Mortality risk prediction in COPD by a prognostic biomarker panel

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.