TY - JOUR
T1 - Association of high-density calcified 1K plaque with risk of acute coronary syndrome
AU - Rosendael, Alexander R. van
AU - Narula, Jagat
AU - Lin, Fay Y.
AU - Hoogen, Inge J. van den
AU - Gianni, Umberto
AU - Alawamlh, Omar Al Hussein
AU - Dunham, Patricia C.
AU - Penã, 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 - Gonçalves, Pedro de Araújo
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.
N1 - Funding Information:
Alawamlh reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Chinnaiyan reported receiving grants from Heartflow Inc outside the submitted work and being an unpaid medical advisory board member of HeartFlow. Dr Chow reported holding the Saul and Edna Goldfarb Chair in cardiac imaging research, receiving research support from CV Diagnostix and Ausculsciences as well as educational support from TeraRecon Inc, and holding equity interest in GE Healthcare. Dr Cury reported receiving personal fees from Cleerly Inc and GE Healthcare outside the submitted work. Dr Hadamitzky reported receiving nonfinancial support from Siemens Healthineers outside the submitted work. Dr Leipsic reported receiving personal fees from HeartFlow and grants from GE Healthcare outside the submitted work. Dr Pontone reported receiving grants and personal fees from GE Healthcare, grants and personal fees from Bracco, and grants from HeartFlow outside the submitted work. Dr Raff reported receiving grants from Blue Cross Blue Shield of Michigan during the conduct of the study and grants from HeartFlow Inc outside the submitted work. Dr Stuijfzand reported receiving grants from the NIH; Leading Foreign Research Institute Recruitment Program of the National Research Foundation of Korea, Ministry of Science, ICT and Future Planning; and Dalio Institute of Cardiovascular Imaging during the conduct of the study. Dr Samady reported serving on the scientific advisory board of Philips, holding equity interest in Covanos Inc, and receiving research grants from Medtronic, Abbott Vascular, and Philips. Dr Budoff reported receiving grants from GE Healthcare during the conduct of the study. Dr Berman reported receiving software royalties from Cedars-Sinai Medical Center. Dr Bax reported receiving departmental grants and other from Medtronic as well as grants from Biotronik, Boston Scientific, Abbott, Edwards Lifescience, and GE Healthcare during the conduct of the study. Dr Min reported receiving funding from the Dalio Foundation, NIH, and GE Healthcare; serving on the scientific advisory board of Arineta and GE Healthcare; and holding equity interest in Cleerly Inc. No other disclosures were reported.
Funding Information:
Funding/Support: This study was funded by grant HL115150 from the NIH and by the Leading Foreign Research Institute Recruitment Program of the National Research Foundation of Korea, Ministry of Science, ICT and Future Planning.
Publisher Copyright:
© 2019 American Medical Association. All rights reserved.
PY - 2020/1/22
Y1 - 2020/1/22
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
C2 - 31968065
AN - SCOPUS:85078654592
SN - 2380-6583
VL - 5
SP - 282
EP - 290
JO - JAMA Cardiology
JF - JAMA Cardiology
IS - 3
ER -
