Under stress: Why women of black African-Caribbean heritage are at elevated risk of stroke

ISRCTN	ISRCTN12925425
DOI	https://doi.org/10.1186/ISRCTN12925425
IRAS number	347113
Secondary identifying numbers	Sponsor Ref: 2024 - 4520, CPMS 64223

Submission date: 03/03/2025
Registration date: 06/03/2025
Last edited: 01/04/2025

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Black African and Caribbean women are three times more likely to experience stroke and are more likely to have a stroke at a young age. What causes this is unknown, but stress appears to play an important role. High levels of daily stress may increase the risk of stroke in Black African Caribbean women. This is because Black women often have bigger spikes in blood pressure during stress. These large and frequent blood pressure spikes may cause damage to the brain over time. Therefore, we want to understand how the brain responds to these spikes in blood pressure and explore whether the blood vessels in the brain are less able to protect against these blood pressure spikes in Black African Caribbean women.

Who can participate?
Women of Black African and Black Caribbean heritage and women of White European heritage, between 18 and 75 years old.

What does the study involve?
Taking part involves two visits: one visit to the Clinical Research Facility in Bristol, which will take about 3 hours and one visit to the Cardiff University Brain Imaging Research Centre in Cardiff, which will take around 2 hours.

Visit 1: Screening tests to ensure eligibility. Completion of questionnaires assessing social determinants of health and health behaviours including physical activity levels, diet, sleep quality, experience of discrimination, and stress levels.
Non-invasive assessment of blood pressure and leg blood flow responses to a math task. Venous blood sample to determine stress hormone levels at rest and during a math task.

Visit 2: Non-invasive assessment of large artery stiffness.
Participants will then undergo a brain MRI. Scans will be taken at rest, during a mental math task and during occlusion of the forearm with a blood pressure cuff pumped to a high pressure (i.e., metaboreflex test).

What are the possible benefits and risks of participating?
This study is testing the impact of stress on blood pressure and brain function. Taking part will help us understand why high levels of stress increase the risk of stroke in Black women. This can also help identify preventative treatments. You will get a full blood pressure screen, which may be of some benefit to you from a health check-up perspective. You will also get information on your cholesterol levels and diabetes risk
This study involves minimal risks
Venous blood sample and cannulation: mild discomfort during venepuncture/cannulation and mild swelling or bruising at the site.
Monitoring heart rate, blood pressure and breathing: mild discomfort from the inflation of the blood pressure cuff around the finger.
Mental math test: the task may cause some stress, however, this will stop when the task stops.
Metaboreflex test: mild arm discomfort with the blood pressure cuff being inflated to stop blood from leaving your arm.
Brain MRI: MRI is a safe, non-invasive and painless procedure. However, some people find being inside the scanner claustrophobic. Some people may experience discomfort from lying down in the scanner for 1 hour.

Where is the study run from?
University of Bristol (UK)

When is the study starting and how long is it expected to run for?
April 2024 to January 2028

Who is funding the study?
British Heart Foundation (UK)

Who is the main contact?
Dr Lydia Simpson, Lydia.simpson@bristol.ac.uk

Contact information

Dr Lydia Simpson
Public, Scientific, Principal Investigator

Biomedical Sciences Building
University of Bristol
Bristol
BS81TD
United Kingdom

Phone	+44 (0)7795123830
Email	Lydia.simpson@bristol.ac.uk

Study information

Study design	Observational cross-sectional study
Primary study design	Observational
Secondary study design	Cross sectional study
Study setting(s)	University/medical school/dental school
Study type	Other
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet.
Scientific title	Under stress: Why women of black African-Caribbean heritage are at elevated risk of stroke
Study objectives	Primary hypothesis 1: There will be a difference in the increase in large and small vessel pulsatility during mental stress in normotensive Black African-Caribbean women versus normotensive White European women. Primary hypothesis 2: There will be a difference in the increase in large and small vessel pulsatility during mental stress in hypertensive Black African-Caribbean women versus hypertensive White European women
Ethics approval(s)	Approved 05/02/2025, North East - Newcastle & North Tyneside 2 Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8086; newcastlenorthtyneside2.rec@hra.nhs.uk), ref: 24/NE/0209
Health condition(s) or problem(s) studied	Hypertension
Intervention	This study will be a cross-sectional study of four groups: normotensive Black African and Black Caribbean women, normotensive White European women, hypertensive Black African and Black Caribbean women and hypertensive White European women. Two study visits: Visit 1: Consent and screening visit and determination of hemodynamic and sympathetic responses to mental stress. Visit 1 will be undertaken at the NIHR Clinical Research Facility, Bristol. First, consent will be obtained, and participants' eligibility will be determined. Following screening, several questionnaires will be completed to assess social determinants of health and health behaviours. Venous blood samples will be taken at rest to measure catecholamines and cortisol. BP, heart rate, respiratory activity and vascular ultrasound will be measured at rest and during a mental arithmetic task, used to induce mental stress. A second blood sample will be taken during the mental arithmetic task to determine changes in catecholamines and cortisol, from rest. Study visit 2: MRI visit and determination of cerebrovascular responses to mental stress. Visit 2 will be undertaken at Cardiff University Brain Research Imaging Centre (CUBRIC). Participants will be familiarised using a mock MRI scanner. Resting pulse wave velocity will be assessed. BP, peripheral oxygen saturation, respiratory activity, and end-tidal partial pressure of CO2 and O2 will be measured, and MRI imaging will be completed at rest and during 1) mental arithmetic task and 2) during metaboreflex testing.
Intervention type	Other
Primary outcome measure	Cerebral pulsatility index measured from MRI at rest and during Paced Auditory Serial Addition Task (PASAT)
Secondary outcome measures	1. White matter hyperintensities measured using MRI at rest 2. Blood-brain barrier integrity measured using MRI at rest 3. Grey matter perfusion measured using MRI at rest 4. Cardiovascular hemodynamics measured continuously during a 10-minute resting period and during the PASAT: 4.1. Heart rate measured continuously via ECG 4.2. Beat-to-beat blood pressure measured via finger photoplethysmography 4.3. Continuous femoral blood flow measured via Doppler ultrasound 5. Stress hormones (cortisol and catecholamines) during mental stress measured from venous blood samples taken at rest and during the PASAT 6. Systemic arterial stiffness measured using carotid-femoral pulse wave velocity at rest 7. Cerebral arterial stiffness measured from MRI at rest
Overall study start date	04/04/2024
Completion date	01/01/2028

