Association of High-Density Calcified 1K Plaque with Risk of Acute Coronary Syndrome

Alexander R. Van Rosendael, Jagat Narula, Fay Y. Lin, Inge J. Van Den Hoogen, Umberto Gianni, Omar Al Hussein Alawamlh, Patricia C. Dunham, Jessica M. Peña, Sang Eun Lee, Daniele Andreini, Filippo Cademartiri, Kavitha Chinnaiyan, Benjamin J.W. Chow, Edoardo Conte, Ricardo C. Cury, Gudrun Feuchtner, Martin Hadamitzky, Yong Jin Kim, Jonathon Leipsic, Erica Maffei & 29 others Hugo Marques, Pedro De Araújo Gonçalves, Fabian Plank, Gianluca Pontone, Gilbert L. Raff, 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, Habib Samady, Peter H. Stone, Renu Virmani, Matthew J. Budoff, Daniel S. Berman, Hyuk Jae Chang, Jeroen J. Bax, James K. Min, Leslee J. Shaw

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and Measures: Association between calcium density and future ACS risk. Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P =.32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P =.02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P <.001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P =.01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

Original languageEnglish
JournalJAMA cardiology
DOIs
Publication statusE-pub ahead of print - 1 Jan 2020

Cite this

Van Rosendael, A. R., Narula, J., Lin, F. Y., Van Den Hoogen, I. J., Gianni, U., Al Hussein Alawamlh, O., ... Shaw, L. J. (2020). Association of High-Density Calcified 1K Plaque with Risk of Acute Coronary Syndrome. JAMA cardiology. https://doi.org/10.1001/jamacardio.2019.5315
Van Rosendael, Alexander R. ; Narula, Jagat ; Lin, Fay Y. ; Van Den Hoogen, Inge J. ; Gianni, Umberto ; Al Hussein Alawamlh, Omar ; Dunham, Patricia C. ; Peña, Jessica M. ; Lee, Sang Eun ; Andreini, Daniele ; Cademartiri, Filippo ; Chinnaiyan, Kavitha ; Chow, Benjamin J.W. ; Conte, Edoardo ; Cury, Ricardo C. ; Feuchtner, Gudrun ; Hadamitzky, Martin ; Kim, Yong Jin ; Leipsic, Jonathon ; Maffei, Erica ; Marques, Hugo ; De Araújo Gonçalves, Pedro ; Plank, Fabian ; Pontone, Gianluca ; Raff, Gilbert L. ; Villines, Todd C. ; Weirich, Harald G. ; Al'Aref, Subhi J. ; Baskaran, Lohendran ; Cho, Iksung ; Danad, Ibrahim ; Han, Donghee ; Heo, Ran ; Lee, Ji Hyun ; Rivzi, Asim ; Stuijfzand, Wijnand J. ; Gransar, Heidi ; Lu, Yao ; Sung, Ji Min ; Park, Hyung Bok ; Samady, Habib ; Stone, Peter H. ; Virmani, Renu ; Budoff, Matthew J. ; Berman, Daniel S. ; Chang, Hyuk Jae ; Bax, Jeroen J. ; Min, James K. ; Shaw, Leslee J. / Association of High-Density Calcified 1K Plaque with Risk of Acute Coronary Syndrome. In: JAMA cardiology. 2020.
@article{27fcd9bfa6b94444847fbe9c8d374bf4,
title = "Association of High-Density Calcified 1K Plaque with Risk of Acute Coronary Syndrome",
abstract = "Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and Measures: Association between calcium density and future ACS risk. Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3{\%}] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P =.32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P =.02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6{\%} [10.4{\%}] vs 24.9{\%} [20.6{\%}]; P <.001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P =.01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.",
author = "{Van Rosendael}, {Alexander R.} and Jagat Narula and Lin, {Fay Y.} and {Van Den Hoogen}, {Inge J.} and Umberto Gianni and {Al Hussein Alawamlh}, Omar and Dunham, {Patricia C.} and Pe{\~n}a, {Jessica M.} and Lee, {Sang Eun} and Daniele Andreini 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 {De Ara{\'u}jo Gon{\cc}alves}, Pedro and Fabian Plank and Gianluca Pontone and Raff, {Gilbert L.} 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 Habib Samady and Stone, {Peter H.} and Renu Virmani and Budoff, {Matthew J.} and Berman, {Daniel S.} and Chang, {Hyuk Jae} and Bax, {Jeroen J.} and Min, {James K.} and Shaw, {Leslee J.}",
year = "2020",
month = "1",
day = "1",
doi = "10.1001/jamacardio.2019.5315",
language = "English",
journal = "JAMA cardiology",
issn = "2380-6583",
publisher = "American Medical Association",

