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)

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, cardioembolic, atherosclerotic, lacunar strokes and age- and sex-adjusted healthy individuals.

Study Overview

• Status: Active, not recruiting
• Conditions: Endothelial Dysfunction; Embolic Stroke of Undetermined Source

Detailed Description

Investigators plan to include male and female patients, aged 18 to 75 years old admitted and hospitalized in the 2nd Neurology Department of Attikon University Hospital for Acute Ischemic Stroke, based on the Trial of Org 10172 in Acute Stroke Treatment TOAST classification. The TOAST classification consists of five categories: 1) large artery atherosclerosis (atherothrombotic), 2) cardioembolic, 3) small artery occlusion (lacunar), 4) stroke of undetermined etiology (ESUS).

In participants (patients and controls) the investigators plan to measure and compare: 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 (Estimated): 215

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

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of 172 consecutive patients with Ischemic stroke of undetermined source (ESUS) that fulfill inclusion criteria and 43 healthy volunteers of similar age and sex (control group)

Description

Inclusion Criteria:

The investigators plan to include participants with Acute Ischemic Stroke, based on the TOAST classification : 1) large artery atherosclerosis (atherothrombotic), 2) cardioembolic, 3) small artery occlusion (lacunar), 4) stroke of undetermined etiology (ESUS). According to the TOAST classification, diagnoses are based on clinical presentation and on data collected by exams such as brain imaging (CT/MRI), cardiac imaging (echocardiography) and laboratory tests for the prothrombotic state. The diagnosis of Embolic Stroke of Undetermined Source (ESUS) was established based on the criteria defined by the Cryptogenic Stroke/ESUS International Working Group.

Exclusion Criteria

1. presence of acute haemorrhagic stroke,
2. the presence of stroke of other determined etiology,
3. the history of previous Ischemic stroke and/or Myocardial Infarction (MI),
4. hypercoagulable state,
5. active malignancy
6. severe chronic kidney disease (eGFR<30 ml/minute). These exclusion criteria are applied to both patients and control subjects.

Study Plan

How is the study designed?

Number of groups / cohorts

5

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).
Lacunar stroke patients; Acute ischemic stroke patients satisfying lacunar stroke diagnostic criteria
Cardioembolic stroke patients; Acute ischemic stroke patients satisfying cardioembolic stroke diagnostic criteria
Atherosclerotic stroke patients; Acute ischemic stroke patients satisfying atherosclerotic stroke diagnostic criteria

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), cardioembolic, atherosclerotic, lacunar strokes 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), cardioembolic, atherosclerotic, lacunar strokes 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), cardioembolic, atherosclerotic, lacunar strokes 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), cardioembolic, atherosclerotic, lacunar strokes and controls.	Baseline
Assessment of left ventricular performance in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.	Investigators plan to assess left ventricular global longitudinal strain (GLS, %) in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.	Baseline
Serum malondialdehyde levels in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.	Investigators plan to compare serum malondialdehyde levels in patients with embolic stroke of undetermined source (ESUS) and controls.	Baseline
Assessment of left atrial performance in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes and controls.	Investigators plan to compare left atrial strain (LA strain) in patients with embolic stroke of undetermined source (ESUS), cardioembolic, atherosclerotic, lacunar strokes 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 (Estimated): October 30, 2025
• Study Completion (Estimated): June 30, 2026

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): July 15, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

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: Ischemic Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Embolic Stroke; 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