Introduction: Ischemic stroke incidence varies significantly with respect to sex and cardiovascular risk factors (CVRFs), a relationship that it is not well understood. Calcification in carotid atherosclerosis is known to impact plaque stability, potentially linked to ischemic stroke. The objective was to assess the in-depth calcification morphometrics within extracranial carotid atherosclerosis, their temporal changes, and associations with sex and CVRFs. 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 multidetector computed tomography angiography (MDCTA) at baseline and after 2 years. The lumen, vessel wall, and calcifications were segmented semiautomatically, and the carotid geometries were 3D reconstructed. A comprehensive morphometric assessment of carotid calcifications was performed on the baseline and followup scans. We investigated distributions of these metrics and their associations with sex and CVRFs 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]) in contrast to men at baseline and follow-up, adjusted for baseline measurements. At the baseline, nonsmokers 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 CVRFs and provided further insight into the pathophysiology of carotid atherosclerosis.

Background and aims: Atherosclerotic plaque onset and progression are known to be affected by local biomechanical factors. While the role of wall shear stress (WSS) has been studied, the impact of another biomechanical factor, namely mechanical wall stress (MWS), remains poorly understood. In this study, we investigated the association of MWS, independently and combined with WSS, towards atherosclerosis in coronary arteries. Methods: Thirty-four human coronary arteries were analyzed using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) at baseline and after 12 months. Baseline WSS and MWS were calculated using computational models, and wall thickness (ΔWT) and lipid-rich necrotic core size (ΔLRNC) change were measured in non-calcified coronary segments. The arteries were further divided into 1.5 mm/45° sectors and categorized as plaque-free or plaque sectors. For each category, associations between biomechanical factors (WSS & MWS) and changes in coronary wall (ΔWT & ΔLRNC) were studied using linear mixed models. Results: In plaque-free sectors, higher MWS (p < 0.001) was associated with greater vessel wall growth. Plaque sectors demonstrated wall thickness reduction over time, likely due to medical therapy, where higher levels of WSS and WMS, individually and combined, (p < 0.05) were associated with a greater reduction. Sectors with low MWS combined with high WSS demonstrated the highest LRNC increase (p < 0.01). Conclusions: In this study, we investigated the association of the (largely-overlooked) biomechanical factor MWS with coronary atherosclerosis, individually and combined with WSS. Our results demonstrated that both MWS and WSS significantly correlate with atherosclerotic plaque initiation and development.