BP control slowed brain damage in elderly hypertensives

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Safety evidence mounts for guideline’s blood pressure goal

This is another dataset showing that blood pressure reduction in elderly people with hypertension is safe and extremely important. Clinicians today often exclude elderly patients from aggressive blood pressure control because of an unrealized fear of causing hypotension and falls. These new data add to what’s already been reported in support of the American College of Cardiology and American Heart Association blood pressure treatment target of less than 130/80 mm Hg for noninstitutionalized, ambulatory, community-dwelling adults who are aged at least 65 years (Hypertension. 2018 June;71[6]:e13-e115). Many clinicians continue to have concerns about what this guideline says about treating older patients. These new findings support the idea that blood pressure can safely be treated to the level the guideline recommends while producing signals of beneficial changes in brain health and in cognitive function.

Dr. Eileen M. Handberg, research professor of medicine, University of Florida, Gainesville Mitchel L. Zoler/MDedge News

Dr. Eileen Handberg

The INFINITY results showed a mechanistic change in the formation of new white matter hyperintensity on MR brain scans. The inability of the study to link this effect to a slowing of declines in cognitive function or movement is not a surprise because these pathologies had already been going on for years and it is easy to think that it might take more than 3 years of lower blood pressures to produce a discernible effect. My guess is that, if the researchers followed these patients for 5 years, they would see an effect in these measures. Follow-up also showed an important reduction in hard cardiovascular events.

Providers worry a lot about the potential for harm from treatment. These findings add to the data that say clinicians can safely follow the blood pressure management guideline to benefit even very old patients.

Eileen Handberg, PhD , is a research professor of medicine and director of the Cardiovascular Clinical Trials Program at the University of Florida in Gainesville. She had no relevant disclosures. She made these comments in an interview.



– Hypertensive elderly patients treated to maintain an ambulatory systolic blood pressure of 130 mm Hg had significantly slower progression of white matter lesions in their brains than did control hypertensive patients maintained at an ambulatory systolic pressure of about 145 mm Hg during 3 years of follow-up in a randomized, single-center study with 199 patients.

Dr. William B. White, professor of medicine, University of Conne ticut, Farmington Mitchel L. Zoler/MDedge News

Dr. William B. White

The results also showed similar rates of death, syncope episodes, and falls in the intensively and less rigorously treated subgroups, and the patients treated to a systolic of 130 mm Hg also had significantly fewer nonfatal cardiovascular disease events, further documenting the safety and efficacy in elderly patients of a more aggressive blood pressure goal like the one promoted in current guidelines from the American College of Cardiology and American Heart Association, William B. White, MD, said at the annual meeting of the American College of Cardiology.

The study’s findings also showed that in one measure of cognitive function, the serial reaction time task, the patients treated to a systolic pressure of 130 mm Hg had an average 23 millisecond improvement in their reaction time from baseline to their 3-year follow-up, while patients in the control group treated to a systolic pressure of 145 mm Hg had a 33 millisecond increase in their average reaction time during follow-up. This 56 millisecond between-group difference from baseline in average change in reaction time over 3 years was both statistically significant and represents a clinically meaningful difference for a measure of both processing speed and executive function, said Dr. White, professor of medicine at the University of Connecticut in Farmington. However, the participants also underwent assessment by five other clinical measures of cognitive function and in none of the other five tests did more intensive blood pressure control link with an improvement, compared with the results in control patients.

The study had two primary endpoints. One was progression of white matter hyperintensity on brain MR images, which is a measure of neuron necrosis in the brain, and this analysis showed that the growth of white matter occurred at a 40% reduced rate among 99 patients treated to an average ambulatory systolic blood pressure of 130 mm Hg, compared with the average progression among 100 controls treated to an average ambulatory systolic of 145 mm Hg. The second measure was improvement during 3 years, compared with controls, in any of six different measures of mobility, including gait speed. The results showed no significant differences between the treatment arms in any of these measures. The average progression of white matter disease among control patients after 3 years was of a magnitude that would trigger concern in a neurologist who saw these scans, said Dr. White. The researchers could already begin to see a between-group difference in the accumulation of white matter hyperintensity on the MR scans of patients at 18 months in the study, he added.

During his presentation, Dr. White suggested that the absence of discerned improvements in mobility from more aggressive blood pressure control despite the observed slowed progression of white matter disease may have resulted from the study’s relatively brief follow-up.

The INFINITY (Intensive versus Standard Ambulatory Blood Pressure Lowering to Prevent Functional Decline in the Elderly) study enrolled hypertensive patients at least 75 years old who already showed visible evidence of white matter hypertrophy on their brain MR scan at baseline but also had normal mobility and mental function (their baseline score on the mini mental state examination had to be within the normal range, with an average score of 28 among enrolled patients), and they had no history of any chronic neurological condition (Am Heart J. 2013 Mar;165[3]:258-65). The median age of enrolled patients was 80 years. They had an average of 15 years of education, indicating a study cohort with a high level of education and function, Dr. White noted. The inclusion and exclusion criteria led to a study population that was substantially older but without as much comorbidity as patients enrolled in the SPRINT MIND study (JAMA. 2019 Jan 28;321[6]:553-61), he said. The study exclusively used 24-hour ambulatory monitoring for baseline and follow-up blood pressure measurements.

The participating clinicians successfully maintained patients in each of the treatment groups at close to their goal systolic blood pressures. At 18 months, the actual average systolic pressures among patients in the two study groups were 132 mm Hg and 146 mm Hg, and at 36 months their pressures averaged 131 mm Hg and 146 mm Hg for 163 patients who remained in the study out to 36-months. Maintenance of the lower pressure generally required treatment with one additional antihypertensive medication, compared with the control patients’ treatment, Dr. White said.

The rates of total falls and falls causing injury were virtually identical in the two treatment groups. The incidence of nonfatal cardiovascular disease events over 3 years, including MI, strokes, and cardiovascular disease hospitalizations, was 4 cases in the intensively-treated patients and 17 among those treated to a higher systolic pressure, a statistically significant and unexpected difference, Dr. White reported.

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