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MR-proADM Predicts Exercise Capacity and Survival Superior to Other Biomarkers in PH

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Abstract

Purpose

Besides the established biomarker NT-proBNP, the new cardiovascular biomarkers MR-proANP, MR-proADM, Copeptin, and CT-proET-1 are promising to evaluate hemodynamics, exercise parameters, and prognosis in patients with pulmonary hypertension (PH).

Methods

125 consecutive patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were prospectively enrolled at five German PH centers. Blood samples were taken during right heart catheterization. The primary study endpoint was the correlation between biomarkers and hemodynamic and exercise parameters. As secondary endpoint, prediction of 1-year mortality was evaluated.

Results

MR-proADM showed the strongest correlations with 6MWD and VO2peak, whereas NT-proBNP showed the strongest correlations with PVR, PAPm, and CI. In multivariate analysis, only MR-proADM was independently associated with exercise variables, whereas only NT-proBNP independently predicted hemodynamic parameters. All biomarkers were associated with 1-year survival, with MR-proADM showing the highest C index of 0.78. In multivariate analysis, MR-proADM predicted survival independent of age, 6-MWD, CI, RAP, and NT-proBNP. The cut-off of 1.08 nmol/l provided a sensitivity of 83 % and specificity of 66 %.

Conclusions

Different biomarkers reflect distinctive disease aspects in PH. NT-proBNP best predicts hemodynamic impairment while MR-proADM strongly correlates with exercise capacity. Additionally, MR-proADM represents a promising new marker to evaluate prognosis in patients with PAH and CTEPH. Multi-marker strategies should further be evaluated.

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Acknowledgments

The study was funded by BRAHMS GmbH, Germany.

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Correspondence to Martin Kolditz.

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Conflict of Interest

Dr. Kolditz reports a grant from BRAHMS including help in collecting and analyzing the data for the submitted work; grants and speaking fees from Pfizer and speaking or advisory board fees from Thermo-Fisher, Gilead, GlaxoSmithKline, Novartis, Basilea, Astra-Zeneca, and Böhringer, all outside the submitted work. Dr. Wilkens reports travel grants from Bayer Vital, Actelion, GSK, Pfizer, speaking fees from Bayer Vital, Actelion, GSK, Pfizer Intermune, consultant fees from Bayer Vital, Actelion, GSK, intermune, outside the submitted work. Dr. Dinter and Dr. Hertel are employees of Thermo Fisher Scientific. Thermo Fisher Scientific supported measurements of biomarkers and compensated study activities with 50 € per patient sample. Dr. Klose reports grants and personal fees from Actelion, GSK, Bayer and personal fees from United Therapeutics, outside the submitted work. Dr. Opitz reports grants from Actelion and speaker fees, Honoraria, Consultancy, Advisory Board fees, Investigator Committee Member from Novartis and Pfizer, outside the submitted work. Dr. Grünig reports lecture and/or consultancy fees from Actelion, Bayer, Gilead, GlaxoSmithKline, Lilly, Miltenyi, Novartis, Pfizer, RotexMedica, Alexion and received honoraria for clinical studies from Actelion, Bayer, GSK, Encysive, Lilly, United Therapeutics and Pfizer. He is a member of the expert committees of BayerHealthCare, GlaxoSmithKline, Actelion, Pfizer. Dr. Halank reports a grant from BRAHMS including help in collecting and analyzing the data for the submitted work. Dr. Halank reports Speaker fees, Honoraria, Consultancy, and Advisory Board fees from Actelion, Bayer, GSK, Novartis, and Pfizer; outside the submitted work. Dr. Seyfarth, Dr. Ewert, Dr. Bollmann, and Dr. Höffken have nothing to disclose.

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Martin Kolditz and Hans-Jürgen Seyfarth have contributed equally to this work.

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Kolditz, M., Seyfarth, HJ., Wilkens, H. et al. MR-proADM Predicts Exercise Capacity and Survival Superior to Other Biomarkers in PH. Lung 193, 901–910 (2015). https://doi.org/10.1007/s00408-015-9802-y

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  • DOI: https://doi.org/10.1007/s00408-015-9802-y

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