A Risk Score Including Carotid Plaque Inflammation and Stenosis Severity Improves Identification of Recurrent Stroke

Abstract

Background and Purpose— In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque 18 F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque 18 F-fluorodeoxyglucose would improve the identification of early recurrent stroke. Methods— We derived the score in a prospective cohort study of recent (<30 days) non-severe (modified Rankin Scale score ≤3) stroke/transient ischemic attack. We derived the SCAIL (symptomatic carotid atheroma inflammation lumen-stenosis) score (range, 0–5) including 18 F-fluorodeoxyglucose standardized uptake values (SUV max <2 g/mL, 0 points; SUV max 2–2.99 g/mL, 1 point; SUV max 3–3.99 g/mL, 2 points; SUV max ≥4 g/mL, 3 points) and stenosis (<50%, 0 points; 50%–69%, 1 point; ≥70%, 2 points). We validated the score in an independent pooled cohort of 2 studies. In the pooled cohorts, we investigated the SCAIL score to discriminate recurrent stroke after the index stroke/transient ischemic attack, after positron emission tomography-imaging, and in mild or moderate stenosis. Results— In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score ( P =0.002, C statistic 0.71 [95% CI, 0.56–0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2–4.5, P =0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9–5], P <0.001; C statistic 0.77 [95% CI, 0.67–0.87]). The SCAIL score independently predicted recurrent stroke after positron emission tomography-imaging (adjusted hazard ratio, 4.52 [95% CI, 1.58–12.93], P =0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46–0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66–0.97], P =0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39–5.39], P =0.004). Conclusions— The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.

A narrative review of plaque and brain imaging biomarkers for stroke risk stratification in patients with atherosclerotic carotid artery disease

“…Studies found that plaque inflammation can be noninvasively visualized on positron emission tomography (PET)/CT by increased 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake, and inflammation is more prevalent in the carotid arteries ipsilateral to the recent ischemic event (48). A recent study constructed a risk score (SCAIL [Symptomatic Carotid Atheroma Inflammation Lumen-Stenosis]) based on plaque 18 F-FDG uptake and lumen stenosis, that improved the prediction of early ipsilateral recurrent stroke after correction for established risk factors, even in patients with mild to moderate stenosis (49). FDG PET/CT seemed promising for the detection of inflammation but enables with poor spatial resolution, which impedes simultaneous tracing of other characteristics.…”

Cohort profile: BIOVASC-late, a prospective multicentred study of imaging and blood biomarkers of carotid plaque inflammation and risk of late vascular recurrence after non-severe stroke in Ireland

“… 33 34 The incorporation of 18 F-FDG plaque uptake into a clinical prediction model also improves discrimination of early recurrent stroke, when compared with risk stratification by luminal stenosis alone. 35 Improved methods to identify patients at the highest risk of stroke may refine selection for carotid revascularisation, allowing surgery to be targeted towards patients most likely to benefit. These findings show that plaque inflammation is a clinically important and independent predictor of early stroke recurrence in symptomatic carotid disease.…”

Concurrent intracranial and extracranial artery stenosis and the prognosis of transient ischaemic symptoms or imaging-negative ischaemic stroke

“…Recent studies emphasised the prognostic value of imaging markers other than luminal stenosis of extracranial arteries, including high-risk non-stenotic carotid plaque, 39 calcification 40 or inflammation. 27 Further study using techniques with a higher spatial resolution to detect the composition of plaques or changes of vessel walls would help distinguish the progress of atherosclerosis. Third, the sample size of our subgroup analysis was relatively small due to our special focus based both on symptom duration and DWI positivity, which could result in limited statistical power.…”