Intensive Blood Pressure Control in Ischaemic Stroke Patients With Severe Cerebral Small Vessel Disease

Objectives: Cerebral small vessel disease (SVD) is a common disease in patients with ischemic stroke and the most common cause of vascular dementia. Blood pressure (BP)-lowering is generally considered neuroprotective. Nevertheless, in patients with severe SVD burden, the optimal BP target is uncertain.Hypothesis: BP-lowering to a systolic BP of 120-129mmHg in ischemic stroke patients with severe SVD is not associated with impaired cerebral perfusion, nor does it associate with worsening of structural connectivity and cognitive function.Design and subjects: One-year trial where patients aged ≥50 with a history of ischaemic stroke and severe cerebral SVD will be randomised (1:1) to a systolic BP target of 120-129mmHg versus 130-140mmHg.Study instruments: At baseline and one-year, all subjects will receive a brain magnetic resonance imaging (MRI) to evaluate their cerebral blood flow (CBF) and white matter integrity. They will also receive neuropsychological batteries to evaluate cognitive functioning. In addition, subjects will receive home BP monitoring with periodic medication changes prescribed by medical doctor to ensure the target BP is achieved.Main outcome measures: Primary end-point is the change in CBF. Secondary end-points include changes in structural connectivity and cognitive performance.

Inclusion Criteria:Aged ≥50Chinese ethnicityHistory of TIA/ischaemic strokeUnderlying severe cerebral SVD as evidenced by brain MRI with total SVD score ≥3Underlying hypertension (defined as either SBP >140mmHg and taking no more than two anti-hypertensive agents, or SBP between 130-140mmHg and on at least one and not more than three anti-hypertensive agents)Able to provide written informed consentAble to perform study cognitive assessmentsModified Rankin Scale (mRS) ≤3Expected life expectancy >2 yearsExclusion Criteria:Unable to, or unwilling to consentTIA/ischaemic stroke within three months (to avoid confounding effects of recovery on cognition from recent stroke)Brain MR angiogram showing significant symptomatic or asymptomatic carotid, vertebral or intracranial large artery stenosis ≥50% as measured using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteriaCortical infarction >2cm in diameterParoxysmal or permanent atrial fibrillationKnown single gene disorder causing cerebral SVD, e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)Symptomatic postural hypotensionModerate- and severe-stage dementia with Montreal Cognitive Assessment (MOCA)-HK score <10Moderate and severe depressive symptoms with Patient Health Questionnaire-9 score ≥10Known secondary hypertension, e.g. hypertension is due to established obstructive sleep apnoea, renal parenchymal disease, renal artery stenosis, primary aldosteronism etc.Unable to complete cognitive assessmentsmRS >3Life expectancy of less than 2 years