title: Circulating miR-323-3p and miR-652: candidate markers for the presence and progression of acute coronary syndromes.
abstract: BACKGROUND
  The prognostic utility of circulating plasma microRNA in patients with acute coronary syndromes (ACS) has been proposed but not yet demonstrated. We set out to investigate circulating microRNA levels in patients incurring recent ACS and examined associations with neurohormones, cardiac structure and function, and survival over 5 years of follow-up.
  
  
  METHODS
  An initial screen of 375 microRNAs was performed in 35 ACS patients and 16 healthy controls. Candidates identified from the initial screen (miR-323-3p, miR-652, miR-27b, miR-103 and miR-208a) were validated in a further cohort of 200 patients at baseline (~ 30 days post-ACS) and at 4 and 12 months post-ACS, and compared with 100 controls.
  
  
  RESULTS
  In the validation cohort, significantly higher levels in patients were replicated for miR-323-3p, miR-652 and miR-27b (10-fold, 2.3-fold and 2.3-fold, respectively, adjusted p<0.05). Lower levels of miR-103 were not replicated and miR-208a was undetectable. From baseline to 4 months post-admission, miR-323-3p and miR-652 remained elevated in patients compared to controls (adjusted p<0.01), with no further change in levels between 4 and 12 months; whereas miR-27b fell to control levels by 4 months. Baseline levels of miR-652 in the lowest tertile were significantly associated with readmission for heart failure (log-rank p<0.001). In combination with NT-proBNP and LVEF, miR-652 significantly improved risk stratification (p<0.001).
  
  
  CONCLUSIONS
  Our study identifies miR-652 as a novel candidate biomarker for post-ACS prognosis beyond existing biomarkers of LVEF and NT-proBNP. Moreover circulating miR-323-3p was markedly elevated in patients for at least a year post-ACS and may be a stable biomarker for ACS.
authors.affiliation: Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch 8011, New Zealand. Electronic address: anna.pilbrow@otago.ac.nz.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Pilbrow
authors.affiliation: Division of Cardiovascular Medicine, ACCI Building, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Lina
authors.initials: L
authors.lastname: Cordeddu
authors.affiliation: Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch 8011, New Zealand.
authors.forename: Vicky A
authors.initials: VA
authors.lastname: Cameron
authors.affiliation: Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch 8011, New Zealand.
authors.forename: Chris M
authors.initials: CM
authors.lastname: Frampton
authors.affiliation: Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch 8011, New Zealand.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Troughton
authors.affiliation: Department of Medicine, Faculty of Medicine and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Doughty
authors.affiliation: Faculty of Social and Health Sciences, Unitec, Private Bag 92025, Auckland 1142, New Zealand.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Whalley
authors.affiliation: Department of Medicine, Faculty of Medicine and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Ellis
authors.affiliation: Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch 8011, New Zealand.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Yandle
authors.affiliation: Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch 8011, New Zealand; Cardiovascular Research Institute, National University Health Systems, Centre for Translational Medicine, Medical Drive, 117599, Singapore.
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
authors.affiliation: Division of Cardiovascular Medicine, ACCI Building, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; Cardiovascular Research Institute, National University Health Systems, Centre for Translational Medicine, Medical Drive, 117599, Singapore.
authors.forename: Roger S-Y
authors.initials: RS
authors.lastname: Foo
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C573188:MIRN323 microRNA, human; C574011:MIRN652 microRNA, human; D035683:MicroRNAs
keywords: Circulating microRNA; Myocardial infarction; Survival