Coronary Atherosclerotic Precursors of Acute Coronary Syndromes

H.-J. Chang, F.Y. Lin, S.-E. Lee, D. Andreini, J. Bax, F. Cademartiri, K. Chinnaiyan, B.J.W. Chow, E. Conte, R.C. Cury, G. Feuchtner, M. Hadamitzky, Y.-J. Kim, J. Leipsic, E. Maffei, H. Marques, F. Plank, G. Pontone, G.L. Raff, A.R. van RosendaelT.C. Villines, H.G. Weirich, S.J. Al'Aref, L. Baskaran, I. Cho, I. Danad, D. Han, R. Heo, J.H. Lee, A. Rivzi, W.J. Stuijfzand, H. Gransar, Y. Lu, J.M. Sung, H.-B. Park, D.S. Berman, M.J. Budoff, H. Samady, L.J. Shaw, P.H. Stone, R. Virmani, J. Narula, J.K. Min

Research output: Contribution to journalArticlepeer-review


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. © 2018
Original languageEnglish
Pages (from-to)2511-2522
Number of pages12
JournalJournal of the American College of Cardiology
Issue number22
Publication statusPublished - 2018


  • acute coronary syndrome
  • atherosclerosis
  • clinical outcome
  • coronary artery disease
  • coronary computed tomography angiography
  • adult
  • age
  • Article
  • case control study
  • cohort analysis
  • computed tomographic angiography
  • controlled study
  • coronary artery atherosclerosis
  • coronary artery obstruction
  • disease association
  • disease classification
  • disease severity
  • follow up
  • gender
  • high risk patient
  • human
  • major clinical study
  • male
  • mouse
  • nonhuman
  • priority journal
  • risk factor


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