title: Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease-results from the large AtheroGene study.
abstract: BACKGROUND
  Stratification for subsequent coronary events among patients with coronary artery disease (CAD) is of considerable interest because of the potential to guide secondary preventive therapies. Recently, we identified eight microRNAs (miRNAs), which facilitated acute coronary syndrome (ACS) diagnosis. In this study, we aimed to evaluate their potential role as prognostic biomarkers for cardiovascular disease.
  
  
  METHODS
  The serum concentrations of eight candidate miRNAs -miR-19a, miR-19b, miR-132, miR-140-3p, miR-142-5p, miR-150, miR-186, and miR-210 were measured in a cohort of 1112 patients with documented CAD-including 430 patients with ACS and 682 patients with stable angina pectoris. Cardiovascular death was the main outcome measure.
  
  
  RESULTS
  During a median follow-up of 4.0 years, most miRNAs reliably predicted cardiovascular death in ACS patients. Cox regression analyses indicated that in particular miR-132 (HR 2.85 per 1 SD increase, P = 0.022), miR-140-3p (HR 2.88 per 1 SD increase, P = 0.022), and miR-210 (HR 3.10 per 1 SD increase, P = 0.039) were able to precisely predict cardiovascular death. Circulating miR-132, miR-140-3p, and miR-210 clearly improved various model performance measures, including C-statistics (AUC [area under the receiver-operating characteristic curve] for miR-132: 0.737; AUC for miR-140-3p: 0.756; AUC for miR-210: 0.754).
  
  
  CONCLUSIONS
  This is the largest study so far evaluating the prognostic value of circulating miRNAs in cardiovascular disease. Our study shows that single miRNAs derived from peripheral blood predict mortality in secondary prevention settings, and thereby represent valuable biomarkers for risk estimation in CAD.
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Lübeck, Kiel, Hamburg, Germany.
authors.forename: Mahir
authors.initials: M
authors.lastname: Karakas
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schulte
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Lübeck, Kiel, Hamburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Appelbaum
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ojeda
authors.affiliation: Department of Laboratory Medicine, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Rhein-Main, Mainz, Germany.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.affiliation: German Center for Cardiovascular Research (DZHK), Partner Site Rhein-Main, Mainz, Germany.|Department of Medicine II, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Lübeck, Kiel, Hamburg, Germany.
authors.forename: Renate B
authors.initials: RB
authors.lastname: Schnabel
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Lübeck, Kiel, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Lübeck, Kiel, Hamburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D000074166:Circulating MicroRNA / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000401:mortality* / Q000517:prevention & control; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018570:Risk Assessment; D055502:Secondary Prevention
chemical_list: D015415:Biomarkers; D000074166:Circulating MicroRNA
keywords: Biomarker; Coronary artery disease; MicroRNA; Prognosis