title: miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease.
abstract: BACKGROUND
  Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction.
  
  
  OBJECTIVE
  The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD.
  
  
  METHODS
  Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR).
  
  
  RESULTS
  The median follow-up period was 4 years (IQR 2.78-5.04). The median age of all patients was 64 years (IQR 57-69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89).
  
  
  CONCLUSIONS
  Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future cardiovascular events.
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schulte
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Molz
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner site Hamburg/Luebeck/Kiel, Hamburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Appelbaum
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner site Hamburg/Luebeck/Kiel, Hamburg, Germany.
authors.forename: Mahir
authors.initials: M
authors.lastname: Karakas
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ojeda
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Lau
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Hartmann
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center 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: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner site Hamburg/Luebeck/Kiel, Hamburg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Westermann
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner site Hamburg/Luebeck/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 Eppendorf, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner site Hamburg/Luebeck/Kiel, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Department of General and Interventional Cardiology, University Heart Center Hamburg Eppendorf, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK), Partner site Hamburg/Luebeck/Kiel, Hamburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
mesh_terms: D000368:Aged; D015415:Biomarkers; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; C546085:MIRN197 microRNA, human; C525067:MIR223, human