Elderly people with high blood
pressure, or hypertension, who took medicine to keep their 24-hour
systolic blood pressure around 130 mm Hg for three years showed
significantly less accumulation of harmful brain lesions compared with
those taking medicine to maintain a systolic blood pressure around 145
mm Hg, according to research presented at the American College of
Cardiology's 68th Annual Scientific Session. However, the reduction in
brain lesions, visible as bright white spots on a magnetic resonance
imaging (MRI) scan, did not translate to a significant improvement in
mobility and cognitive function. Researchers said it is likely that
three years was too short a time for such benefits to become apparent.
The study, called INFINITY, is the first to demonstrate an effective
way to slow the progression of cerebrovascular disease, a condition
common in older adults that restricts the flow of blood to the brain.
The study is also unique in its use of around-the-clock ambulatory blood
pressure monitors, which measured participants' blood pressure during
all activities of daily living, rather than only in the medical care
environment. In addition to seeing beneficial effects in the brain,
those who kept their blood pressure lower also were less likely to
suffer major cardiovascular events, such as a heart attack or stroke.
"I think it's an important clinical finding, and a very hopeful one
for elderly people who have vascular disease of the brain and
hypertension," said William B. White, MD, professor of medicine at the
University of Connecticut School of Medicine's Calhoun Cardiology Center
and one of the study's principal investigators. "With the intensive
24-hour blood pressure treatment we reduced the accrual of this brain
damage by 40 percent in a period of just three years. That is highly
clinically significant, and I think over a longer time period intensive
reduction of the ambulatory blood pressure will have a substantial
impact on function in older persons, as well."
By reducing blood flow to the brain, cerebrovascular disease causes a
gradual buildup of lesions that represent areas with damaged nerve
cells in the brain's white matter. Older people with more of these
lesions tend to have slower reflexes, problems with mobility and more
signs of cognitive decline.
Having high systolic blood pressure over a long period of time is
known to exacerbate damage to small arteries in the deep regions of the
brain, but it was not previously known whether the process could be
stopped or slowed by controlling ambulatory blood pressure. The new
findings suggest keeping the 24-hour systolic blood pressure around 130
mm Hg is a safe and effective way to slow the progression of the
disease, White said.
The trial enrolled 199 people who were an average age of 81 years
old. All participants had hypertension at the start of the trial, with
an average systolic blood pressure around 150 mm Hg, as well as evidence
of some cerebrovascular disease on an MRI scan. Half of the
participants were randomly assigned to receive standard blood pressure
control and half were assigned to receive more intensive blood pressure
Doctors worked closely with each patient to manage their medications
until they achieved the target blood pressure. They used ambulatory
blood pressure monitors to guide blood pressure treatment. Since blood
pressure measurements taken in the clinical environment may not be truly
representative of the out-of-office blood pressure, ambulatory blood
pressure monitoring is known to provide a more accurate picture of blood
pressure behavior, White said.
Patients receiving standard blood pressure control maintained an
average systolic blood pressure of 146 mm Hg, close to the study's
target level of 145 mm Hg. Patients receiving the more intensive
treatment had an average systolic blood pressure of 131 mm Hg, close to
the target level of 130 mm Hg.
After three years, those maintaining the lower systolic blood
pressure level had about a 40 percent relative reduction in the
accumulation of the white matter lesions, the study's first co-primary
endpoint, than those with higher blood pressure. However, the groups
showed no significant difference in gait speed, a marker of mobility
function and the other co-primary endpoint.
A sensitivity analysis showed that 60 percent of the patients
maintained their target blood pressure throughout the full three years.
An analysis of data from these patients revealed even more pronounced
differences in the number of brain lesions among participants with
higher versus lower blood pressure. Because this reduction in accrual of
brain lesions was so significant, it is reasonable to expect that those
in the more intensive treatment group would begin to show benefits over
the standard treatment group in mobility and cognitive function after a
few more years, White said.
"The average 80-year-old without a major illness such as cancer or
heart failure can expect to live about 13 more years, and if you cut
back the accrual of vascular damage over the course of that timeframe it
could substantially improve a person's quality of life," White said.
"In addition, this benefit would likely be amplified in people with more
severe or longer-duration hypertension."
Intensive blood pressure control also brought cardiovascular
benefits. Even in this small group of 199 patients, participants in the
standard therapy group were four times as likely to suffer a major
non-fatal cardiovascular event compared with those in the intensive
Having blood pressure that is too low can cause a person to faint or
have falls with injury. However, the rates of fainting and falling were
the same in both treatment groups, suggesting that the 24-hour systolic
blood pressure target of 130 mm Hg was not an unacceptably low target,
White said that the study was limited by its relatively small size
and the likelihood that three years was not enough time to show
measurable cognitive benefits.