Making a difference – at a stroke

Stroke is the second most common cause of death worldwide and is predicted to become the leading cause of death within the next 20 years as the incidence of ischaemic heart disease falls in developed countries. At present, the risk of someone having a stroke within their lifetime is about 25 per cent, with the risk being higher for the over-65s. Spotting and treating the warning signs that a stroke is likely to occur are therefore important strategies.

Research has indicated that hypertension – raised blood pressure – plays a major role in causing stroke, although the mechanism by which this happens is not fully understood. About half of all adults in the UK have hypertension and this is generally treated by doctors with drugs aimed at lowering an individual’s average blood pressure level. In March 2010, however, four research papers published simultaneously in The Lancet and The Lancet Neurology by Peter Rothwell, Oxford’s Professor of Clinical Neurology, showed that variability in blood pressure is also a risk factor for stroke, people with intermittent high blood pressure (’episodic hypertension’) being at higher risk of stroke than those with consistently high readings.

‘Our findings have important implications for the identification of individuals at risk of stroke and for the effective prevention of stroke’, says Professor Rothwell, who is also Director of the Stroke Prevention Research Unit at the John Radcliffe Hospital. ‘Current clinical guidance tells doctors who see patients whose blood pressure is very high at one clinic visit to repeat measurements several times over the next few weeks and only diagnose hypertension and consider treatment if the blood pressure is consistently raised.’

The discovery is the result of analysis of data from several cohort studies and clinical trials, including the Oxford Vascular Study – a study of all strokes, heart attacks and other acute vascular events in a local population of 100,000 people. As well as identifying the prognostic importance of variability in blood pressure, the research showed that the different drugs used to treat high blood pressure differed in their effects on variability, which correlated with their effectiveness in preventing stroke. ‘The evidence was there, but no one had looked’, says Professor Rothwell. ‘Previously, everyone had assumed it was just lowering the average blood pressure that correlated with the better outcomes.’ This has important implications for treatment, he stresses: ‘Some of the drugs currently used to treat high blood pressure – beta blockers, for example – actually increase variability and therefore paradoxically increase stroke risk despite lowering average pressure, whereas others, such as calcium channel blockers, reduce both variability and the average level and are therefore much more effective at preventing stroke.’ He urges pharmaceutical companies to develop new antihypertensive drugs that both lower and stabilise blood pressure. Drugs that stabilise blood pressure without lowering it are also needed for some elderly patients who cannot tolerate reductions in their average blood pressure.

Professor Rothwell believes that the significance of blood pressure variability in assessing the risk of a stroke should now be incorporated into clinical guidelines. He and his team are therefore studying how best to identify variability and instability in blood pressure in routine clinical practice, with particular emphasis on measurements done by people at home. Professor Rothwell’s patients in the Oxford Vascular Study are currently being asked to take three blood pressure readings three times each day at home, with the results being transmitted automatically to the research centre using Bluetooth. ‘It’s a real education about how little what we see in clinic tells us about what’s actually going on,’ he says. ‘We are able to monitor blood pressure and change medication in real time so that blood pressure is properly controlled.’

Home monitoring is also helping researchers investigate how long a period they need to spend assessing variability in blood pressure. Early indications are that variation on a day-to-day basis is a reliable indicator of week-to-week and month-to-month fluctuations.Also on the research agenda is the significance of blood pressure variability in other brain diseases. In vascular dementia, which is also associated with hypertension, high variability in blood pressure looks again to be a predictor of the condition; it may be that reducing variability can lessen the likelihood of vascular dementia developing.

‘The work on variability in blood pressure and other work we have done recently, such as demonstrating the benefits of urgent investigation and treatment of patients with transient ischaemic attacks (“mini-strokes”) and minor strokes, and identifying the beneficial effect of aspirin in preventing cancer, have taught me how big an impact simple clinical research can have’, says Professor Rothwell. ‘All this work could have been tackled 30 years ago, but was neglected at least partly because new fields like molecular biology and genetics were opening up. The headline-grabbing laboratory-based work is great, but we also need to do the simple stuff if we really want to make a difference in practice.’