2.1 Study design and patients
This pilot study is a prospective observational single-blind study of patients who underwent CEA at the Department of Cardiovascular Surgery in the Magdalena - Clinic for Cardiovascular Diseases and at the Department of Vascular Surgery in the University Hospital Merkur in Croatia over a 3-year study period. Institutional ethic committee approvals and Zagreb University School of Medicine ethic committee approval were obtained, and all patients gave their written informed consent. This study has been registered at the ISRCTN registry with study ID ISRCTN46536832. The study was conducted as per the Helsinki Declaration guidelines [24]. Identity of patients during data collection was anonymised and protected using a unique patient number.
Clinical history taking and physical examination including a neurological exam were performed by a surgeon. Clinical data including history of cardiovascular disease, risk factors for atherosclerosis, neurological event and timing since the most recent one, current medical treatment and computed tomography (CT) scans of brain were recorded. Stroke aetiology was determined based on a work-up including neurological examination, duplex ultrasound, MRI, CT scan of brain and echocardiography if required. Routine biochemical tests and highly sensitive C-reactive protein (hsCRP) were performed preoperatively. Before surgery, all patients underwent a duplex ultrasound plus MRI to grade internal carotid artery (ICA) stenosis and assess the supra-aortic and intracranial arterial system. The severity of carotid artery stenosis was defined using the North American Symptomatic Carotid Endarterectomy Trial Collaborators’ (NASCET) criteria [25]. Inclusion criteria were that the patient should be already scheduled for CEA based on the indication for surgery with the consent to participate in the study. CEA was indicated according to the ESVS guidelines and recommendations of multicentric randomised controlled trials [1, 4, 25-27]. Exclusion criteria were contraindications to MRI (pacemaker, metallic implant, claustrophobia), presence of suboptimal MRI visualization of the carotid plaque or surgical specimen inadequate for histological or immunohistochemical analysis.
Patients were divided into two groups based on the presence of symptoms and the timing of the most recent symptom. Symptomatic patients were any patients who suffered a carotid stenosis territory symptom within the previous 6 months including ipsilateral stroke, transient ischaemic attack (TIA) or amaurosis fugax. Patients without any history of recent neurological symptoms or with nonspecific, non-hemispheric symptoms such as dizziness or vertigo were considered as asymptomatic.