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Clinical Investigations
Respiration 2010;80:543–552
DOI: 10.1159/000319038
Biomarkers and Peak Oxygen Uptake in
Patients with Chronic Lung Disease
Micha T. Maeder
a, b
Martin H. Brutsche
c
Nisha Arenja
d
Thenral Socrates
d
Miriam Reiter
d
Julia Meissner
d
Daniel Staub
d
Nils G. Morgenthaler
e
Andreas Bergmann
e
Christian Mueller
d
a
Baker IDI Heart and Diabetes Institute, Melbourne, Vic., Australia; Divisions of
b
Cardiology and
c
Pneumology,
Kantonsspital, St. Gallen, and
d
Department of Internal Medicine, University Hospital Basel, Basel, Switzerland;
e
Department of Research, BRAHMS AG, Biotechnology Center, Hennigsdorf, Germany
associated with lower peak V O
2
, and these associations were
independent of age, gender, medication, FEV
1
and oxygen-
ation. The relationship between MR-proANP, MR-proADM,
and CT-proET-1 and peak V O
2
was significant whether pa-
tients had an obstructive ventilatory disease or not. Conclu-
sions: In patients with chronic lung disease, several biomark-
ers known to reflect measures of cardiac function were
associated with peak V O
2
independent of lung function,
indicating that cardiac strain may contribute to exercise lim-
itation in these patients due to concomitant cardiac disease
or in the context of a pulmonary-cardiac interaction.
Copyright © 2010 S. Karger AG, Basel
Introduction
Cardiopulmonary exercise testing (CPET) is an estab-
lished tool for risk stratification in patients with a variety
of pulmonary diseases including chronic obstructive pul-
monary disease (COPD), interstitial lung disease, pulmo-
nary vascular disorders, and cystic fibrosis [1–3]. The
prognostic power of peak oxygen uptake (peak V O
2
) in
these patients is explained by the fact that peak V O
2
is not
only a measure of the degree of impairment of ventilation
and gas exchange but also reflects nonpulmonary com-
Key Words
Biomarkers Cardiopulmonary exercise testing
Endothelin Peak oxygen consumption
Abstract
Background: Peak oxygen uptake (peak V O
2
) is a predictor
of outcome in patients with lung disease. In these patients,
peak V O
2
is typically determined by ventilation and gas ex-
change. However, it is not well known whether cardiac strain
contributes to peak V O
2
in patients with chronic lung disease.
Objective: To assess the relationship between several novel
biomarkers reflecting different aspects of cardiac function
and peak V O
2
in patients with chronic lung disease. Methods:
Plasma concentrations of midregional pro-A-type natriuret-
ic peptide (MR-proANP), midregional proadrenomedullin
(MR-proADM), C-terminal proendothelin-1 (CT-proET-1), and
C-terminal provasopressin (copeptin) were measured in 85
patients with a variety of chronic pulmonary diseases [age
57 8 14 years, forced expiratory volume in the 1st second
(FEV
1
) 76 8 23% of the predicted value] undergoing maxi-
mal cardiopulmonary exercise testing (peak V O
2
18.6 8 6.6
ml/kg/min). Results: Raised MR-proANP (r = –0.54), MR-
proADM (r = –0.54), and CT-proET-1 (r = –0.49; p ! 0.001 for
all) but not copeptin (r = –0.05; p = 0.68) concentrations were
Received: August 24, 2009
Accepted after revision: April 12, 2010
Published online: July 17, 2010
Micha T. Maeder, MD
Division of Cardiology, Kantonsspital St. Gallen
Rorschacherstrasse 95
CH–9007 St. Gallen (Switzerland)
Tel. +41 71 494 11 76, Fax +41 71 494 61 42, E-Mail micha.maeder @ kssg.ch
© 2010 S. Karger AG, Basel
0025–7931/10/0806–0543$26.00/0
Accessible online at:
www.karger.com/res