Soluble low-density lipoprotein receptor-related protein 1 as a surrogate marker of carotid plaque inflammation assessed by 18F-FDG PET in patients with a recent ischemic stroke

Abstract

Background 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) identifies carotid plaque inflammation and predicts stroke recurrence. Aim Our aim was to evaluate the performance of soluble low-density lipoprotein receptor-related protein 1 (sLRP1) as an indicator of carotid plaque inflammation. Methods A prospective study was conducted among adult patients with recent (< 7 days) anterior circulation ischemic stroke and at least one atherosclerotic plaque in the ipsilateral internal carotid artery. Patients underwent an early (< 15 days from inclusion) 18F-FDG PET, and the maximum standardized uptake value (SUVmax) within the plaque was measured. sLRP1 levels were measured in plasma samples by ELISA. The association of sLRP1 with SUVmax was assessed using bivariate and multivariable linear regression analyses. Hazard ratios (HR) were estimated with Cox regression to evaluate the association between circulating sLRP1 and stroke recurrence. Results The study was conducted with 64 participants, of which 57.8% had ≥ 50% carotid stenosis. The multivariable linear and logistic regression analyses showed that sLRP1 was independently associated with (i) SUVmax within the plaque (β = 0.159, 95% CI 0.062–0.257, p = 0.002) and (ii) a probability of presenting SUVmax ≥ 2.85 g/mL (OR = 1.31, 95% CI 1.00–1.01, p = 0.046), respectively. Participants with stroke recurrence showed higher sLRP1 levels at baseline [6447 ng/mL (4897–11163) vs. 3713 ng/mL (2793–4730); p = 0.018]. Conclusions sLRP1 was independently associated with carotid plaque inflammation as measured by 18F-FDG PET in patients with recent ischemic stroke and carotid atherosclerosis.

Increased sLRP1 and decreased atrial natriuretic peptide plasma levels in newly diagnosed T2DM patients are normalized after optimization of glycemic control

“…Here, we also observed that the reduction in sLRP1 after reaching optimal glycemic control correlated with the changes in other lipid parameters, such as TC, LDL-C and ApoB100. Such correlations were previously observed in different populations, in which sLRP1 is associated with cardiovascular risk (7)(8)(9). Further studies will be required to know whether sLRP1 reduction is associated to a decrease of atherosclerosis in patients.…”

“…sLRP1 can be detected in the circulation after either constitutive or induced cleavage ( 6 ). Previous studies from our group have shown that atherogenic lipoproteins promote sLRP1 release from vascular smooth muscle cells of human atherosclerotic plaque explants, and that circulating levels of sLRP1 are associated with carotid atherosclerosis in familial hypercholesterolemic patients ( 7 ) and with carotid plaque inflammation measured by 18F-FDG PET in patients with a recent ischemic stroke ( 8 ). In line with this, we further demonstrated that circulating sLRP1 levels are also associated with coronary artery disease risk, independently of potential confounding factors ( 9 ).…”

Novel Therapeutic Approaches to Prevent Atherothrombotic Ischemic Stroke in Patients with Carotid Atherosclerosis

“…sLRP1 had been postulated as being a predictive biomarker for coronary artery disease (CAD) risk [ 95 ]. A recent study revealed that it was also independently associated with the degree of carotid plaque inflammation measured by 18 F-FGD PET in ischemic stroke patients and predicted highly inflamed plaques with high sensitivity [ 96 ]. These results suggest that sLRP1 is a surrogate marker of carotid plaque inflammation that may be targeted in future therapeutic strategies.…”