Association Between Left Ventricular Deformation and Aerobic Exercise Capacity in Untreated Arterial Hypertension

Study Overview
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Brief Summary
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Impaired myocardial deformation may determine cardiac diastolic dysfunction. The investigators will investigate the vascular determinants of myocardial deformation and twisting-untwisting and their interrelation with exercise capacity in patients with untreated arterial hypertension

Detailed Description
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The investigators plan to examine 320 untreated hypertensives and 160 controls. They will measure: the carotid to femoral pulse wave velocity (PWVc) using the Complior apparatus the coronary flow reserve (CFR) at baseline and after adenosine infusion (140 μg x kg-1 x min-1) by Doppler echocardiography the Global Longitudinal strain and strain rate, peak twisting, the percentage changes between peak twisting and untwisting at mitral valve opening (UtwMVO), at peak (UtwPEF) and end of early LV diastolic filling (UtwEDF) by speckle tracking imaging the perfusion boundary region (PBR-micrometers) of the sublingual arterial microvessels (ranged from 5-25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck). Increased PBR is considered an accurate non invasive index of reduced endothelial glycocalyx thickness transforming growth factor (TGFb-1), metalloproteinase-9 (MMP-9), markers of collagen synthesis (N-terminal procollagen type-III propeptide , carboxy-terminal propeptide and telopeptide of procollagen type-1, representing cardiac extracellular matrix turnover) and N-terminal pro-brain natriuretic peptide (NT-proBNP) and soluble angiotensin-converting enzyme (sACE). Twenty-four hour daytime and night-time average systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rates as well as 24h-pulse pressure (PP) by means of 24h ambulatory blood pressure monitoring (ABPM) Monitoring will be carried out on the non-dominant arm using the valid recorder TONOPORT V (General Electric, Health Care, Berlin, Germany) after validation of readings against a mercury sphygmomanometer by means of a Y tube. The ABPM device will set to obtain BP readings at 15 min intervals during the day (07.00-23.00) and at 20 min intervals during the night (23.00-07.00). The patients will be instructed to attend their usual day-to-day activities but to keep still at the times of measurements. Recordings will be analysed to obtain oxygen consumption as an absolute value and in relation to body weight (VO2/Kg) and maximum work load (METS) by means of a physician-supervised maximal, symptom-limited cardiopulmonary exercise test (CPET) on a bicycle ergometer using a standard ramping protocol (Oxycon Pro system, Jaeger, Germany).

Official Title
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Vascular and Biochemical Determinants of Left Ventricular Deformation and Twisting-untwisting and Their Interrelation With Aerobic Exercise Capacity in Untreated Arterial Hypertension

Conditions
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Arterial Hypertension

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: untreated patients with newly diagnosed essential hypertension normotensive subjects Exclusion Criteria: history of diabetes familiar hyperlipidemia coronary CAD cardiomyopathy chronic pulmonary disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hypertensives<br>Untreated consecutive patients with newly diagnosed essential hypertension | |
| Controls<br>Normotensive individuals | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular function in hypertensive and normotensive subjects | Pulse wave velocity by Complior,endothelial glycocalyx thickness by Miscroscan camera and coronary flow reserve by Doppler echocardiography were measured in hypertensive and normotensive subjects | Baseline | 
| Myocardial deformation in hypertensive and normotensive subjects | Longitundinal, circumferential and radial strain-strain rate were measured by speckle tracking imaging | Baseline | 
| Left ventricular twisting-untwisting in hypertensive and normotensive subjects | Peak twisting-untwisting ,twisting-untwisting velocity, the percentage difference between peak twisting and untwisting at mitral valve opening , peak and end of early diastolic filling of the left ventricle was measured by speckle tracking imaging | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Collagen synthesis in hypertensive and normotensive subjects | Blood levels of N-terminal procollagen type-III propeptide , carboxy-terminal propeptide and telopeptide of procollagen type-1, representing cardiac extracellular matrix turnover were measured in patients with untreated arterial hypertension and normotensive subjects | Baseline | 
| Inflammation in hypertensive and normotensive subjects | Transforming growth factor b-1, metalloproteinase-9, soluble angiotensin converting enzyme blood levels were measured in patients with untreated arterial hypertension and normotensive subjects | Baseline | 
| Neurohumoral activation in hypertensive and normotensive subjects | N-terminal pro-brain natriuretic peptide blood levels were measured in patients with untreated arterial hypertension and normotensive subjects | Baseline | 
| Exercise capacity in hypertensive subjects | Peak oxygen consumption during cardiopulmonary exercise test was measured in patients with untreated arterial hypertension | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LV deformation, Endothelial glycocalyx, Coronary flow reserve