In the JournalsPerspective

SPRINT MIND: Intensive BP treatment beneficial in cerebral small vessel ischemic disease

R. Nick Bryan

Patients with hypertension whose target systolic BP was less than 120 mm Hg had a greater decrease in total brain volume and a smaller increase in cerebral white matter lesion volume compared with those whose target was less than 140 mm Hg, according to results from the SPRINT MIND trial published in JAMA.

The differences between both target groups were small, according to the trial.

“This SPRINT MIND study is important because it shows that more aggressive treatment of hypertension may slow or diminish adverse effects of hypertension on brain structure, supporting the previous SPRINT MIND study showing beneficial effects on cognition.,” R. Nick Bryan, MD, PhD, chair of the department of diagnostic medicine at The University of Texas at Austin Dell Medical School, told Healio. “These results suggest that more aggressive treatment of hypertension, to less than 120 mm Hg systolic BP, may be beneficial to the brain, not harmful.”

Baseline and follow-up MRIs

Ilya M. Nasrallah, MD, PhD, assistant professor of radiology at the Hospital of the University of Pennsylvania and active radiologist at Phoenixville Hospital in Pennsylvania, and colleagues analyzed data from 670 patients (mean age, 67 years; 40% women) aged 50 years or older with hypertension and an increased CV risk. MRIs were performed at baseline and 48 months after randomization. Patients were assigned a systolic BP goal of less than 120 mm Hg (n = 355), considered the intensive treatment group, or less than 140 mm Hg (n = 315) for the standard treatment group.

As Healio and Cardiology Today previously reported, the SPRINT MIND trial found that intensive BP control did not significantly reduce the risk for the primary outcome of probable dementia in patients with hypertension, but was associated with a significant reduction in the risks for secondary outcomes of mild cognitive impairment and a composite of mild composite impairment or probable dementia.

The primary outcome was a change in total white matter lesion volume, and the secondary outcome was change in total brain volume.

Of the patients who underwent MRI at baseline, additional MRIs were completed in 67% of patients after a median follow-up of 3.97 years and a median intervention period of 3.4 years.

Mean white matter lesion volume increased from 4.57 cm3 to 5.49 cm3 in patients assigned intensive treatment (difference = 0.92; 95% CI, 0.69-1.14) compared with an increase from 4.4 cm3 to 5.85 cm3 in those assigned standard treatment (difference = 1.45; 95% CI, 1.21-1.7; between-group difference in change = –0.54; 95% CI, –0.87 to –0.2).

Patients assigned intensive treatment had a decrease in mean total brain volume from 1,134.5 cm3 to 1,104 cm3 (difference = –30.6; 95% CI, –32.3 to –28.8), whereas those assigned standard care had a decrease from 1,134 cm3 to 1,107.1 cm3 (difference = –26.9; 95% CI, 24.8-28.8; between-group difference in change = –3.7; 95% CI, –6.3 to –1.1).

“SPRINT MIND participants were generally older and had many years of hypertension, but still showed benefit from intensive BP control during a relatively short treatment period (4 years),” Bryan said in an interview. “Important next questions are how much benefit might be seen from more aggressive management of hypertension in younger populations. The clinical significance of the slightly greater brain volume loss requires further investigation.”

Risk factor management

“Uncertainties still exist in the care of asymptomatic patients with moderate to severe subclinical cerebrovascular disease changes on brain imaging or known large-artery disease such as carotid or intracranial stenosis,” Shyam Prabhakaran, MD, MS, chairman of the department of neurology at the University of Chicago, wrote in a related editorial. “Based on current guidelines, management of vascular risk factors is warranted for primary prevention; however, the optimal targets for blood pressure are unknown in this group of patients in whom relative hypotension may result in further ischemic damage and increase the risk of dementia and stroke.” – by Darlene Dobkowski

For more information:

R. Nick Bryan, MD, PhD, can be reached at 1701 Trinity St., Stop Z0300, Austin, TX 78712; email: nick.bryan@austin.utexas.edu.

Disclosures: The SPRINT trial was funded by the NHLBI, the National Institute of Diabetes and Digestive and Kidney Disease, the National Institute on Aging and the National Institute of Neurological Disorders and Stroke, and was supported in part by the U.S. Department of Veterans Affairs and the Intramural Research Program of the National Institute on Aging. Medications used in the study were provided by Takeda Pharmaceuticals with additional support from the Kulynych Family Foundation and the Oristano Family Foundation. Bryan reports he received grants from the NIH, has equity in GalileoCDS and has a licensed and issued patent for a system and method for medical imaging analysis and probabilistic diagnosis. Nasrallah and Prabhakaran report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

 

R. Nick Bryan

Patients with hypertension whose target systolic BP was less than 120 mm Hg had a greater decrease in total brain volume and a smaller increase in cerebral white matter lesion volume compared with those whose target was less than 140 mm Hg, according to results from the SPRINT MIND trial published in JAMA.

The differences between both target groups were small, according to the trial.

“This SPRINT MIND study is important because it shows that more aggressive treatment of hypertension may slow or diminish adverse effects of hypertension on brain structure, supporting the previous SPRINT MIND study showing beneficial effects on cognition.,” R. Nick Bryan, MD, PhD, chair of the department of diagnostic medicine at The University of Texas at Austin Dell Medical School, told Healio. “These results suggest that more aggressive treatment of hypertension, to less than 120 mm Hg systolic BP, may be beneficial to the brain, not harmful.”

