Tuesday July 8 2008
The HYVET trial was stopped early after it was found that blood pressure treatment reduced stroke and deaths
The Daily Mail reports that “cutting high blood pressure in middle age could save thousands from suffering and dying from dementia”. The findings come from two studies: the HYpertension in the Very Elderly Trial (HYVET) and a review of nine studies that will come out later this year. The HYVET findings suggest that controlling high blood pressure in those aged 80 and over could reduce dementia risk by 13%. The Mail says that the review, which is due to be published later this year, “found that treating high blood pressure among the middle-aged could cut by 600% the risk of developing vascular dementia”.
The study that has been published (the HYVET trial) was stopped early because high blood pressure medication was found to reduce stroke and deaths compared with an inactive placebo. By itself, this study did not find a significant reduction in the risk of dementia, but pooling its results with those from other similar studies suggests that it may reduce risk to some extent. However, a full systematic review of the evidence needs to be carried out before conclusions can be drawn.
Where did the story come from?
Dr Ruth Peters and colleagues from Imperial College London and other universities, hospitals and medical institutes in France, Finland, China, Romania and the UK carried out this research. The study was funded by Imperial College London. It was published in the peer-reviewed medical journal: Lancet Neurology.
What kind of scientific study was this?
This was a double-blind, randomised controlled trial, which looked at the effect of blood pressure control in elderly people – the HYpertension in the Very Elderly Trial (HYVET). This particular publication looked at the effect on the onset of dementia. The trial was stopped early, in 2007, after it was found that blood pressure treatment reduced stroke and deaths.
The researchers enrolled people aged 80 years and over who had high blood pressure (systolic blood pressure [SBP] 160–200mmHg and diastolic blood pressure [DBP] more than 110mmHg while sitting; SBP 140mmHg or above when standing). Participants were recruited from Europe, China, Tunisia, southeast Asia and Australia between 2001 and 2007. People with dementia, who had conditions that would limit their lifespan or who needed ongoing nursing care, were excluded from the study.
The 3,845 eligible adults were randomly assigned to receive either blood pressure medication (slow release indapine) or identical placebo tablets. The target blood pressure was 150mmHg SBP and 80mmHg DBP, and an additional treatment (perindopril) or placebo could be added to try to reach this target.
Participants had their cognitive function measured at the start of the study and every year subsequently, using a standard measurement tool called the Mini Mental State Examination (MMSE). People whose MMSE scores indicated that they might have dementia (a score of less than 24 or a drop of 3 points or more in a year) underwent further examination and testing, including brain CT scans. They were given a diagnosis based on standard criteria by a panel of experts. The researchers compared the proportion of each group developing dementia during follow-up. The researchers also pooled their results with results from three other placebo-controlled trials looking at the effect of treatment for high blood pressure on development of dementia.
What were the results of the study?
The researchers followed participants for just over two years on average. Treatment reduced blood pressure compared with the placebo at two years (a reduction of 15mmHg SBP and almost 6mmHg DBP). During the study 263 people developed dementia. The rates of dementia were not significantly different in the treatment and placebo groups. There was about one case for every 26 patient years in the treatment group and about one case for every 30 patient years in the placebo group.
However, when the researchers pooled their findings with those from other studies they found that treatment reduced risk of developing dementia by about 13% compared with the placebo, and this reduction just reached statistical significance (hazard ratio 0.87, 95% confidence intervals 0.76 to 1.00).
What interpretations did the researchers draw from these results?
The researchers concluded that their trial found that treatment for high blood pressure does not reduce the risk of dementia in the very elderly by a statistically significant amount. They suggest that this may be because the trial was stopped early and did not continue long enough to find a difference, or because there is only a “modest” effect of treatment on dementia risk. They say that pooling their results with those of similar studies may support the use of treatment for high blood pressure for reducing the risk of dementia in the very elderly.
What does the NHS Knowledge Service make of this study?
This was a well-designed and conducted trial. Its main findings, that treatment for high blood pressure reduce the risk of stroke and death, have already been published (Behind the headlines coverage here). There are a few points to note when interpreting this study:
- Ending the trial early means that it could not follow up the participants for as long as the researchers would have liked. This meant that the study did not have enough statistical power to detect the difference in dementia that they expected between groups based on previous trials.
- It is unclear whether the authors carried out a systematic search and appraisal to identify studies assessing the same question with which to pool their results. This may mean that some relevant studies that could have been pooled have been missed. The results of this pooling should be seen as preliminary and indicative of the need for a full systematic review to address this question.
- According to the newspaper reports, such a review has been conducted and will be published later in the year. This review should help to clarify whether antihypertensive treatment has a role to play in reducing the risk of dementia.
- The trial did not find any effect of antihypertensive treatment on the risk of dementia when they looked at the separate subtypes of vascular dementia and Alzheimer’s disease. The pooling of results only looked at ‘dementia’ as a whole. Therefore, no conclusions can be made about the effect of reducing blood pressure by antihypertensive medication on specific types of dementia. Although the news reports have focused on vascular dementia, a reduction in risk of this type of dementia, or other types, has not been demonstrated by this research.
Although this study did not find a significant reduction in dementia, it did find a reduction in stroke and death with antihypertensive treatment in the very elderly. It seems likely that doctors who prescribe this treatment for people with high blood pressure will be doing so for these important outcomes. Whether antihypertensive treatment also reduces the risk of dementia currently remains unclear.