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

Abstract

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”.

Risk Factors for Ankle Brachial Index and Carotid Artery Stenosis in Patients with Type 2 Diabetes

“…Besides CRP, novel biomarkers like matrix metalloproteinases (MMPs) 3,7, and 9 and the tissue inhibitors of metalloproteinase (TIMP)-1 are elevated in those with carotid atherosclerosis, and the elevation of those biomarkers parallel with the percentage of carotid artery stenosis. Patients with elevated TIMP-1, MMP-3, MMP-7, and MMP-9 more often require carotid revascularization than those without carotid artery stenosis or those under conservative treatment [ 45 ]. The early detection of the inflammation and calcification at the molecular level in bilateral carotid artery atherosclerosis was recently detected using positron emission tomography/computed tomography (PET/CT) with (18F) sodium fluoride (NaF) as a tracer.…”

Altered Arterial Stiffness, Ventricular–Arterial Coupling and Troponin Levels in Patients with Systemic Lupus Erythematosus

“…Regarding the prognostic utility of CAVI in SLE patients, its employment for cardiovascular risk stratification could revolutionize patients' management by endorsing more aggressive therapeutic approaches in otherwise uncomplicated SLE patients. Numerous studies have demonstrated the association of CAVI with the development of cardiovascular events in patients with established atherosclerotic CVDs (ASCVDs) [33,34] or those at high risk for ASCVDs [35]. No data are available for the prognostic value of CAVI in the SLE population and this remains to be proved.…”

Altered Arterial Stiffness, Ventricular-Arterial Coupling and Troponin Levels in Patients with Systemic Lupus Erythematous

“…Regarding the prognostic utility of CAVI in SLE patients, its employment for cardiovascular risk stratification could revolutionize patients' management by endorsing more aggressive therapeutic approaches in otherwise uncomplicated SLE patients. Numerous studies have demonstrated the association of CAVI with the development of cardiovascular events in patients with established atherosclerotic CVDs (ASCVDs) [29,30] or those at high risk for ASCVDs [31]. No data are available for the prognostic value of CAVI in SLE population and this remains to be proved.…”