Eligibility

Participant type(s)	Healthy volunteer, Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	75 Years
Sex	Female
Target number of participants	16 normotensive Black African-Caribbean women, 16 normotensive White European women, 16 hypertensive Black African-Caribbean women and 16 hypertensive White European women matched for age and BMI
Key inclusion criteria	All participants: 1. Female 2. 18-75 years of age 3. Non-obese (BMI <35 kg/m2) Normotensive participants: 1. Office BP < 140/90 mmHg and daytime ambulatory BP <135/85 mmHg 2. No medications except oral contraceptives Hypertensive participants: 1. Office BP > 140/90 mmHg and daytime ambulatory BP > 135/85 mmHg or diagnosis of hypertension 2. No medications except treatment for hypertension and/or oral contraceptives
Key exclusion criteria	All participants: 1. Body mass index ≥35 kg/m2 2. Major illness e.g. cancer, inflammatory disease (including vasculitis) or receiving palliative care 3. Medical history of respiratory, cardiovascular (excluding hypertension), cerebrovascular, metabolic, renal or endocrine disorders (i.e. severe cardiac electrical conduction abnormalities, chronic heart failure, Chronic Obstructive Pulmonary disease, diabetes, polycystic ovary syndrome) 4. Inherited disorders e.g., sickle cell anaemia 5. Pregnancy/breastfeeding women 6. Taking nitrate, steroid, anti-coagulant or immunosuppressant medication or medication as part of a clinical trial 7. Diagnosed cardiovascular (including arrhythmia), respiratory (including asthma), renal or ophthalmic disease 8. Congenital or acquired neurological conditions (including dementia), language disorders, repeated or chronic pain conditions (excluding menstrual pain and minor sporadic headaches) 9. Diabetes or HbA1c >6.5% 10. Symptoms of febrile illness within two weeks of participation 11. Excessive alcohol consumption (exceeding 28 units/week) or intravenous drug use 12. Needle phobia 13. History of panic attacks 14. Inability to understand instructions given in English 15. Current smoker 16. Pacemaker, implantable cardiac defibrillator, cerebral metallic clips or other implanted metallic devices/structures 17. Unable to tolerate scanner or history of claustrophobia 18. Learning disability or significant hearing and/or visual impairment, which may affect participants ability to communicate from within the MRI scanner 19. Inability to understand English Normotensive: 1. Women with a history of hypertension, including hypertension in pregnancy Hypertensive participants: 2. Secondary causes of hypertension
Date of first enrolment	18/02/2025
Date of final enrolment	01/10/2027

Locations

Countries of recruitment

England
United Kingdom
Wales

Study participating centres

NIHR Bristol Clinical Research Facility

60 St Michael's Hill
Bristol
BS2 8DX
United Kingdom

Cardiff University Brain Imaging Centre

Maindy Road
Cardiff
CF24 4HQ
United Kingdom

Sponsor information

British Heart Foundation
Charity

Greater London House
Hampstead Road
London
NW17AW
England
United Kingdom

Phone	+44 (0)20 7554 0434
Email	research@bhf.org.uk
Website	https://www.bhf.org.uk/
"ROR"	https://ror.org/02wdwnk04

Funders

Funder type

Charity

British Heart Foundation
Private sector organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): the_bhf, The British Heart Foundation, BHF
Location: United Kingdom

Results and Publications

Intention to publish date	01/12/2028
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Plan to publish findings in peer-reviewed scientific journals, where it can be accessed by researchers and other medical professionals. The findings will also be disseminated at international conferences. Dissemination workshops in local communities will also be conducted to provide an overview of findings.
IPD sharing plan	The datasets generated and/or analysed during the current study will be available upon request from Dr Lydia Simpson (Lydia.simpson@bristol.ac.uk)

Editorial Notes

01/04/2025: Internal review.
03/03/2025: Study's existence confirmed by the HRA.