Brief Summary

Hypertension, also known as high blood pressure, is a chronic medical condition, in which the blood pressure is elevated. This is a common condition, which can lead to severe complications such as cardiovascular disease, heart attack, stroke and kidney disease, if not detected and treated early. Accumulating evidence suggests that the incidence of hypertension varies according to age, ethnicity and obesity. In order to obtain an in-depth knowledge of the pathophysiological mechanisms of hypertension, we aim to investigate the haemodynamic and biochemical correlates of elevated blood pressure across the adult age-span, and determine the extent to which body size and ethnicity impact on these associations. We also wish to investigate the impact of hypertension on key target organs (end-organ damage). The primary objective of this study is to compare the mechanisms regulating blood pressure in hypertensive and non-hypertensive participants across the adult age span, and to assess the influence of body mass index and ethnic background on these mechanisms. Secondary objectives are to investigate the association between blood pressure and cardiovascular physiology across the adult age span at rest and during sub-maximal exercise and to investigate the impact of blood pressure haemodynamics on key organs including the arteries and heart by assessing end-organ damage such as endothelial function, arterial structure and left ventricular mass/function. This study will be a combined case-control and cross-sectional study describing the procedures and time commitment required to investigate our scientific aims. This is a single centre study that will be conducted in a secondary care environment. Both male and females aged 18 and over and that are able provide informed consent will be considered for this study. People who are pregnant, currently receiving dialysis, illness with a life expectancy \<1 year, current active malignancy and cannot provide informed consent are ineligible for this study. The study will be open for five years and each patient will complete a maximum of four visits in a 12 month period. Participants will complete a variety of non-invasive physiological assessments of their cardiovascular system and lung function. There will be some minimally invasive procedures completed, including a blood test and assessment of small artery endothelial function which involves insertion of a small needle under local anesthetic.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

500

participants targeted

Target at P75+ for all trials

Timeline

Completed

Started Feb 2017

Longer than P75 for all trials

Geographic Reach

1 country

1 active site

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

6.9 years study duration

First Submitted

Initial submission to the registry

January 6, 2017

Completed

3 days until next milestone

First Posted

Study publicly available on registry

January 9, 2017

Completed

1 month until next milestone

Study Start

First participant enrolled

February 21, 2017

Completed

6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2024

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2024

Completed

Last Updated

August 23, 2022

Status Verified

August 1, 2022

Enrollment Period

6.9 years

First QC Date

January 6, 2017

Last Update Submit

August 21, 2022

Conditions

Cardiovascular Diseases Vascular Diseases Hypertension

Keywords

EpidemiologyEthnicityAgeWeightHypertensiveCardiac OutputPeripheral Vascular ResistanceArterial StiffnessHealthy VolunteersEndothelial functionArterial StructureLeft ventricular mass/function

Outcome Measures

Primary Outcomes (3)

Cardiac Output (Measured by the inert gas re-breathing technique L/Min)
5 years
Peripheral vascular resistance (Calculated using Cardiac Output and Blood pressure data dynes/sec/cm^5 )
5 years
Pulse wave velocity (Measured by ECG-gated applanation tonometry meters/sec)
5 years

Study Arms (3)

Healthy Volunteers

No IMP to be administered, only challenge agents as part of the physiological assessments. Large artery endothelial function: * Glyceryl trinitrate 500 μg (Sublingual administration to stimulate endothelium-independent vasodilatation) * Salbutamol 2 x 200 μg (Administered by spacer device to stimulate endothelium-dependent vasodilatation) Forearm blood flow * Acetylcholine: 7.5μg/min, 15μg/min and 30μg/min (Intra-arterial administration via brachial artery to stimulate endothelium-dependent vasodilatation) * Sodium nitroprusside: 3μg/min, 10μg/min (Intra-arterial administration via brachial artery to stimulate endothelium-independent vasodilatation) * LNMMA: 2μmol/min, 4μmol/min (Intra-arterial administration via brachial artery to block basal nitric oxide production)

Other: Brief lifestyle/medical history questionnaireOther: Anthropometric measuresOther: Blood pressure and arterial stiffnessOther: Cardiac output and lung functionOther: Heart rate variabilityOther: Blood sample & spot urine sampleOther: 24 hour ambulatory blood pressure monitorOther: 24 hour urine collectionOther: Echocardiograph: Left ventricular massOther: Large artery structure: Carotid intima-media thicknessOther: Small artery structure: Minimum forearm vascular resistanceOther: Large artery endothelial functionOther: Small artery endothelial function: Forearm blood flowOther: Dundee step testOther: Detailed haemodynamic response to submaximal exerciseOther: Cardiopulmonary fitness: Maximum oxygen consumptionOther: Haemodynamic response to mental stressOther: Small artery dilatory function: Forearm blood flow

Hypertensive Patients (Case-control)

No IMP to be administered, only challenge agents as part of the physiological assessments. Large artery endothelial function: * Glyceryl trinitrate 500 μg (Sublingual administration to stimulate endothelium-independent vasodilatation) * Salbutamol 2 x 200 μg (Administered by spacer device to stimulate endothelium-dependent vasodilatation) Forearm blood flow * Acetylcholine: 7.5μg/min, 15μg/min (Intra-arterial administration via brachial artery to stimulate endothelium-dependent vasodilatation) * Sodium nitroprusside: 3μg/min, 10μg/min (Intra-arterial administration via brachial artery to stimulate endothelium-independent vasodilatation) * LNMMA: 2μmol/min, 4μmol/min (Intra-arterial administration via brachial artery to block basal nitric oxide production)

Hypertensive Patients (Cross-sectional)

No IMP to be administered, only challenge agents as part of the physiological assessments. Large artery endothelial function: Same challenge agents as healthy volunteer and hypertensive patient (Case-control) arms Forearm blood flow Same challenge agents as healthy volunteer and hypertensive patient (Case-control) arms Recruited from community-based cohort studies - CLEAREST and ACCT Equal recruitment across the following parameters: * Age: 3 groups \<30, 30-60, \>60 years * Gender * BMI: 3 groups \<25, 25-30, \>30 Kg/m2