Importance of coronary artery lumen size in the relationship between coronary artery plaque and vessel-specific ischemia: A post hoc analysis of CREDENCE and PACIFIC-1

Abstract

Background: While coronary artery plaque burden and stenosis are important for development of ischemia, the role of lumen size remains underexplored. This study evaluated the relationship between average lumen area (ALA) and vessel-specific ischemia beyond diameter stenosis (DS) and percent atheroma volume (PAV). Methods: This post-hoc analysis included coronary arteries from the CREDENCE (n ​= ​1716) and PACIFIC-1 (n ​= ​612) trials, involving patients with suspected stable coronary artery disease (CAD) who underwent coronary computed tomography angiography (CTA) and invasive fractional flow reserve (FFR) measurement. AI-enabled quantitative CTA was used to assess plaque burden and composition. Ischemia was defined as FFR≤0.80. Each major coronary artery was analyzed. ALA was stratified into tertiles. Results: Larger ALA was associated with younger age, higher body mass index, and more nitrate use in both cohorts (all p ​< ​0.05). Increasing ALA correlated with lower diameter stenosis, reduced ischemia prevalence, and smaller plaque burden despite greater total plaque and non-calcified plaque volumes. In both cohorts, ischemia prevalence increased with stenosis severity, yet within each stenosis category, vessels with smaller ALA showed consistently higher ischemia rates. E.g., in CREDENCE vessels with 50 ​%–70 ​% stenosis, ischemia was observed in 60.0 ​% of small, 43.8 ​% of medium, and 27.8 ​% of large vessels (all p ​< ​0.05). Similar patterns were observed within PAV strata across all plaque subtypes. Multivariable analysis confirmed ALA independently associated with lower ischemia prevalence in both studies (both p ​< ​0.001). Conclusions: Coronary artery lumen size significantly attenuates the relationship between atherosclerosis/stenosis and ischemia. These findings support integrating lumen assessment in coronary CTA-based risk stratification.