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Intensive Blood Pressure Management May Reduce the Risk of MCI

Data suggest that antihypertensive agents may be disease-modifying therapies for cerebrovascular dementia.


CHICAGO—Lowering systolic blood pressure to a target of 120 mm Hg or less in people with cardiovascular risk factors reduces the risk of mild cognitive impairment (MCI) by 19% and reduces the risk of probable all-cause dementia by 17%, compared with achieving a less intensive target of lower than 140 mm Hg, according to research presented at AAIC 2018.

The class of antihypertensive did not affect the association. Generic drugs were as effective as branded drugs. Antihypertensive agents provided equal benefits to men, women, whites, blacks, and Hispanics. Furthermore, maintaining systolic blood pressure at 120 mm Hg or lower prevented MCI as well in patients older than 75 as it did in younger patients.

Jeff D. Williamson, MD, Chief of Geriatric Medicine at Wake Forest University in Winston-Salem, North Carolina, presented the results of the four-year SPRINT MIND study. Strict blood pressure control (ie, a systolic target of 120 mm Hg or lower) for 3.2 years reduced the incidence of MCI to a greater extent than any amyloid-targeting investigational drug has done.

“This is the first disease-modifying strategy to reduce the risk of MCI,” said Dr. Williamson. Although the effect of strict blood pressure control on the primary end point (ie, a 17% risk reduction for probable all-cause dementia) was not statistically significant, “it is comforting to see that the benefit went in the same direction and was of the same magnitude,” said Dr. Williamson. “Three years of treatment and 3.2 years of follow-up absolutely reduced the risk.”

Brain imaging underscored the clinical importance of this finding and showed its physiologic pathway. Participants who underwent strict blood pressure control had 18% fewer white matter hyperintensities after four years of follow-up than other participants.

The results may represent a step forward in a field that has seen few of them recently. Generic antihypertensive agents can be inexpensive. They are widely available and confer benefits not only on cardiovascular health, but on kidney health as well, said Dr. Williamson.

“Hypertension is a highly prevalent condition…. The 19% overall risk reduction for MCI will have a huge impact,” he added.

“The most we can say right now is that we are able to reduce risk,” said Maria Carrillo, PhD, Chief Scientific Officer of the Alzheimer’s Association, in an interview. “Reducing the risk of MCI by 19% will have a huge impact on dementia overall. Slowing down the disease progress is a disease modification, versus developing symptoms. So, if that is the definition we are using, then I would say yes, it is disease modifying,” for dementias arising from cerebrovascular pathology.

A Substudy of the SPRINT Trial

SPRINT MIND was a substudy of the Hypertension Systolic Blood Pressure Intervention Trial (SPRINT). It compared two strategies for managing hypertension in older adults. The intensive strategy had a target systolic blood pressure of less than 120 mm Hg, and the standard care strategy had a target of less than 140 mm Hg. SPRINT showed that intensive blood pressure control reduced the risk of cardiovascular events, stroke, and cardiovascular death by 30%. The study results helped inform the 2017 American Heart Association and American College of Cardiology clinical guidelines for treating high blood pressure.

The SPRINT MIND substudy examined whether intensive blood pressure management affected the risk of probable all-cause dementia or MCI or affected white matter lesion volume and brain volume.

The investigators examined data for 9,361 SPRINT subjects who were age 50 or older (mean age, 68) and had at least one cardiovascular risk factor. Approximately 30% of participants were black, and 10% were Hispanic. The primary outcome was incident probable dementia. Secondary outcomes were MCI and a composite of MCI and probable dementia.

In SPRINT, physicians could choose any appropriate antihypertensive regimen, but were encouraged to use drugs with the strongest evidence of cardiovascular benefit. These drugs included thiazide-type diuretics, loop diuretics, and beta-adrenergic blockers. About 90% of the drugs used during the study were generic.

Subjects were seen monthly for the first three months. During this time, medications were adjusted to achieve the target blood pressure. After the third month, subjects were examined every three months. Medications could be adjusted monthly.

Results Favored Intensive Treatment

At one year, mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard treatment group. Treatment was stopped early after a median follow-up of 3.26 years because of the observed cardiovascular disease benefit.

The SPRINT MIND study did not meet its primary end point. Incident probable all-cause dementia occurred in 175 people in the standard care group and 147 people in the intensive treatment group. The difference between groups in the rate of 17% risk reduction was not statistically significant.

The results for both secondary end points were significant, however. Incident MCI occurred in 348 participants in the standard treatment group and 285 participants in the intensive treatment group. The difference indicated a statistically significant 19% risk reduction associated with intensive treatment. Furthermore, intensive treatment significantly reduced the risk of the combined secondary end point of MCI and probable dementia by 15%. In all, 463 participants in the standard care group met this end point, compared with 398 in the intensive care group.

The imaging study included 454 subjects who had brain MRI at baseline and at four years after randomization. Total brain volume did not change, said Ilya Nasrallah, MD, Assistant Professor of Radiology at the University of Pennsylvania in Philadelphia. Patients in the intensively managed group, however, had 18% lower white matter lesion load than those in the standard care group.

White matter lesions often indicate small-vessel disease, which is associated with vascular dementia and, perhaps, Alzheimer’s disease. Most patients with Alzheimer’s disease have a mixed dementia that includes a vascular component, said Dr. Carrillo.

David Knopman, MD

The Gravity of MCI

SPRINT MIND did not follow subjects for longer than four years or include follow-up for amyloid positivity or Alzheimer’s disease diagnosis. Nevertheless, preventing MCI is a significant achievement, according to David Knopman, MD, a consultant in the department of neurology at Mayo Clinic in Rochester, Minnesota.

“There is nothing benign about MCI,” said Dr. Knopman. “It is the first sign of overt cognitive dysfunction, and although the rate at which MCI progresses to dementia is slow, the appearance of it is just as important as the appearance of more severe dementia. To be able to see an effect in 3.2 years is quite remarkable. I think this study is going to change clinical practice for people in primary care, and the benefits at the population level are going to be substantial.”

Physicians may want to think about how the SPRINT MIND results might apply to younger patients with hypertension, whether they have other cardiovascular risk factors or not, said Dr. Williamson. “I will adhere to the guidelines we have and keep blood pressure at less than 130 mm Hg and certainly start treating people in their 50s, and probably in their 40s,” he concluded.

—Michele G. Sullivan

Suggested Reading

SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-2116.

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