Study Links Blood Pressure to Brain Scan Differences in Seniors

Officially, the INFINITY trial presented Monday at the 68th Scientific Session of the American College of Cardiology (ACC) did not prove its premise: that visible brain lesions connected to high blood pressure (BP) would in turn signal cognitive decline.

In this case, the researchers drew the connection between high BP and brain lesions, but these physical signs did not translate into a measurable loss of gait, the endpoint used to assess cognitive decline. However, a commenter on the study said that results connecting higher BP to physical changes in the brain are significant and that, most likely, the trial ended before cognitive problems appeared.

“The fact that you demonstrated a mechanistic change in brain matter intensity is important,” said Eileen Handberg, PhD, ARNP-BC, FACC, chair of the ACC Cardiovascular Team Council and research professor of medicine, University of Florida, where she is director of the Clinical Trials Program.

Clinical trials must necessarily focus on the primary outcome, Handberg said, but even when that is not met, it doesn’t mean that the data are not “extremely meaningful.” Many studies are linking elevated BP with cognitive decline—she shared the belief that if the trial had run longer, those signs might have appeared as well.

INFINITY began before the 2017 change to hypertension guidelines, when the ACC and the American Heart Association (AHA) dropped the level at which high BP begins to 130/80 mm Hg, calling the new lower level before 140/90 mm Hg “stage 1” hypertension. But INFINITY is a product of the debate on how strictly seniors should manage BP, as some believe that letting BP fall too low can lead to fainting spells and falls.

Authors described the study as “the first hypertension study that has used ambulatory BP to guide therapy in patients with vascular disease of the brain, and showed a significant reduction in accrual in subcortical white matter disease in older people receiving more antihyperintensive therapy.”

The study randomized 199 seniors, with an average age of 81 years, who started with a systolic BP close to 150 mm Hg. Seniors who took medicine to keep their 24-hour systolic BP around 130 mm Hg for 3 years had less accumulation of white matter disease compared with those whose medication kept their systolic BP around 145 mm Hg, which was closer to the cutoff for high BP under ACC/AHA guidelines prior to 2017.

White matter disease shows up as lesions on the brain in a magnetic resonance imaging scan, which study coauthor William B. White, MD, professor of medicine at the University of Connecticut School of Medicine’s Calhoun Cardiology Center, demonstrated in a presentation and at a press conference. “The brain is the most famous target organ in hypertension,” he said.

“Accumulation of vascular disease in the brain affects the ability to function. The higher a person’s blood pressure, the more likely they are to get this as they get older,” White said, pointing to the scans. “Two-thirds of people over age 75 have vascularization like this.”

But, as White explained, intensive BP treatment can reduce the accrual of brain lesions. In INFINITY, seniors whose systolic BP was managed to 130 mm Hg saw their lesions reduced by 40% in just 3 years. Results showed:

• The groups started with systolic BPs of 151 ± 16 and 149 ± 13 mm Hg, respectively, with white matter/intracranial cavity volumes of 1.4 ± 1.1%.
• After 3 years, 24-hour BPs were 131/65 mm Hg for the intensive group and 146/74 mm Hg for the standard group. Changes from baseline in white matter were smaller in the intensive group (0.29 ± 0.39%) compared with the standard group (0.50 ± 0.70%; P = .025 between groups), meaning that there was less white matter disease in the intensive group.
• There were no differences in speed of gait. Evaluations of quality of life and other cognitive responses are ongoing.

“This is highly clinically significant,” he said. Over a longer period, White believes that intensive reduction of ambulatory BP will make a difference in seniors’ cognitive function, and the differences between the groups would become amplified. “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.”

INFINITY is not the only study drawing connections among hypertension, white matter, and possible cognitive decline. In January, the journal Circulation published a study that found even when patients were taking medication, if they had blood vessel damage in white matter and high BP, they were more likely to show signs of early cognitive impairment.

Handberg said that White and his fellow researchers should be encouraged by what they have found so far. Accumulated brain vascularization can result from a lifetime of dietary choices and bad decisions, she said. “For us to think that we’re going to reverse it in 3 years—that’s the McDonald’s ‘I want it now’ approach. I would walk away a little stronger for sure.”