Pericarotid adipose tissue attenuation is associated with plaque inflammatory markers in symptomatic carotid atherosclerosis

Background Perivascular adipose tissue is associated with vascular inflammation, and inflammation plays a central role in atherosclerotic lesions. The Hounsfield unit (HU) of perivascular adipose tissue measured by computed tomography angiography (CTA) is considered to reflect the degree of inflammation, however, the relationship between this CTA-derived metric and plaque inflammatory markers remains poorly understood. Purpose This study investigated the association between pericarotid adipose tissue (PCAT) attenuation measured by CTA and inflammatory markers of atherosclerotic plaque. Methods This study included consecutive patients who underwent preoperative neck CTA followed by carotid endarterectomy, from whom plaque specimens were obtained and frozen. For CTA analysis, the most stenotic segment was first identified, and a 10 mm vessel segment extending proximally and distally along the centerline was evaluated. PCAT was defined as tissue within a 5 mm radial distance from the outer vessel wall, with HU between −190 and −30. Proteomic profiling of the carotid plaques was performed using the NULISAseq Inflammation Panel targeting a combined total of approximately 250 proteins. Analyses were restricted to markers with ≤20% values below the limit of detection, and their associations with PCAT attenuation were assessed, with analyses stratified by the preoperative symptom status defined as symptomatic, patients who experienced ipsilateral cerebrovascular ischemic event such as stroke, transient ischemic attack, or amaurosis fugax, or asymptomatic. Results Among 96 patients (age 74 [67, 79] years; 66 [68.8%] male), 66 (68.8%) were symptomatic. Median PCAT attenuation was −58.1 [−64.5, −52.3] HU and did not differ by symptom status (p=0.941). Among 107 analytes meeting the prespecified detection criterion, the distribution of correlation coefficients (Spearman’s ρ) between PCAT attenuation and plaque protein levels was shifted toward positive values in symptomatic compared with asymptomatic patients (median ρ 0.125 vs −0.058, p<0.001, Figure 1). The proportion of analytes demonstrating a positive correlation was also greater in symptomatic patients (84.1% vs 40.2%, p<0.001). In paired analyte-level comparisons, 54 analytes were positive only in the symptomatic group whereas 7 were positive only in the asymptomatic group; 36 were positive in both groups (McNemar p<0.001). Within the symptomatic group, PCAT attenuation showed statistically significant positive correlations by Spearman’s correlation with IL6, IL16, IL18, CD80, CD4, GZMB, VSNL1, MMP9, TNFRSF18, S100A9, LIF, FTH1, LGALS9, and TREM1 (Figure 2). Conclusions PCAT attenuation was positively correlated with multiple plaque inflammatory markers, particularly in symptomatic patients. Several correlated markers are implicated in plaque instability, suggesting that CTA-based PCAT assessment may help identify plaque inflammatory activity in carotid atherosclerotic lesions.