Carotid Plaque Inflammation Imaged by PET and Prediction of Recurrent Stroke at 5 Years.

Objective: To determine whether carotid plaque inflammation identified by 18F-fluorodeoxyglucose (18FDG)-PET is associated with late (5-year) recurrent stroke. Methods: We did an individual-participant data pooled analysis of three prospective studies with near-identical study methods. Eligible patients had recent non-severe (modified Rankin Score ≤3) ischaemic stroke/TIA and ipsilateral carotid stenosis (50-99%). Participants underwent carotid 18FDG-PET/CT angiography ≤14 days after recruitment. 18FDG uptake was expressed as maximum standardized uptake value (SUVmax) in the axial single hottest slice of symptomatic plaque. We calculated the previously-validated Symptomatic Carotid Atheroma Inflammation Lumen-stenosis (SCAIL) score, which incorporates a measure of stenosis severity and 18FDG uptake. The primary outcome was 5-year recurrent ipsilateral ischaemic stroke after PET imaging. Results: Of 183 eligible patients, 181 patients completed follow-up (98.9%). The median duration of follow-up was 4.9 years (interquartile range 3.3-6.4, cumulative follow-up period 901.8 patient-years). After PET imaging, 17 patients had a recurrent ipsilateral ischemic strokes at 5 years (recurrence rate 9.4%, 95% CI 5.6-14.6%). Baseline plaque SUVmax independently predicted 5-year ipsilateral recurrent stroke after adjustment for age, gender, carotid revascularization, stenosis severity, NIH Stroke Scale, and diabetes mellitus (adjusted HR 1.98; 95 % CI, 1.10-3.56, p=0.02, per 1g/mL increase SUVmax). On multivariable Cox regression, SCAIL score predicted 5-year ipsilateral stroke (adjusted HR 2.73 per 1-point increase; 95% CI 1.52-4.90, p=0.001). Conclusion: Plaque inflammation-related 18FDG uptake improved identification of 5-year recurrent ipsilateral ischaemic stroke. Addition of plaque inflammation to current selection strategies may target patients most likely to have late as well as early benefit from carotid revascularization. Classification of Evidence: This study provides Class I evidence that in individuals with recent ischemic stroke/TIA and ipsilateral carotid stenosis, carotid plaque inflammation-related 18FDG uptake on PET/CT angiography was associated with 5-year recurrent ipsilateral stroke.