Cardiovascular Longitudinal ALSPAC Research Investigations Following Hypertensive Pregnancy in Young Adulthood (CLARITY)

Cardiovascular Longitudinal the Avon Longitudinal Study of Parents and Children (ALSPAC) Research Investigations Following Hypertensive Pregnancy in Young Adulthood

The purpose of this study is to understand more about why young people who were born to a hypertensive pregnancy may have increased risk of high blood pressure and are often at increased risk of heart and blood vessel disease later in life.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Vascular Diseases; Hypertension; Hypertension in Pregnancy; Young Adult; Cerebrovascular Diseases
• Intervention / Treatment: Other: History of being born to hypertensive or normal pregnancy

Detailed Description

Women who develop blood pressure problems during pregnancy are more likely to have high blood pressure (hypertension) in later life as well as heart attacks or strokes. The children born to the pregnancy also tend to have higher blood pressure and are often at increased risk of heart and blood vessel disease later in life. Previous work has shown that children born to pregnancies where the mother has high blood pressure have changes in their blood vessels, heart and brain that can be measured long before they develop high blood pressure or other clinical symptoms. By understanding the pattern of changes cross multiple parts of the body, over a lifetime, the investigators can identify how advanced the underlying disease is for an individual and how their disease is likely to develop over the next few years.

The aim of this study is to understand the heart and blood vessel changes of people born to a hypertensive pregnancy once they are in their 20s and 30s. The investigators then hope to use this information to develop new ways to prevent early onset heart and blood vessel disease in these people.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Katie Suriano; Phone Number: 01865 226845; Email: clarity@cardiov.ox.ac.uk

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Recruiting
      • University of Oxford
      • Contact: Katie Suriano; Phone Number: 01865 226845; Email: clarity@cardiov.ox.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Of the 200 young adults followed up from the ALSPAC study, 100 will have been born to a hypertensive pregnancy and 100 following an uncomplicated pregnancy. At time of follow-up, they will be 30 to 40 years of age. At the 25-year follow-up in Bristol, there were 610 individuals born to hypertensive pregnancies.

Description

Inclusion Criteria:

• Participant is willing and able to give informed consent for participation in the study
• Male or female, aged 30 to 40 years at time of enrolment
• Participant previously took part in the ALSPAC study
• Able (in the investigator's opinion) and willing to comply with all study requirements
• Adequate understanding of verbal and written English

Exclusion Criteria:

• Pregnant or lactating when they are due to attend for study visit 1
• Less than six months postpartum
• Planning to donate blood within two weeks prior to study visit 1
• Any significant disease or disorder which, in the opinion of the investigator, might influence the participant's ability to participate in the study
• Evidence of congenital heart disease or significant chronic disease relevant to cardiovascular or metabolic status

For exclusion of MRI component only:

• Unsuitable for MRI based on participant screening; the participant may still be included in other parts of the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac right ventricular mass	Magnetic resonance imaging (MRI) assessment of cardiac right ventricular mass indexed to body surface area (in g and g/m^2)	30-40 years of old

