PLoS ONE (Jan 2014)

Prognostic value of circulating microRNA-210 levels in patients with moderate to severe aortic stenosis.

  • Helge Røsjø,
  • Mai Britt Dahl,
  • Anja Bye,
  • Johanna Andreassen,
  • Marit Jørgensen,
  • Ulrik Wisløff,
  • Geir Christensen,
  • Thor Edvardsen,
  • Torbjørn Omland

DOI
https://doi.org/10.1371/journal.pone.0091812
Journal volume & issue
Vol. 9, no. 3
p. e91812

Abstract

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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.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.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.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.