title: Circulating microRNAs as candidate markers to distinguish heart failure in breathless patients.
abstract: OBJECTIVE
  Since their identification in the circulation, microRNAs have received considerable interest as putative biomarkers of cardiovascular disease. We have investigated the diagnostic utility of microRNAs in differentiating between patients with heart failure (HF) and non-HF-related breathlessness, and between HF with reduced (HF-REF) and preserved (HF-PEF) EF.
  
  
  RESULTS
  MicroRNA profiling was performed on plasma from 32 HF and 15 COPD patients, as well as 14 healthy controls. Seventeen microRNAs were selected for validation in 44 HF, 32 COPD, 59 other breathless, and 15 controls. Cases of HF were split evenly between HF-REF and HF-PEF. Diagnostic utility was compared with NT-proBNP and high sensitivity troponin T (hs-troponin T). MiR-103 [area under the curve (AUC) = 0.642, P = 0.007], miR-142-3p (AUC = 0.668, P = 0.002), miR-199a-3p (AUC = 0.668, P = 0.002), miR-23a (AUC = 0.637, P = 0.010), miR-27b (AUC = 0.642, P = 0.008), miR-324-5p (AUC = 0.621, P = 0.023), and miR-342-3p (AUC = 0.644, P = 0.007) were associated with HF diagnosis in regression and receiver operating characteristic (ROC) analyses. Individually, NT-proBNP (AUC = 0.896, P = 9.68 × 10(-14)) and hs-troponin T (AUC = 0.750, P = 2.50 × 10(-6)) exhibited greater sensitivity and specificity. However, combining significantly associated microRNAs with NT-proBNP improved the AUC of NT-proBNP by 4.6% (P = 0.013). Four microRNAs, miR-103, miR-142-3p, miR-30b, and miR-342-3p, were differentially expressed between HF and controls, COPD, and other breathless patients (P = 0.002-0.030). Eight microRNAs that distinguished between HF-REF and HF-PEF in screening (P = 0.017-0.049) were not replicated in the validation.
  
  
  CONCLUSIONS
  Four microRNAs distinguished between HF and exacerbation of COPD, other causes of dyspnoea, and controls. Seven were associated with HF diagnosis in regression and ROC analysis. Although individually NT-proBNP was far superior in predicting HF, combining microRNA levels with NT-proBNP may add diagnostic value.
authors.affiliation: Christchurch Heart Institute, Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Ellis
authors.forename: Vicky A
authors.initials: VA
authors.lastname: Cameron
authors.forename: Richard W
authors.initials: RW
authors.lastname: Troughton
authors.forename: Chris M
authors.initials: CM
authors.lastname: Frampton
authors.forename: Leigh J
authors.initials: LJ
authors.lastname: Ellmers
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004417:Dyspnea / Q000097:blood* / Q000209:etiology; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D012372:ROC Curve; D012044:Regression Analysis; D013318:Stroke Volume; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Biomarkers; Diagnosis; Heart failure; MicroRNA; Plasma