Alexander R van Rosendael1,2, Jagat Narula3, Fay Y Lin1, Inge J van den Hoogen1,2, Umberto Gianni1, Omar Al Hussein Alawamlh1, Patricia C Dunham1, Jessica M Peña1, Sang-Eun Lee4, Daniele Andreini5, Filippo Cademartiri6, Kavitha Chinnaiyan7, Benjamin J W Chow8, Edoardo Conte5, Ricardo C Cury9, Gudrun Feuchtner10, Martin Hadamitzky11, Yong-Jin Kim12, Jonathon Leipsic13, Erica Maffei14, Hugo Marques15, Pedro de Araújo Gonçalves15, Fabian Plank10, Gianluca Pontone5, Gilbert L Raff7, Todd C Villines16, Harald G Weirich10, Subhi J Al'Aref1, Lohendran Baskaran1,17, Iksung Cho1,4,18, Ibrahim Danad19, Donghee Han4, Ran Heo20, Ji Hyun Lee4, Asim Rivzi21, Wijnand J Stuijfzand1, Heidi Gransar22, Yao Lu23, Ji Min Sung4, Hyung-Bok Park4, Habib Samady24, Peter H Stone25, Renu Virmani26, Matthew J Budoff27, Daniel S Berman28, Hyuk-Jae Chang4, Jeroen J Bax2, James K Min1, Leslee J Shaw1. 1. Dalio Institute of Cardiovascular Imaging, Department of Radiology, New York-Presbyterian Hospital, Weill Cornell Medicine, New York, New York. 2. Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands. 3. Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, Zena and Michael A. Wiener Cardiovascular Institute, and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, New York, New York. 4. Division of Cardiology, Severance Cardiovascular Hospital, Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Seoul, South Korea. 5. Department of Clinical Sciences and Community Health, University of Milan, Centro Cardiologico Monzino, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), Milan, Italy. 6. Cardiovascular Imaging Center, SDN IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), Naples, Italy. 7. Department of Cardiology, William Beaumont Hospital, Royal Oak, Michigan. 8. Department of Medicine and Radiology, University of Ottawa, Ottawa, Ontario, Canada. 9. Department of Radiology, Miami Cardiac and Vascular Institute, Miami, Florida. 10. Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria. 11. Department of Radiology and Nuclear Medicine, German Heart Center Munich, Munich, Germany. 12. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. 13. Department of Medicine and Radiology, University of British Columbia, Vancouver, British Columbia, Canada. 14. Department of Radiology, Area Vasta 1/ASUR Marche, Urbino, Italy. 15. UNICA, Unit of Cardiovascular Imaging, Hospital da Luz, Lisboa, Portugal. 16. Cardiology Service, Walter Reed National Military Center, Bethesda, Maryland. 17. Department of Cardiovascular Medicine, National Heart Centre Singapore, Singapore. 18. Division of Cardiology, Chung-Ang University Hospital, Seoul, South Korea. 19. Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands. 20. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 21. Department of Radiology, Mayo Clinic, Rochester, Minnesota. 22. Department of Imaging, Cedars Sinai Medical Center, Los Angeles, California. 23. Department of Healthcare Policy and Research, New York-Presbyterian Hospital/Weill Cornell Medical College, New York, New York. 24. Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia. 25. Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 26. Department of Pathology, CVPath Institute, Gaithersburg, Maryland. 27. Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, California. 28. Department of Imaging and Medicine, Cedars Sinai Medical Center, Los Angeles, California.
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.
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.
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