Coronary Atherosclerotic Precursors of Acute Coronary Syndromes

Hyuk Jae Chang, Severance Hospital
Fay Y. Lin, New York Presbyterian Hospital
Sang Eun Lee, Severance Hospital
Daniele Andreini, Università degli Studi di Milano
Jeroen Bax, Leiden University Medical Center - LUMC
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
Fabian Plank, Medizinische Universitat Innsbruck
Gianluca Pontone, Università degli Studi di Milano
Gilbert L. Raff, William Beaumont Hospital
Alexander R. van Rosendael, Leiden University Medical Center - LUMC
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, Severance Hospital
Ibrahim Danad, Amsterdam UMC - Vrije Universiteit Amsterdam
Donghee Han, Severance Hospital
Ran Heo, University of Ulsan, College of Medicine
Ji Hyun Lee, Severance Hospital
Asim Rivzi, New York Presbyterian Hospital
Wijnand J. Stuijfzand, New York Presbyterian Hospital
Heidi Gransar, Cedars-Sinai Medical Center
Yao Lu, New York Presbyterian Hospital


© 2018 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.