Prognostic implications of functional significance, high-risk plaque and vessel characteristics in patients with diabetes mellitus

Song, Jin-Eun; Yang, Seokhun; Hoshino, Masahiro; Yonetsu, Taishi; Zhang, Jinlong; Shin, Eun-Seok; Doh, Joon-Hyung; Nam, Chang-Wook; Wang, Jianan; Chen, Shaoliang; Tanaka, Nobuhiro; Matsuo, Hitoshi; Kubo, Takashi; Chang, Hyuk-Jae; Kakuta, Tsunekazu; Koo, Bon-Kwon

doi:2026.41.5.873

Korean J Intern Med > Volume 41(5); 2026 > Article

ORIGINAL ARTICLE

Korean J Intern Med. 2026;41(5):873-883. doi: https://doi.org/10.3904/kjim.2026.005

Prognostic implications of functional significance, high-risk plaque and vessel characteristics in patients with diabetes mellitus

Jin-Eun Song¹, Seokhun Yang¹, Masahiro Hoshino², Taishi Yonetsu³, Jinlong Zhang⁴, Eun-Seok Shin⁵, Joon-Hyung Doh⁶, Chang-Wook Nam⁷, Jianan Wang⁴, Shaoliang Chen⁸, Nobuhiro Tanaka⁹, Hitoshi Matsuo¹⁰, Takashi Kubo⁹, Hyuk-Jae Chang¹¹, Tsunekazu Kakuta², and Bon-Kwon Koo¹

¹Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea
²Division of Cardiovascular Medicine, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
³Department of Interventional Cardiology, Tokyo Medical and Dental University, Tokyo, Japan
⁴Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
⁵Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
⁶Department of Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
⁷Department of Medicine, Keimyung University Dongsan Medical Center, Daegu, Korea
⁸Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
⁹Department of Cardiology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan
¹⁰Department of Cardiology, Gifu Heart Center, Gifu, Japan
¹¹Division of Cardiology, Severance Cardiovascular Hospital, Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Seoul, Korea

Corresponding Author: Bon-Kwon Koo , Tel: +82-2-2072-2062, Fax: +82-2-3675-0805, Email: bkkoo@snu.ac.kr

Received: January 3, 2026; Revised: January 31, 2026; Accepted: March 9, 2026.

Abstract

Background/Aims: We investigated the prognostic value of high-risk plaque (HRP) and high-risk vessel (HRV) characteristics on coronary computed tomography angiography (CCTA) alongside fractional flow reserve (FFR) in patients with diabetes mellitus (DM).
Methods: We analyzed 307 vessels from 184 diabetic patients who underwent both CCTA and invasive FFR. HRP was defined as the presence of ≥ 3 high-risk features (minimal lumen area < 4 mm², plaque burden ≥ 70%, low-attenuation plaque, positive remodeling, spotty calcification, or napkin-ring sign). HRV was defined as the presence of ≥ 1 quantitative volumetric parameter above the optimal cutoff. The primary endpoint was target vessel failure (TVF). HRs were adjusted for FFR, HRP, HRV, and the number of clinical risk factors.
Results: Functional significance (FFR ≤ 0.80; adjusted HR 2.56; 95% CI 1.07–6.12; p = 0.034), HRP (adjusted HR 2.29; 95% CI 1.10–4.77; p = 0.028), and HRV (adjusted HR 2.37; 95% CI 1.12–5.01; p = 0.025) were independent predictors of TVF. Notably, deferred vessels with FFR > 0.80 harboring HRP and/or HRV had a significantly higher risk of TVF compared to the deferred low-risk group (HR 4.78; 95% CI 1.68–13.57; p = 0.003), and their prognosis was comparable to that of deferred vessels with functional significance (FFR ≤ 0.80; HR 5.57; 95% CI 1.70–18.24; p = 0.005).
Conclusions: In patients with DM, both lesion-level (HRP) and vessel-level (HRV) characteristics provided incremental prognostic value beyond FFR. Integrating these anatomical risk features may refine risk stratification for diabetic patients, particularly for those with functionally insignificant lesions.

Keywords: Coronary artery disease ; Diabetes mellitus ; Fractional flow reserve, myocardial ; Computed tomography angiography ; Plaque, atherosclerotic