title: Multimarker strategy for short-term risk assessment in patients with dyspnea in the emergency department: the MARKED (Multi mARKer Emergency Dyspnea)-risk score.
abstract: OBJECTIVE
  The study aim was to determine the prognostic value of a multimarker strategy for risk-assessment in patients presenting to the emergency department (ED) with dyspnea.
  
  
  BACKGROUND
  Combining biomarkers with different pathophysiological backgrounds may improve risk stratification in dyspneic patients in the ED.
  
  
  METHODS
  The study prospectively investigated the prognostic value of the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), Cystatin-C (Cys-C), high-sensitivity C-reactive protein (hs-CRP), and Galectin-3 (Gal-3) for 90-day mortality in 603 patients presenting to the ED with dyspnea as primary complaint.
  
  
  RESULTS
  hs-CRP, hs-cTnT, Cyst-C, and NT-proBNP were independent predictors of 90-day mortality. The number of elevated biomarkers was highly associated with outcome (odds ratio: 2.94 per biomarker, 95% confidence interval [CI]: 2.29 to 3.78, p < 0.001). A multimarker approach had incremental value beyond a single-marker approach. Our multimarker emergency dyspnea-risk score (MARKED-risk score) incorporating age ≥75 years, systolic blood pressure <110 mm Hg, history of heart failure, dyspnea New York Heart Association functional class IV, hs-cTnT ≥0.04 μg/l, hs-CRP ≥25 mg/l, and Cys-C ≥1.125 mg/l had excellent prognostic performance (area under the curve: 0.85, 95% CI: 0.81 to 0.89), was robust in internal validation analyses and could identify patients with very low (<3 points), intermediate (≥3, <5 points), and high risk (≥5 points) of 90-day mortality (2%, 14%, and 44% respectively; p < 0.001).
  
  
  CONCLUSIONS
  A multimarker strategy provided superior risk stratification beyond any single-marker approach. The MARKED-risk score that incorporates hs-cTnT, hs-CRP, and Cys-C along with clinical risk factors accurately identifies patients with very low, intermediate, and high risk.
authors.affiliation: Department of Cardiology, Maastricht University Medical Center, CARIM, Maastricht, the Netherlands. l.eurlings@mumc.nl
authors.forename: Luc W
authors.initials: LW
authors.lastname: Eurlings
authors.forename: Sandra
authors.initials: S
authors.lastname: Sanders-van Wijk
authors.forename: Roland
authors.initials: R
authors.lastname: van Kimmenade
authors.forename: Aart
authors.initials: A
authors.lastname: Osinski
authors.forename: Lidwien
authors.initials: L
authors.lastname: van Helmond
authors.forename: Maud
authors.initials: M
authors.lastname: Vallinga
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Crijns
authors.forename: Marja P
authors.initials: MP
authors.lastname: van Dieijen-Visser
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Brunner-La Rocca
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D016001:Confidence Intervals; D004417:Dyspnea / Q000097:blood* / Q000453:epidemiology; D004636:Emergency Service, Hospital; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends
chemical_list: D015415:Biomarkers