Intensive BP Lowering May Have Cognitive Benefits: SPRINT MIND

Treating systolic blood pressure to a target of less than 120 mm Hg instead of less than 140 mm Hg has already been shown in SPRINT to reduce cardiovascular outcomes and mortality in high-risk, nondiabetic patients with hypertension. Now, results of the SPRINT MIND study—part of the larger trial—suggest that the approach might positively influence brain health as well.

Intensive BP lowering did not significantly reduce the risk of probable dementia (HR 0.83; 95% CI 0.67-1.04), the primary outcome of the cognitive study, but it was associated with lower risks of two secondary outcomes: mild cognitive impairment (MCI; HR 0.81; 95% CI 0.69-0.95) and a composite of MCI or probable dementia (HR 0.85; 95% CI 0.74-0.97).

Jeff Williamson, MD (Wake Forest School of Medicine, Winston-Salem, NC), and colleagues note in their paper published online January 28, 2019, ahead of print in JAMA that the premature stoppage of the trial resulted in fewer cases of dementia than were anticipated and, as a consequence, a possible lack of statistical power for the primary outcome.

To TCTMD, Williamson speculated that the apparent advantage for intensive treatment would have been statistically significant had the trial run its course: “My own personal thinking is that yes it would have. . . . Because we really only needed a few more cases to achieve statistical significance.” He added that the study investigators are currently seeking funding for extended follow-up to see whether that might be true.

Uncertain Effects of Lower BP

Currently, there are no treatments that have been shown to reduce the risk of developing MCI or dementia. Prior studies have been mixed as to whether lower BP is associated with improved cognition, with some suggesting a benefit and others suggesting harm related to hypotension and cerebral hypoperfusion.

SPRINT MIND was designed to test the effect of reducing blood pressure on cognitive health. As part of the larger trial, 9,361 hypertensive, nondiabetic patients (mean age 68; 35.6% women) were randomized to intensive or more conventional BP lowering. The median treatment period was 3.34 years, and the total median follow-up was 5.11 years.

Per 1,000 person-years, adjudicated probable dementia developed at a rate of 7.2 in the intensive group and 8.6 in the conventional group, a nonsignificant difference. Intensive treatment resulted in significantly lower rates of adjudicated MCI (14.6 vs 18.3) and the composite of MCI or probable dementia (20.2 vs 24.1), both secondary endpoints.

“This is the first trial, to our knowledge, to demonstrate an intervention that significantly reduces the occurrence of MCI, a well-established risk factor for dementia, as well as the combined occurrence of MCI or dementia,” the authors say. “However, some caution should be exercised in interpreting this result, both because MCI was not the primary cognitive outcome of the trial and because it is not clear what this effect may mean for the longer-term incidence of dementia. Although MCI considerably increases the risk of progression to dementia, such progression is not certain and reversion to normal cognition is also possible.”

Study ‘Offers Great Hope’

Despite those caveats, Williamson said the findings have changed his practice.

“I’m already doing this in my own patients. And I was a skeptic. At the beginning when we designed the trial, I actually thought that lower blood pressure would be harmful, perhaps, to the brain,” he told TCTMD. “So it’s influenced my practice already, and if people in the age group of this trial who meet the trial entry criteria can lower their blood pressure to the 120s and still feel the same, then I have them do it.”

Williamson said he now recommends intensive BP lowering to his family members, too. “Because this is the only thing we can offer right now to lower someone’s chance of developing the worst possible life situation that people can face, I think,” he said. “Most of my patients, even more than death, fear becoming demented.”

The cognitive results could also have an impact on adherence to antihypertensive therapy, Williamson added. “I think that this has been in some ways a game changer for many of my patients to say, ‘I really want to take blood pressure control seriously now.’ . . . Now for the first time, in terms of hypertension, we can say what is good for your heart is good for your brain.”

In an accompanying editorial, Kristine Yaffe, MD (University of California, San Francisco and San Francisco VA Health Care System), notes some challenges when it comes to interpreting the results, including the early termination of the trial, which hinders assessment of true effect sizes; the lack of information on adverse events after the intervention ended; and a limited ability to compare the effects of different antihypertensive classes or to examine the impact of race.

Nonetheless, “for older adults, almost all of whom have concern about being diagnosed with Alzheimer disease and related dementia, SPRINT MIND offers great hope,” Yaffe says. In fact, while it might not be the “final” strategy for the prevention of Alzheimer disease and other cognitive impairments, the SPRINT MIND trial “represents a major leap forward in what has emerged as a marathon journey.”

Yaffe believes the intensive treatment approach evaluated in SPRINT “should be studied with other vascular health interventions, such as physical activity and other promising approaches for prevention,” she argues. “Indeed, the timing is right to investigate multidomain risk reduction strategies personalized for older adults and their individual risk profiles.”