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac left ventricular mass	MRI assessment of cardiac left ventricular mass indexed to body surface area (in g and g/m^2)	30-40 years of old
Cardiac right ventricular end-diastolic volume	MRI assessment of cardiac right ventricular end-diastolic volume indexed to body surface area (in ml and ml/m^2)	30-40 years of old
Cardiac right ventricular stroke volume	MRI assessment of cardiac right ventricular stroke volume indexed to body surface area (in ml and ml/m^2)	30-40 years of old
Cardiac left ventricular end-diastolic volume	MRI assessment of cardiac left ventricular end-diastolic volume indexed to body surface area (in ml and ml/m^2)	30-40 years of old
Cardiac left ventricular stroke volume	MRI assessment of cardiac left ventricular stroke volume indexed to body surface area (in ml and ml/m^2)	30-40 years of old
Cardiac right ventricular systolic function	Echocardiography and MRI assessment of right ventricular systolic function: tricuspid annular plane systolic excursion (in cm) and right ventricular ejection fraction measured by cardiac MRI (in %)	30-40 years of old
Cardiac left ventricular systolic function	Echocardiography and MRI assessment of left ventricular systolic function: left ventricular ejection fraction (in %)	30-40 years of old
Cardiac right ventricular diastolic function	Echocardiography assessment of right ventricular (RV) diastolic function: RV Doppler early/late diastolic tricuspid inflow velocity ratio (E/A)	30-40 years of old
Cardiac left ventricular diastolic function	Echocardiography assessment of left ventricular (LV) diastolic function: LV Doppler early/late diastolic mitral inflow velocity ratio (E/A) and LV early Doppler inflow velocity/peak early diastolic tissue velocity ratio (E/e')	30-40 years of old
Morphology of the right ventricles	MRI assessment of the right ventricles morphology using cardiac statistical atlas and principal component analysis	30-40 years of old
Morphology of the left ventricles	MRI assessment of the left ventricles morphology using cardiac statistical atlas and principal component analysis	30-40 years of old
Aortic compliance	Aortic distensibility by MRI (in 10^-3 mmHg^-1) and aortic/central blood pressure by cuff measurement (in mmHg)	30-40 years of old
Intra-hepatic lipid content, steatohepatitis and hepatic fibrosis	MRI assessment of the liver to quantify proton density fat fraction (in %) and fibro-inflammatory status from iron-corrected T1 (cT1 in ms)	30-40 years of old
Renal function	MRI assessment of fibro-inflammatory status from T1 (in ms) and surrogate measure of blood perfusion from T2* (in ms) and volumes (in ml and ml/m^2)	30-40 years of old
Oxygen uptake across sub-maximal and peak exercise	Cardiopulmonary exercise test to measure oxygen uptake (VO2 in ml/kg/min)	30-40 years of old
Carbon dioxide exchange kinetics across sub-maximal and peak exercise	Cardiopulmonary exercise test to measure respiratory exchange ratio (RER calculated as carbon dioxide production divided by oxygen consumption)	30-40 years of old
Retinal arteriolar structure	Central retinal arteriolar equivalent (CRAE in μm) measured using retinal imaging	30-40 years of old
Retinal venular structure	Central retinal venular equivalent (CRVE in μm) measured using retinal imaging	30-40 years of old
Retinal arteriolar-to-venular diameter ratio (AVR)	The ratio of average retinal arteriolar diameter (CRAE in μm) and average retinal venous diameter (CRVE in μm) measured using retinal imaging	30-40 years of old
Ear microvascular structure	Superior crus of anti-helix earlobe vascular caliber (in μm) measured using ear vascular imaging	30-40 years of old
Lung function	The forced expiratory volume in one second (FEV1 in L), forced vital capacity (FVC in L), and the ratio of FEV1 to FVC (FEV1/FVC) measured using spirometry	30-40 years of old
Objective measure of physical activity	The amount of moderate to vigorous physical activity (in h/week) and vigorous physical activity (in h/week) measured using wrist worn accelerometer	30-40 years of old
Total white matter volume	Total white matter volumes (in mm3) assessed on T1-weighted sequence of brain MRI	30-40 years of old
Total grey matter volume	Total grey matter volumes (in mm3) assessed on T1-weighted sequence of brain MRI	30-40 years of old
Subcortical brain volume of thalamus	Subcortical brain volume of thalamus (in mm3) assessed on T1-weighted sequence of brain MRI	30-40 years of old
Subcortical brain volume of hippocampus	Subcortical brain volume of hippocampus (in mm3) assessed on T1-weighted sequence of brain MRI	30-40 years of old
White matter hyperintensities volume	Total volume of white matter hyperintensities (in mm3) assessed on T2-weighted sequence of brain MRI	30-40 years of old
