Endothelial Extracellular Vesicles as Biomarkers of Endothelial Activation in Children With Newly Diagnosed Hypertension (HYPER-endoEV-c)

Endothelial Extracellular Vesicles as Biomarkers of Blood Pressure-Induced Endothelial Activation in Children With Newly Diagnosed Untreated Primary Hypertension

Childhood hypertension is associated with early endothelial dysfunction and an increased risk of future cardiovascular disease. Endothelial extracellular vesicles (EEVs) have emerged as promising biomarkers of endothelial activation; however, their role in pediatric hypertension remains poorly understood. This observational case-control study aims to compare circulating EEV concentrations between normotensive children and children with newly diagnosed, untreated primary hypertension. The study will also investigate the associations between EEV levels, blood pressure, microvascular endothelial function assessed by laser Doppler flowmetry, and circulating biomarkers of endothelial activation. The findings may improve understanding of endothelial injury in pediatric hypertension and support the development of non-invasive biomarkers for early cardiovascular risk assessment.

Study Overview

• Status: Recruiting
• Conditions: Endothelial Dysfunction; Primary Hypertension; Pediatric Hypertension

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Ana Stupin, MD, PhD; Phone Number: +38531512800; Email: medicina@mefos.hr
• Study Contact Backup: Name: Ivana Jukić, MD, PhD; Phone Number: +38531512800; Email: medicina@mefos.hr

Study Locations

• Croatia
  • Osijek, Croatia, 31000
    • Recruiting
    • Faculty of Medicine Osijek
    • Contact: Mia Damašek, MD; Email: mdmiadamasek@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population will include children and adolescents recruited from the outpatient clinics of the Department of Pediatrics, University Hospital Centre Osijek, Croatia. Participants will comprise normotensive children and adolescents and those with newly diagnosed, previously untreated primary hypertension, classified according to current pediatric hypertension guidelines.

Description

Inclusion Criteria:

• Children and adolescents aged 6-17 years.
• Written informed consent from a parent or legal guardian and assent from the participant when appropriate.
• Normotensive status or newly diagnosed, previously untreated primary hypertension according to current pediatric hypertension guidelines.
• Ability to comply with study procedures.

Exclusion Criteria:

• Secondary hypertension.
• Previous antihypertensive treatment.
• Congenital heart disease or other significant cardiovascular disease.
• Diabetes mellitus.
• Chronic kidney disease.
• Autoimmune or chronic inflammatory disease.
• Acute infection at the time of enrollment.
• Malignancy.
• Use of medications known to affect endothelial function.
• Inability to comply with study procedures.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Normotensive Controls; Children and adolescents with normal blood pressure according to current pediatric hypertension guidelines.
Newly Diagnosed Untreated Primary Hypertension; Children and adolescents with newly diagnosed, previously untreated primary hypertension according to current pediatric hypertension guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma endothelial extracellular vesicle concentration	Concentration of circulating endothelial extracellular vesicles quantified by flow cytometry following size-exclusion chromatography isolation.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-occlusive reactive hyperemia (PORH)	Microvascular endothelium-dependent vasodilation assessed by laser Doppler flowmetry following 1-minute arterial occlusion.	Baseline
Acetylcholine-induced vasodilation (AChID)	Endothelium-dependent microvascular vasodilation assessed by acetylcholine iontophoresis and laser Doppler flowmetry.	Baseline
Sodium nitroprusside-induced vasodilation (SNPID)	Endothelium-independent microvascular vasodilation assessed by sodium nitroprusside iontophoresis and laser Doppler flowmetry.	Baseline
VCAM-1 concentration	Plasma vascular cell adhesion molecule-1 (VCAM-1) concentration measured as a marker of endothelial activation.	Baseline
ICAM-1 concentration	Plasma intercellular adhesion molecule-1 (ICAM-1) concentration measured as a marker of endothelial activation.	Baseline
Endocan concentration	Plasma endocan concentration measured as a marker of endothelial dysfunction.	Baseline
von Willebrand factor (vWF)	Plasma von Willebrand factor concentration measured as a marker of endothelial injury.	Baseline
Matrix metalloproteinase-9 (MMP-9)	Plasma MMP-9 concentration measured as a marker of vascular remodeling and endothelial dysfunction.	Baseline

Collaborators and Investigators

• Sponsor: Josip Juraj Strossmayer University of Osijek
• Collaborators: Osijek University Hospital
• Investigators: Study Chair: Ivana Jukić, MD, PhD, Faculty of Medicine Osijek, Josip Juraj Strossmayer of Osijek

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: July 22, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Biomarkers; Cardiovascular Risk; Endothelial Dysfunction; Pediatric Hypertension; Primary Hypertension; Microvascular Function; Laser Doppler Flowmetry; Endothelial Extracellular Vesicles; Endothelial Activation; Childhood Hypertension
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: HYPER-endoEV-children

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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