Differential atherosclerotic burden and ischemic risk across major coronary arteries: a comparative analysis using quantitative coronary computed tomography angiography; a CREDENCE trial substudy

Background Coronary CT angiography (CCTA) is the first-line modality for coronary artery disease (CAD) assessment, providing precise quantification of plaque characteristics and vascular morphology. Atherosclerotic plaque distribution varies among coronary arteries, but its relationship with ischemia, as measured by invasive fractional flow reserve (FFR), remains underexplored. Purpose This study evaluates the differential morphology and atherosclerotic burden in the left anterior descending artery (LAD), right coronary artery (RCA), and left circumflex artery (LCx) using CCTA-derived quantitative data and examines their association with ischemia. Methods A post hoc analysis of the CREDENCE (Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia) trial was performed, including 612 symptomatic patients (1,727 vessels) with suspected stable CAD. All patients underwent CCTA and invasive coronary angiography with FFR measurements. Atherosclerotic plaque volume was quantified and categorized by Hounsfield units. Per-vessel quantitative parameters were compared using linear mixed models with random intercept mode. Ischemia was defined as FFR ≤ 0.8, and the ischemic risk of each vessel was assessed using regression analysis. Results Ischemia was significantly more prevalent in LAD (44.23%) than in RCA (18.07%) and LCx (16.99%) (p < 0.001). Plaque burden was significantly greater in the LAD (20.87% ± 11.99%) compared to the RCA (17.90% ± 13.66%, p < 0.001) and LCx (12.53% ± 11.28%, p < 0.001). Median stenosis severity was also highest in the LAD (52%) compared to the RCA (38%) and LCx (33%) (p < 0.001). After adjusting for stenosis severity, lumen area and noncalcified plaque volume, LAD remained at a significantly higher ischemic risk, with a 3.16-fold increase (95% CI: 2.27 -4.43) compared to LCx and a 2.27-fold (95% CI: 1.66 – 3.12) increase compared to RCA. Especially, non-obstructive CAD in the LAD exhibited a greater ischemic risk than those in RCA and LCx (adjusted OR: 3.3 95%CI [1.83 – 6.22], and adjusted OR : 4.11 95% CI[2.31 – 7.51], p < 0.001, respectively). The prevalence of ischemia in non-obstructive CAD in the LAD, LCx, and RCA was 18.1%, 5.3%, and 4.0%, respectively. Conclusion CAD in the LAD was associated with a greater likelihood of causing ischemia compared with the RCA and LCX. Independently from plaque burden and average lumen area, non-obstructive CAD in the LAD had 4 times more ischemia than the other vessels, with a prevalence of 18%. These findings have implications for clinical management of symptomatic patients with non-obstructive LAD stenosis by CCTA.Table 1.Vessels Characteristics Fig 1.Prevalence and Ischemic Risk