Reducing risk of recurrent stroke and cognitive decline after TIA and stroke through characterisation and treatment of novel physiological markers (360G-Wellcome-206589_Z_17_Z)

Despite optimal medical management, there is significant post-stroke residual risk of recurrent cardiovascular events and cognitive decline. This fellowship aims to reduce this risk through characterisation and modification of novel physiological factors, including BP variability and cerebrovascular pulsatility, whose relative prognostic significance is currently unclear but which represent potential therapeutic targets to further reduce cardiovascular risk. I will develop and lead the Cardiovascular Laboratory in the new Centre for Prevention of Stroke and Dementia, measuring BP variability, arterial stiffness, autonomic, cerebrovascular and endothelial function and chronic cerebrovascular injury on MRI to: l. Detemine these physiological indices' relative prognostic significance for cerebrovascular events and vascular-type cognitive decline in 1000 Oxford Vascular Study patients, creating the largest fully-phenotyped cohort after TIA and stroke with clinical, cognitive and physiological follow-up; 2. Test potential treatments in exploratory randomised trials, including antihypertensives (amlodipine/losartan/atenolol) and vasodilators (sildenafil/hydralazine); 3. Assess drug tolerability and novel intermediate endpoints for future potential phase 3 trials ; 4. Develop the skills and facilities to manage large, physiologically-guided clinical trials, testing novel interventions to treat well characterised physiological effects; leading to phase 3 trials assessing effects of novel treatments on cardiovascular risk and chronic cerebrovascular injury in stage 2 of the fellowship.