Influence of Age, Weight and Ethnic Background on Blood Pressure

• Conditions: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Interventions: Other: Brief lifestyle/medical history questionnaire; Other: Anthropometric measures; Other: Blood pressure and arterial stiffness; Other: Cardiac output and lung function; Other: Heart rate variability; Other: Blood sample & spot urine sample; Other: 24 hour ambulatory blood pressure monitor; Other: 24 hour urine collection; Other: Large artery endothelial function; Other: Dundee step test; Other: Detailed haemodynamic response to submaximal exercise; Other: Haemodynamic response to mental stress

• Registration Number: NCT03014791
• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-01-06
• Study First Submitted QC: 2017-01-06
• Study First Posted: 2017-01-09
• Study Start: 2017-02-21
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-21
• Last Update Posted: 2022-08-23
• Primary Completion: 2024-02
• Study Completion: 2024-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Male or Female, aged 18 or above
• Able to give informed consent and willing to participate

Exclusion Criteria

• Pregnancy
• Current active malignancy
• Currently receiving dialysis
• Any illness with a life expectancy < 1 year
• Lack of written informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy Volunteers	Blood sample & spot urine sample	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)
Healthy Volunteers	Large artery endothelial function	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)
Hypertensive Patients (Case-control)	Brief lifestyle/medical history questionnaire	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)
Healthy Volunteers	Brief lifestyle/medical history questionnaire	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)
Healthy Volunteers	Dundee step test	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)
Hypertensive Patients (Case-control)	Blood pressure and arterial stiffness	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 (Case-control)	Cardiac output and lung function	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)
Healthy Volunteers	Heart rate variability	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)
Healthy Volunteers	24 hour ambulatory blood pressure monitor	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)
Healthy Volunteers	Detailed haemodynamic response to submaximal exercise	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)
Hypertensive Patients (Cross-sectional)	Anthropometric measures	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
Hypertensive Patients (Cross-sectional)	Large artery endothelial function	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
Healthy Volunteers	Anthropometric measures	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)
Hypertensive Patients (Case-control)	Anthropometric measures	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 (Case-control)	Heart rate variability	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 (Case-control)	Blood sample & spot urine sample	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 (Case-control)	24 hour urine collection	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)
Healthy Volunteers	Blood pressure and arterial stiffness	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)
Healthy Volunteers	Cardiac output and lung function	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)
Healthy Volunteers	24 hour urine collection	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)
Healthy Volunteers	Haemodynamic response to mental stress	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)
Hypertensive Patients (Case-control)	24 hour ambulatory blood pressure monitor	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 (Case-control)	Detailed haemodynamic response to submaximal exercise	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)	Cardiac output and lung function	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
Hypertensive Patients (Case-control)	Large artery endothelial function	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)	Blood sample & spot urine sample	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
Hypertensive Patients (Case-control)	Dundee step test	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)	24 hour ambulatory blood pressure monitor	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
Hypertensive Patients (Cross-sectional)	24 hour urine collection	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
Hypertensive Patients (Case-control)	Haemodynamic response to mental stress	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)	Brief lifestyle/medical history questionnaire	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
Hypertensive Patients (Cross-sectional)	Blood pressure and arterial stiffness	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
Hypertensive Patients (Cross-sectional)	Dundee step test	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
Hypertensive Patients (Cross-sectional)	Haemodynamic response to mental stress	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
Hypertensive Patients (Cross-sectional)	Heart rate variability	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
Hypertensive Patients (Cross-sectional)	Detailed haemodynamic response to submaximal exercise	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

Primary Outcome Measures

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

Trial Locations

Locations (1)

Vascular Research Clinic, Addenbrooke's Hospital; 🇬🇧 Cambridge, Cambridgeshire, United Kingdom