Predicting Mortality in COPD with Validated and Sensitive Biomarkers; Fibrinogen and Mid-Range-Proadrenomedullin (MR-proADM)

Abstract

Although fibrinogen is a FDA qualified prognostic biomarker in COPD, it still lacks sufficient resolution to be clinically useful. Next to replication of findings in different cohorts also the combination with other validated biomarkers should be investigated. Therefore, the aim of this study was to confirm in a large well-defined population of COPD patients whether fibrinogen can predict mortality and whether a combination with the biomarker MR-proADM can increase prognostic accuracy. From the COMIC cohort study we included COPD patients with a blood sample obtained in stable state (n = 640) and/or at hospitalization for an acute exacerbation of COPD (n = 262). Risk of death during 3 years of follow up for the separate and combined biomarker models was analyzed with Cox regression. Furthermore, logistic regression models for death after one year were constructed. When both fibrinogen and MR-proADM were included in the survival model, a doubling in fibrinogen and MR-proADM levels gave a 2.2 (95% CI 1.3–3.7) and 2.1 (95% CI 1.5–3.0) fold increased risk of dying, respectively. The prediction model for death after 1 year improved significantly when MR-proADM was added to the model with fibrinogen (AUC increased from 0.78 to 0.83; p = 0.02). However, the combined model was not significantly more adequate than the model with solely MR-proADM (AUC 0.83 vs 0.82; p = 0.34). The study suggests that MR-proADM is more promising than fibrinogen in prediciting mortality. Adding fibrinogen to a model containing MR-proADM does not significantly increase the predictive capacity of the model.

Keywords:

• COPD
• mortality prediction
• biomarkers

Acknowledgements

The authors thank the Research Department of Thermofischer, Hennigsdorf, Berlin for supplying the MR-proADM and the use of the Kryptor®. We thank B. Steenhuis for the measurement of MR-proADM and Dr. Ir. A.H.L. Mulder for the measurement of fibrinogen.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

An unrestricted research grant of Glaxo Smith Kline was obtained for the COMIC cohort. Thermofisher supported this study by providing the Kryptor and the MR-proADM kits.