Rationale and Objectives: While calcification is a highly prevalent component in atherosclerotic extracranial carotid arteries and is known to impact plaque stability, the link between carotid calcification and ischemic events is yet to be identified. We aimed to investigate the associations of geometric features of carotid calcifications, and their temporal changes, with ischemic events. Materials and Methods: We retrospectively analyzed 128 mildly stenotic carotid arteries (Plaque At Risk study) from 64 patients with recent ischemic event, using multi-detector computed tomography angiography data at baseline and after 2 years. The 3D artery and calcification geometries were reconstructed with a semi-automatic pipeline, and an in-depth calcification morphometric assessment was performed. We examined the distribution of the calcification morphometrics and their temporal changes and investigated their associations with ischemic events at the time of inclusion, using generalized linear mixed models. Results: At baseline, compared to contralateral asymptomatic arteries, symptomatic carotids had more calcification bodies (mean [95%CI]: 1.9 [1.4–2.6] vs. 1.6 [1.2–2.2]). These calcifications were smaller (mean area [95%CI]: 3.7 mm² [2.9–5.1] vs. 4.5 mm² [3.5–5.8]) and narrower (mean width [95%CI]: 2.7 mm [2.3–3.4] vs. 3.1 mm [2.5–3.6]). At 2-year follow-up, adjusting for baseline measurements, these calcifications were smaller (mean width [95%CI]: 2.9 mm [2.5–3.5] vs. 3.3 mm [2.7–3.7]) and longer (mean [95%CI]: 8.6 mm [7.1–10.5] vs. 7.5 mm [6.3–9.5]) compared to asymptomatic side. Conclusion: Symptomatic carotid arteries presented more and smaller calcifications with a tendency to grow more in the longitudinal artery direction, providing insights into the role of carotid calcifications in ischemic events.

Background and aims: Local biomechanical factors are known to influence atherosclerosis in extracranial carotid arteries. While the role of some flow-driven biomechanical factors has been investigated, the influence of pressure-driven mechanical wall stress (MWS) has received limited attention. In this study, the association of the pressure-driven and flow-driven biomechanical factors with carotid atherosclerosis was examined. Methods: Carotid arteries (n = 150) with mild-to-moderate stenosis from 75 symptomatic patients (Plaque-At-Risk study) were imaged using multi-detector computed tomography angiography (MDCTA) at the time of inclusion and after 2 years. Structural changes in carotid wall and calcifications were quantified from MDCTA data while the local baseline biomechanical factors in the carotids were determined using fluid-structure interaction (FSI) computational models. The associations of the local pressure-driven and flow-driven biomechanical factors with the carotid wall and calcification changes were studied using Generalized Linear Mixed models. Results: Over two years, plaque sectors, with calcified and non-calcified sectors combined, exhibited minimal change in wall thickness, likely due to medical treatment. High MWS was associated (p < 0.001) with a reduction in plaque thickness. In calcified plaque sectors, high MWS and low oscillatory shear index (OSI) were associated (p < 0.001) with greater calcification thickness increase. The distance between the lumen and calcification decreased over time, especially in the sectors exposed to high time-averaged wall shear stress (TAWSS) and high MWS. Conclusions: Our results suggest that the pressure-driven local MWS and flow-driven OSI and TAWSS significantly correlate with the development of calcified and non-calcified plaques in carotid arteries. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01208025.