title: Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations.
abstract: OBJECTIVE
  Circulating microRNAs (miRNAs) have been implicated in both heart failure and atherosclerotic disease. The aim of this study was to examine associations between heart failure specific circulating miRNAs, atherosclerotic disease and cardiovascular-related outcome in patients with heart failure.
  
  
  METHODS
  The levels of 11 heart failure-specific circulating miRNAs were compared in plasma of 114 heart failure patients with and without different manifestations of atherosclerotic disease. We then studied these miRNAs in relation to biomarkers associated to atherosclerosis and to cardiovascular-related rehospitalizations during 18 months of follow-up.
  
  
  RESULTS
  At least one manifestation of atherosclerotic disease was found in 70 (61%) of the heart failure patients. A consistent trend was found between an increasing number of manifestations of atherosclerosis (peripheral arterial disease in specific), and lower levels of miR-18a-5p, miR-27a-3p, miR-199a-3p, miR-223-3p and miR-652-3p (all P < 0.05). Target prediction and network analyses identified several interactions between miRNA targets and biomarkers related to inflammation, angiogenesis and endothelial dysfunction. Lower miRNA levels were associated with higher levels of these atherosclerosis-related biomarkers. In addition, lower miRNA levels were significantly associated with rehospitalizations due to cardiovascular causes within 18 months, with let-7i-5p as strongest predictor [HR 2.06 (95% CI 1.29-3.28), C-index 0.70, P = 0.002].
  
  
  CONCLUSIONS
  A consistent pattern of lower levels of circulating miRNAs was found in heart failure patients with atherosclerotic disease, in particular peripheral arterial disease. In addition, lower levels of miRNAs were associated with higher levels of biomarkers involved in atherosclerosis and an increased risk of a cardiovascular-related rehospitalization.
authors.affiliation: Department of Cardiology, AB31, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Eline L
authors.initials: EL
authors.lastname: Vegter
authors.affiliation: Department of Cardiology, AB31, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.|European Research Institute for the Biology of Ageing, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
authors.forename: Ekaterina S
authors.initials: ES
authors.lastname: Ovchinnikova
authors.affiliation: Department of Cardiology, AB31, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Faculty of Medical and Health Sciences, University of Linkoping, 581 83, Linköping, Sweden.
authors.forename: Tiny
authors.initials: T
authors.lastname: Jaarsma
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
authors.forename: Eugene
authors.initials: E
authors.lastname: Berezikov
authors.affiliation: Department of Cardiology, AB31, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
authors.affiliation: Department of Cardiology, AB31, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. a.a.voors@umcg.nl.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000150:complications; D015415:Biomarkers / Q000097:blood; D000074166:Circulating MicroRNA / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000150:complications; D006801:Humans; D008297:Male; D010359:Patient Readmission / Q000639:trends*; D011379:Prognosis
chemical_list: D015415:Biomarkers; D000074166:Circulating MicroRNA
keywords: Atherosclerosis; Biomarkers; Circulating microRNAs; Heart failure; Rehospitalization