamson, William N WhiteleyJoanna M. Wardlaw, Piotr J Slomka, Michelle C Williams, David E Newby, Marc R Dweck^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Objective:
To investigate whether thoracic 18F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke.

Background:
Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke.

Methods:
In a post-hoc observational cohort study, we quantified thoracic aortic and coronary 18F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable logistic regression.

Results:
After 12·7±2·7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18F-sodium fluoride activity (n=140, r=0·31, p=0·00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6·1±2·3 years of follow up. High thoracic aortic 18F-sodium fluoride activity was strongly associated with ischemic stroke (HR 10·3 [3·1 to 34·8], p=0·0017), but not myocardial infarction (p=0·40). Conversely, high coronary 18F-sodium fluoride activity was associated with myocardial infarction (HR 4·8 [1·9 to 12·2], p=0·00095) but not ischemic stroke (p=0·39). In a multivariable logistic regression model including imaging and clinical risk factors, thoracic aortic 18F-sodium fluoride activity was the only variable associated with ischemic stroke (OR 1·76 [1·12 to 2·78], p=0·0014).

Conclusion:
In patients with established cardiovascular disease, thoracic aortic 18F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18F-sodium fluoride activity identifies localised areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events.

Original language	English
Journal	JACC: Cardiovascular Imaging
DOIs	https://doi.org/10.1016/j.jcmg.2021.12.013
Publication status	Published - 16 Feb 2022

Keywords / Materials (for Non-textual outputs)

Stroke
Calcification
Computed tomography
Positron emission tomography
Sodium fluoride
Thoracic aorta

Access to Document

10.1016/j.jcmg.2021.12.013

Clean_Manuscript_file_finAccepted author manuscript, 70.4 KBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

Impact of COVID-19 on short and long term outcomes after stroke: R4VaD and COVID-19
Wardlaw, J. (Principal Investigator) & Doubal, F. (Co-investigator)
UK-based charities
1/11/20 → 31/05/23
Project: Research
Non-invasive detection of bicuspid aortic valve¿related thoracic aortopathy
Newby, D. (Principal Investigator) & Walker, N. (Co-investigator)
UK-based charities
1/04/19 → 31/07/21
Project: Research
18F-Sodium Fluoride Positron Emission Tomography in Patients with Acute Aortic Syndrome
Newby, D. (Principal Investigator)
UK-based charities
1/10/18 → 30/09/20
Project: Research

Edinburgh Imaging Facility
Grant, A. (Manager), van Beek, E. (Manager) & Semple, S. (Manager)
Deanery of Clinical Sciences
Facility/equipment: Facility

Cite this

Fletcher , A. J., Tew, Y. Y., Tzolos, E., Joshi, S., Kaczynski, J., Nash, J., Debono, S., Lembo, M., Kwiecinski, J., Bing, R., Syed, M. B. J., Doris, M., van Beek, E. J. R., Moss, A. J., Jenkins, W., Walker, N. L., Joshi, N. V., Pawade, T. A., Adamson, P. D., ... Dweck, M. R. (2022). Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients with Established Cardiovascular Disease. JACC: Cardiovascular Imaging. https://doi.org/10.1016/j.jcmg.2021.12.013

@article{e58ebe84d3474485b8f3410cfb90a93d,

title = "Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients with Established Cardiovascular Disease",

abstract = "Objective:To investigate whether thoracic 18F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke.Background:Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke.Methods:In a post-hoc observational cohort study, we quantified thoracic aortic and coronary 18F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable logistic regression.Results:After 12·7±2·7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18F-sodium fluoride activity (n=140, r=0·31, p=0·00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6·1±2·3 years of follow up. High thoracic aortic 18F-sodium fluoride activity was strongly associated with ischemic stroke (HR 10·3 [3·1 to 34·8], p=0·0017), but not myocardial infarction (p=0·40). Conversely, high coronary 18F-sodium fluoride activity was associated with myocardial infarction (HR 4·8 [1·9 to 12·2], p=0·00095) but not ischemic stroke (p=0·39). In a multivariable logistic regression model including imaging and clinical risk factors, thoracic aortic 18F-sodium fluoride activity was the only variable associated with ischemic stroke (OR 1·76 [1·12 to 2·78], p=0·0014).Conclusion:In patients with established cardiovascular disease, thoracic aortic 18F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18F-sodium fluoride activity identifies localised areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events.",

