Hyperintense: Midlife Hypertension and the Brain

Radboud University Medical Center

Status: Enrolling

Conditions: Hypertension; Small Vessel Cerebrovascular Disease

Treatments: Drug: Antihypertensive medication withdrawal

Study type: Observational

Funder types: Other

Identifiers

NCT06175663

NL75003.091.20

Details and patient eligibility

About

Cerebral small vessel disease (SVD) describes a set of pathologies affecting the smallest blood vessels in the brain. SVD contributes to up to a fifth of ischemic and hemorrhagic strokes en is the main vascular cause of dementia. On MRI, SVD is marked by different types of lesions, including white matter abnormalities, and small infarcts and hemorrhages. Recent studies indicate that SVD develops slowly over the years, starting presumably decades before the typical MRI lesions become apparent. High blood pressure plays an important role in the development of SVD MRI lesions. However, it remains unclear exactly how hypertension leads to vascular pathology. To gain more insight into how hypertension leads to SVD it is important to study mechanisms in individuals (largely) free of SVD, that is before midlife.

Therefore, the investigators aim to examine abnormalities in brain (micro) structure and vascular function in young patients with hypertension. Furthermore, the investigators aim to determine the effects of blood pressure increase and subsequent blood pressure reduction during a period of withdrawal and restart of blood pressure lowering drugs on brain (micro)structure and vascular function.

Enrollment: 130 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Study 1: cross-sectional study

Inclusion Criteria:

• Age 18-40 years
• Blood pressure above 140/90 mmHg, measured within three months prior to study participation

Exclusion Criteria:

• Pre-existing cerebrovascular disease
• Pregnancy
• Contraindications for 3 T MRI
• Renal function eGFR below 30 ml/min (for Dynamic Contrast Enhanced [DCE]-MRI
• Major risk factors for acute ischemic stroke other than SVD according to the TOAST criteria, including, but not limited to, large-artery atherosclerosis, cardioembolism and vasculitis based on medical history and ultrasound of the carotids collected at baseline or any chronic disease that could lead to brain lesions mimicking SVD
• Major (neurological/psychiatric) disease (e.g. multiple sclerosis)
• Not able to give informed consent

Study 2: longitudinal study

Inclusion criteria:

• Age 18-55 years
• Undergoing diagnostic routine of temporary antihypertensive withdrawal for biochemical analysis as part of clinical work-up

Exclusion criteria:

• Pre-existing cerebrovascular disease
• Pregnancy
• Contraindications for 3 T MRI
• Renal function eGFR below 30 ml/min (for Dynamic Contrast Enhanced [DCE]-MRI
• Major risk factors for acute ischemic stroke other than SVD according to the TOAST criteria,22 including, but not limited to, large-artery atherosclerosis, cardioembolism and vasculitis based on medical history and ultrasound of the carotids collected at baseline or any chronic disease that could lead to brain lesions mimicking SVD
• Major (neurological/psychiatric) disease (e.g. multiple sclerosis)
• Not able to give informed consent

Trial design

130 participants in 2 patient groups

Cross-sectional study

Description:

To examine if there are cerebral abnormalities present following hypertension before MRI markers of SVD have manifested, we will do high-resolution 3T MRI in 100 young (18-40 years) hypertensive adults.

Longitudinal study

Description:

In a cohort study, we will examine the effects of an increase and decrease in blood pressure on the brain. For this analysis, we will include hypertensive patients that are referred to the Radboudumc Department of Internal Medicine for a diagnostic work up on the cause(s) of their hypertension. The diagnostic procedure entails withdrawal of antihypertensives for approximately four weeks, as per the routine diagnostic protocol to allow for diagnosis of the cause of hypertension, and subsequent restart of treatment until the target blood pressure is reached (normotension). Measurements are performed just before antihypertensive medication is withdrawn (baseline), approximately four weeks after withdrawal (T=1), once patients have reached their target blood pressure and blood pressure is stable, estimated to occur within 2-4 months (T=2) and approximately 1 year after T=2 (T=3).

Treatment:

Drug: Antihypertensive medication withdrawal