Antihypertensive Treatment in Very Elderly Patients May Reduce Dementia Risk
Results from a substudy of the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG) suggest that lowering blood pressure in individuals 80 years and older might reduce the risk for dementia.
When combined with results from other placebo-controlled trials, the results of the HYVET-COG study show that antihypertensive treatment leads to a 13% reduction in this patient population.
"The results from HYVET-COG suggest a possible additional benefit associated with antihypertensive treatment in addition to the cardiovascular benefits as already demonstrated in this very elderly group," study investigator Ruth Peters, PhD, from the Imperial College in London, United Kingdom, said in a statement.
The study is published in the July 8 Online First issue of the Lancet Neurology.
Inconclusive Evidence
Although observational epidemiologic studies have linked hypertension to an increased risk for incident dementia, the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting, the study authors note. Furthermore, they point out that meta-analyses of such trials have failed to provide conclusive evidence of benefit.
Designed to assess the risks and benefits of treating hypertension in elderly patients, HYVET also included an assessment of cognitive function. The main trial was stopped early when investigators found a substantial reduction in total mortality and stroke rates during a second preplanned interim analysis.
The HYVET-COG study was a double-blind, placebo-controlled trial that included 3336 participants. Subjects 80 years and older diagnosed with hypertension (systolic pressure between 160 and 200 mm Hg and diastolic pressure < 110 mm Hg) were randomly assigned to receive 1.5 mg of slow-release indapamide, with the option of 2 to 4 mg of perindopril or placebo.
Target blood pressure was 150 mm Hg systolic over 80 mm Hg diastolic. Participants had no dementia at baseline, and cognitive function was assessed at baseline and annually with the Mini-Mental State Examination (MMSE).
Combined Results Favor Treatment
Possible dementia cases, which were defined as the cases of those participants who had MMSE scores that decreased by more than 24 points or by more than 3 points in 1 year, were assessed with standard diagnostic criteria and expert review.
A total of 3336 individuals who had at least 1 follow-up assessment (mean, 2.2 years) were included in the analysis. Of these individuals, 1687 were assigned to the active treatment group and 1649 to placebo.
The mean reduction in blood pressure at 2 years between the treatment and placebo groups was a 15-mm Hg reduction in systolic pressure and a 5.9-mm Hg reduction in diastolic pressure.Rates of dementia were 38 per 1000 patient-years in the placebo group vs 33 per 1000 patient-years in those taking antihypertensive therapy.
The difference did not reach statistical significance. However, the researchers report, when these data were combined in a meta-analysis of other placebo-controlled trials of antihypertensive therapy, the combined risk ratio favored treatment.
"Antihypertensive treatment in elderly patients does not statistically reduce incidence of dementia. This negative finding might have been due to the short follow-up owing to the early termination of the trial, or the modes effect of treatment. Nevertheless, the HYVET findings, when included in a meta-analysis, might support antihypertensive treatment to reduce incident dementia," they conclude.
Still Worthwhile
In an accompanying editorial, Ingmar Skoog, MD, PhD, at Goteburg University, Goteburg, Sweden, says regardless of whether antihypertensive therapy reduces the risk for dementia, the results of the HYVET study show that treating high blood pressure in very elderly patients is a worthwhile endeavor because it protects against stroke and total mortality.
Furthermore, he writes, "antihypertensive treatment seems to be safe in relation to brain function in elderly people. Most individuals with hypertension or dementia are not detected by the healthcare system, but the importance of diagnosing cognitive impairment in elderly patients with hypertension needs to be emphasized because low cognitive function might have implications for patient compliance."
The study was funded by the British Heart Foundation and the Institute de Recherches Internationales Servier. Four of the study authors have received support by Imperial College from academic grants from the British Heart Foundation and Servier. One of the study authors has received consultancy fees from Imperial College after his retirement in 2005 from an academic grant from Servier. Investigator fees to cover the costs of the trial and investigations, such as computed tomography scans, were paid to 2 of the study authors by Imperial College. The remaining study authors have disclosed no relevant financial relationships.
