Novel Biomarkers and Imaging Indices for the "Vulnerable Patient" with Carotid Stenosis: A Single-Center Study

Background: We investigated the relationship of matrix metalloproteinases (MMPs), cardio-ankle vascular index (CAVI), and Gray-Scale Median (GSM) score with the severity and vulnerability of carotid atherosclerosis and major adverse cardiovascular events (MACE) during follow-up of carotid artery revascularization. Methods: We enrolled 262 patients undergoing carotid revascularization therapy (GRT), 109 asymptomatic patients with low-grade carotid stenosis (40-70%) receiving conservative treatment (GCT), and 92 age- and sex-matched control subjects without carotid atherosclerosis (GCO). All participants underwent carotid ultrasound and we assessed at baseline clinical parameters, metabolic profile, CAVI, GSM, and circulating levels of hsCRP, MMP-3,-7,-9, and TIMP-1. Results: Both GRT and GCT presented with elevated CAVI, MMPs, and TIMP-1 levels compared to GCO (p < 0.001). The escalation highly correlated to the presence of symptoms or paralleled the degree of carotid stenosis (p < 0.001). During follow-up (mean duration: 55 months), 51 GRT patients experienced MACE unrelated to the revascularization procedure. Within GRT, diabetes (HR: 2.07; CI: 1.55-2.78, p < 0.001), smoking (HR: 1.67; CI: 1.35-1.95, p < 0.001), high CAVI (HR: 1.22; CI: 1.09-1.43, p = 0.023) and MMP-9 (HR: 1.44; CI: 1.29-2.15, p = 0.005), and low GSM (HR: 1.40; CI: 1.16-2.12, p = 0.002) independently predicted MACE occurrences, despite the optimum medical therapy. Conclusions: Novel imaging and biochemical biomarkers were positively associated with atherosclerosis severity, while CAVI, MMP-9, and low GSM showed a positive, independent relationship with MACE after carotid revascularization, describing "vulnerable patients".