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

Alexander R. Van Rosendael, New York Presbyterian Hospital
Jagat Narula, Icahn School of Medicine at Mount Sinai
Fay Y. Lin, New York Presbyterian Hospital
Inge J. Van Den Hoogen, New York Presbyterian Hospital
Umberto Gianni, New York Presbyterian Hospital
Omar Al Hussein Alawamlh, New York Presbyterian Hospital
Patricia C. Dunham, New York Presbyterian Hospital
Jessica M. Penã, New York Presbyterian Hospital
Sang Eun Lee, Severance Hospital
Daniele Andreini, Università degli Studi di Milano
Filippo Cademartiri, IRCCS Fondazione SDN
Kavitha Chinnaiyan, William Beaumont Hospital
Benjamin J.W. Chow, University of Ottawa, Canada
Edoardo Conte, Università degli Studi di Milano
Ricardo C. Cury, Baptist Cardiac and Vascular Institute
Gudrun Feuchtner, Medizinische Universitat Innsbruck
Martin Hadamitzky, Deutsches Herzzentrum München
Yong Jin Kim, Seoul National University Hospital
Jonathon Leipsic, The University of British Columbia
Erica Maffei
Hugo Marques, Hospital da Luz
Pedro De Araújo Goncąlves, Hospital da Luz
Fabian Plank, Medizinische Universitat Innsbruck
Gianluca Pontone, Università degli Studi di Milano
Gilbert L. Raff, William Beaumont Hospital
Todd C. Villines, Walter Reed National Military
Harald G. Weirich, Medizinische Universitat Innsbruck
Subhi J. Al'Aref, New York Presbyterian Hospital
Lohendran Baskaran, New York Presbyterian Hospital
Iksung Cho, New York Presbyterian Hospital
Ibrahim Danad, Amsterdam UMC - Vrije Universiteit Amsterdam
Donghee Han, Severance Hospital
Ran Heo, University of Ulsan, College of Medicine


© 2019 American Medical Association. All rights reserved. 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.