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Respiratory Research
Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Research

GDF-15 plasma levels in chronic obstructive pulmonary disease are associated with subclinical coronary artery disease

Authors: Carlos H. Martinez, Christine M. Freeman, Joshua D. Nelson, Susan Murray, Xin Wang, Matthew J. Budoff, Mark T. Dransfield, John E. Hokanson, Ella A. Kazerooni, Gregory L. Kinney, Elizabeth A. Regan, J. Michael Wells, Fernando J. Martinez, MeiLan K. Han, Jeffrey L. Curtis, for the COPDGene Investigators

Published in: Respiratory Research | Issue 1/2017

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Abstract

Background

Growth differentiation factor-15 (GDF-15), a cytokine associated with cardiovascular mortality, increases during chronic obstructive pulmonary disease (COPD) exacerbations, but any role in stable COPD is unknown. We tested associations between GDF-15 and subclinical coronary atherosclerosis, assessed by coronary artery calcium (CAC) score, in COPD subjects free of clinical cardiovascular disease (CVD).

Methods

Cross-sectional analysis of COPD participants (GOLD stages 2–4) in the COPDGene cohort without CVD at enrollment, using baseline CAC (from non-EKG-gated chest computed tomography) and plasma GDF-15 (by custom ELISA). We used multinomial logistic modeling of GDF-15 associations with CAC, adjusting for demographics, baseline risk (calculated using the HEART: Personal Heart Early Assessment Risk Tool (Budoff et al. 114:1761-1791, 2006) score), smoking history, measures of airflow obstruction, emphysema and airway disease severity.

Results

Among 694 participants with COPD (47% women, mean age 63.6 years) mean GDF-15 was 1,304 pg/mL, and mean CAC score was 198. Relative to the lower GDF-15 tertile, higher tertiles showed bivariate association with increasing CAC score (mid tertile odds ratio [OR] 1.80, 95% confidence interval [CI] 1.29, 2.51; higher tertile OR 2.86, CI 2.04, 4.02). This association was maintained after additionally adjusting for baseline CVD risk, for co-morbidities and descriptors of COPD severity and impact, markers of cardiac stress (N-terminal pro–B-type natriuretic peptide, troponin T) and of inflammation (Interleukin-6), and in subgroup analysis excluding men, diabetics, current smokers or those with limited ambulation.

Conclusions

In ever-smokers with COPD free of clinical CVD, GDF-15 contributes independently to subclinical coronary atherosclerosis.

Trial registration

ClinicalTrials.gov, NCT00608764. Registered 28 January 2008.
Appendix
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Metadata
Title
GDF-15 plasma levels in chronic obstructive pulmonary disease are associated with subclinical coronary artery disease
Authors
Carlos H. Martinez
Christine M. Freeman
Joshua D. Nelson
Susan Murray
Xin Wang
Matthew J. Budoff
Mark T. Dransfield
John E. Hokanson
Ella A. Kazerooni
Gregory L. Kinney
Elizabeth A. Regan
J. Michael Wells
Fernando J. Martinez
MeiLan K. Han
Jeffrey L. Curtis
for the COPDGene Investigators
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-017-0521-1

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