title: Prognostic value of circulating microRNA-210 levels in patients with moderate to severe aortic stenosis.
abstract: BACKGROUND
  Circulating micro-RNAs have been proposed as a novel class of cardiovascular (CV) biomarkers, but whether they meet analytical requirements and provide additional information to establish risk indices have not been established. miR-210 levels are increased in subjects with low VO2 max, which is a recognized risk factor in patients with aortic stenosis (AS), and we hypothesized that circulating miR-210 levels may be increased in patients with AS and associated with a poor prognosis.
  
  
  METHODS
  We measured circulating miR-210 levels by real-time PCR in 57 patients with moderate to severe AS and in 10 age- and gender-matched healthy controls. The merit of miR-210 as a biomarker was assessed according to established criteria, including by comparing miR-210 levels with NT-proBNP and miR-22 levels, which is another miRNA biomarker candidate.
  
  
  RESULTS
  All patients and control subjects had miR-210 levels within the range of detection (Cq<35) and the analytical variability was low. Circulating miR-210 levels were 2.0±0.2 [mean±SEM] fold increased in AS patients compared to controls (p = 0.002), whereas miR-22 levels were not differently expressed in the AS patients (0.12±0.06 fold increase, p = 0.45). The increase in miR-210 levels in AS patients was comparable to the increment in NT-proBNP levels: [AUC] 0.82 (95% CI 0.70-0.90) vs. 0.85 (0.75-0.93), respectively, p = 0.71. During a median follow-up of 1287 days, 15 patients (26%) died. There was a significant association between higher circulating levels of miR-210 and increased mortality during follow-up: hazard ratio [supra- vs. inframedian levels] 3.3 (95% CI 1.1-10.5), p = 0.039. Adjusting for other risk indices in multivariate analysis did not attenuate the prognostic merit of circulating miR-210 levels.
  
  
  CONCLUSIONS
  Circulating miR-210 levels are increased in patients with AS and provide independent prognostic information to established risk indices. Analytical characteristics were also excellent supporting the potential of micro-RNAs as novel CV biomarkers.
authors.affiliation: Division of Medicine, Akershus University Hospital, Lørenskog, Norway; K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Helge
authors.initials: H
authors.lastname: Røsjø
authors.affiliation: Division of Medicine, Akershus University Hospital, Lørenskog, Norway; K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Biology (EpiGen), UiO, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Mai Britt
authors.initials: MB
authors.lastname: Dahl
authors.affiliation: K.G. Jebsen Centre for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian Institute of Science and Technology, Trondheim, Norway.
authors.forename: Anja
authors.initials: A
authors.lastname: Bye
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Johanna
authors.initials: J
authors.lastname: Andreassen
authors.affiliation: Division of Medicine, Akershus University Hospital, Lørenskog, Norway; K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Biology (EpiGen), UiO, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Jørgensen
authors.affiliation: K.G. Jebsen Centre for Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian Institute of Science and Technology, Trondheim, Norway.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisløff
authors.affiliation: K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Institute for Experimental Medical Research, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Christensen
authors.affiliation: K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Edvardsen
authors.affiliation: Division of Medicine, Akershus University Hospital, Lørenskog, Norway; K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Omland
mesh_terms: D000328:Adult; D000368:Aged; D001024:Aortic Valve Stenosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C543800:MIRN210 microRNA, human; D035683:MicroRNAs