Statins were associated with slower progression of overall coronary atherosclerosis volume, with increased plaque calcification and reduction of high-risk plaque features. Statins did not affect the progression of percentage of stenosis severity of coronary artery lesions but induced phenotypic plaque transformation. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).

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.

Objective We evaluated the association between atherosclerotic plaque characteristics (APCs) by coronary CT angiography (CT) and lesion ischemia by fractional flow reserve (FFR). Background FFR is the gold standard for determining lesion ischemia. While APCs by CT—including aggregate plaque volume % (%APV), positive remodeling (PR), low attenuation plaque (LAP) and spotty calcification (SC)—are associated with future coronary syndromes, their relationship to lesion ischemia is unclear. Methods 252 patients (17 centers, 5 countries) [mean age 63 years, 71% males] underwent CT, with FFR performed for 407 coronary lesions. CT was interpreted for < and >50% stenosis, with the latter considered obstructive. APCs by CT were defined as: (1) PR, lesion diameter/reference diameter >1.10; (2) LAP, any voxel <30 HU; and (3) SC, nodular calcified plaque <3 mm. Odds ratios (OR) and net reclassification improvement (NRI) of APCs for lesion ischemia, defined by FFR <0.8, were analyzed. Results By FFR, ischemia was present in 151 lesions (37%). %APV was associated with a 10% increased risk of ischemia per 5% additional APV. PR, LAP and SC were associated with ischemia, with a 3-5 times higher prevalence than in non-ischemic lesions. In multivariable analyses, a stepwise increased risk of ischemia was observed for 1 [OR 4.5, p<0.001)] and ≥2 (OR 13.2, p<0.001) APCs. These findings were APC-dependent, with PR (OR 5.4, p<0.001) and LAP (OR 2.2, p=0.028) associated with ischemia, but not SC. When examined by stenosis severity, PR remained a predictor of ischemia for all lesions, while %APV and LAP were associated with ischemia for only >50% but not for <50% stenosis. Conclusions %APV and APCs by CT improve identification of coronary lesions that cause ischemia. PR is associated with all ischemia-causing lesions, while %APV and LAP are only associated with ischemia-causing lesions >50%.