title: Utility of 14 novel biomarkers in patients with acute chest pain and undetectable levels of conventional cardiac troponin.
abstract: BACKGROUND
  Patients with acute chest pain having serial undetectable cardiac troponin (cTn) levels, as measured with conventional assays, are considered at very low risk. The aim of this multicenter study was to determine the accuracy of multiple biomarkers in these patients.
  
  
  METHODS
  We enrolled 1247 consecutive patients with suspected AMI. Of these, 325 had undetectable levels of cTnT (Roche, 4th generation assay) at presentation and at 6h. Fourteen novel markers quantifying cardiomyocyte damage, inflammation and/or plaque rupture, and neurohormonal activation were measured at presentation. The occurrence of death or acute myocardial infarction (AMI) (primary end point) and unplanned coronary revascularization (secondary endpoint) were recorded during long-term follow-up.
  
  
  RESULTS
  During a mean follow-up of 668 ± 241 days, death/AMI occurred in 23 patients (7%), unplanned revascularization in 46 (14%). Among all biomarkers, high-sensitive cTnT (hs-cTnT), Midregional pro-adrenomedullin (MR-proADM) and growth differentiation factor-15 (GDF-15) were independently associated with future death/AMI; hs-cTnT was 0.013 (0.008-0.017) μg/l versus 0.006 (0.003-0.010) μg/l, MR-proADM was 0.78 (0.66-1.09) nmol/l versus 0.60 (0.18-0.80) nmol/l and GDF-15 was 1800 (1600-2200) ng/l versus 1100 (800-1700) ng/l in patients with versus without death/AMI during follow-up (p<0.001 each). The area under the receiver-operating characteristics curve to predict death/AMI was 0.73 (95%CI 0.63-0.83) for hs-cTnT, 0.71 (95% CI 0.62-0.81) for MR-proADM and 0.78 (95%CI 0.71-0.86) for GDF-15.
  
  
  CONCLUSIONS
  Patients with serial undetectable levels of cTnT using the contemporary 4th generation assay are at low but not negligible risk of future cardiac events. Hs-cTnT, MR-proADM and/or GDF-15 might help to further improve risk-stratification in this group.
authors.affiliation: Department of Internal Medicine, University Hospital, Basel, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Meune
authors.forename: Cathrin
authors.initials: C
authors.lastname: Balmelli
authors.forename: Raphael
authors.initials: R
authors.lastname: Twerenbold
authors.forename: Miriam
authors.initials: M
authors.lastname: Reiter
authors.forename: Tobias
authors.initials: T
authors.lastname: Reichlin
authors.forename: Ronny
authors.initials: R
authors.lastname: Ziller
authors.forename: Beatrice
authors.initials: B
authors.lastname: Drexler
authors.forename: Claudia
authors.initials: C
authors.lastname: Stelzig
authors.forename: Michael
authors.initials: M
authors.lastname: Freese
authors.forename: Claudia
authors.initials: C
authors.lastname: Wolf
authors.forename: Philip
authors.initials: P
authors.lastname: Haaf
authors.forename: Stefan
authors.initials: S
authors.lastname: Osswald
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002637:Chest Pain / Q000097:blood* / Q000175:diagnosis*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D020107:Troponin T