Impaired Endothelial Integrity in Patients With Embolic Stroke of Undetermined Source (ESUS) (ESUS)

Impaired Endothelial Glycocalyx Integrity and Arterial Elastic Properties in Patients With Embolic Stroke of Undetermined Source (ESUS)

Cardioembolism is a postulated mechanism of an embolic stroke of undetermined source (ESUS). The investigators will measure endothelial glycocalyx, aortic elastic properties, oxidative stress, and their association with left ventricular (LV) and left atrial (LA) function in ESUS and age- and sex-adjusted healthy individuals.

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction; Embolic Stroke of Undetermined Source

Detailed Description

The investigators aim to evaluate consecutive acute ischemic stroke (AIS) patients satisfying ESUS diagnostic criteria in a single tertiary care stroke center (University Hospital, Athens, Greece). Moreover, baseline characteristics and outcome measures for all AIS patients are going to be recorded and further be classified, according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) and ESUS criteria. Healthy volunteers (colleagues, friends, relatives and others) will be included in the control group.

In participants (patients and controls) the investigators plan to measure: a) perfused boundary region (PBR) of the sublingual arterial microvessels (range 5-25 micrometers), a marker inversely related with glycocalyx thickness, b) pulse wave velocity (PWV), central systolic blood pressure (cSBP) and augmentation index (AIx), c) LV Global Longitudinal strain (GLS), d) LA volume and strain using speckle-tracking strain imaging, e) Malondialdehyde (MDA), as an oxidative stress marker.

• Study Type: Observational
• Enrollment (Actual): 124

Contacts and Locations

Study Locations

• Greece
  • Attiki
    • Athens, Attiki, Greece, 12461
      • Konstantinos Katogiannis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of 83 consecutive patients with embolic stroke of undetermined source (ESUS) that fulfill inclusion criteria and of 41 healthy volunteers of similar age and sex (control group)

Description

Inclusion Criteria:

The clinical entity of ESUS is defined according to the criteria proposed by the Cryptogenic Stroke/ESUS International Working Group:

(1) stroke visualized by computed tomography (CT) or magnetic resonance imaging (MRI) that is not lacunar (Lacunar defined as a subcortical infarct 1.5 cm or 2.0 cm on MRI diffusion images in largest dimension), (2) absence of extra-cranial or intra-cranial atherosclerosis causing >50% luminal stenosis or occlusion of arteries supplying the area of ischemia (Requires extra-cranial and intra-cranial arterial imaging using sonography, computed tomography angiography, or magnetic resonance angiography of the relevant arteries) (3) no major-risk cardioembolic source of embolism by history, electrocardiography, echocardiography and >24 h of cardiac rhythm monitoring [Permanent or paroxysmal atrial fibrillation, sustained atrial flutter, intra-cardiac thrombus, mechanical prosthetic cardiac valve, atrial myxoma or other cardiac tumors, moderate/severe mitral stenosis, recent (<4 weeks) myocardial infarction, valvular vegetations, or infective endocarditis] (4) no other specific cause of ischemic stroke identified (e.g. arteritis, dissection, migraine/vasospasm, drug abuse)

Exclusion Criteria

1. factors associated with a medium or high risk for thrombus formation in patients with stroke, such as the presence of aortic or mitral valvular prostheses, history of atrial fibrillation (AF) or atrial flutter, known or suspected cardiomyopathy, infective endocarditis, atrial septal defect and intracardiac tumor or thrombus
2. potential confounders in the measurement of left atrial (LA) mechanical function, including the presence of significant (>50% luminal) coronary artery stenosis, previous myocardial infarction or regional wall motion abnormality, prior administration of cardiotoxic chemotherapeutic agents, sick sinus syndrome, any valvular lesion of >2+ severity and pregnancy.

These exclusion criteria are applied to both patients and control subjects.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ESUS patients; Acute ischemic stroke patients satisfying embolic stroke of undetermined source (ESUS) diagnostic criteria.
Controls; Healthy volunteers (colleagues, friends, relatives and others).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of endothelial glycocalyx thickness between patients with embolic stroke of undetermined source (ESUS) and controls	Investigators will assess endothelial glycocalyx thickness by evaluating perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels (range 5-25 micrometers) for patients with embolic stroke of undetermined source (ESUS) and controls.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of arterial stiffness between patients with embolic stroke of undetermined source (ESUS) and controls.	Investigators aim to evaluate arterial stiffness by pulse wave velocity (PWV,m/sec) using tonometry in patients with embolic stroke of undetermined source (ESUS) and controls.	Baseline
Assessment of left ventricular global longitudinal strain (GLS, %) in patients with embolic stroke of undetermined source (ESUS) and controls.	Investigators plan to assess left ventricular in patients with embolic stroke of undetermined source (ESUS) and controls.	Baseline
Serum malondialdehyde levels in patients with embolic stroke of undetermined source (ESUS) and controls.	Investigators plan to compare serum malondialdehyde levels in patients with embolic stroke of undetermined source (ESUS) and controls.	Baseline

Collaborators and Investigators

• Sponsor: University of Athens
• Investigators: Principal Investigator: Ignatios Ikonomidis, University of Athens

Publications and helpful links

General Publications

• Ikonomidis I, Frogoudaki A, Vrettou AR, Andreou I, Palaiodimou L, Katogiannis K, Liantinioti C, Vlastos D, Zervas P, Varoudi M, Lambadiari V, Triantafyllidi H, Pavlidis G, Efentakis P, Tsoumani M, Tsantes AE, Parissis J, Revela I, Andreadou I, Tsivgoulis G. Impaired Arterial Elastic Properties and Endothelial Glycocalyx in Patients with Embolic Stroke of Undetermined Source. Thromb Haemost. 2019 Nov;119(11):1860-1868. doi: 10.1055/s-0039-1694752. Epub 2019 Aug 17.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: July 15, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): August 1, 2018
• Last Update Submitted That Met QC Criteria: July 24, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Oxidative stress; Endothelial function; Arterial stiffness; Left ventricular function; Endothelial glycocalyx; Embolic stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Ischemic Stroke; Stroke; Embolic Stroke
• Other Study ID Numbers: esus-endothelium-attikon

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No