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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". [ABSTRACT FROM AUTHOR]

Arterial stiffness and its valid index, the cardio-ankle vascular index (CAVI), have emerged as predictors of adverse cardiovascular outcomes. We investigated the relationship of the CAVI with significant carotid stenosis (> 50%) and the related cerebrovascular symptoms or carotid plaque echogenicity, assessed by ultrasound gray-scale median (GSM) score, at baseline and after carotid artery stenting (CAS). We prospectively enrolled 113 patients with carotid stenosis (70-99% for asymptomatic and > 50% for symptomatic participants) eligible for CAS. Age- and sex-matched individuals (n = 38) served as controls (CON). Clinical data, CAVI, and biochemical profile were obtained at baseline. Clinical assessment and CAVI measurement were performed 6 months after CAS. Compared with the CON group, the CAS group had a higher incidence of co-morbidities (diabetes, hypertension, and hyperlipidemia), higher CAVI values (9.94 ± 2.14 vs 7.85 ±.97 m/sec, P <.001), but a better lipid profile due to increased prescription of statins. The symptomatic CAS subgroup showed higher CAVI (P <.001), high-sensitivity C-reactive protein (P =.048), and osteoprotegerin (P =.002) levels than the asymptomatic one. In multivariate analysis, CAVI at baseline was independently associated with the presence of significant carotid atherosclerosis (β =.695, P <.001), cerebrovascular events (β =.474, P <.001), and GSM score (β = −.275, P =.042). Raised CAVI values were independently associated with significant carotid stenosis and plaque vulnerability. [ABSTRACT FROM AUTHOR]