White matter hyperintensities count	The number of white matter hyperintensities on T2-weighted sequence of brain MRI	30-40 years of old
Cerebral vessel lumen diameter	Cerebral vessel lumen diameter (in μm) assessed on the time-of-flight sequence of brain MRI	30-40 years of old
Cerebral vessel density	Cerebral vessel density (in mm3) assessed on the time-of-flight sequence of brain MRI	30-40 years of old
Cerebral vessel tortuosity	The ratio of cerebral vessel tortuosity assessed on the time-of-flight sequence of brain MRI	30-40 years of old
Whole brain grey matter perfusion or cerebral blood flow (CBF)	Whole brain grey matter perfusion/CBF (in ml/100g/min) assessed on arterial spin labelling of brain MRI	30-40 years of old
Arterial cerebral blood volume fraction	Arterial cerebral blood volume fraction (in %) assessed on arterial spin labelling of brain MRI	30-40 years of old
Circulating vascular endothelial growth factor A (VEGF-A) as an angiogenic marker	The level of VEGF-A (in pg/mL) measured from plasma blood samples	30-40 years of old
Circulating soluble endoglin (sENG) as an angiogenic marker	The level of sENG (in ng/mL) measured from plasma blood samples	30-40 years of old
Circulating soluble fms-like tyrosine kinase-1 (sFlt-1) as an antiangiogenic marker	The level of sFlt-1 (in pg/mL) measured from plasma blood samples	30-40 years of old
Circulating total cholesterol as a metabolic marker	The level of total cholesterol (in mmol/L) measured from serum blood samples	30-40 years of old
Circulating high-density lipoprotein as a metabolic marker	The level of HDL (in mmol/L) measured from serum blood samples	30-40 years of old
Circulating low-density lipoprotein as a metabolic marker	The level of LDL (in mmol/L) measured from serum blood samples	30-40 years of old
Circulating triglycerides as a metabolic marker	The level of triglycerides (in mmol/L) measured from serum blood samples	30-40 years of old
Circulating fasting glucose concentration as a metabolic marker	The level of fasting glucose (in mmol/L) measured from whole blood samples	30-40 years of old
Circulating fasting insulin concentration as a metabolic marker	The level of fasting insulin (in pmol/L) measured from serum blood samples	30-40 years of old
Insulin resistance index (HOMA-IR) as a metabolic marker	The index calculated as fasting glucose (in mmol/L) x fasting insulin (in μIU/mL) ÷ 22.5	30-40 years of old
Circulating C-reactive protein (CRP) as an inflammatory marker	The level of CRP (in mmol/L) measured from serum blood samples	30-40 years of old
Circulating soluble intercellular adhesion molecule-1 (sICAM-1) as an inflammatory marker	The level of sICAM-1 (in ng/mL) measured from serum blood samples	30-40 years of old
Circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) as an inflammatory marker	The level of sVCAM-1 (in ng/mL) measured from serum blood samples	30-40 years of old
Body weight	Body weight measured in kg	30-40 years of old
Body height	Body height measured in m	30-40 years of old
Body mass index	Body weight divided by the square of height (in kg/m2)	30-40 years of old
Mid-arm circumference	Mid-arm circumference measured in cm	30-40 years of old
Waist-to-hip ratio	The ratio of waist circumference (in cm) to hip circumference (in cm)	30-40 years of old
Systolic blood pressure	Resting brachial blood pressure measurement (in mmHg)	30-40 years of old
Diastolic blood pressure	Resting brachial blood pressure measurement (in mmHg)	30-40 years of old
Mean arterial pressure	The average arterial pressure from resting brachial blood pressure measurement (in mmHg)	30-40 years of old
Pulse pressure	The difference between systolic and diastolic blood pressure (in mmHg)	30-40 years of old
Heart rate	The frequency of the heart contractions per minute (in beats per minute or bpm)	30-40 years of old
Smoking status	The number and percentage of current smokers	30-40 years of old
Alcohol consumption	Weekly alcoholic unit intake (in units per week)	30-40 years of old

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: University of Bristol
• Investigators: Principal Investigator: Adam J Lewandowski, Cardiovascular Clinical Research Facility

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2022
• Primary Completion (Anticipated): March 1, 2026
• Study Completion (Anticipated): January 31, 2027

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: January 5, 2023
• First Posted (Actual): January 12, 2023

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Exercise Capacity; Cardiovascular Risk; Young Adult; Birth History; Hypertension in Pregnancy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pregnancy Complications; Hypertension; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Hypertension, Pregnancy-Induced
• Other Study ID Numbers: 22/WA/0227

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No