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

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.

Figure 1.. Eligibility, Randomization, and Follow-up for Participants in the MRI Substudy

MRI indicates magnetic resonance imaging; SBP, systolic blood pressure; SPRINT, Systolic Blood Pressure Intervention Trial; WML, white matter lesion. ^aOther reasons for unwillingness to participate include participant could not lie flat for extended period (n = 7), participant reported metal in body before formal screening (n = 8), participant concerns about stent or other cardiac device (n = 8), concerns about body size (n = 2), other reasons (n = 7), and unknown reason (n = 22). ^bOther reasons for ineligibility include participant concerns about stent or other cardiac device (n = 8), use of pain pump (n = 2), prolonged hospitalization (n = 2), participant declined consent (n = 2), participant too large for MRI scanner (n = 1), and other reasons (n = 7).

Figure 2.. Change in Transformed White Matter Lesion Volume According to Subgroups

Estimates denote the estimated change for transformed white matter lesion (WML) volume at 1452 days (3.98 years) among participants with WML measurement at baseline and follow-up, based on a linear mixed model, adjusting for intracranial volume and days since randomization, with random effects for participant and magnetic resonance imaging facility. Negative values denote decreases from baseline; positive values, increases from baseline. Differences represent intensive treatment group minus standard treatment group. WML volumes were transformed using inverse hyperbolic sine transformation, f(x) = log(x + (x² + 1)^0.5). BP indicates blood pressure; CVD, cardiovascular disease; SE, standard error.

Figure 3.. Change in Total Brain Volume According to Subgroups

Estimates denote the estimated change in total brain volume at 1452 days (3.98 years) among participants with WML measurement at baseline and follow-up, based on a linear mixed model, adjusting for intracranial volume and days since randomization, with random effects for participant and magnetic resonance imaging facility. Differences represent intensive treatment group minus standard treatment group. BP indicates blood pressure; CVD, cardiovascular disease; SE, standard error.