Hypertension, Small Vessel Cerebrovascular Disease
Conditions
Brief summary
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.
Interventions
DRUGAntihypertensive medication withdrawal
To determine if high blood pressure is caused by an overproduction of aldosterone in the adrenal gland (i.e. primary hyperaldosteronism), the plasma aldosterone/renin ratio (ARR) can be determined. Because many common hypertensive drugs are known to interfere with this ratio, patients often have to discontinue drugs prior to screening or switch to drugs that are known not to affect ARR (i.e. doxazosin, verapamil, diltiazem, hydralazine). Drugs have to be stopped for at least four weeks (for mineralocorticoid receptor antagonists) or two weeks (for diuretics, Angiotensin Converting Enzyme (ACE) inhibitors, Angiotensin Receptor Blockers (ARBs)). This often leads to a temporary increase in blood pressure. After diagnostics are completed, medication is adjusted accordingly and blood pressure levels drop again.
Sponsors
Radboud University Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resting state fMRI | Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later. | Functional connectivity |
| DCE-MRI outcomes | Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later. | Leakage rate (Ki) |
| DTI outcomes | Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later. | Fractional Anisotropy (FA) |
| Intravoxel Incoherent Motion outcomes | Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later. | Parenchimal Diffusivity (D) |
| Standard neuroimaging markers of SVD, assessed using STRIVE criteria | Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later. | This includes white matter hyperintensity volumes, lacunes, microbleeds, DWI+ positive lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Motor functioning | Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later. | Motor functioning is assessed using a 6-m walking test (in seconds) and the Timed Up & Go test (in seconds) |
| Blood markers | Four weeks after antihypertensive drug withdrawal and after 1-4 months when blood pressure is stable. | This includes circulating markers of inflammation, including cytokines and chemokines, in mmol/l measured in blood. |
| Cognition | Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later. | Cognitive functioning is assessed using a 60-min cognitive assessment covering six domains: processing speed, attention, executive functioning, verbal memory, working memory and psychomotor functioning. |
Countries
Netherlands
Contacts
Primary ContactEsther Janssen
Outcome results
None listed