keywords = "Stroke, Calcification, Computed tomography, Positron emission tomography, Sodium fluoride, Thoracic aorta",

author = "Fletcher, {Alexander J} and Tew, {Yong Yong} and Evangelos Tzolos and Shruti Joshi and Jakub Kaczynski and Jennifer Nash and Samuel Debono and Maria Lembo and Jacek Kwiecinski and Rong Bing and Syed, {Maaz B J} and Mhairi Doris and {van Beek}, {Edwin J R} and Moss, {Alistair J} and William Jenkins and Walker, {Niki L} and Joshi, {Nikhil V} and Pawade, {Tania A} and Adamson, {Philip D} and Whiteley, {William N} and Wardlaw, {Joanna M.} and Slomka, {Piotr J} and Williams, {Michelle C} and Newby, {David E} and Dweck, {Marc R}",

note = "Funding Information: Drs Fletcher (FS/19/15/34155), Tzolos (FS/17/51/33096), Syed (FS/18/31/33676), Moss (AA/18/3/34220), Walker (FS/19/15/34155), Williams (FS/ICRF/20/26002), Newby (CH/09/002, RG/16/10/32375, RE/18/5/34216), and Dweck (FS/14/78/31020) are supported by the British Heart Foundation. Dr Lembo is supported by the International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh). Dr van Beek is supported by SINAPSE. Dr Adamson is supported by a Heart Foundation of New Zealand Senior Fellowship (1844). Dr Wardlaw is supported by the UK Dementia Research Institute (funded by the MRC, Alzheimer Society and Alzheimer Research UK). Dr Slomka and FusionQuant Development are supported by the National Institute of Health Grant HL135557 (PI: Dr Slomka); and his laboratory is supported by National Institutes of Health R01HL135557. Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA); and holds investigator-initiated research grants from Siemens Healthineers. Dr Dweck is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). The Edinburgh Imaging facility QMRI (Edinburgh) is supported by the National Health Service Research Scotland through National Health Service Lothian Health Board. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = feb,

day = "16",

doi = "10.1016/j.jcmg.2021.12.013",

language = "English",

journal = "JACC: Cardiovascular Imaging",

issn = "1936-878X",

publisher = "Elsevier Inc.",

}

Fletcher , AJ, Tew, YY, Tzolos, E, Joshi, S, Kaczynski, J, Nash, J, Debono, S, Lembo, M, Kwiecinski, J, Bing, R, Syed, MBJ, Doris, M, van Beek, EJR, Moss, AJ, Jenkins, W, Walker, NL, Joshi, NV, Pawade, TA, Adamson, PD, Whiteley, WN, Wardlaw, JM, Slomka, PJ, Williams, MC , Newby, DE & Dweck, MR 2022, 'Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients with Established Cardiovascular Disease', JACC: Cardiovascular Imaging. https://doi.org/10.1016/j.jcmg.2021.12.013

TY - JOUR

T1 - Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients with Established Cardiovascular Disease

AU - Fletcher , Alexander J

AU - Tew, Yong Yong

AU - Tzolos, Evangelos

AU - Joshi, Shruti

AU - Kaczynski, Jakub

AU - Nash, Jennifer

AU - Debono, Samuel

AU - Lembo, Maria

AU - Kwiecinski, Jacek

AU - Bing, Rong

AU - Syed, Maaz B J

AU - Doris, Mhairi

AU - van Beek, Edwin J R

AU - Moss, Alistair J

AU - Jenkins, William

AU - Walker, Niki L

AU - Joshi, Nikhil V

AU - Pawade, Tania A

AU - Adamson, Philip D

AU - Whiteley, William N

AU - Wardlaw, Joanna M.

