Effect of intensive blood pressure control on the prevention of white matter hyperintensity: Systematic review and meta‐analysis of randomized trials

Abstract

Hypertension is an important cause of cerebral small vessel disease, especially of white matter hyperintensity (WMH). The ability of intensive blood pressure (BP) control in preventing this pathological progression remains unclear. The authors systematically searched PubMed, EMBASE, SCOPUS, and Cochrane library for publications until July 20, 2020. Studies included were clinical trials with random allocation to an antihypertensive medication against placebo, or different treatment targets. The primary outcome was intergroup differences in the change of WMH volume. A random‐effect model was applied for pooling effect measures. Subgroup analysis and meta‐regression were conducted to explore heterogeneity. Seven studies with 2693 patients were identified. Compared with the control group, patients in the intensive BP control group had a slower progression of WMH, with a pooled intergroup standard mean difference (SMD) for WMH change of −0.22 (95% CI: −0.35 ~ −0.09, I2 = 63%). For studies comparing intensive and standard BP target, the pooled SMD is −0.37 (95% CI:‐0.50~‐0.24, I2 = 0%), while the pooled SMD of studies comparing active antihypertensive medication and placebo was only −0.08 (95% CI: −0.17 ~ 0.01, I2 = 0%). Meta‐regression analysis showed that the reduction in WMH progression is proportional to the magnitude of intensive BP control (β = −0.028, P < .001). In conclusion, intensive BP control prevents WMH progression, and its effect is associated with the magnitude of intensive BP control.

ESO Guideline on covert cerebral small vessel disease

“…Overall, compared with the control group, patients in the (intensive) BP management group had a slower progression of WMH, with a pooled intergroup SMD for WMH change of −0.26 (95% CI: −0.45, −0.07, I 2 = 72%). For the three studies comparing intensive vs. standard BP targets (SPRINT-MIND, ACCORD-MIND, INFINITY), 20 , 54 , 55 the pooled SMD was identical to the last published meta-analysis by Lai et al., 57 while the pooled SMD of studies comparing active antihypertensive medication vs placebo (SCOPE, Zhang et al). 21 , 51 was only −0.03 (95% CI: −0.17, 0.11, I 2 = 0%) and non-significant.…”

“…For the three studies comparing intensive vs. standard BP targets (SPRINT-MIND, ACCORD-MIND, INFINITY), 20,54,55 the pooled SMD was identical to the last published meta-analysis by Lai et al, 57 while the pooled SMD of studies comparing active antihypertensive medication vs placebo (SCOPE, Zhang et al). 21,51 was only À0.03 (95% CI: À0.17, 0.11, I 2 ¼ 0%) and non-significant.…”

“…20,21,[51][52][53][54][55] 52,53 seeking additional data from study authors where necessary (Figure 2). The main characteristics of the five trials included in this meta-analysis are described in Table 3 20,54,55 the pooled SMD was identical to the last published meta-analysis by Lai et al, 57 while the pooled SMD of studies comparing active antihypertensive medication vs placebo (SCOPE, Zhang et al). 21,51 was only À0.03 (95% CI: À0.17, 0.11, I 2 ¼ 0%) and non-significant.…”

“… 49 , 50 Moreover, several trials have examined the impact of antihypertensive treatment on WMH progression (either as a primary outcome, 20 , 21 or, in most instances, as a secondary outcome in a subset of the trial participants 46 , 51 – 55 ) and have been combined in two systematic reviews and meta-analyses. 56 , 57 The latest, largest systematic review 57 combined seven trials on 2693 participants, with a mean follow-up duration between 24 and 60 months. 20 , 21 , 51 – 55 Overall, compared with the control group, patients in the (intensive) BP management group had a slower progression of WMH, with a pooled intergroup standard mean difference (SMD) for WMH change of −0.22 (95% CI: −0.35, −0.09, I 2 = 63%).…”

Five years of exercise intervention at different intensities and development of white matter hyperintensities in community dwelling older adults, a Generation 100 sub-study

“…The absence of an association between VO 2peak and WMH volume and change in VO 2peak and change in WMH volume at any timepoint during the intervention makes it unlikely that VO 2peak by itself is a central mechanism in preventing WMH. Since nonexercise/physical activity intervention studies in adults between 40-90 years of age find significantly reduced growth of WMH following pharmacological (e.g., antihypertensives, intranasal insulin), life-style (e.g., diabetes mellitus type 2), and physiological (e.g., preconditioning) interventions [40][41][42][43], it might be that aerobic exercise intervention alone is less effective at reducing WMH compared to targeting other or several mechanisms associated with WMH.…”