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Original Investigation
February 2018

Use of High-Risk Coronary Atherosclerotic Plaque Detection for Risk Stratification of Patients With Stable Chest Pain: A Secondary Analysis of the PROMISE Randomized Clinical Trial

Author Affiliations
  • 1Knight Cardiovascular Institute, Oregon Health and Science University, Portland
  • 2Cardiac MR PET CT Program, Massachusetts General Hospital, Harvard Medical School, Boston
  • 3School of Business Studies, Stralsund University of Applied Sciences, Stralsund, Germany
  • 4Department of Cardiology, University Hospital Erlangen, Friedrich-Alexander University, Erlangen-Nürnberg, Germany
  • 5Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
  • 6Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
  • 7Tufts University School of Medicine and the Cardiovascular Center, Tufts Medical Center, Boston, Massachusetts
JAMA Cardiol. 2018;3(2):144-152. doi:10.1001/jamacardio.2017.4973
Key Points

Question  Is high-risk plaque, as detected by coronary computed tomographic angiography, associated with incident major adverse cardiovascular events?

Findings  In this substudy of the PROMISE trial, we evaluated the presence of high-risk plaque in 4415 patients. High-risk plaque was present in 676 patients (15%) and carried a 70% increased risk of major adverse cardiovascular events independent of cardiovascular risk factors and obstructive coronary artery disease; detection was most useful in younger patients, women, and those with nonobstructive coronary artery disease.

Meaning  The findings suggest the potential significance of detecting high-risk plaques in patients with stable ischemic heart disease; however, the low absolute rates of major adverse cardiovascular events and low positive predictive value of high-risk plaque detection might limit its clinical applicability.


Importance  Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasive method of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care.

Objective  To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors.

Design, Setting, and Participants  This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months.

Exposures  Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign).

Main Outcomes and Measures  The primary end point was an adjudicated composite of MACE (defined as death, myocardial infarction, or unstable angina).

Results  The study included 4415 patients, of whom 2296 (52%) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and a MACE rate of 3% (131 events). A total of 676 patients (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4% vs 2.4%; hazard ratio, 2.73; 95% CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95% CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95% CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95% CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences in MACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95% CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95% CI, 1.25-4.64) vs men (aHR, 1.40; 95% CI, 0.81-2.39) and younger patients (aHR, 2.33; 95% CI, 1.20-4.51) vs older ones (aHR, 1.36; 95% CI, 0.77-2.39).

Conclusions and Relevance  High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque.

Trial Registration  clinicaltrials.gov Indentifier: NCT01174550