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July 25, 2018 -- When it comes to blood pressure, lower is better for the brain as well as the heart, according to the results of a large government-funded study known as SPRINT.

High blood pressure is a problem for about 100 million Americans, roughly half of all U.S. adults.

Even modestly higher blood pressure in midlife is a major reason for memory loss. Recent studies have shown that having systolic blood pressure -- the top number -- over 130 by age 50 raises a person’s odds of getting dementia by about 50%, compared with someone without high blood pressure at the same age.

The good news is that aggressively lowering high blood pressure to a goal of 120/80 -- the definition of normal -- may trim the risk of getting mild cognitive impairment, the kind of thinking and memory changes that lead to dementia, by about 15%. That’s compared with people with higher blood pressures, according to new research presented this week at the 2018 Alzheimer’s Association International Conference in Chicago.

Overall, intensive blood pressure treatment cut a person’s  lifetime chance of having mild cognitive impairment by about 1%, the study found. That may sound small, but it would make an important difference for public health, the study authors say.

Even better, it doesn’t take long to see that benefit. Patients in the study were treated for an average of about 3 years, and followed for about 5.

“This is the first time in history that a randomized clinical trial has shown that we can reduce the occurrence of mild cognitive impairment” by lowering blood pressure, said lead study author Jeff Williamson, MD, a geriatrician at the Wake Forest School of Medicine in Winston-Salem, NC.

The study authors showed statistically significant reduction in mild cognitive impairment, but not dementia alone. Williamson says that while it was comforting to see the study results going in the right direction for dementia, the results just fell short of showing a statistical significance. He says he doesn’t know if they might have seen a bigger difference if they had followed the patients for longer.

Experts who were not involved in the study said it should send a strong message.

“For middle-aged and older individuals, this underscores the importance of having regular checkups and working with your doctor to ensure that proper blood pressure levels are achieved, and that blood pressure levels are achieved at closer to 120/80 versus the traditional 140,” says Whitney Wharton, PhD, a cognitive neuroscientist at Emory University in Atlanta. Wharton has studied the relationship between blood pressure medications and Alzheimer’s. She was not involved in the SPRINT study.

“I think that’s particularly true for individuals at risk for Alzheimer’s or vascular dementia, including individuals with a family history and also African-Americans,” she says.

The brain is filled with tiny blood vessels that deliver oxygen and nutrients to working nerve cells. High blood pressure silently damages these small vessels over time.

“These are like little microstrokes that cause these lesions you can see with MRI. It’s clumps of tissue that aren’t working properly,” says Jim Hendrix, PhD, director of global science initiatives for the Alzheimer’s Association.

The lesions show up on brain scans as glowing white spots scattered throughout the brain’s communication network, giving them the clinical name “white matter hyperintensities.”

The new study found that more aggressive blood pressure treatment not only lowered the chance of mild cognitive impairment and dementia as measured by written and verbal tests, but it also cut the number of these lesions in 450 participants who had follow-up brain scans.

All the patients got more white matter lesions over the course of the study. That’s an unavoidable part of aging, says Ilya Nasrallah, MD, PhD, a radiologist at the University of Pennsylvania, who led the brain imaging part of the study.

Patients in the intensive treatment arm of the study had about 18% fewer white matter hyperintensities over the 5 years they were followed, compared with patients treated to the standard targets.

“We managed to slow the worsening of this one measure of brain health,” Nasrallah says.

For Blood Pressure: How Low to Go?

A key question for doctors and patients has been whether aggressively lowering blood pressure to a goal of 120/80 could protect the brain from this kind of damage.

In 2010, the National Institutes of Health launched a major clinical trial testing whether it was indeed better to prescribe more medication to try to help patients achieve normal blood pressure, compared with the old, widely accepted goal of 140/90.

The study enrolled more than 9,300 people who had high blood pressure and at least one thing that made heart disease more likely. It did not include people with diabetes or those who’d had a stroke.

On average, patients needed one additional medication to reach the goal of normal blood pressure. Patients in the standard group took 2 different blood pressure medications, compared with 3 for the more aggressively managed group. Doctors could prescribe any combination of medications they deemed necessary to reach the treatment goal.

In 2015, after following patients for about 3 years, doctors took the unusual step of stopping the study early after the extra treatment showed clear benefits for people getting more aggressive treatment. On average, more medication cut the combined risk of having a heart attack, stroke, sudden heart failure, or heart-related death by about 25%, compared with the group that got standard care. In absolute terms, there were 243 heart-related events or deaths in the intensive treatment group and 319 in the standard treatment group.

