NHS National Institute for Health Research

Cerebral small vessel disease (SVD)

Ongoing clinical study in stroke research - Dr Charles Dafe, Newcastle University

Background
Cerebral small vessel disease (SVD) accounts for about 20% of all strokes (lacunar strokes) and is the leading cause for vascular cognitive impairment/dementia. SVD appears typically as areas of hyperintensities on T2 sequences on MRI (these white matter hyperintensities are termed leukoaraiosis).

Hypertension, apart from the normal ageing process is the major risk factor for developing SVD and is present in up to 80-90% of patients with lacunar stroke and leukoaraiosis. An important mechanism underlying the development of leukoaraiosis is hypo-perfusion in the deep white matter structures (via atherosclerosis in the small blood vessels – a process accelerated by hypertension).

It has previously been demonstrated that intensive lowering of blood pressure in otherwise healthy elderly people with hypertension resulted in the reversal of the right-ward shift of the cerebral auto-regulation curve and an improvement in grey matter cerebral blood flow (CBF).  While this was demonstrated in otherwise healthy individuals, it is unknown whether this same process occurs in people with established SVD. There have also been questions raised about how beneficial or otherwise intensive lowering of blood pressure is – due to concerns about increased risk of falls and possibly also potentially worsening of cerebral hypo-perfusion.

Study Objectives
Ths study aims primarily to determine whether a strategy of intensive (<125mmHg), versus standard (130-140mmHg), treatment of blood pressure in individuals with small vessel disease and leukoaraiosis is associated with reduced cognitive decline.

Patients will be recruited and randomised into two treatment groups (intensive or standard) and followed up over a 2-year period to determine whether a strategy of intensive, versus standard, treatment of blood pressure is associated with a reduced rate of cognitive decline. 

We also aim to determine the pathophysiological effect of blood pressure lowering on cerebral blood flow using the MRI arterial spin labelling (ASL) technique and to determine the effect of blood pressure lowering on the progression of white matter damage assessed using the MRI diffusion tensor imaging (DTI) technique

On the whole the study aims to recruit 422 participants across various trial centres within the stroke research network. One hundred and sixty of these participants will be enrolled into the imaging sub-studies.

A joint collaborative study between Newcastle and St Georges Universities and a British hypertension/The Stroke Association funded clinical trial.