Supplementary Material for: THE IMPACT OF VASCULAR RISK FACTORS ON CEREBRAL AMYLOID ANGIOPATHY: A COHORT STUDY IN HEREDITARY CAA AND A SYSTEMATIC REVIEW IN SPORADIC CAA

Background: Cerebral amyloid angiopathy (CAA) has a remarkably variable disease course, even in monogenetic hereditary forms. Our aim was to investigate the prevalence of vascular risk factors and their effect on disease onset and course in Dutch-type hereditary (D-)CAA and sporadic CAA.
Methods: We performed a cohort study in D-CAA to investigate the association between vascular risk factors (hypertension, hypercholesterolemia, smoking and alcohol use) and age of intracerebral hemorrhage (ICH) onset and time of ICH recurrence with survival analyses. In addition, we performed a systematic review to assess the prevalence of vascular risk factors and their effect on clinical outcome in sporadic CAA. We searched PubMed, Embase, Web of Science and COCHRANE Library, from 1987-2022 and included cohorts with ≥10 patients. We created forest plots, calculated pooled estimates and reported variability (heterogeneity plus sampling variability) and risk of bias.
Results: We included 70 participants with D-CAA (47% women, mean age 53y). Sixteen (23%) had hypertension, 15 (21%) hypercholesterolemia, 45 (64%) were smokers and 61 (87%) used alcohol. We found no clear effect of vascular risk factors on age of first ICH (log-rank test hypertension: p=0.35, hypercholesterolemia: p=0.41, smoking: p=0.61 and alcohol use: p=0.55) or time until ICH recurrence (log-rank test hypertension: p=0.71, hypercholesterolemia: p=0.20 and smoking: p=0.71). We identified 25 out of 1234 screened papers that assessed the prevalence of risk factors in CAA and 6 that reported clinical outcomes. The pooled prevalence estimates of hypertension was 62% (95%CI:55%-69%), diabetes 17% (95%CI:14%-20%), dyslipidemia 32% (95%CI:23%-41%), and tobacco use 27% (95%CI:18%-36%). One study reported study diabetes and hypertension to be associated with a lower risk of recurrent ICH, whereas another study reported hypertension to be associated with an increased risk. All other studies showed no association between vascular risk factors and clinical outcome. High quality studies focusing on vascular risk factors were lacking.
Conclusions: In patients with D-CAA and sporadic CAA the prevalence of vascular risk factors is high. Although this suggests an opportunity for prevention, there is no clear association between these risk factors and CAA-related ICH onset and recurrence.

研究背景：脑淀粉样血管病（Cerebral amyloid angiopathy, CAA）即使在单基因遗传性亚型中，疾病进程也存在显著异质性。本研究旨在探究荷兰型遗传性脑淀粉样血管病（Dutch-type hereditary (D-)CAA）与散发性脑淀粉样血管病患者的血管危险因素患病率，及其对疾病发病与病程的影响。

研究方法：本研究针对D-CAA开展队列研究，通过生存分析探究血管危险因素（高血压、高胆固醇血症、吸烟与饮酒）与脑出血（intracerebral hemorrhage, ICH）发病年龄及ICH复发时间的关联。此外，本研究还开展了系统综述，以评估散发性CAA患者的血管危险因素患病率及其对临床结局的影响。我们检索了1987年至2022年间PubMed、Embase、Web of Science及Cochrane Library数据库，纳入≥10例患者的队列研究。随后绘制森林图，计算合并效应量，并报告了变异度（异质性与抽样变异）及偏倚风险。

研究结果：本研究共纳入70例D-CAA患者（女性占比47%，平均年龄53岁）。其中16例（23%）合并高血压，15例（21%）合并高胆固醇血症，45例（64%）为吸烟者，61例（87%）有饮酒史。分析显示，各类血管危险因素对首次ICH发病年龄（对数秩检验：高血压p=0.35，高胆固醇血症p=0.41，吸烟p=0.61，饮酒p=0.55）及ICH复发时间（对数秩检验：高血压p=0.71，高胆固醇血症p=0.20，吸烟p=0.71）均无显著影响。本系统综述共筛选1234篇文献，最终纳入25篇评估CAA患者危险因素患病率的研究，以及6篇报告临床结局的研究。合并后的患病率估计值为：高血压62%（95%CI：55%~69%）、糖尿病17%（95%CI：14%~20%）、血脂异常32%（95%CI：23%~41%）、烟草使用27%（95%CI：18%~36%）。有1项研究报道糖尿病与高血压可降低ICH复发风险，另有1项研究则认为高血压会增加ICH复发风险，其余研究均未发现血管危险因素与临床结局存在显著关联。目前尚缺乏针对血管危险因素的高质量研究。

研究结论：无论是D-CAA患者还是散发性CAA患者，其血管危险因素的患病率均较高。尽管这提示存在预防干预的潜在空间，但此类危险因素与CAA相关的ICH发病及复发并无明确关联。