On the flip side, people taking more medication to get their blood pressure down also had more severe side effects, including more episodes of severe low blood pressure, fainting, falls that resulted in trips to the ER, and kidney injuries.

While the final results of the cardiovascular portion of the study were released in late 2015, doctors continued to follow patients to see what effect the treatments might have on their brains.

The last data for the brain-portion of the study, known as SPRINT-MIND, were just collected in June, says Williamson, the lead study author from Wake Forest.

He cautions that these numbers are hot off the presses and haven’t been reviewed by other professionals, so they may still shift a bit, “although the message that lower is better will definitely not change,” he says.

“Many of my patients tell me that they don’t fear death as much as they fear losing their ability to interact with my family,” Williamson says.

“Here’s something you can do to prevent something that’s even more feared than death -- losing your memory -- they’ll say, ‘Well, that’s worth a try for me to get a little bit lower.’ ” He says.

Key Questions Remain

Williamson also knows the results won’t come without controversy or questions.

For example, while high blood pressure in midlife clearly raises your odds of having dementia, several studies have found that high blood pressure may not be as bad for the brains of people who get it at older ages.

Aggressive management of blood pressure in the elderly may also make side effects like falls more likely.

Williamson says his findings challenged previous research. About 28% of patients in the study were over age 75 when the study started. They saw the same reduction in risk as younger patients, he says.

He says previous studies were observational and may have mischaracterized the risks and benefits to older adults.

“Until you test, you don’t really know. Observation is not causation,” he says. “So now we can say in a randomized trial, the highest form of evidence, this benefits older people and younger people,” he says.

There’s also the fact that many people who have high blood pressure find it difficult to get their blood pressure back down to normal, even when they eat right, exercise, and take their medication as prescribed.

In fact, in the 2 years after the study was stopped, people in the group that had been aggressively managed saw their blood pressure start to creep back up. On average, they gained back about 10 points.

Williamson says he has patients of his own who can’t get their blood pressure back to normal.

“We get them as close to the goal as they can, as long as they still function well and feel well. Every clinician has to work with their patients to individualize their therapy, but to be clear, the goal should be lower,” he says.

Finally, the study doesn’t help doctors home in on which drugs might protect he brain the most.

Previous studies have suggested that drugs that affect the production of a hormone called angiotensin, which raises blood pressure by causing blood vessels to constrict, may protect the brain better.

These drugs include ACE inhibitors and renin-angiotensin-aldosterone blockers, or RAAS blockers for short.

“We think those types of medication confer additional benefits above and beyond blood pressure control,” Wharton says.

In a study published in 2015, Wharton found that people with mild cognitive impairment -- an early stage of dementia -- who were on these types of drugs were less likely to progress to dementia, compared with people taking other types of blood pressure medications.

Researchers are still trying to understand why those drugs might help more, but there are tantalizing clues.

“We have preliminary data that they may act on tau, which is one of the two pathological hallmarks of Alzheimer’s disease,” she says.

Williamson agrees that they need to look more closely at the types of drugs people in the SPRINT study were taking.

“SPRINT was really a study designed to test the goal, not how to get to the goal. I think future research in this area will show whether one blood pressure medication versus another has a greater impact on lowering risk,” Williamson says. He says the team plans to mine the data to see if some kinds of drugs might have had bigger effects than others.

Show Sources

Whitney Wharton, PhD, cognitive neuroscientist, Emory University, Atlanta.

Jim Hendrix, PhD, director of global science initiatives, Alzheimer’s Association International.

Ilya Nasrallah, MD, PhD, radiologist, University of Pennsylvania, Perelman School of Medicine, Pittsburgh.

Jeff Williamson, MD, geriatrician, Wake Forest School of Medicine, Winston-Salem, NC.

News briefing, 2018 Alzheimer’s Association International Conference, Chicago.

European Heart Journal: “Association between systolic blood pressure and dementia in the Whitehall II cohort study: role of age, duration, and threshold used to define hypertension.”

New England Journal of Medicine: “A Randomized Trial of Intensive versus Standard Blood-Pressure Control.”

Journal of the American Geriatric Society: “Modulation of Renin-Angiotensin System May Slow Conversion from Mild Cognitive Impairment to Alzheimer's Disease.”

Alzheimer’s & Dementia: “Age of onset of hypertension and risk of dementia in the oldest-old: The 90+ Study.”

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