Use of Atherosclerotic Plaque Detection for Risk Stratification in Stable Chest Pain

Study Questions:

Is high-risk plaque detected by coronary computed tomographic angiography (CTA) associated with incident major adverse cardiovascular events (MACE) independently of significant stenosis (SS) and cardiovascular risk factors?


A prespecified nested observational cohort study was conducted within the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and were randomized to receive coronary CTA were included and followed up for a median of 25 months. Stenosis was estimated visually with SS ≥70% in any vessel and ≥50% in the left main. Calcification was assessed, and high-risk plaque was defined by positive remodeling, low CT attenuation, or napkin-ring sign. The primary endpoint was an adjudicated composite of MACE defined as death, myocardial infarction, or unstable angina.


The study included 4,415 patients, of whom 2,296 (52%) were women, with a mean age of 60.5 years, a median American College of Cardiology/American Heart Association 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 significantly higher MACE rate (6.4% vs. 2.4%; hazard ratio [HR], 2.73). This association persisted after adjustment for ASCVD risk score and SS (adjusted HR, 1.72). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95% confidence interval, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease (CAD) relative to patients without high-risk plaque (adjusted HR [aHR], 4.31 vs. 2.64). 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. High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41) versus men (aHR, 1.40) and younger patients (aHR, 2.33) versus older ones (aHR, 1.36).


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 CAD, younger patients, and women. The importance of these findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque.


The finding that plaque imaging by CTA identifies a cohort with a 70% increased risk of major CV events in outpatients with stable chest pain requiring a noninvasive stress imaging study is novel and important, particularly considering the value in nonobstructive CAD in younger persons and women in whom risk stratification is difficult and for whom the findings might be considered when deciding intensity of treatment(s). The results should not infer value for screening asymptomatic persons.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Nuclear Imaging

Keywords: Angina, Unstable, Angiography, Atherosclerosis, Chest Pain, Constriction, Pathologic, Coronary Artery Disease, Coronary Stenosis, Diagnostic Imaging, Myocardial Infarction, Plaque, Atherosclerotic, Primary Prevention, Risk Factors, Tomography, X-Ray Computed

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