OCT‐Derived Index of Plaque Attenuation as a Quantitative Metric for Histological Plaque Vulnerability in Human Coronary Atherosclerosis

ABSTRACT Background Vulnerable plaque rupture is a major mechanism underlying acute coronary events, but imaging‐based risk assessment using individual plaque features remains limited. The histology‐derived vulnerability index (VI) integrates multiple plaque components and is associated with adverse cardiovascular outcomes but requires ex vivo assessment. Optical coherence tomography (OCT) enables high‐resolution in vivo plaque characterization, and the OCT‐derived index of plaque attenuation (IPA) may provide a quantitative measure of integrated plaque vulnerability. AIMS: This study aimed to determine the association between OCT‐derived IPA and histological VI and to identify the histological plaque components contributing to IPA. Methods In 240 coronary blocks from 10 human cadaveric hearts, co‐registered OCT and histology were performed. IPA was calculated from attenuation images. Histology quantified necrotic core, collagen, α‐SMA + area, and macrophages (CD68 + , CD206 + ). Associations were assessed using correlation and multivariable regression. Results IPA at a 9 mm −1 threshold (IPA 9 ) correlated with VI ( r = 0.714, p < 0.001) and discriminated high‐VI blocks (AUC = 0.852). CD68 + macrophage area ( β = 17.20, p < 0.001) and necrotic core ( β = 1.39, p = 0.013) predicted higher IPA, whereas collagen and α‐SMA + area were inversely associated. CD206 + areas were not independently related with IPA, but the CD206 + /CD68 + ratio significantly improved IPA model performance (Δ R 2 = 0.023, p = 0.004). Conclusions OCT‐derived IPA closely corresponds to histological VI and is primarily driven by necrotic core and pro‐inflammatory macrophage infiltration. IPA may serve as a clinically obtainable quantitative OCT marker for integrated assessment of inflammation‐weighted plaque vulnerability.