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JAMA. 2019 Aug 13;322(6):524-534. doi: 10.1001/jama.2019.10551.

Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions.

Author information

1
Department of Radiology, University of Pennsylvania, Philadelphia.
2
Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina.
3
Department of Neurology, University of Mississippi Medical Center, Jackson.
4
Department of Neurology, University of Utah School of Medicine, Salt Lake City.
5
Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City.
6
Section of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
7
Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, North Carolina.
8
Department of Psychology, University of Alabama at Birmingham.
9
Preventive Medicine Section, Veterans Affairs Medical Center, Memphis, Tennessee.
10
Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
11
Clinical Applications and Prevention Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
12
Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis.
13
Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Disorders, Bethesda, Maryland.
14
Division of Nephrology, Stanford University School of Medicine, Palo Alto, California.
15
Neuroepidemiology Section, Intramural Research Program, National Institute on Aging, Bethesda, Maryland.
16
Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
17
Department of Epidemiology, University of Alabama at Birmingham.
18
National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
19
Department of Medicine, University of Alabama at Birmingham.
20
Department of Medicine, Louis Stokes Cleveland Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, Ohio.
21
Department of Psychiatry and Behavioral Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
22
Section of Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
23
Department of Neurology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
24
Now with Genentech, South San Francisco, California.
25
Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio.
26
Division of Geriatrics, University of Utah School of Medicine, Salt Lake City.
27
Division of Nephrology, Tufts Medical Center, Boston, Massachusetts.
28
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.
29
Division of Nephrology and Hypertension, Department of Medicine, Case Western Reserve University, Cleveland, Ohio.

Abstract

Importance:

The effect of intensive blood pressure lowering on brain health remains uncertain.

Objective:

To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes.

Design, Setting, and Participants:

A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016.

Interventions:

Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315).

Main Outcomes and Measures:

The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome.

Results:

Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]).

Conclusions and Relevance:

Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small.

Trial Registration:

ClinicalTrials.gov Identifier: NCT01206062.

PMID:
31408137
PMCID:
PMC6692679
[Available on 2020-02-13]
DOI:
10.1001/jama.2019.10551
[Indexed for MEDLINE]

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