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.

背景与目的：高血压是脑小血管病（cerebral small vessel disease, SVD）发生的重要危险因素。本研究旨在评估强化降压治疗对脑小血管病影像学标志物进展及认知功能的影响。方法：由2名独立评价者检索探讨强化降压治疗与脑小血管病影像学标志物（包括脑白质高信号（white matter hyperintensities, WMHs）、脑萎缩、腔隙灶、脑微出血）及认知功能评分进展相关性的随机对照试验（randomised controlled trials, RCTs）。针对脑白质高信号、脑萎缩及严重不良事件的数据，采用固定效应模型进行合并分析；认知功能评分则采用随机效应模型进行合并分析，以标准化均数差（standardised mean differences, SMDs）及比值比（odds ratios, ORs）作为效应量。结果：本荟萃分析共纳入8项随机对照试验，涉及2891名受试者，随访周期为24至49个月。与标准降压治疗相比，强化降压治疗可更有效地延缓脑白质高信号进展（标准化均数差 = -0.33，95%置信区间：-0.44，-0.21），但会导致更显著的脑体积丢失（标准化均数差 = 4.06，95%置信区间：1.97，6.15）。未观察到强化降压治疗会增加新发腔隙灶的风险（比值比[OR] = 1.11，95%置信区间：0.57，2.19），亦未发现其与认知功能变化存在显著关联（标准化均数差 = -0.08，95%置信区间：-0.23，0.06）。然而，由于本荟萃分析纳入的合格研究数量较少，针对脑微出血的合并分析存在一定局限性。