Dr. Skoog has received consultancy fees from AstraZeneca during the Study on Cognition and Prognosis in the Elderly trial and has been on the speakers' bureau for Shire, AstraZeneca, Janssen-Cilag, Pfizer, Novartis, Eisai, and Hoechst Marion Roussel.Lancet Neurol. Published online July 8, 2008.
Although observational studies suggest a positive association between hypertension and the risk for incident dementia, controlled trials of the effect of antihypertensive therapy on cognitive function have shown conflicting results. Meta-analyses of the trials have not clearly demonstrated whether antihypertensive treatment decreases the incidence of dementia.
Because blood pressure, notably systolic pressure, increases with age, hypertension is highly prevalent in older people. In a similar fashion, dementia increases dramatically with aging, with prevalence estimated to be approximately 20% at age 80 years and 40% at age 90 years. High blood pressure in midlife may predict later dementia.
Risk of Gallbladder Disease Lower With Transdermal Rather Than Oral HRT
Results from a substudy of the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG) suggest that lowering blood pressure in individuals 80 years and older might reduce the risk for dementia.
When combined with results from other placebo-controlled trials, the results of the HYVET-COG study show that antihypertensive treatment leads to a 13% reduction in this patient population.
"The results from HYVET-COG suggest a possible additional benefit associated with antihypertensive treatment in addition to the cardiovascular benefits as already demonstrated in this very elderly group," study investigator Ruth Peters, PhD, from the Imperial College in London, United Kingdom, said in a statement.
The study is published in the July 8 Online First issue of the Lancet Neurology.
Inconclusive Evidence
Although observational epidemiologic studies have linked hypertension to an increased risk for incident dementia, the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting, the study authors note. Furthermore, they point out that meta-analyses of such trials have failed to provide conclusive evidence of benefit.
Designed to assess the risks and benefits of treating hypertension in elderly patients, HYVET also included an assessment of cognitive function. The main trial was stopped early when investigators found a substantial reduction in total mortality and stroke rates during a second preplanned interim analysis.
The HYVET-COG study was a double-blind, placebo-controlled trial that included 3336 participants. Subjects 80 years and older diagnosed with hypertension (systolic pressure between 160 and 200 mm Hg and diastolic pressure < 110 mm Hg) were randomly assigned to receive 1.5 mg of slow-release indapamide, with the option of 2 to 4 mg of perindopril or placebo.
Target blood pressure was 150 mm Hg systolic over 80 mm Hg diastolic. Participants had no dementia at baseline, and cognitive function was assessed at baseline and annually with the Mini-Mental State Examination (MMSE).
Combined Results Favor Treatment
Possible dementia cases, which were defined as the cases of those participants who had MMSE scores that decreased by more than 24 points or by more than 3 points in 1 year, were assessed with standard diagnostic criteria and expert review.
A total of 3336 individuals who had at least 1 follow-up assessment (mean, 2.2 years) were included in the analysis. Of these individuals, 1687 were assigned to the active treatment group and 1649 to placebo.
The mean reduction in blood pressure at 2 years between the treatment and placebo groups was a 15-mm Hg reduction in systolic pressure and a 5.9-mm Hg reduction in diastolic pressure.Rates of dementia were 38 per 1000 patient-years in the placebo group vs 33 per 1000 patient-years in those taking antihypertensive therapy.
The difference did not reach statistical significance. However, the researchers report, when these data were combined in a meta-analysis of other placebo-controlled trials of antihypertensive therapy, the combined risk ratio favored treatment.
"Antihypertensive treatment in elderly patients does not statistically reduce incidence of dementia. This negative finding might have been due to the short follow-up owing to the early termination of the trial, or the modes effect of treatment. Nevertheless, the HYVET findings, when included in a meta-analysis, might support antihypertensive treatment to reduce incident dementia," they conclude.
