title: Non-invasive endothelial function testing and the risk of adverse outcomes: a systematic review and meta-analysis.
abstract: OBJECTIVE
  We performed a systematic review and meta-analysis to understand the role of flow-mediated dilatation (FMD) of the brachial artery (BA) and peripheral arterial tonometry (PAT) in predicting adverse events, including cardiovascular (CV) events and all-cause mortality.
  
  
  BACKGROUND
  FMD of the BA and PAT are non-invasive measures of endothelial function. Impairment of endothelial function is associated with increased CV events. While FMD is the more widely used and studied technique, PAT offers several advantages. The purpose of this systematic review and meta-analysis is to determine whether brachial FMD and PAT are independent risk factors for future CV events and mortality.
  
  
  METHODS
  Multiple electronic databases were searched for articles relating FMD or PAT to CV events. Data were extracted on study characteristics, study quality, and study outcomes. Relative risks (RRs) from individual studies were combined and a pooled multivariate RR was calculated.
  
  
  RESULTS
  Thirty-six studies for FMD were included in the systematic review, of which 32 studies consisting of 15, 191 individuals were meta-analysed. The pooled RR of CV events and all-cause mortality per 1% increase in brachial FMD, adjusting for potential confounders, was 0.90 (0.88-0.92). In contrast, only three studies evaluated the prognostic value of PAT for CV events, and the pooled RR per 0.1 increase in reactive hyperaemia index was 0.85 (0.78-0.93).
  
  
  CONCLUSIONS
  Brachial FMD and PAT are independent predictors of CV events and all-cause mortality. Further research to evaluate the prognostic utility of PAT is necessary to compare it with FMD as a non-invasive endothelial function test in clinical practice.
authors.affiliation: Section of Nephrology, Seven Oaks General Hospital, 2PD-13 2300 McPhillips Street, Winnipeg, Canada R2V 3M3.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Section of Cardiac Surgery, St. Boniface General Hospital, Winnipeg, Canada.
authors.forename: Rakesh C
authors.initials: RC
authors.lastname: Arora
authors.affiliation: Section of Cardiac Surgery, St. Boniface General Hospital, Winnipeg, Canada.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Hiebert
authors.affiliation: Section of Nephrology, Seven Oaks General Hospital, 2PD-13 2300 McPhillips Street, Winnipeg, Canada R2V 3M3.
authors.forename: Blake
authors.initials: B
authors.lastname: Lerner
authors.affiliation: Section of Nephrology, St. Boniface General Hospital, Winnipeg, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Szwajcer
authors.affiliation: Section of Nephrology, Seven Oaks General Hospital, 2PD-13 2300 McPhillips Street, Winnipeg, Canada R2V 3M3.
authors.forename: Kerry
authors.initials: K
authors.lastname: McDonald
authors.affiliation: Section of Nephrology, Seven Oaks General Hospital, 2PD-13 2300 McPhillips Street, Winnipeg, Canada R2V 3M3.
authors.forename: Claudio
authors.initials: C
authors.lastname: Rigatto
authors.affiliation: Section of Nephrology, Seven Oaks General Hospital, 2PD-13 2300 McPhillips Street, Winnipeg, Canada R2V 3M3.
authors.forename: Paul
authors.initials: P
authors.lastname: Komenda
authors.affiliation: Section of Nephrology, St. Boniface General Hospital, Winnipeg, Canada.
authors.forename: Manish M
authors.initials: MM
authors.lastname: Sood
authors.affiliation: Section of Nephrology, Seven Oaks General Hospital, 2PD-13 2300 McPhillips Street, Winnipeg, Canada R2V 3M3 ntangri@sogh.mb.ca.
authors.forename: Navdeep
authors.initials: N
authors.lastname: Tangri
mesh_terms: D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology*; D003935:Diagnostic Techniques, Cardiovascular / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000503:physiopathology; D011237:Predictive Value of Tests; D018570:Risk Assessment; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
keywords: Cardiovascular outcomes; Endothelial function