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

Abstract

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 cm 3 (difference, 0.92 cm 3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm 3 (difference, 1.45 cm 3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, −0.54 cm 3 [95% CI, −0.87 to −0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm 3 (difference, −30.6 cm 3 [95% CI, −32.3 to −28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm 3 (difference, −26.9 cm 3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, −3.7 cm 3 [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.

Small Vessel Disease

“…In terms of the cardiovascular risk factors, hypertension is a major driver of SVD (41), and ambulatory measurements of blood pressure are better predictors of WMH than self-reported measurements (42). In the setting of hypertension, the risk of accumulating WMH rises rapidly above a resting systolic blood pressure of approximately 120 mmHg (43). Systolic blood pressure sustained above this threshold also predicts a growing risk for dementia and strokes (42, 44).…”

Hypertension and Its Impact on Stroke Recovery: From a Vascular to a Parenchymal Overview

“…However, this study displayed a trend towards a reduction in mild cognitive impairment. The recent SPRINT MIND substudy found a smaller increase in white matter lesions in the intensive group but a greater decrease in total brain volume in this group, although with small differences [157]. In the past few years, several studies have raised concerns about the possible negative impact of excessive BP reduction in elderly patients (>80 years old) [158].…”

Hypertension and Drug Adherence in the Elderly

“…Today, there is a strong evidence that hypertension in the elderly as well as in the very elderly must be treated and this is supported by international guidelines and a Cochrane meta-analysis (9-13). A sub-analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) in elderly has recently confirmed the benefits of lowering BP in hypertensive patients older than 75 years with some potential benefits on cognitive function and white matter lesions (14)(15)(16)(17).…”