AU - Slomka, Piotr J

AU - Williams, Michelle C

AU - Newby, David E

AU - Dweck, Marc R

N1 - Funding Information: Drs Fletcher (FS/19/15/34155), Tzolos (FS/17/51/33096), Syed (FS/18/31/33676), Moss (AA/18/3/34220), Walker (FS/19/15/34155), Williams (FS/ICRF/20/26002), Newby (CH/09/002, RG/16/10/32375, RE/18/5/34216), and Dweck (FS/14/78/31020) are supported by the British Heart Foundation. Dr Lembo is supported by the International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh). Dr van Beek is supported by SINAPSE. Dr Adamson is supported by a Heart Foundation of New Zealand Senior Fellowship (1844). Dr Wardlaw is supported by the UK Dementia Research Institute (funded by the MRC, Alzheimer Society and Alzheimer Research UK). Dr Slomka and FusionQuant Development are supported by the National Institute of Health Grant HL135557 (PI: Dr Slomka); and his laboratory is supported by National Institutes of Health R01HL135557. Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA); and holds investigator-initiated research grants from Siemens Healthineers. Dr Dweck is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). The Edinburgh Imaging facility QMRI (Edinburgh) is supported by the National Health Service Research Scotland through National Health Service Lothian Health Board. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2022 The Authors

PY - 2022/2/16

Y1 - 2022/2/16

N2 - Objective:To investigate whether thoracic 18F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke.Background:Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke.Methods:In a post-hoc observational cohort study, we quantified thoracic aortic and coronary 18F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable logistic regression.Results:After 12·7±2·7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18F-sodium fluoride activity (n=140, r=0·31, p=0·00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6·1±2·3 years of follow up. High thoracic aortic 18F-sodium fluoride activity was strongly associated with ischemic stroke (HR 10·3 [3·1 to 34·8], p=0·0017), but not myocardial infarction (p=0·40). Conversely, high coronary 18F-sodium fluoride activity was associated with myocardial infarction (HR 4·8 [1·9 to 12·2], p=0·00095) but not ischemic stroke (p=0·39). In a multivariable logistic regression model including imaging and clinical risk factors, thoracic aortic 18F-sodium fluoride activity was the only variable associated with ischemic stroke (OR 1·76 [1·12 to 2·78], p=0·0014).Conclusion:In patients with established cardiovascular disease, thoracic aortic 18F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18F-sodium fluoride activity identifies localised areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events.

AB - Objective:To investigate whether thoracic 18F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke.Background:Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke.Methods:In a post-hoc observational cohort study, we quantified thoracic aortic and coronary 18F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable logistic regression.Results:After 12·7±2·7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18F-sodium fluoride activity (n=140, r=0·31, p=0·00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6·1±2·3 years of follow up. High thoracic aortic 18F-sodium fluoride activity was strongly associated with ischemic stroke (HR 10·3 [3·1 to 34·8], p=0·0017), but not myocardial infarction (p=0·40). Conversely, high coronary 18F-sodium fluoride activity was associated with myocardial infarction (HR 4·8 [1·9 to 12·2], p=0·00095) but not ischemic stroke (p=0·39). In a multivariable logistic regression model including imaging and clinical risk factors, thoracic aortic 18F-sodium fluoride activity was the only variable associated with ischemic stroke (OR 1·76 [1·12 to 2·78], p=0·0014).Conclusion:In patients with established cardiovascular disease, thoracic aortic 18F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18F-sodium fluoride activity identifies localised areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events.

KW - Stroke

KW - Calcification

KW - Computed tomography

KW - Positron emission tomography

KW - Sodium fluoride

KW - Thoracic aorta

U2 - 10.1016/j.jcmg.2021.12.013

DO - 10.1016/j.jcmg.2021.12.013

M3 - Article

SN - 1936-878X

JO - JACC: Cardiovascular Imaging

JF - JACC: Cardiovascular Imaging

ER -

Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients with Established Cardiovascular Disease

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Projects

Impact of COVID-19 on short and long term outcomes after stroke: R4VaD and COVID-19

Non-invasive detection of bicuspid aortic valve¿related thoracic aortopathy

18F-Sodium Fluoride Positron Emission Tomography in Patients with Acute Aortic Syndrome

Equipment

Edinburgh Imaging Facility

Cite this