Peri-Coronary Adipose Tissue Density Is Associated With 18F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques

Jacek Kwiecinski; Damini Dey; Sebastien Cadet; Sang Eun Lee; Yuka Otaki; Phi T. Huynh; Mhairi K. Doris; Evann Eisenberg; Mijin Yun; Maurits A. Jansen; Michelle C. Williams; Balaji K. Tamarappoo; John D. Friedman; Marc R. Dweck; David E. Newby; Hyuk Jae Chang; Piotr J. Slomka; Daniel S. Berman

doi:10.1016/j.jcmg.2018.11.032

Peri-Coronary Adipose Tissue Density Is Associated With ¹⁸F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques

Jacek Kwiecinski, Damini Dey, Sebastien Cadet, Sang Eun Lee, Yuka Otaki, Phi T. Huynh, Mhairi K. Doris, Evann Eisenberg, Mijin Yun, Maurits A. Jansen, Michelle C. Williams, Balaji K. Tamarappoo, John D. Friedman, Marc R. Dweck, David E. Newby, Hyuk Jae Chang, Piotr J. Slomka, Daniel S. Berman

Department of Internal Medicine

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

99 Citations (Scopus)

Abstract

Objectives: This study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary ¹⁸F-sodium fluoride (¹⁸F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA). Background: Coronary ¹⁸F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and ¹⁸F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized. Methods: Patients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm³). Patients with HRPs were recruited to undergo ¹⁸F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion−corrected ¹⁸F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured. Results: Forty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary ¹⁸F-NaF activity. Lesions with ¹⁸F-NaF uptake had higher surrounding PCAT density than those without ¹⁸F-NaF uptake (−73 HU; interquartile range −79 to −68 HU vs. −86 HU; interquartile range −94 to −80 HU; p < 0.001). ¹⁸F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with ¹⁸F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP). Conclusions: In patients with HRP features on coronary CTA, increased density of PCAT was associated with focal ¹⁸F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by ¹⁸F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features.

Original language	English
Pages (from-to)	2000-2010
Number of pages	11
Journal	JACC: Cardiovascular Imaging
Volume	12
Issue number	10
DOIs	https://doi.org/10.1016/j.jcmg.2018.11.032
Publication status	Published - 2019 Oct

Bibliographical note

Funding Information:
This research was supported in part by the National Heart, Lung, and Blood Institute/National Institute of Health (NHLBI/NIH) (grants R01HL135557 and R01HL133616) and by a grant from the Miriam and Sheldon G. Adelson Medical Research Foundation. Dr. Doris was supported by the British Heart Foundation (FS/14/78/31020). Dr. Williams is supported by The Chief Scientist Office of the Scottish Government Health and Social Care Directorates (PCL/17/04). Dr. Newby was supported by the British Heart Foundation (CH/09/002, RE/13/3/30183) and received a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr. Dweck was supported by the British Heart Foundation (FS/17/79/33226). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Drs. Dey, Slomka, and Berman have received software royalties from Cedars-Sinai Medical Center and have a patent (US8885905B2 in U.S. and WO patent WO2011069120A1 worldwide). Mr. Cadet has received software royalties from Cedars-Sinai Medical. Dr. Williams has been a consultant for GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2019 American College of Cardiology Foundation

All Science Journal Classification (ASJC) codes

Radiology Nuclear Medicine and imaging
Cardiology and Cardiovascular Medicine

Access to Document

10.1016/j.jcmg.2018.11.032

Cite this

Kwiecinski, J., Dey, D., Cadet, S., Lee, S. E., Otaki, Y., Huynh, P. T., Doris, M. K., Eisenberg, E., Yun, M., Jansen, M. A., Williams, M. C., Tamarappoo, B. K., Friedman, J. D., Dweck, M. R., Newby, D. E., Chang, H. J., Slomka, P. J., & Berman, D. S. (2019). Peri-Coronary Adipose Tissue Density Is Associated With ¹⁸F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques. JACC: Cardiovascular Imaging, 12(10), 2000-2010. https://doi.org/10.1016/j.jcmg.2018.11.032

@article{f3f50b3bd0644f94977b41fe684297a9,

title = "Peri-Coronary Adipose Tissue Density Is Associated With 18F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques",

abstract = "Objectives: This study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary 18F-sodium fluoride (18F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA). Background: Coronary 18F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and 18F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized. Methods: Patients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm3). Patients with HRPs were recruited to undergo 18F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion−corrected 18F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured. Results: Forty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary 18F-NaF activity. Lesions with 18F-NaF uptake had higher surrounding PCAT density than those without 18F-NaF uptake (−73 HU; interquartile range −79 to −68 HU vs. −86 HU; interquartile range −94 to −80 HU; p < 0.001). 18F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with 18F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP). Conclusions: In patients with HRP features on coronary CTA, increased density of PCAT was associated with focal 18F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by 18F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features.",

author = "Jacek Kwiecinski and Damini Dey and Sebastien Cadet and Lee, {Sang Eun} and Yuka Otaki and Huynh, {Phi T.} and Doris, {Mhairi K.} and Evann Eisenberg and Mijin Yun and Jansen, {Maurits A.} and Williams, {Michelle C.} and Tamarappoo, {Balaji K.} and Friedman, {John D.} and Dweck, {Marc R.} and Newby, {David E.} and Chang, {Hyuk Jae} and Slomka, {Piotr J.} and Berman, {Daniel S.}",

