The haemodynamic and vascular effects of angiotensin-converting enzyme inhibition following acute stroke
Stroke is the third commonest cause of adult death and the commonest cause of adult disability in the UK. Arterial stiffness is a recognised independent risk factor for cerebrovascular disease. Phase I of the thesis examines arterial stiffness in the context of stroke, evaluating its role as a risk factor and relevance to other abnormalities of cardiovascular regulation during the acute stroke phase. Central, but not peripheral, arterial stiffness was increased in acute ischaemic stroke, particularly in lacunar and atherothrombotic but not cardioembolic subtypes compared to matched controls. Prognostically-important haemodynamic parameters following stroke, for example impaired cardiac baroreceptor sensitivity and increased beat-to-beat blood pressure (BP) variability, were related to central arterial stiffness.;There is uncertainty over the treatment of elevated BP levels following acute stroke. Angiotensin-converting enzyme inhibitors (ACEI) have not been tested in the immediate post-stroke phase, but studies suggest beneficial effects in secondary stroke prevention. Phase II of the thesis presents pilot work evaluating the oral ACEI, Lisinopril, for hypertension treatment immediately following acute stroke. A single 5mg dose resulted in prompt BP reduction within the first 4 hours of administration and a once-daily regimen over the subsequent 14 days lead to sustained BP reduction. Measures of patient outcome in the short and medium-term showed a neutral effect of treatment. However, no drug-related improvement was shown in other cardiovascular variables such as arterial stiffness, BP variability and cardiac baroreceptor sensitivity despite the hypotensive effect.;Reduction of arterial stiffness might be a valid therapeutic target in the primary prevention of stroke and in the acute phase of stroke. Lisinopril administered early in the acute stroke phase appears to be an effective hypotensive agent and is well-tolerated. On the basis of these findings, larger multicentre studies are now ongoing evaluating the effects of ACEI and other drugs on outcome immediately following acute stroke.