Clinical trial NCT02346695: Association Between Left Ventricular Deformation and Aerobic Exercise Capacity in Untreated Arterial Hypertension
Official title: Vascular and Biochemical Determinants of Left Ventricular Deformation and Twisting-untwisting and Their Interrelation With Aerobic Exercise Capacity in Untreated Arterial Hypertension
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Arterial Hypertension
Keywords: LV deformation
Endothelial glycocalyx
Coronary flow reserve
Lead sponsor: University of Athens
Sponsor class: OTHER
First posted: 2015-01-27
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: 320 ntreated consecutive patients with newly diagnosed essential hypertension and 160 normotensive individuals

Brief summary: 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: The investigators plan to examine 320 untreated hypertensives and 160 controls. They will measure:

1. the carotid to femoral pulse wave velocity (PWVc) using the Complior apparatus
2. the coronary flow reserve (CFR) at baseline and after adenosine infusion (140 μg x kg-1 x min-1) by Doppler echocardiography
3. 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
4. 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
5. 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).
6. 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
7. 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).

Eligibility criteria: Inclusion Criteria:

* untreated patients with newly diagnosed essential hypertension
* normotensive subjects

Exclusion Criteria:

* history of diabetes
* familiar hyperlipidemia
* coronary CAD
* cardiomyopathy
* chronic pulmonary disease

Primary outcomes:
measure: Vascular function in hypertensive and normotensive subjects
timeFrame: Baseline
measure: Myocardial deformation in hypertensive and normotensive subjects
timeFrame: Baseline
measure: Left ventricular twisting-untwisting in hypertensive and normotensive subjects
timeFrame: Baseline
Secondary outcomes:
measure: Collagen synthesis in hypertensive and normotensive subjects
timeFrame: Baseline
measure: Inflammation in hypertensive and normotensive subjects
timeFrame: Baseline
measure: Neurohumoral activation in hypertensive and normotensive subjects
timeFrame: Baseline
measure: Exercise capacity in hypertensive subjects
timeFrame: Baseline
Other outcomes:
Locations:
city: Haidari, Athens
country: Greece
facility: "Attikon" University General Hospital
state: Attiki
Study officials:
affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece
name: Ignatios Ikonomidis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece
name: Helen Triantafyllidi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece
name: John Lekakis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tzortzis S, Ikonomidis I, Triantafyllidi H, Trivilou P, Pavlidis G, Katsanos S, Katogiannis K, Birba D, Thymis J, Makavos G, Varoudi M, Frogoudaki A, Vrettou AR, Vlastos D, Parissis J, Lekakis J. Optimal Blood Pressure Control Improves Left Ventricular Torsional Deformation and Vascular Function in Newly Diagnosed Hypertensives: a 3-Year Follow-up Study. J Cardiovasc Transl Res. 2020 Oct;13(5):814-825. doi: 10.1007/s12265-019-09951-9. Epub 2020 Jan 2.