Coronary Atherosclerotic Precursors of Acute Coronary Syndromes

Hyuk Jae Chang; Fay Y. Lin; Sang Eun Lee; Daniele Andreini; Jeroen Bax; Filippo Cademartiri; Kavitha Chinnaiyan; Benjamin J.W. Chow; Edoardo Conte; Ricardo C. Cury; Gudrun Feuchtner; Martin Hadamitzky; Yong Jin Kim; Jonathon Leipsic; Erica Maffei; Hugo Marques; Fabian Plank; Gianluca Pontone; Gilbert L. Raff; Alexander R. van Rosendael; Todd C. Villines; Harald G. Weirich; Subhi J. Al'Aref; Lohendran Baskaran; Iksung Cho; Ibrahim Danad; Donghee Han; Ran Heo; Ji Hyun Lee; Asim Rivzi; Wijnand J. Stuijfzand; Heidi Gransar; Yao Lu; Ji Min Sung; Hyung Bok Park; Daniel S. Berman; Matthew J. Budoff; Habib Samady; Leslee J. Shaw; Peter H. Stone; Renu Virmani; Jagat Narula; James K. Min

doi:10.1016/j.jacc.2018.02.079

Coronary Atherosclerotic Precursors of Acute Coronary Syndromes

Hyuk Jae Chang, Fay Y. Lin, Sang Eun Lee, Daniele Andreini, Jeroen Bax, Filippo Cademartiri, Kavitha Chinnaiyan, Benjamin J.W. Chow, Edoardo Conte, Ricardo C. Cury, Gudrun Feuchtner, Martin Hadamitzky, Yong Jin Kim, Jonathon Leipsic, Erica Maffei, Hugo Marques, Fabian Plank, Gianluca Pontone, Gilbert L. Raff, Alexander R. van RosendaelTodd C. Villines, Harald G. Weirich, Subhi J. Al'Aref, Lohendran Baskaran, Iksung Cho, Ibrahim Danad, Donghee Han, Ran Heo, Ji Hyun Lee, Asim Rivzi, Wijnand J. Stuijfzand, Heidi Gransar, Yao Lu, Ji Min Sung, Hyung Bok Park, Daniel S. Berman, Matthew J. Budoff, Habib Samady, Leslee J. Shaw, Peter H. Stone, Renu Virmani, Jagat Narula, James K. Min

Department of Internal Medicine

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

248 Citations (Scopus)

Abstract

Background: The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden. Objectives: The purpose of this study was to identify atherosclerotic features associated with precursors of ACS. Methods: We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA–evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs). Results: We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm³ fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm³ necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP. Conclusions: Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden.

Original language	English
Pages (from-to)	2511-2522
Number of pages	12
Journal	Journal of the American College of Cardiology
Volume	71
Issue number	22
DOIs	https://doi.org/10.1016/j.jacc.2018.02.079
Publication status	Published - 2018 Jun 5

Bibliographical note

Funding Information:
This trial was supported by National Institutes of Health Grant HL115150 and the Leading Foreign Research Institute Recruitment Program of the National Research Foundation of Korea, Ministry of Science, ICT & Future Planning. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Dr. Chang has received funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (Grant No. 2012027176). Dr. Min has received funding from the National Institutes of Health (grants R01 HL111141, R01 HL115150, R01 118019, and U01 HL 105907), the Qatar National Priorities Research Program (grant 09-370-3-089), and GE Healthcare. Dr. Bax has received unrestricted research grants from Biotronik, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr. Leipsic has served as a consultant for and has stock options in HeartFlow and Circle Cardiovascular Imaging; and has received speaking fees from GE Healthcare. Dr. Chow has received research support from CV Diagnostix; and educational support from TeraRecon Inc. Dr. Pontone has received institutional speaker honoraria and research grants from GE Healthcare, HeartFlow, Medtronic, Bracco, and Bayer. Dr. Raff has received grant support from HeartFlow. Dr. van Rosendael is supported by a research grant from the Netherlands Heart Institute. Dr. Berman has received software royalties from Cedars-Sinai. Dr. Budoff has received grant support from the National Institutes of Health and General Electric. Dr. Samady has received grant support from Phillips, Volcano, St. Jude Medical, Abbott, Medtronic, and Gilead; and has served on the medical advisory board of Volcano and Phillips. Dr. Virmani has received institutional research support from 480 Biomedical, Abbott Vascular, ART, BioSensors International, Biotronik, Boston Scientific, Celonova, Claret Medical, Cook Medical, Cordis, Edwards Lifesciences, Medtronic, MicroVention, OrbusNeich, ReCord, SINO Medical Technology, Spectranetics, Surmodics, Terumo Corporation, W.L. Gore, and Xeltis; has received honoraria from 480 Biomedical, Abbott Vascular, Boston Scientific, Cook Medical, Lutonix, Medtronic, Terumo Corporation, and W.L. Gore; and has served as a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. Dr. Min has served as a consultant to HeartFlow; has served on the scientific advisory board of Arineta; has ownership in MDDX; and has a research agreement with GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John Ambrose, MD, served as Guest Editor for this paper.