Still Worthwhile
In an accompanying editorial, Ingmar Skoog, MD, PhD, at Goteburg University, Goteburg, Sweden, says regardless of whether antihypertensive therapy reduces the risk for dementia, the results of the HYVET study show that treating high blood pressure in very elderly patients is a worthwhile endeavor because it protects against stroke and total mortality.
Furthermore, he writes, "antihypertensive treatment seems to be safe in relation to brain function in elderly people. Most individuals with hypertension or dementia are not detected by the healthcare system, but the importance of diagnosing cognitive impairment in elderly patients with hypertension needs to be emphasized because low cognitive function might have implications for patient compliance."
The study was funded by the British Heart Foundation and the Institute de Recherches Internationales Servier. Four of the study authors have received support by Imperial College from academic grants from the British Heart Foundation and Servier. One of the study authors has received consultancy fees from Imperial College after his retirement in 2005 from an academic grant from Servier. Investigator fees to cover the costs of the trial and investigations, such as computed tomography scans, were paid to 2 of the study authors by Imperial College. The remaining study authors have disclosed no relevant financial relationships.
Dr. Skoog has received consultancy fees from AstraZeneca during the Study on Cognition and Prognosis in the Elderly trial and has been on the speakers' bureau for Shire, AstraZeneca, Janssen-Cilag, Pfizer, Novartis, Eisai, and Hoechst Marion Roussel.Lancet Neurol. Published online July 8, 2008.
Clinical Context
Although observational studies suggest a positive association between hypertension and the risk for incident dementia, controlled trials of the effect of antihypertensive therapy on cognitive function have shown conflicting results. Meta-analyses of the trials have not clearly demonstrated whether antihypertensive treatment decreases the incidence of dementia.
Because blood pressure, notably systolic pressure, increases with age, hypertension is highly prevalent in older people. In a similar fashion, dementia increases dramatically with aging, with prevalence estimated to be approximately 20% at age 80 years and 40% at age 90 years. High blood pressure in midlife may predict later dementia.
Risk of Gallbladder Disease Lower With Transdermal Rather Than Oral HRT
 | |
 Risk of Gallbladder Disease Lower With Transdermal Rather Than Oral HRT
NEW YORK (Reuters Health) Jul 10 - No matter how hormone replacement therapy (HRT) is administered, it appears to increase the risk of gallbladder disease, but new research suggests that the risk is lower if HRT is given transdermally rather than orally. According to the report in the July 11th Online First issue of the British Medical Journal, using transdermal HRT instead of oral HRT could prevent one cholecystectomy in every 140 users over a 5-year period. The findings are based on an analysis of data for roughly 1 million postmenopausal women registered with the National Health Service in England and Scotland (Million Women Study). The subjects were recruited from breast screening centers (1996 to 2001) and were followed for gallbladder disease through the use of NHS hospital admission data. Overall, 19,889 women were hospitalized for gallbladder disease during follow-up, including 17,190 who underwent cholecystectomy, Dr. Bette Liu, from the University of Oxford in the UK, and co-researchers note. Relative to never-users of HRT, current users were 64% more likely to be admitted for gallbladder disease. Further analysis showed that the relative risk in transdermal HRT users was lower than that in oral HRT users: 1.17 vs. 1.74 (p < 0.001). In terms of oral HRT, equine estrogens upped the risk of gallbladder disease by 79%, slightly but significantly higher than the 62% increased risk seen with estradiol (p < 0.001). With both types of oral HRT, the risk was directly related to the dose. In former HRT users, the risk of gallbladder disease fell as the time since last use increased (p = 0.004). As for why transdermal HRT carries a lower risk of gallbladder disease than does oral therapy, the authors speculate that by avoiding the first pass metabolism seen with gut absorption, the transdermal route results in lower bile levels of estrogen and its metabolites, which may in turn cut the risk of gallbladder disease. |
Posts
No comments:
Post a Comment