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

Abstract

PurposeInflammation is important in stroke. Anti-inflammatory therapy reduces vascular events in coronary patients. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) identifies plaque inflammation-related metabolism. However, long-term prospective cohort studies investigating the association between carotid plaque inflammation, identified on 18F-FDG PET and the risk of recurrent vascular events, have not yet been undertaken in patients with stroke.ParticipantsThe Biomarkers Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease (BIOVASC) study and Dublin Carotid Atherosclerosis Study (DUCASS) are two prospective multicentred observational cohort studies, employing near-identical methodologies, which recruited 285 patients between 2008 and 2016 with non-severe stroke/transient ischaemic attack and ipsilateral carotid stenosis (50%–99%). Patients underwent coregistered carotid 18F-FDG PET/CT angiography and phlebotomy for measurement of inflammatory cytokines. Plaque 18F-FDG-uptake is expressed as maximum standardised uptake value (SUVmax) and tissue-to-background ratio. The BIOVASC-Late study is a follow-up study (median 7 years) of patients recruited to the DUCASS/BIOVASC cohorts.Findings to dateWe have reported that 18F-FDG-uptake in atherosclerotic plaques of patients with symptomatic carotid stenosis predicts early recurrent stroke, independent of luminal narrowing. The incorporation of 18F-FDG plaque uptake into a clinical prediction model also improves discrimination of early recurrent stroke, when compared with risk stratification by luminal stenosis alone. However, the relationship between 18F-FDG-uptake and late vascular events has not been investigated to date.Future plansThe primary aim of BIOVASC-Late is to investigate the association between SUVmax in symptomatic ‘culprit’ carotid plaque (as a marker of systemic inflammatory atherosclerosis) and the composite outcome of any late major vascular event (recurrent ischaemic stroke, coronary event or vascular death). Secondary aims are to investigate associations between: (1) SUVmax in symptomatic plaque, and individual vascular endpoints (2) SUVmax in asymptomatic contralateral carotid plaque and SUVmax in ipsilateral symptomatic plaque (3) SUVmax in asymptomatic carotid plaque and major vascular events (4) inflammatory cytokines and vascular events.

Role of plaque inflammation in symptomatic carotid stenosis

“…Certain limitations of our study merit mention. First, while FDG-PET appears to be a useful clinical adjunct, the high cost of FDG-PET and limited availability may affect the generalized applicability of our findings ( 18 ). Other modalities to quantify plaque inflammation such as magnetic resonance imaging with contrast may offer a cheaper alternative, but data regarding its use is limited ( 19 ).…”

Association Between 18-FDG Positron Emission Tomography and MRI Biomarkers of Plaque Vulnerability in Patients With Symptomatic Carotid Stenosis

“…MRI is a validated technique for characterising luminal stenosis, plaque volume, and composition. Positron emission tomography (PET) using 18 F-fluorodeoxyglucose (FDG) has been validated for non-invasive imaging of inflammation-related plaque metabolism ( 5 , 6 ). Almost no data exist on the association between plaque inflammation imaged with PET and biomarkers of unstable plaque imaged with MRI in patients with recently symptomatic carotid atherosclerosis.…”

Novel Imaging-Based Biomarkers for Identifying Carotid Plaque Vulnerability

“…In addition, Fujimoto et al demonstrated that the uptake of 18F-NaF was related to the severity of ischemic vascular brain disease on MRI, which suggests that it may be useful in the risk assessment of cerebrovascular disease [ 180 ]. In this way, the Biomarkers Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease (BIOVASC) trial, involving patients with carotid stenosis and a recent stroke/transient ischemic attack, found that in patients with recent symptomatic carotid stenosis, plaque 18F-FDG uptake was associated with early recurrent stroke [ 181 ]. The study showed for the first time that plaque FDG uptake independently predicts early stroke after PET.…”