Publisher Copyright:
© 2018

All Science Journal Classification (ASJC) codes

Cardiology and Cardiovascular Medicine

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10.1016/j.jacc.2018.02.079

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Chang, H. J., Lin, F. Y., Lee, S. E., Andreini, D., Bax, J., Cademartiri, F., Chinnaiyan, K., Chow, B. J. W., Conte, E., Cury, R. C., Feuchtner, G., Hadamitzky, M., Kim, Y. J., Leipsic, J., Maffei, E., Marques, H., Plank, F., Pontone, G., Raff, G. L., ... Min, J. K. (2018). Coronary Atherosclerotic Precursors of Acute Coronary Syndromes. Journal of the American College of Cardiology, 71(22), 2511-2522. https://doi.org/10.1016/j.jacc.2018.02.079

@article{a47b5d562b264bb3acf09e8b8d4a33d6,

title = "Coronary Atherosclerotic Precursors of Acute Coronary Syndromes",

abstract = "Background: The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden. Objectives: The purpose of this study was to identify atherosclerotic features associated with precursors of ACS. Methods: We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA–evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs). Results: We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm3 fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm3 necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP. Conclusions: Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden.",

author = "Chang, {Hyuk Jae} and Lin, {Fay Y.} and Lee, {Sang Eun} and Daniele Andreini and Jeroen Bax and Filippo Cademartiri and Kavitha Chinnaiyan and Chow, {Benjamin J.W.} and Edoardo Conte and Cury, {Ricardo C.} and Gudrun Feuchtner and Martin Hadamitzky and Kim, {Yong Jin} and Jonathon Leipsic and Erica Maffei and Hugo Marques and Fabian Plank and Gianluca Pontone and Raff, {Gilbert L.} and {van Rosendael}, {Alexander R.} and Villines, {Todd C.} and Weirich, {Harald G.} and Al'Aref, {Subhi J.} and Lohendran Baskaran and Iksung Cho and Ibrahim Danad and Donghee Han and Ran Heo and Lee, {Ji Hyun} and Asim Rivzi and Stuijfzand, {Wijnand J.} and Heidi Gransar and Yao Lu and Sung, {Ji Min} and Park, {Hyung Bok} and Berman, {Daniel S.} and Budoff, {Matthew J.} and Habib Samady and Shaw, {Leslee J.} and Stone, {Peter H.} and Renu Virmani and Jagat Narula and Min, {James K.}",

note = "Funding Information: This trial was supported by National Institutes of Health Grant HL115150 and the Leading Foreign Research Institute Recruitment Program of the National Research Foundation of Korea, Ministry of Science, ICT & Future Planning. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Dr. Chang has received funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (Grant No. 2012027176). Dr. Min has received funding from the National Institutes of Health (grants R01 HL111141, R01 HL115150, R01 118019, and U01 HL 105907), the Qatar National Priorities Research Program (grant 09-370-3-089), and GE Healthcare. Dr. Bax has received unrestricted research grants from Biotronik, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr. Leipsic has served as a consultant for and has stock options in HeartFlow and Circle Cardiovascular Imaging; and has received speaking fees from GE Healthcare. Dr. Chow has received research support from CV Diagnostix; and educational support from TeraRecon Inc. Dr. Pontone has received institutional speaker honoraria and research grants from GE Healthcare, HeartFlow, Medtronic, Bracco, and Bayer. Dr. Raff has received grant support from HeartFlow. Dr. van Rosendael is supported by a research grant from the Netherlands Heart Institute. Dr. Berman has received software royalties from Cedars-Sinai. Dr. Budoff has received grant support from the National Institutes of Health and General Electric. Dr. Samady has received grant support from Phillips, Volcano, St. Jude Medical, Abbott, Medtronic, and Gilead; and has served on the medical advisory board of Volcano and Phillips. Dr. Virmani has received institutional research support from 480 Biomedical, Abbott Vascular, ART, BioSensors International, Biotronik, Boston Scientific, Celonova, Claret Medical, Cook Medical, Cordis, Edwards Lifesciences, Medtronic, MicroVention, OrbusNeich, ReCord, SINO Medical Technology, Spectranetics, Surmodics, Terumo Corporation, W.L. Gore, and Xeltis; has received honoraria from 480 Biomedical, Abbott Vascular, Boston Scientific, Cook Medical, Lutonix, Medtronic, Terumo Corporation, and W.L. Gore; and has served as a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. Dr. Min has served as a consultant to HeartFlow; has served on the scientific advisory board of Arineta; has ownership in MDDX; and has a research agreement with GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John Ambrose, MD, served as Guest Editor for this paper. Publisher Copyright: {\textcopyright} 2018",

year = "2018",

month = jun,

day = "5",

doi = "10.1016/j.jacc.2018.02.079",

language = "English",

volume = "71",

pages = "2511--2522",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "22",

}

Chang, HJ, Lin, FY, Lee, SE, Andreini, D, Bax, J, Cademartiri, F, Chinnaiyan, K, Chow, BJW, Conte, E, Cury, RC, Feuchtner, G, Hadamitzky, M, Kim, YJ, Leipsic, J, Maffei, E, Marques, H, Plank, F, Pontone, G, Raff, GL, van Rosendael, AR, Villines, TC, Weirich, HG, Al'Aref, SJ, Baskaran, L, Cho, I, Danad, I, Han, D, Heo, R, Lee, JH, Rivzi, A, Stuijfzand, WJ, Gransar, H, Lu, Y, Sung, JM, Park, HB, Berman, DS, Budoff, MJ, Samady, H, Shaw, LJ, Stone, PH, Virmani, R, Narula, J & Min, JK 2018, 'Coronary Atherosclerotic Precursors of Acute Coronary Syndromes', Journal of the American College of Cardiology, vol. 71, no. 22, pp. 2511-2522. https://doi.org/10.1016/j.jacc.2018.02.079

