Supplementary Material for: Intensive antihypertensive treatment and cerebral small vessel disease: A systematic review and meta-analysis of randomized clinical trials

Background and Objectives
Hypertension is a significant risk factor for the development of cerebral small vessel disease (SVD). This study was performed to evaluate the impact of intensive antihypertensive treatment on the progression of imaging markers and cognitive fuction of SVD.
Methods
Two independent reviewers searched for randomised controlled trials (RCTs) that investigated the associations between intensive antihypertensive treatment and the progression of imaging markers of SVD, including white matter hyperintensities (WMHs), brain atrophy, lacunes, or microbleeds and cognitive function scores. Fixed-effects models were used to pool the data for WMHs, brain atrophy, and severe adverse events, whereas cognitive function scores were synthesised with a random-effects model and were measured as standardised mean differences (SMDs) and odds ratios (ORs).
Results
A total of 8 RCTs were included in this meta-analysis, involving 2,891 participants with a follow-up period of 24 to 49 months. Compared with standard blood pressure treatment, intensive antihypertensive treatment was observed to be more effective at delaying WMH progression (SMD = -0.33, 95% CI: -0.44, -0.21) but was associated with greater brain volume loss (SMD = 4.06, 95% CI: 1.97 6.15). No increased risk of incident lacunes (odds ratio [OR] = 1.11, 95% CI: 0.57 2.19) or significant association with cognitive function changes (SMD = -0.08, 95% CI: -0.23 0.06) was observed. However, the pooled analysis of cerebral microbleeds was limited by the small number of eligible studies included in this meta-analysis.