title: Clinical assessment of endothelial function in patients with rheumatoid arthritis: A meta-analysis of literature studies.
abstract: BACKGROUND
  Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with rheumatoid arthritis (RA). Flow-mediated (FMD) and nitrate-mediated dilation (NMD) are considered non-invasive methods to assess endothelial function and surrogate markers of subclinical atherosclerosis.
  
  
  METHODS
  We performed a systematic review with meta-analysis and meta-regression of literature studies evaluating the impact of RA on FMD and NMD. Studies evaluating the relationship between RA and markers of CV risk (FMD and NMD) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. The random-effect method was used for analyses and results were expressed as mean difference (MD).
  
  
  RESULTS
  A total of 20 studies (852 RA patients, 836 controls) were included in the final analysis. In detail, 20 studies with data on FMD (852 cases, 836 controls) and 5 studies with data on NMD (207 cases, 147 controls) were analyzed. Compared to controls, RA patients showed a significantly lower FMD (MD: -2.16%; 95% CI: -3.33, -0.98; P=0.0003), with no differences in NMD (MD: -0.41%; 95% CI: -2.89, 2.06; P=0.74). Interestingly, a lower FMD (MD: -2.00%; 95% CI: -3.20, -0.80; P=0.001) and no differences in NMD (P=0.49) were confirmed when excluding data on patients with early-RA. Meta-regression models showed that a more severe inflammatory status was associated with a more significant impairment in FMD.
  
  
  CONCLUSIONS
  RA patients show impaired FMD, which is currently considered an independent predictor of CV events. The presence of endothelial dysfunction in RA should be taken into account to plan adequate prevention strategies and therapeutic approaches.
authors.affiliation: Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy. Electronic address: dario.diminno@hotmail.it.
authors.forename: Matteo Nicola Dario
authors.initials: MN
authors.lastname: Di Minno
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ambrosino
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Lupoli
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Minno
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tasso
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Peluso
authors.affiliation: Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
mesh_terms: D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000503:physiopathology; D058070:Asymptomatic Diseases / Q000453:epidemiology; D050197:Atherosclerosis / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D012307:Risk Factors; D014664:Vasodilation
chemical_list: D015415:Biomarkers
keywords: Cardiovascular risk; Endothelial dysfunction; Flow-mediated dilation; Nitrate-mediated dilation; Rheumatoid arthritis