Kooi, M. Eline

Abstract Background and aims Carotid calcification features are readily quantifiable by CTA, yet their relationship with plaque vulnerability and rupture remains controversial. We investigated whether calcium score, volume, density, and residual (volume-normalized) calcium density are associated with carotid plaque vulnerability, symptomatic status, and recurrent ipsilateral ischemic stroke and transient ischemic attack (TIA). Methods Patients with recent TIA or ischemic stroke and ≥2mm carotid plaque with <70% stenosis underwent baseline CTA and MRI. Carotid calcifications were segmented on CTA (≥130 Hounsfield units), yielding calcium score, volume, and density. Volume-normalized residual calcium density was calculated as the standardized residuals from a log-transformed calcium density-volume model (Figure 1). Vulnerable plaque features (intraplaque hemorrhage, thin-or-ruptured fibrous cap, and lipid-rich necrotic core, and ulceration) were linked to calcium metrics. Associations between calcium metrics and recurrent ipsilateral TIA or ischemic stroke were assessed using Cox regression and adjusted for age, sex, stenosis. Results Among 193 patients (mean age 67.8±8.5 years, 144 (75%) men), 26 experienced ipsilateral ischemic stroke or TIA over median 5-year follow-up. Lower calcium density and residual calcium density were independently associated with vulnerable plaques (adjusted ORs: 0.40-0.60; Figure 2). Residual calcium density remained independently associated with symptomatic side (adjusted OR: 0.64, 95%CI: 0.47-0.88) and with recurrent TIA/stroke (adjusted HR: 0.53, 95%CI: 0.29-0.95). Calcium score, volume, and density were not independently associated with symptomatic side or recurrent events (Figure 3). Conclusions Residual calcium density is a robust, independent marker of carotid plaque vulnerability and ipsilateral ischemic stroke and TIA risk in patients with symptomatic carotid artery disease. Conflict of interest Juul Bierens: nothing to disclose; Daniel Bos: nothing to disclose; Paul J. Nederkoorn: nothing to disclose; Pim A. de Jong: nothing to disclose; Robert J. van Oostenbrugge: nothing to disclose; Luc J.M. Smits: nothing to disclose; Jae W. Song: nothing to disclose; Giuseppe Lanzino: nothing to disclose; M. Eline Kooi: nothing to disclose; Luca Saba: nothing to disclose. Figure 1 - belongs to Methods Figure 2 - belongs to Results Figure 3 - belongs to Conclusions

Background Carotid artery calcification represents a common feature of atherosclerotic plaques. However, the geometric relationships of calcific clusters have not been systematically investigated. This study aimed to develop a geometry-based atlas, independent of symptom status, characterizing the three-dimensional properties of calcium clusters within carotid plaques and quantifying population-level distributions and data-driven couplings between size, shape, and density. Methods Standardized three-dimensional calcium masks of clinical CT scans were analyzed using connected-component labeling. Extracted features included cluster volume, aspect ratio, eccentricity, compactness, and CT attenuation values (mean μ, standard deviation σ). Associations between cluster features were assessed using Spearman correlations with Benjamini–Hochberg false discovery rate correction. Independent associations were determined using partial Spearman correlation and restricted cubic spline regression. Results Among 107 plaques, 149 distinct clusters were identified, most frequently presenting as a single elongated cluster (aspect ratio = 2.23). Independent associations (all p < 0.001) were identified for: eccentricity with μ (ρ = −0.39), volume with μ (ρ = 0.47), compactness with μ (ρ = 0.39), and volume with eccentricity (ρ = 0.82). Multi-cluster plaques exhibited smaller mean cluster volume (76.1 vs 359.5 mm 3 ; p < 0.001) and lower eccentricity (0.5 vs 1.6; p < 0.001) compared with single-cluster plaques. Conclusion Carotid calcification most frequently manifests as a single elongated cluster, with robust couplings between cluster size, shape, and density. These geometric archetypes provide a quantifiable framework for future biomechanical and biological studies of plaque vulnerability.

Abstract Cardiovascular disease remains a prominent cause of disability and premature death worldwide. Within this spectrum, carotid artery atherosclerosis is a complex and multifaceted condition, and a prominent precursor of acute ischaemic stroke and other cardiovascular events. The intricate interplay among inflammation, oxidative stress, endothelial dysfunction, lipid metabolism, and immune responses participates in the development of lesions, leading to luminal stenosis and potential plaque instability. Even non-stenotic plaques can precipitate a sudden cerebrovascular event, regardless of the degree of luminal encroachment. In this context, carotid imaging modalities have proved their efficacy in providing in vivo characterization of plaque features, contributing substantially to patient risk stratification and clinical management. This review emphasizes the importance of identifying high-risk individuals by use of current imaging modalities, biomarkers, and risk stratification tools. Such approaches inform early intervention and the implementation of personalized therapeutic strategies, ultimately enhancing patient outcomes in the realm of cardiovascular disease management.

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German–Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients. The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German–Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German–Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.