Perivascular adipose tissue attenuation in CT angiography and plaque inflammation in patients with carotid atherosclerosis

Background and Aims Quantifying arterial inflammation can augment risk stratification and drug development in atherosclerosis. While perivascular adipose tissue (PVAT) density, captured as fat attenuation index (FAI) on CT angiography (CTA), is an emerging biomarker of coronary inflammation, it remains unclear whether this concept extends to carotid atherosclerosis. Methods Using routine CTA data from hospital-based stroke cohorts, we developed a pipeline to quantify attenuation metrics of PVAT surrounding the distal common and proximal internal carotid arteries. We compared PVAT metrics between culprit and contralateral non-culprit plaques in patients with symptomatic carotid atherosclerosis and between culprit plaques and control carotid segments from patients without symptomatic atherosclerosis. In patients undergoing carotid endarterectomy, we assessed associations of CTA-derived PVAT metrics with histological and proteomic markers of plaque inflammation and stability. Results Across 107 patients with symptomatic carotid atherosclerosis (75.5±8.7 years; 63% men), PVAT attenuation metrics did not show significant differences between culprit and contralateral non-culprit lesions (all p>0.2). We also found no evidence for higher PVAT attenuation in culprit lesions, when compared to arteries of patients without symptomatic atherosclerosis. In 82 patients undergoing endarterectomy, pre-operative CTA-derived metrics of PVAT attenuation showed no significant correlations with CD68+ macrophage areas in excised plaques (r -0.11 to 0.07, all p>0.3). Similarly, no PVAT attenuation metrics were associated with thinner fibrous cap or higher plaque levels of pro-inflammatory cytokines (IL-6, TNF). Conclusions In contrast to coronary atherosclerosis, carotid PVAT attenuation was not associated with symptomatic culprit lesions or histological and molecular markers of plaque inflammation and vulnerability. Structured Graphical Abstract Key Question Can perivascular adipose tissue (PVAT) attenuation on CT, proposed as a marker of coronary artery inflammation, also capture atherosclerotic plaque inflammation and vulnerability in the carotid arteries? Key Finding In 107 patients with carotid atherosclerosis-associated stroke, PVAT attenuation did not differ between culprit and contralateral non-culprit lesions and was not associated with histopathological or molecular markers of plaque inflammation and vulnerability. Take-home Message PVAT attenuation did not capture local carotid plaque inflammation or vulnerability in this cohort, questioning the transferability of this CT-based marker from coronary to carotid atherosclerosis.