Clinical trial NCT02124928: Morphological and Serological Criteria of Plaque Vulnerability: Risk Assessment for Symptomatic and Asymptomatic Carotid Artery Stenosis
Official title: Morphological and Serological Criteria of Plaque Vulnerability: Risk Assessment for Symptomatic and Asymptomatic Carotid Artery Stenosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Atherosclerosis
Carotid Artery Disease
Keywords: stroke
biomarkers
vulnerable plaque
carotid endarterectomy
carotid artery disease
Lead sponsor: Wilhelminenspital Vienna
Sponsor class: OTHER
Collaborators: name: Wilhelminenspital Vienna
First posted: 2014-04-28
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Four hundred patients with symptomatic or asymptomatic carotid artery stenosis undergoing carotid endarterectomy, after written informed consent will be included in this study. The inclusion would be done through our ambulatory care clinic.

Brief summary: The aim of this study is to investigate the association of sonographic and histological features of the plaque among each other and with biomarkers of cardiovascular risk. The predictive value of these factors concerning the long-term clinical outcome after carotid endarterectomy will also be assessed. This may help to improve the identification of patients with carotid artery stenosis who will benefit most from carotid endarterectomy. The investigators major hypothesis is that the morphology of carotid plaques is associated with objectifiable sonographic parameters, in particular with the greyscale median. Second, the investigators hypothesize that sonographic and histological plaque morphology are associated with certain biomarkers of cardiovascular risk. Identification of 'vulnerable plaques' on the basis of a peripheral blood draw and a sonographic investigation may enable the treating physician to focus resources on patients who will benefit most form therapeutic interventions for primary prevention of ischemic stroke.

Detailed description: The indication for revascularization of carotid artery stenoses is typically based on the degree of stenosis and the presence of symptoms. Recent evidence suggests that the risk of embolization from an atherosclerotic plaque may be associated with plaque density as assessed sonographically by determination of the greyscale median. Also, an association of serum proteins vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF) and pigment epithelium-derived factor (PEDF), matrix metalloproteinases 2, 8 and 9 with unstable plaques has been reported.

The VUCAP study will include patients undergoing carotid endarterectomy for symptomatic or asymptomatic carotid artery disease. Sonographic and serological markers of plaque vulnerability will be compared with histological features of the plaque and clinical presentation (symptomatic vs. asymptomatic). Preoperatively, the greyscale median of the plaque is assessed. Histomorphological investigation of the carotid plaques will be performed. Serological investigations will include markers of inflammation, thrombo-modulatory factors, lipid fractions and other parameters that have been associated with unstable plaques.

The aim of the present study is to assess the ability of pigment epithelium-derived factor (PEDF), vascular endothelial growth factor (VEGF), hypoxia-induced factor 1 alpha (HIF 1-α), matrix metalloproteinases 2, 8 and 9 to differentiate between vulnerable and stable carotid artery plaques. Identification of 'vulnerable plaques' on the basis of a peripheral blood draw and a sonographic investigation may enable the treating physician to focus resources on patients who will benefit most form therapeutic interventions for primary prevention of ischemic stroke.

Eligibility criteria: Inclusion Criteria:

* asymptomatic stenosis of internal carotid artery \>70%
* symptomatic stenosis of internal carotid artery \>60%
* planed surgical treatment of the stenosis

Exclusion Criteria:

* pregnancy
* symptomatic coronary heart disease
* myocardial infarction or acute coronary syndrome in the past 3 months
* acute peripheral artery occlusion in the past 3 months
* immaturity
* existence of a guardianship

Primary outcomes:
measure: serum levels of PEDF, VEGF, HIF-1 alpha, MMP-2, -8 and -9 compared to histomorphological classification of the plaque based on AHA classification and ultrasonographic data- grey scale median (GSM)
timeFrame: ultrasonographical data are assessed a day before the surgery, carotid artery plaque will be taken during the surgery, whole blood on the day of operation,
Secondary outcomes:
measure: change in blood serum levels as well as protein level expression of PEDF, VEGF, HIF-1 alpha, MMP-2, -8 and -9 after plaque removal
timeFrame: serum blood levels are evaluated from the whole blood twice: on the day of surgery and 6 weeks after removal of the plaque
Other outcomes:
measure: composite end point of death, stroke, myocardial infarction
timeFrame: From date of randomization until the date of first documented or date of death from any cause assessed up to 5 years
Locations:
city: Vienna
country: Austria
facility: Surgery Departement, Georg Hagmüller Institute for Vascular Research Wilheminenspital
Study officials:
affiliation: Georg Hagmüller Institute for Vascular Research Wilheminenspital Vienna, Austria
name: Afshin Assadian, Prim PD Dr
role: PRINCIPAL_INVESTIGATOR
References: