INFINITY: Aggressive Blood Pressure Lowering May Slow Cerebrovascular Disease in Elderly
Brain lesions were cut by 40% when a 24-hour systolic BP of 130 mm Hg was maintained for 3 years, although improvements in function didn’t materialize.
NEW ORLEANS, LA—Intensive hypertension lowering to maintain a systolic BP reading around 130 mm Hg may help slow the process of aging-related brain disease, the INFINITY trial suggests.
Elderly patients in the study who achieved the lower target not only had less accrual of subcortical white matter on imaging, they also had fewer cardiovascular events than did those with blood pressure around 145 mm Hg during the same 3-year period. However, the benefits of intensive BP-lowering did not translate into significant differences between the groups in terms of cognitive function or walking ability.
“It’s probable that 3 years was too short a duration to observe functional differences between the intensive and the standard treatment arms, at least that's our working hypothesis,” said principal study investigator William B. White, MD (University of Connecticut School of Medicine, Farmington).
In a press conference following White’s presentation, discussant Eileen Handberg, PhD (University of Florida, Gainesville), agreed, noting that expecting older people to demonstrate quick turnarounds in function, especially if they have lived with hypertension for years, is unrealistic.
“This is another data set that shows that lowering blood pressure in the elderly is extremely important,” she observed. It also offers some reassurances in the long-running debate over the potential dangers of aggressive BP-lowering in older patients. INFINITY, Handberg continued, shows “you can accomplish it without fear of them falling . . . I think we exclude people from aggressive blood pressure lowering because of this unrealized fear in the elderly,” she observed.
The study randomized patients with a mean age of 80 years and a diagnosis of hypertension to receive intensive therapy (n = 99) or standard therapy (n = 100). Intensive therapy aimed to reduce systolic pressure to < 135 mm Hg, while standard therapy aimed for 140 mm Hg. All patients underwent MRI prior to enrollment to assess white matter hyperintensivity. They also had baseline cognitive and mobility function testing. Ambulatory blood pressure monitoring was used to guide antihypertensive therapy rather than clinical measurements to exclude white coat hypertension. According to White, about one additional drug was used per patient in the intensive group compared with the standard group. Neuroimaging, ambulatory blood pressure, and functional testing were performed at baseline, 18 months, and 36 months.
White Matter Differences Apparent By 18 Months
Over the course of the study, 24-hour systolic blood pressures were lowered from a mean of 151.2 mm Hg to 146 mm Hg in the standard-therapy group and from 147.8 mm Hg to 130.9 mm Hg in the intensive-therapy group. The median time to target blood pressure was 3 months in the intensive group and 3.2 months in the standard group.
White matter changes from baseline were about 40% smaller with intensive therapy compared with standard therapy (0.29% vs 0.48%; P = 0.03). According to White, the difference in changes between the groups was apparent by 18 months, and it was magnified at 36 months in a sensitivity analysis of the approximately 60% of patients whose blood pressures stayed within their assigned group for the entire period of the study (P < 0.01).
Mobility—including gait speed, time needed to climb stairs, and time from sitting to standing—declined in both groups of patients, but was not significantly different between groups at 3 years. Among six parameters of cognitive functioning, only sequential reaction time, which estimates processing speed and executive functioning, showed a difference that favored intensive therapy over standard therapy (P < 0.01).
Patients in the intensive arm also had numerically fewer serious adverse events including death than those in the standard arm, but the only one that was significant was the lower rate of nonfatal cardiovascular events (4.1% vs 17%; P < 0.01).
Findings Support SPRINT Recommendations
White noted that the INFINITY group as a whole was highly educated, averaging 15 years of school, and had relatively high scores on cognitive testing at baseline. He described the hour-long neurocognitive tests as “pretty brutal,” but noted that patients were consistently willing and able to finish them even if they were left fatigued at the end. White also said that while the high degree of functioning may explain why so few changes were seen from baseline, the enrollment of those patients was necessary because his group felt that if participants had too many impairments they would not be able to complete the study.
During the press conference, White described the lower rate of cardiovascular events in the intensive group as surprising and said, “We did not expect to see such a big difference as we did.” But he noted that the lack of difference in cognitive function and mobility as a result of slowing down white matter is disappointing. Nevertheless, he said, the overall findings of INFINITY are aligned with those of SPRINT, suggesting that even patients with advanced age benefit from a morbidity standpoint in having their blood pressure comply with lower targets.
Handberg commented that while endpoints are important, the signal of a change and the ability to successfully lower blood pressure in elderly patients without the adverse events that so many physicians are concerned about is equally impressive.
"The fact that you were able to demonstrate a mechanistic change in brain-matter intensity is important," she said. “I would walk away a little stronger than apologetic, for sure."
Speaking with TCTMD, White said another positive observation that came out of the study was the ease of use of the ambulatory BP monitoring strategy, which is still fairly novel. Although it can be cumbersome, he said the elderly participants—some of whom were in their late 90s—did not have any issues with it.
"They were resilient and able to tolerate the monitor very well," he commented. A minimum of four ambulatory monitorings were required, with some patients needing many more than that if results were too variable.
"Some of them had six or eight ambulatory readings and none of them ever said 'I'm never wearing that monitor again,'" White added. "It was actually very refreshing that we were able to get it done and keep them within their goal. It just interrupted them for 1 day here or there."
White WB. Primary results of the intensive versus standard ambulatory blood pressure lowering to lessen functional decline in the elderly trial (INFINITY). Presented at: ACC 2019. March 18, 2019. New Orleans, LA.
- White reports research grants from the National Institutes of Health.