Yipu Ding, Putri Annisa Kamila, Nick S. Nurmohamed, Ibrahim Danad, Ruurt A. Jukema, Pieter G. Raijmakers, Roel S. Driessen, Gianluca Pontone, Daniele Andreini, Hyuk-Jae Chang, Andrew D. Choi, Paul Knaapen, Hongbin Liu, Jeroen J. Bax, Alexander van Rosendael, Ran Heo, Hyung-Bok Park, Hugo Marques, Wijnand J. Stuijfzand, Michiel J. Bom, Pepijn van Diemen, Jung Hyun Choi, Joon-Hyung Doh, Ae-Young Her, Bon-Kwon Koo, Chang-Wook Nam, Sang-Hoon Shin, Jason Cole, Alessia Gimelli, Muhammad Akram Khan, Bin Lu, Yang Gao, Faisal Nabi, Mouaz H. Al-Mallah, Ryo Nakazato, U. Joseph Schoepf, Randall C. Thompson, James J. Jang, Michael Ridner, Chris Rowan, Erick Avelar, Philippe Généreux, Guus A. de Waard
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. © 2026 The Authors
Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands; School of Medicine, Nankai University, Tianjin, China; Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Department of Cardiology, Radboud University Medical Center, Nijmegen, Netherlands; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Netherlands; Department of Cardiovascular Imaging, Centro Cardiologico Monzino, IRCCS, Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; Department of University Cardiology and Cardiac Imaging, IRCCS Ospedale Galeazzi Sant'Ambrogio, Milan, Italy; Division of Cardiology, Severance Cardiovascular Hospital and Severance Biomedical Science Institute, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea; Division of Cardiology, The George Washington University School of Medicine, Washington, DC, United States; Turku University Hospital and University of Turku, Turku, Finland; Division of Cardiology, Department of Internal Medicine, Hanyang University Medical Center, Seoul, Korea College of Medicine, Hanyang University, Seoul, South Korea; Division of Cardiology, Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, South Korea; Faculdade de Medicina da Universidade Católica Portuguesa, Lisboa, Portugal; UNICA, Cardiovascular CT and MRI Unit, Hospital da Luz, Lisboa, Portugal; Department of Cardiology, Pusan National University Hospital, Busan, South Korea; Division of Cardiology, Inje University Ilsan Paik Hospital, South Korea; Division of Cardiology, Department of Internal Medicine, Kangwon National University, College of Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Cardiovascular Center, Keimyung University Dongsan Hospital, Daegu, South Korea; Division of Cardiology, Department of Internal Medicine, Ewha Women's University Seoul Hospital, Seoul, South Korea; Mobile Cardiology Associates, Mobile, AL, United States; Department of Imaging, Fondazione Toscana Gabriele Monasterio, Pisa, Italy; Cardiac Center of Texas, McKinney, TX, United States; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Beijing, China; Houston Methodist Hospital, Houston, TX, United States; Cardiovascular Center, St. Luke's International Hospital, Tokyo, Japan; Medical University of South Carolina, Charleston, SC, United States; Saint Luke's Mid America Heart Institute, Kansas City, MO, United States; San Jose Medical Center, Kaiser Permanente, San Jose, CA, United States; University of Alabama-Birmingham, Birmingham, AL, United States; University of Wisconsin, Madison, WI, United States; Mayo Clinic, Rochester, MN, United States; Morristown Medical Center, Morristown, NJ, United States