TY - JOUR

T1 - Coronary Atherosclerotic Precursors of Acute Coronary Syndromes

AU - Chang, Hyuk Jae

AU - Lin, Fay Y.

AU - Lee, Sang Eun

AU - Andreini, Daniele

AU - Bax, Jeroen

AU - Cademartiri, Filippo

AU - Chinnaiyan, Kavitha

AU - Chow, Benjamin J.W.

AU - Conte, Edoardo

AU - Cury, Ricardo C.

AU - Feuchtner, Gudrun

AU - Hadamitzky, Martin

AU - Kim, Yong Jin

AU - Leipsic, Jonathon

AU - Maffei, Erica

AU - Marques, Hugo

AU - Plank, Fabian

AU - Pontone, Gianluca

AU - Raff, Gilbert L.

AU - van Rosendael, Alexander R.

AU - Villines, Todd C.

AU - Weirich, Harald G.

AU - Al'Aref, Subhi J.

AU - Baskaran, Lohendran

AU - Cho, Iksung

AU - Danad, Ibrahim

AU - Han, Donghee

AU - Heo, Ran

AU - Lee, Ji Hyun

AU - Rivzi, Asim

AU - Stuijfzand, Wijnand J.

AU - Gransar, Heidi

AU - Lu, Yao

AU - Sung, Ji Min

AU - Park, Hyung Bok

AU - Berman, Daniel S.

AU - Budoff, Matthew J.

AU - Samady, Habib

AU - Shaw, Leslee J.

AU - Stone, Peter H.

AU - Virmani, Renu

AU - Narula, Jagat

AU - Min, James K.

N1 - Funding Information: This trial was supported by National Institutes of Health Grant HL115150 and the Leading Foreign Research Institute Recruitment Program of the National Research Foundation of Korea, Ministry of Science, ICT & Future Planning. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Dr. Chang has received funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (Grant No. 2012027176). Dr. Min has received funding from the National Institutes of Health (grants R01 HL111141, R01 HL115150, R01 118019, and U01 HL 105907), the Qatar National Priorities Research Program (grant 09-370-3-089), and GE Healthcare. Dr. Bax has received unrestricted research grants from Biotronik, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr. Leipsic has served as a consultant for and has stock options in HeartFlow and Circle Cardiovascular Imaging; and has received speaking fees from GE Healthcare. Dr. Chow has received research support from CV Diagnostix; and educational support from TeraRecon Inc. Dr. Pontone has received institutional speaker honoraria and research grants from GE Healthcare, HeartFlow, Medtronic, Bracco, and Bayer. Dr. Raff has received grant support from HeartFlow. Dr. van Rosendael is supported by a research grant from the Netherlands Heart Institute. Dr. Berman has received software royalties from Cedars-Sinai. Dr. Budoff has received grant support from the National Institutes of Health and General Electric. Dr. Samady has received grant support from Phillips, Volcano, St. Jude Medical, Abbott, Medtronic, and Gilead; and has served on the medical advisory board of Volcano and Phillips. Dr. Virmani has received institutional research support from 480 Biomedical, Abbott Vascular, ART, BioSensors International, Biotronik, Boston Scientific, Celonova, Claret Medical, Cook Medical, Cordis, Edwards Lifesciences, Medtronic, MicroVention, OrbusNeich, ReCord, SINO Medical Technology, Spectranetics, Surmodics, Terumo Corporation, W.L. Gore, and Xeltis; has received honoraria from 480 Biomedical, Abbott Vascular, Boston Scientific, Cook Medical, Lutonix, Medtronic, Terumo Corporation, and W.L. Gore; and has served as a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. Dr. Min has served as a consultant to HeartFlow; has served on the scientific advisory board of Arineta; has ownership in MDDX; and has a research agreement with GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John Ambrose, MD, served as Guest Editor for this paper. Publisher Copyright: © 2018

PY - 2018/6/5

Y1 - 2018/6/5

N2 - Background: The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden. Objectives: The purpose of this study was to identify atherosclerotic features associated with precursors of ACS. Methods: We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA–evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs). Results: We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm3 fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm3 necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP. Conclusions: Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden.

AB - Background: The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden. Objectives: The purpose of this study was to identify atherosclerotic features associated with precursors of ACS. Methods: We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA–evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs). Results: We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm3 fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm3 necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP. Conclusions: Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden.

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JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

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Coronary Atherosclerotic Precursors of Acute Coronary Syndromes

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