title: Mortality risk prediction in COPD by a prognostic biomarker panel.
abstract: Chronic obstructive pulmonary disease (COPD) is a complex disease with various phenotypes. The simultaneous determination of multiple biomarkers reflecting different pathobiological pathways could be useful in identifying individuals with an increased risk of death. We derived and validated a combination of three biomarkers (adrenomedullin, arginine vasopressin and atrial natriuretic peptide), assessed in plasma samples of 385 patients, to estimate mortality risk in stable COPD. Biomarkers were analysed in combination and defined as high or low. In the derivation cohort (n = 142), there were 73 deaths during the 5-year follow-up. Crude hazard ratios for mortality were 3.0 (95% CI 1.8-5.1) for one high biomarker, 4.8 (95% CI 2.4-9.5) for two biomarkers and 9.6 (95% CI 3.3-28.3) for three high biomarkers compared with no elevated biomarkers. In the validation cohort (n = 243), 87 individuals died. Corresponding hazard ratios were 1.9 (95% CI 1.1-3.3), 3.1 (95% CI 1.8-5.4) and 5.4 (95% CI 2.5-11.4). Multivariable adjustment for clinical variables as well as the BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index and stratification by the Global Initiative for Chronic Obstructive Lung Disease stages provided consistent results. The addition of the panel of three biomarkers to the BODE index generated a net reclassification improvement of 57.9% (95% CI 21.7-92.4%) and 45.9% (95% CI 13.9-75.7%) at 3 and 5 years, respectively. Simultaneously elevated levels of adrenomedullin, arginine vasopressin and atrial natriuretic peptide are associated with increased risk of death in patients with stable COPD.
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland stolzd@uhbs.ch.
authors.forename: Daiana
authors.initials: D
authors.lastname: Stolz
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Janko
authors.initials: J
authors.lastname: Rakic
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Boeck
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scherr
authors.affiliation: Clinic of Pneumology and Respiratory Cell Research, University Hospital, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Tamm
mesh_terms: D053607:Adrenomedullin / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D001127:Arginine Vasopressin / Q000097:blood*; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000401:mortality*; D015203:Reproducibility of Results; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; D001127:Arginine Vasopressin; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor