Can an aggressive lowering of the average daily blood pressure in a hypertensive patient slow the brain’s aging process?

University of Connecticut Health Center physicians are conducting a federally funded clinical trial to compare treatment approaches and their effect on changes in the brain related to mobility, memory and urinary function in older people with hypertension.

“We already know that 24-hour blood pressure monitoring can give us data that we can use to predict disease of the brain,” says Dr. William White, one of the study’s lead researchers. “The next step is to see if we can lower someone’s blood pressure enough to prevent or at least slow functional decline.”

White, professor of medicine and chief of the Calhoun Cardiology Center Division of Hypertension and Clinical Pharmacology, is a principal investigator along with Dr. Leslie Wolfson, professor and chair of the Department of Neurology, on a multi-year study backed by a $3.4 million grant from the National Institute on Aging, part of the National Institutes of Health.

“After 75 years of age, limited mobility becomes an increasingly important constraint on functional independence,” Wolfson says. “Our previous work demonstrated that two-thirds of older persons have significant amounts of a brain abnormality called white matter hyperintensities. These were observed to double in volume during four years of observation suggesting that this was a widespread, progressive problem in certain older people. Increased volume of these white matter lesions was associated with poorer mobility as well as having effects on cognition and urinary function.”

In 2011, White and Wolfson published a study in Circulation: Journal of the American Heart Association that showed 24-hour blood pressure monitoring can best predict progression of small vessel brain disease cognitive function decline in older people.

They found the group with lower average daily blood pressures did better. In contrast, the doctor’s office blood pressure was not an important correlate of progression of the white matter lesions.

“Thus, developing strategies to control blood pressure over the entire 24-hour period that medication is taken may limit this process, thereby improving the function and lives of older persons,” Wolfson says.

Named the INFINITY trial, the study’s official title is “Intensive Versus Standard Ambulatory Blood Pressure Levels to Prevent Functional Decline in the Elderly.” Study participants receive blood pressure care and treatment, including medications, over a three-year period, during which they will undergo a series of tests to measure mobility, cognitive function, and white matter hyperintensities, the signs of small vessel brain damage. White, who is also president of the American Society of Hypertension, and his staff develop an individualized treatment program for each participant based on the results of the first 24-hour blood pressure recording.

“They changed my pills, and this group seems to be working beautifully,” says Joan Larkins, who joined the study last summer shortly after her 80th birthday. Diagnosed with hypertension 12 years ago, she says her blood pressure has been under control since November and today is down to 130/70.

The 130, the systolic blood pressure reading, is a focal value used to guide therapy. It represents the blood pressure when the heart is contracting. For half the study participants, their 24-hour systolic blood pressure will be treated to lower their number to around 140 to 145, which is standard. The other half make up the “intensive control” group, in which the target is 130 or less.

The researchers will compare three years of data from periodic magnetic resonance imaging (MRI) of the brain, mobility testing, cognitive testing, electrocardiograms, and ambulatory blood pressure monitoring to see whether the intensive control group fairs any better.

“I have some concern about myself, not because of family history, but just because I’m aging,” Larkins says. “But I hope being in this study might really do good for someone else someday.”

Study participants must be at least 75 years old, have a history of hypertension, and cannot have a history of stroke or major neurologic disability. The doctors and project managers can help to determine potential eligibility by a simple phone interview.

“The INFINITY trial is the first to guide antihypertensive therapy using ambulatory blood pressure monitoring rather than clinic BP to reduce cerebrovascular disease,” White writes in a design paper for the clinical trial published in American Heart Journal. “The results of this trial could allow for improved management of systolic hypertension that would eventually lessen functional decline in older patients at increased risk of microvascular disease of the brain.”

More information about the study is available at bit.ly/INFINITYtrial or by calling 860-679-2705.

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