Background: The future risk of myocardial infarction is commonly assessed using cardiovascular risk scores, coronary artery calcium score, or coronary artery stenosis severity. We assessed whether noncalcified low-attenuation plaque burden on coronary CT angiography (CCTA) might be a better predictor of the future risk of myocardial infarction. Methods: In a post hoc analysis of a multicenter randomized controlled trial of CCTA in patients with stable chest pain, we investigated the association between the future risk of fatal or nonfatal myocardial infarction and low-attenuation plaque burden (% plaque to vessel volume), cardiovascular risk score, coronary artery calcium score or obstructive coronary artery stenoses. Results: In 1769 patients (56% male; 58±10 years) followed up for a median 4.7 (interquartile interval, 4.0–5.7) years, low-attenuation plaque burden correlated weakly with cardiovascular risk score ( r =0.34; P &lt;0.001), strongly with coronary artery calcium score ( r =0.62; P &lt;0.001), and very strongly with the severity of luminal coronary stenosis (area stenosis, r =0.83; P &lt;0.001). Low-attenuation plaque burden (7.5% [4.8–9.2] versus 4.1% [0–6.8]; P &lt;0.001), coronary artery calcium score (336 [62–1064] versus 19 [0–217] Agatston units; P &lt;0.001), and the presence of obstructive coronary artery disease (54% versus 25%; P &lt;0.001) were all higher in the 41 patients who had fatal or nonfatal myocardial infarction. Low-attenuation plaque burden was the strongest predictor of myocardial infarction (adjusted hazard ratio, 1.60 (95% CI, 1.10–2.34) per doubling; P =0.014), irrespective of cardiovascular risk score, coronary artery calcium score, or coronary artery area stenosis. Patients with low-attenuation plaque burden greater than 4% were nearly 5 times more likely to have subsequent myocardial infarction (hazard ratio, 4.65; 95% CI, 2.06–10.5; P &lt;0.001). Conclusions: In patients presenting with stable chest pain, low-attenuation plaque burden is the strongest predictor of fatal or nonfatal myocardial infarction. These findings challenge the current perception of the supremacy of current classical risk predictors for myocardial infarction, including stenosis severity. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01149590.

Low-Attenuation Noncalcified Plaque on Coronary Computed Tomography Angiography Predicts Myocardial Infarction