Baseline and follow-up MRIs

Ilya M. Nasrallah, MD, PhD, assistant professor of radiology at the Hospital of the University of Pennsylvania and active radiologist at Phoenixville Hospital in Pennsylvania, and colleagues analyzed data from 670 patients (mean age, 67 years; 40% women) aged 50 years or older with hypertension and an increased CV risk. MRIs were performed at baseline and 48 months after randomization. Patients were assigned a systolic BP goal of less than 120 mm Hg (n = 355), considered the intensive treatment group, or less than 140 mm Hg (n = 315) for the standard treatment group.

As Healio and Cardiology Today previously reported, the SPRINT MIND trial found that intensive BP control did not significantly reduce the risk for the primary outcome of probable dementia in patients with hypertension, but was associated with a significant reduction in the risks for secondary outcomes of mild cognitive impairment and a composite of mild composite impairment or probable dementia.

The primary outcome was a change in total white matter lesion volume, and the secondary outcome was change in total brain volume.

Of the patients who underwent MRI at baseline, additional MRIs were completed in 67% of patients after a median follow-up of 3.97 years and a median intervention period of 3.4 years.

Mean white matter lesion volume increased from 4.57 cm3 to 5.49 cm3 in patients assigned intensive treatment (difference = 0.92; 95% CI, 0.69-1.14) compared with an increase from 4.4 cm3 to 5.85 cm3 in those assigned standard treatment (difference = 1.45; 95% CI, 1.21-1.7; between-group difference in change = –0.54; 95% CI, –0.87 to –0.2).

Patients assigned intensive treatment had a decrease in mean total brain volume from 1,134.5 cm3 to 1,104 cm3 (difference = –30.6; 95% CI, –32.3 to –28.8), whereas those assigned standard care had a decrease from 1,134 cm3 to 1,107.1 cm3 (difference = –26.9; 95% CI, 24.8-28.8; between-group difference in change = –3.7; 95% CI, –6.3 to –1.1).

“SPRINT MIND participants were generally older and had many years of hypertension, but still showed benefit from intensive BP control during a relatively short treatment period (4 years),” Bryan said in an interview. “Important next questions are how much benefit might be seen from more aggressive management of hypertension in younger populations. The clinical significance of the slightly greater brain volume loss requires further investigation.”

Risk factor management

“Uncertainties still exist in the care of asymptomatic patients with moderate to severe subclinical cerebrovascular disease changes on brain imaging or known large-artery disease such as carotid or intracranial stenosis,” Shyam Prabhakaran, MD, MS, chairman of the department of neurology at the University of Chicago, wrote in a related editorial. “Based on current guidelines, management of vascular risk factors is warranted for primary prevention; however, the optimal targets for blood pressure are unknown in this group of patients in whom relative hypotension may result in further ischemic damage and increase the risk of dementia and stroke.” – by Darlene Dobkowski

For more information:

R. Nick Bryan, MD, PhD, can be reached at 1701 Trinity St., Stop Z0300, Austin, TX 78712; email: nick.bryan@austin.utexas.edu.

Disclosures: The SPRINT trial was funded by the NHLBI, the National Institute of Diabetes and Digestive and Kidney Disease, the National Institute on Aging and the National Institute of Neurological Disorders and Stroke, and was supported in part by the U.S. Department of Veterans Affairs and the Intramural Research Program of the National Institute on Aging. Medications used in the study were provided by Takeda Pharmaceuticals with additional support from the Kulynych Family Foundation and the Oristano Family Foundation. Bryan reports he received grants from the NIH, has equity in GalileoCDS and has a licensed and issued patent for a system and method for medical imaging analysis and probabilistic diagnosis. Nasrallah and Prabhakaran report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

 

    Perspective
    Carl J. Pepine

    Carl J. Pepine

    In addition to the publication of SPRINT MIND, another study was published this week in JAMA (Walker KA, et al. JAMA. 2019;doi:10.1001/jama.2019.10575) which found that the risk for dementia increases in patients with sustained hypertension in midlife to late life and those with midlife hypertension and late-life hypotension compared with those with normal BP during both of those periods. These are two very important publications that directly relate to the increasing numbers of patients that we are seeing with cognitive impairment as well as hypertension.

    While both are associated with the development of atherosclerosis (larger vessel disease), it is known that a major component of cognitive impairment and hypertension is related to microvascular disease/dysfunction. But the mechanisms are not completely understood, and why these two conditions are much more prevalent among older women than men remain unclear.

    These recent reports help to shed light on the timing of this relationship throughout life and its remarkable sensitivity to only a few years of lower BP. The latter data from SPRINT MIND are also important because this beneficial response to lower BP was observed in a relatively low-risk cohort for cerebral vascular disease (eg, no diabetes or prior stroke).

    More recently, the gut microbiota has emerged as a contributor to both hypertension and cognitive impairment via the “brain-gut axis” and its influence on vascular, neural, immune and metabolic pathways. Altering the “bugs” in our GI tract may emerge as a novel management tool for these conditions. This is clearly a hot area, so stay tuned!

    • Carl J. Pepine, MD, MACC
    • Cardiology Today Chief Medical Editor
      University of Florida, Gainesville

    Disclosures: Pepine reports no relevant financial disclosures.