Cardiovascular Longitudinal ALSPAC Research Investigations Following Hypertensive Pregnancy in Young Adulthood

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Young Adult, Hypertension in Pregnancy, Hypertension, Cardiovascular Diseases, Cerebrovascular Diseases, Vascular Diseases

Intervention / Treatment
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* Other: History of being born to hypertensive or normal pregnancy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: History of being born to hypertensive or normal pregnancy|CLARITY is an observational study whereby participants will attend one 4-hr visit the Division of Cardiovascular Medicine, University of Oxford at the John Radcliffe Hospital in Oxford, with the option to split the study visit over two days for convenience. Participants will be invited by the ALSPAC study team to attend a study visit in Oxford where the investigators will use MRI and other imaging modalities to study the brain, heart, liver, kidneys, and vasculature using standardised protocols. A dataset including information from previous follow-up of these cohorts and the detailed pregnancy data available within ALSPAC will be generated by the study team in Bristol and integrated with available data from the Oxford cohorts.|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Young Adult, Birth History, Hypertension in Pregnancy, Cardiovascular Risk, Exercise Capacity