Supplementary Material for: In-depth carotid calcification morphometrics and their temporal changes are associated with cardiovascular risk factors in patients with recent ischemic event: The Plaque at Risk (PARISK) Study

Introduction: Ischemic stroke incidence varies significantly with respect to sex and cardiovascular risk factors (CVRF), a relationship that it is not well understood. Calcification in carotid atherosclerosis is known to impact plaque stability, potentially linked to ischemic stroke. The aim of this study was to assess the in-depth calcification morphometrics within extracranial carotid atherosclerosis, their temporal changes, and associations with sex and CVRF. Methods: Carotid arteries (n=144) with confirmed atherosclerosis and mild-to-moderate stenosis from 72 symptomatic patients (Plaque-At-Risk study) with recent ischemic event due to ischemia in the territory of a carotid artery were imaged using multi-detector computed tomography angiography (MDCTA) at baseline and after 2 years. The lumen, vessel wall, and calcifications were segmented semi-automatically and the carotid geometries were 3D reconstructed. A comprehensive morphometric assessment of carotid calcifications was performed on the baseline and follow-up scans. We investigated distributions of these metrics and their associations with sex and CVRF using Generalized Linear Mixed Models. Results: Our findings suggest that women have larger (4.5 mm2 (95%CI: 3.2-6.2) vs 3.2 mm2 (95%CI: 2.4-4.2)) calcifications, located closer to the lumen (0.6 mm (95%CI: 0.4-0.8) vs 0.9 mm (95%CI: 0.7-1.2)) compared to men at baseline and follow-up, adjusted for baseline measurements. At the baseline, non-smokers had larger (5.3 mm2 (95%CI: 3.7-7.5) vs 3.2 mm2 (95%CI: 2.3-4.4)), and longer (5.7 mm (95%CI: 4.1-7.3) vs 2.4 mm (95%CI: 1.6-3.6)) calcifications than the current smokers. Diabetic patients had thicker (1.1 mm (95%CI: 0.8-1.3) vs. 0.8 mm (95%CI: 0.7-0.9)) carotid calcifications at baseline. Conclusion: Our in-depth analyses exposed several geometric features of carotid calcifications associated with sex and CVRF, and provided further insight into the pathophysiology of carotid atherosclerosis.引言：缺血性脑卒中的发病率因性别与心血管危险因素（cardiovascular risk factors, CVRF）存在显著差异，二者间的关联机制目前尚未得到充分阐明。已知颈动脉粥样硬化斑块的钙化会影响斑块稳定性，且可能与缺血性脑卒中存在关联。本研究旨在深入评估颅外颈动脉粥样硬化斑块的钙化形态计量学特征、随时间的变化情况，以及其与性别和心血管危险因素的关联。 方法：本研究纳入72例因颈动脉供血区域缺血发生近期缺血性事件的有症状患者（Plaque-At-Risk研究），共144条经确认存在粥样硬化且狭窄程度为轻至中度的颈动脉。分别在基线及第2年时，采用多排探测器计算机断层血管造影（multi-detector computed tomography angiography, MDCTA）对受试者进行影像学扫描。通过半自动分割技术提取管腔、血管壁及钙化区域，并对颈动脉几何结构进行三维重建。对基线及随访扫描图像中的颈动脉钙化进行全面的形态计量学分析。采用广义线性混合模型（Generalized Linear Mixed Models）探究上述计量指标的分布特征，及其与性别和心血管危险因素的关联。 结果：校正基线测量值后，相较于男性，女性在基线及随访时的钙化面积更大[4.5 mm²（95%CI：3.2~6.2）vs 3.2 mm²（95%CI：2.4~4.2）]，且钙化位置更靠近管腔[0.6 mm（95%CI：0.4~0.8）vs 0.9 mm（95%CI：0.7~1.2）]。基线时，非吸烟者的钙化面积更大[5.3 mm²（95%CI：3.7~7.5）vs 3.2 mm²（95%CI：2.3~4.4）]，且钙化长度更长[5.7 mm（95%CI：4.1~7.3）vs 2.4 mm（95%CI：1.6~3.6）]，均显著高于当前吸烟者。基线时，糖尿病患者的颈动脉钙化厚度更厚[1.1 mm（95%CI：0.8~1.3）vs 0.8 mm（95%CI：0.7~0.9）]。 结论：本研究的深入分析揭示了颈动脉钙化的多项几何特征与性别及心血管危险因素的关联，为颈动脉粥样硬化的病理生理机制提供了新的见解。