About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
adults of both sexes with normotensive, prehypertensive and grade I hypertension blood pressure values
Disqualifiers
cardiovascular diseases, but grade I hypertension (BP 140-150/90-100 mmHg)
diabetes
kidney disease
cerebrovascular diseases
Trial 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.
Trial design
Case-crossover
Cross-sectional
Treatments tested in this trial
Not listed
Trial groups
Trial outcomes
Primary outcomes
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)
Systemic macrovascular function
Vascular ultrasound measurement of brachial artery flow mediated dilation (FMD)
Aortic stiffness
Measurement of pulse wave velocity (PWV) using impedance cardiography.
Left ventricle global longitudinal strain
Global longitudinal strain (GLS) of left ventricle obtained by two-dimensional speckle tracking echocardiography.
Secondary outcomes
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.
Activity of renin-angiotensin system (RAS)
ELISA measurement of plasma renin activity (PRA).
Endothelial progenitor cells (EPCs)
Detection of EPCs using a two laser flow cytometer (FacsCanto II, Becton Dickinson) and CBA kits (cytometry beads assays).
Endothelial extracellular vesicles (eEVs)
Detection of eEVs using a two laser flow cytometer (FacsCanto II, Becton Dickinson) and CBA kits (cytometry beads assays).
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Josip Juraj Strossmayer University of Osijek
Lead sponsor
University Hospital Center Osijek
Collaborator
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