title: Exercise modalities and endothelial function: a systematic review and dose-response meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Regular exercise is associated with enhanced nitric oxide (NO) bioavailability. Flow-mediated dilation (FMD) is used widely to assess endothelial function (EF) and NO release.
  
  
  OBJECTIVE
  The aims of this systematic review and meta-analysis were to (i) investigate the effect of exercise modalities (aerobic, resistance or combined) on FMD; and (ii) determine which exercise and participant characteristics are most effective in improving FMD.
  
  
  METHODS
  We searched the MEDLINE, Embase, Cochrane Library, and Scopus databases for studies that met the following criteria: (i) randomized controlled trials of exercise with comparative non-exercise, usual care or sedentary groups; (ii) duration of exercise intervention ≥4 weeks; (iii) age ≥18 years; and (iv) EF measured by FMD before and after the intervention. Weighted mean differences (WMDs) with 95% confidence interval were entered into a random effect model to estimate the pooled effect of the exercise interventions.
  
  
  RESULTS
  All exercise modalities enhanced EF significantly: aerobic (WMD 2.79, 95% CI 2.12-3.45, p = 0.0001), resistance (WMD 2.52, 95% CI 1.11-3.93, p = 0.0001) and combined (WMD 2.07, 95% CI 0.70-3.44, p = 0.003). A dose-response relationship was observed between aerobic exercise intensity and improvement in EF. A 2 metabolic equivalents (MET) increase in absolute exercise intensity or a 10% increase in relative exercise intensity resulted in a 1% unit improvement in FMD. There was a positive relationship between frequency of resistance exercise sessions and improvement in EF (β 1.14, CI 0.16-2.12, p = 0.027).
  
  
  CONCLUSIONS
  All exercise modalities improve EF significantly and there was a significant, positive relationship between aerobic exercise intensity and EF. Greater frequency, rather than intensity, of resistance exercise training enhanced EF.
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle on Tyne, NE4 5PL, UK, a.w.ashor@newcastle.ac.uk.
authors.forename: Ammar W
authors.initials: AW
authors.lastname: Ashor
authors.forename: Jose
authors.initials: J
authors.lastname: Lara
authors.forename: Mario
authors.initials: M
authors.lastname: Siervo
authors.forename: Carlos
authors.initials: C
authors.lastname: Celis-Morales
authors.forename: Clio
authors.initials: C
authors.lastname: Oggioni
authors.forename: Djordje G
authors.initials: DG
authors.lastname: Jakovljevic
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
mesh_terms: D004730:Endothelium, Vascular / Q000502:physiology*; D015444:Exercise / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D012039:Regional Blood Flow; D055070:Resistance Training; D014664:Vasodilation
chemical_list: D009569:Nitric Oxide