}

Van Rosendael, AR, Narula, J, Lin, FY, Van Den Hoogen, IJ, Gianni, U, Al Hussein Alawamlh, O, Dunham, PC, Peña, JM, Lee, SE, Andreini, D, Cademartiri, F, Chinnaiyan, K, Chow, BJW, Conte, E, Cury, RC, Feuchtner, G, Hadamitzky, M, Kim, YJ, Leipsic, J, Maffei, E, Marques, H, De Araújo Gonçalves, P, Plank, F, Pontone, G, Raff, GL, 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, Samady, H, Stone, PH, Virmani, R, Budoff, MJ, Berman, DS, Chang, HJ, Bax, JJ, Min, JK & Shaw, LJ 2020, 'Association of High-Density Calcified 1K Plaque with Risk of Acute Coronary Syndrome' JAMA cardiology. https://doi.org/10.1001/jamacardio.2019.5315

Association of High-Density Calcified 1K Plaque with Risk of Acute Coronary Syndrome. / Van Rosendael, Alexander R.; Narula, Jagat; Lin, Fay Y.; Van Den Hoogen, Inge J.; Gianni, Umberto; Al Hussein Alawamlh, Omar; Dunham, Patricia C.; Peña, Jessica M.; Lee, Sang Eun; Andreini, Daniele; Cademartiri, Filippo; Chinnaiyan, Kavitha; Chow, Benjamin J.W.; Conte, Edoardo; Cury, Ricardo C.; Feuchtner, Gudrun; Hadamitzky, Martin; Kim, Yong Jin; Leipsic, Jonathon; Maffei, Erica; Marques, Hugo; De Araújo Gonçalves, Pedro; Plank, Fabian; Pontone, Gianluca; Raff, Gilbert L.; Villines, Todd C.; Weirich, Harald G.; Al'Aref, Subhi J.; Baskaran, Lohendran; Cho, Iksung; Danad, Ibrahim; Han, Donghee; Heo, Ran; Lee, Ji Hyun; Rivzi, Asim; Stuijfzand, Wijnand J.; Gransar, Heidi; Lu, Yao; Sung, Ji Min; Park, Hyung Bok; Samady, Habib; Stone, Peter H.; Virmani, Renu; Budoff, Matthew J.; Berman, Daniel S.; Chang, Hyuk Jae; Bax, Jeroen J.; Min, James K.; Shaw, Leslee J.

In: JAMA cardiology, 01.01.2020.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Association of High-Density Calcified 1K Plaque with Risk of Acute Coronary Syndrome

AU - Van Rosendael, Alexander R.

AU - Narula, Jagat

AU - Lin, Fay Y.

AU - Van Den Hoogen, Inge J.

AU - Gianni, Umberto

AU - Al Hussein Alawamlh, Omar

AU - Dunham, Patricia C.

AU - Peña, Jessica M.

AU - Lee, Sang Eun

AU - Andreini, Daniele

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 - De Araújo Gonçalves, Pedro

AU - Plank, Fabian

AU - Pontone, Gianluca

AU - Raff, Gilbert L.

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 - Samady, Habib

AU - Stone, Peter H.

AU - Virmani, Renu

AU - Budoff, Matthew J.

AU - Berman, Daniel S.

AU - Chang, Hyuk Jae

AU - Bax, Jeroen J.

AU - Min, James K.

AU - Shaw, Leslee J.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and Measures: Association between calcium density and future ACS risk. Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P =.32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P =.02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P <.001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P =.01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

AB - Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and Measures: Association between calcium density and future ACS risk. Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P =.32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P =.02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P <.001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P =.01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

UR - http://www.scopus.com/inward/record.url?scp=85078654592&partnerID=8YFLogxK

U2 - 10.1001/jamacardio.2019.5315

DO - 10.1001/jamacardio.2019.5315

M3 - Article

JO - JAMA cardiology

JF - JAMA cardiology

SN - 2380-6583

ER -

Van Rosendael AR, Narula J, Lin FY, Van Den Hoogen IJ, Gianni U, Al Hussein Alawamlh O et al. Association of High-Density Calcified 1K Plaque with Risk of Acute Coronary Syndrome. JAMA cardiology. 2020 Jan 1. https://doi.org/10.1001/jamacardio.2019.5315