title: Renin-angiotensin system-targeting antihypertensive drugs and risk of vascular cognitive impairment: A meta-analysis.
abstract: OBJECTIVE
  To evaluate the effects of renin-angiotensin system (RAS)-targeting antihypertensive drugs and its classes on the incidence of vascular cognitive impairment (VCI).
  
  
  METHODS
  Pubmed, Embase, and Cochrane Library database of selected articles, and previous systematic reviews through May 2015 were searched. Studies that evaluated the association between use of RAS-targeting drugs and VCI were included. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using fixed effects models or random effects models.
  
  
  RESULTS
  In all studies as a whole, the use of RAS-targeting drugs was significantly associated with a reduced risk of VCI (RR, 0.87; 95% CI, 0.75-0.98) and vascular dementia (VD) (RR, 0.78; 95% CI, 0.64-0.93), compared no use of RAS-targeting drugs. Subgroup analysis showed that subjects with Angiotensin-Converting Enzyme Inhibitors (ACEI) use significantly associated with a reduced incidence of VCI (RR, 0.81; 95% CI 0.70-0.91) and VD (RR, 0.75; 95% CI, 0.57-0.93); however, subjects with Angiotensin Receptor Blockers (ARB) use had not this effect on VCI (RR, 0.94; 95% CI 0.76-1.13) or VD (RR, 0.94; 95% CI, 0.45-1.44). In an analysis of subgroups, case-control studies found that the use of RAS-targeting drugs could effectively decrease the incidence of VCI (RR, 0.77; 95% CI 0.66-0.87) and VD (RR, 0.77; 95% CI, 0.66-0.88); however, the randomized trials alone showed no significant effect on the incidence of VCI (RR, 0.94; 95% CI 0.82-1.07) or VD (RR, 0.94; 95% CI, 0.35-1.53). Meanwhile, in an analysis of cognitive impairment of vascular origin (VaCI), no significant association was found between RAS-targeting drugs, ACEI, or ARB and the incidence of VaCI.
  
  
  CONCLUSIONS
  RAS-targeting drugs treatment may produce remarkable efficacy on reducing the incidence of VCI and VD. Meanwhile, ACEI use, rather than ARB use, significantly protects against VCI and VD incidence. However, among the classes of RAS-targeting drugs, neither ACEI nor ARB plays protective role in VaCI incidence. Further more RCTs are required to reliably establish whether RAS-targeting drugs use decreases the risk of VCI (VD and VaCI).
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhuang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Hai-feng
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Wei-jie
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China. Electronic address: xingchengming@medmail.com.cn.
authors.forename: Cheng-ming
authors.initials: CM
authors.lastname: Xing
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D060825:Cognitive Dysfunction / Q000453:epidemiology*; D015140:Dementia, Vascular / Q000453:epidemiology*; D006801:Humans; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012306:Risk
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents
keywords: Angiotensin Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Meta-analysis; Renin–angiotensin system; Vascular cognitive impairment; Vascular dementia