Endothelial Function in Prehypertension

Endothelial Dysfunction and Cardiovascular Remodeling in Pathophyisiology of Prehypertension

In the frame of this proposal investigators will test the hypothesis that high normal blood pressure (prehypertension; PreHT) induces systemic endothelial dysfunction and endothelial activation in both micro- and macrocirculation, reduces re-endothelialization potential of human endothelial progenitor cells (EPCs) and increases the level of endothelial extracellular vesicles (EVs), which are accompanied by increased oxidative stress level. Furthermore, initial vascular and left ventricle (LV) remodeling contributes to changes in systemic hemodynamics and may be influenced by altered regulatory role of renin-angiotensin system (RAS) and autonomic nervous system (ANS) in PreHT but otherwise healthy individuals. To distinguish high normal blood pressure effect from those considered normal or high, study will be performed in three groups of individuals: prehypertensive (BP 130-139/85-89 mmHg), hypertensive (stage I, BP 140-150/90-100 mmHg), and controls (BP less than or equal to 129/85 mmHg). Altogether, the impairment of normal vascular relaxation mechanisms, endothelial activation as well as vascular and LV remodeling could play crucial role in increased cardiovascular risk and CVDs incidence in PreHT individuals. Moreover, the prognostic significance of assessing endotehlial dysfunction in hypertension (as well as in PreHT) is yet to be established.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension,Essential

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Ines Drenjančević, MD, PhD; Phone Number: +38531512800; Email: ines.drenjancevic@mefos.hr

Study Locations

• Croatia
  • Osijek, Croatia, 31000
    • Faculty of Medicine Osijek

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Healthy subjects will be divided in the three study groups based on BP assessment using ambulatory blood pressure monitoring (ABPM). Hypertensive group will include only newly diagnosed patients who have not taken antihypertensive therapy.

Description

Inclusion Criteria:

• adults of both sexes with normotensive, prehypertensive and grade I hypertension blood pressure values

Exclusion Criteria:

• cardiovascular diseases, but grade I hypertension (BP 140-150/90-100 mmHg)
• diabetes
• kidney disease
• cerebrovascular diseases
• peripheral artery disease
• taking oral contraceptives or any drugs that could affect the endothelium

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Normotensive Group; BP less than or equal to 129/84 mmHg
Prehypertensive Group; BP 130-139/85-89 mmHg
Hypertensive Group; BP 140-150/90-100 mmHg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic microvascular function	Skin microvascular reactivity assessed by Laser Doppler flowmetry (post-occlusive reactive hyperemia, iontophoresis of acetylcholine and sodium nitroprusside, local thermal hyperemia) - measured in perfusion units (PU)	Day 1
Systemic macrovascular function	Vascular ultrasound measurement of brachial artery flow mediated dilation (FMD)	Day 1
Aortic stiffness	Measurement of pulse wave velocity (PWV) using impedance cardiography.	Day 1
Left ventricle global longitudinal strain	Global longitudinal strain (GLS) of left ventricle obtained by two-dimensional speckle tracking echocardiography.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxidative stress - 8-iso-prostaglandin F2α (8-iso-PGF2α)	ELISA measurement of serum 8-iso-PGF2α concentration. 8-iso-PGF2α is an isoprostane that is produced by the non-enzymatic peroxidation of arachidonic acid in membrane phospholipids.	Day 1
Activity of renin-angiotensin system (RAS)	ELISA measurement of plasma renin activity (PRA).	Day 1
Endothelial progenitor cells (EPCs)	Detection of EPCs using a two laser flow cytometer (FacsCanto II, Becton Dickinson) and CBA kits (cytometry beads assays).	Day 1
Endothelial extracellular vesicles (eEVs)	Detection of eEVs using a two laser flow cytometer (FacsCanto II, Becton Dickinson) and CBA kits (cytometry beads assays).	Day 1
Systemic peripheral vascular resistance	Systemic peripheral vascular resistance assessement using non-invasive impedance cardiography (ICG).	Day 1
Autonomic nervous system (ANS) activity	Assessment of a 5-minute heart rate variability (5-min HRV).	Day 1
Matrix metalloproteinase 9	ELISA measurement of serum matrix metalloproteinase 9 level.	Day 1

Collaborators and Investigators

• Sponsor: Josip Juraj Strossmayer University of Osijek
• Collaborators: University Hospital Center Osijek

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 2, 2024
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: hypertension; hemodynamics; prehypertension; endothelium; left ventricle
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Prehypertension; Essential Hypertension
• Other Study ID Numbers: PreHT 2024

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