Carotid artery atherosclerosis is a key contributor to ischemic stroke. In this state-of-the-art review by Saba et al., the authors emphasize the importance of identifying high-risk plaques using modern imaging and biomarker analysis, regardless of luminal narrowing. 
The authors argue that up to 30% of ischemic strokes occur in patients with non-stenotic but vulnerable plaques, underling the need for improved risk stratification. The authors offer a detailed analysis of both histological and imaging characteristics that define a high-risk, or “vulnerable,” carotid plaque, such as a thin fibrous cap, a large lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), ulceration, and active inflammation. These features are strongly associated with an increased risk of stroke and can be reliably identified using advanced imaging modalities such as MRI, CT, PET, and ultrasound. A key takeaway from the article is the need to shift clinical focus from simply measuring the degree of arterial narrowing (stenosis) to thoroughly evaluating the biological and structural features of the plaque itself, which may offer a more accurate assessment of stroke risk.
The authors explore also the emerging role of circulating biomarkers such as hsCRP, IL-6, TNF-α, and MMP-9 as well as omics technologies (e.g. proteomics, metabolomics) and artificial intelligence in refining risk stratification and guiding therapy.
The authors advocate for the integration of these advanced tools into routine clinical workflows and supports the standardization of plaque assessment through systems like Plaque-RADS. 
In conclusion, this review reinforces the shift towards personalized medicine in vascular care, moving from assessment only of the degree of carotid stenosis to a more sophisticated approach including plaque characteristics, artificial intelligence, omics, and biomarkers.