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.
Bibliographical noteFunding Information:
This trial was supported by National Institutes of Health Grant HL115150 and the Leading Foreign Research Institute Recruitment Program of the National Research Foundation of Korea, Ministry of Science, ICT & Future Planning. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Dr. Chang has received funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (Grant No. 2012027176). Dr. Min has received funding from the National Institutes of Health (grants R01 HL111141, R01 HL115150, R01 118019, and U01 HL 105907), the Qatar National Priorities Research Program (grant 09-370-3-089), and GE Healthcare. Dr. Bax has received unrestricted research grants from Biotronik, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr. Leipsic has served as a consultant for and has stock options in HeartFlow and Circle Cardiovascular Imaging; and has received speaking fees from GE Healthcare. Dr. Chow has received research support from CV Diagnostix; and educational support from TeraRecon Inc. Dr. Pontone has received institutional speaker honoraria and research grants from GE Healthcare, HeartFlow, Medtronic, Bracco, and Bayer. Dr. Raff has received grant support from HeartFlow. Dr. van Rosendael is supported by a research grant from the Netherlands Heart Institute. Dr. Berman has received software royalties from Cedars-Sinai. Dr. Budoff has received grant support from the National Institutes of Health and General Electric. Dr. Samady has received grant support from Phillips, Volcano, St. Jude Medical, Abbott, Medtronic, and Gilead; and has served on the medical advisory board of Volcano and Phillips. Dr. Virmani has received institutional research support from 480 Biomedical, Abbott Vascular, ART, BioSensors International, Biotronik, Boston Scientific, Celonova, Claret Medical, Cook Medical, Cordis, Edwards Lifesciences, Medtronic, MicroVention, OrbusNeich, ReCord, SINO Medical Technology, Spectranetics, Surmodics, Terumo Corporation, W.L. Gore, and Xeltis; has received honoraria from 480 Biomedical, Abbott Vascular, Boston Scientific, Cook Medical, Lutonix, Medtronic, Terumo Corporation, and W.L. Gore; and has served as a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. Dr. Min has served as a consultant to HeartFlow; has served on the scientific advisory board of Arineta; has ownership in MDDX; and has a research agreement with GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John Ambrose, MD, served as Guest Editor for this paper.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine