Effects of Amlodipine and Other Blood Pressure Lowering Agents on Microvascular Function

Inclusion Criteria: Patients may be enrolled in the trial if all of the following criteria have been met: * Symptomatic SVD defined as * History of clinical lacunar stroke in the last 5 years with a corresponding small subcortical infarct visible on MRI scan or CT scan\* compatible with the clinical syndrome. \*On MRI, recent infarct is defined as a diffusion-weighted imaging (DWI) lesion on the acute MRI scan. On CT, recent infarct is defined as a novel infarct on CT within 3 weeks after the event that was not visible on the admission CT. Patients admitted to the hospital with an obvious lacunar syndrome and an admission CT/CT perfusion compatible with a lacunar infarct but without an MRI in the (sub)acute stage and no repeat CT performed in the context of clinical care can be recruited for TREAT-SVDs. After providing informed consent they will be invited for the screening visit including a 3T MRI. The 3T MRI will be used to verify the presence of a new lesion, relative to the admission CT, compatible with a lacunar infarct and compatible with the lacunar syndrome. If such a lesion is present the patient will undergo the further TREAT-SVDs workup. If no such lesion is observed the patient will be excluded from the study and considered as a screening failure. * or cognitive impairment defined as visiting a memory clinic with cognitive complaints, objective cognitive impairment\*, and capacity to consent, and with confluent deep white matter hyperintensities (WMH) on MRI (defined on the Fazekas scale as deep WMH score ≥ 2) \*concluded by the treating physician based on a validated cognitive measurement tool (for example but not limited to MoCA or CAMCOG) * or a diagnosis of CADASIL established by molecular genetic testing of the NOTCH3 gene (presence of an archetypical, cysteine-affecting mutation) or the presence of granular osmiophilic material in ultrastructural, electron microscopy analysis of skin biopsy * Indication for antihypertensive treatment (as defined by meeting one of the following): * Hypertension defined as SBP ≥ 140 mmHg or diastolic BP (DBP) ≥ 90 mmHg without antihypertensive treatment or use of an antihypertensive drug for previously diagnosed hypertension * Prior history of stroke or transient ischaemic attack (TIA) * Age 18 years or older * Written informed consent Exclusion Criteria: Patients will be excluded from the trial for any of the following reasons: * Inclusion criteria are not met * Unwillingness or inability to give written consent * Pregnant or breastfeeding women, women of childbearing age not taking contraception. Acceptable contraception in women of childbearing age is a "highly effective" contraceptive measure as defined by the Clinical Trials Facilitation Group and includes combined (oestrogen and progesterone containing) or progesterone-only contraception associated with inhibition of ovulation, or intrauterine device, or bilateral tubal occlusion. * Contraindications to MRI (pacemaker, aneurysm clip, cochlear implant etc.) * Other major neurological or psychiatric conditions affecting the brain and interfering with the trial design (e.g. multiple sclerosis) * In case of clinical lacunar stroke syndrome other causes of stroke such as * ≥ 50% luminal stenosis (NASCET) in large arteries supplying the area of ischaemia * major-risk cardioembolic source of embolism (permanent or paroxysmal atrial fibrillation, sustained atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumours, mitral stenosis, recent (\< 4 weeks) myocardial infarction, left ventricular ejection fraction less than 30%, valvular vegetations, or infective endocarditis) * other specific causes of stroke identified (e.g. arteritis, dissection, migraine/vasospasm, drug misuse) * Other stroke risk factor requiring immediate intervention that would preclude involvement in the trial * Renal impairment (eGFR \< 35ml/min) * Life expectancy \< 2 years * Use of \> 2 antihypertensive drugs at maximum dose or equivalent (one drug at the maximum dose and two drugs at half of the maximum dose) for an appropriate BP control * Contraindications to the applied antihypertensive drugs as known * Severe aortic stenosis * Bilateral renal artery stenosis * Severe arterial circulatory disorders * Atrioventricular block II° or III° or sick sinus syndrome * Heart failure (NYHA III or IV) * Bradycardia, resting heart rate \< 50/min * Bronchospastic diseases such as severe bronchial asthma * Severe hepatic dysfunction such as liver cirrhosis * Use of monoamine oxidase (MAO)-A-blockers * Use of simvastatin \> 20mg/d * Metabolic acidosis * Disturbed electrolyte homeostasis such as hypercalcaemia, hypokalaemia, and hyponatraemia * Symptomatic hyperuricaemia (gout)