note = "Funding Information: This research was supported in part by the National Heart, Lung, and Blood Institute/National Institute of Health (NHLBI/NIH) (grants R01HL135557 and R01HL133616) and by a grant from the Miriam and Sheldon G. Adelson Medical Research Foundation. Dr. Doris was supported by the British Heart Foundation (FS/14/78/31020). Dr. Williams is supported by The Chief Scientist Office of the Scottish Government Health and Social Care Directorates (PCL/17/04). Dr. Newby was supported by the British Heart Foundation (CH/09/002, RE/13/3/30183) and received a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr. Dweck was supported by the British Heart Foundation (FS/17/79/33226). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Drs. Dey, Slomka, and Berman have received software royalties from Cedars-Sinai Medical Center and have a patent (US8885905B2 in U.S. and WO patent WO2011069120A1 worldwide). Mr. Cadet has received software royalties from Cedars-Sinai Medical. Dr. Williams has been a consultant for GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2019 American College of Cardiology Foundation",

year = "2019",

month = oct,

doi = "10.1016/j.jcmg.2018.11.032",

language = "English",

volume = "12",

pages = "2000--2010",

journal = "JACC: Cardiovascular Imaging",

issn = "1936-878X",

publisher = "Elsevier Inc.",

number = "10",

}

Kwiecinski, J, Dey, D, Cadet, S, Lee, SE, Otaki, Y, Huynh, PT, Doris, MK, Eisenberg, E, Yun, M, Jansen, MA, Williams, MC, Tamarappoo, BK, Friedman, JD, Dweck, MR, Newby, DE, Chang, HJ, Slomka, PJ & Berman, DS 2019, 'Peri-Coronary Adipose Tissue Density Is Associated With ¹⁸F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques', JACC: Cardiovascular Imaging, vol. 12, no. 10, pp. 2000-2010. https://doi.org/10.1016/j.jcmg.2018.11.032

TY - JOUR

T1 - Peri-Coronary Adipose Tissue Density Is Associated With 18F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques

AU - Kwiecinski, Jacek

AU - Dey, Damini

AU - Cadet, Sebastien

AU - Lee, Sang Eun

AU - Otaki, Yuka

AU - Huynh, Phi T.

AU - Doris, Mhairi K.

AU - Eisenberg, Evann

AU - Yun, Mijin

AU - Jansen, Maurits A.

AU - Williams, Michelle C.

AU - Tamarappoo, Balaji K.

AU - Friedman, John D.

AU - Dweck, Marc R.

AU - Newby, David E.

AU - Chang, Hyuk Jae

AU - Slomka, Piotr J.

AU - Berman, Daniel S.

N1 - Funding Information: This research was supported in part by the National Heart, Lung, and Blood Institute/National Institute of Health (NHLBI/NIH) (grants R01HL135557 and R01HL133616) and by a grant from the Miriam and Sheldon G. Adelson Medical Research Foundation. Dr. Doris was supported by the British Heart Foundation (FS/14/78/31020). Dr. Williams is supported by The Chief Scientist Office of the Scottish Government Health and Social Care Directorates (PCL/17/04). Dr. Newby was supported by the British Heart Foundation (CH/09/002, RE/13/3/30183) and received a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr. Dweck was supported by the British Heart Foundation (FS/17/79/33226). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Drs. Dey, Slomka, and Berman have received software royalties from Cedars-Sinai Medical Center and have a patent (US8885905B2 in U.S. and WO patent WO2011069120A1 worldwide). Mr. Cadet has received software royalties from Cedars-Sinai Medical. Dr. Williams has been a consultant for GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2019 American College of Cardiology Foundation

PY - 2019/10

Y1 - 2019/10

N2 - Objectives: This study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary 18F-sodium fluoride (18F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA). Background: Coronary 18F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and 18F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized. Methods: Patients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm3). Patients with HRPs were recruited to undergo 18F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion−corrected 18F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured. Results: Forty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary 18F-NaF activity. Lesions with 18F-NaF uptake had higher surrounding PCAT density than those without 18F-NaF uptake (−73 HU; interquartile range −79 to −68 HU vs. −86 HU; interquartile range −94 to −80 HU; p < 0.001). 18F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with 18F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP). Conclusions: In patients with HRP features on coronary CTA, increased density of PCAT was associated with focal 18F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by 18F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features.

AB - Objectives: This study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary 18F-sodium fluoride (18F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA). Background: Coronary 18F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and 18F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized. Methods: Patients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm3). Patients with HRPs were recruited to undergo 18F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion−corrected 18F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured. Results: Forty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary 18F-NaF activity. Lesions with 18F-NaF uptake had higher surrounding PCAT density than those without 18F-NaF uptake (−73 HU; interquartile range −79 to −68 HU vs. −86 HU; interquartile range −94 to −80 HU; p < 0.001). 18F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with 18F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP). Conclusions: In patients with HRP features on coronary CTA, increased density of PCAT was associated with focal 18F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by 18F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features.

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