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Respir Res. 2017 Feb 28;18(1):42. doi: 10.1186/s12931-017-0521-1.

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

Author information

1
Division of Pulmonary & Critical Care Medicine, University of Michigan Health System, 2215 Fuller Road, Ann Arbor, MI, 48105-2303, USA.
2
Research Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
3
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
4
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
5
The Lung Health Center, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
6
Medical Service, Birmingham Veteran Affairs Medical Center, Birmingham, AL, USA.
7
School of Public Health, University of Colorado, Aurora, CO, USA.
8
Radiology Department, University of Michigan Health System, Ann Arbor, MI, USA.
9
National Jewish Health & Research Center, Denver, CO, USA.
10
Pulmonary & Critical Care Medicine Division, Department of Medicine, University of Colorado, Denver, CO, USA.
11
Pulmonary & Critical Care Medicine Division, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
12
Division of Pulmonary & Critical Care Medicine, University of Michigan Health System, 2215 Fuller Road, Ann Arbor, MI, 48105-2303, USA. jlcurtis@umich.edu.
13
Graduate Program in Immunology, University of Michigan, 2215 Fuller Road, Ann Arbor, MI, 48105-2303, USA. jlcurtis@umich.edu.
14
Medical Service, VA Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI, 48105-2303, USA. jlcurtis@umich.edu.

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.

KEYWORDS:

Adult; Biomarkers; Coronary Artery Disease; Cross-Sectional Studies; Multivariate Analysis; Risk Factors

PMID:
28245821
PMCID:
PMC5331711
DOI:
10.1186/s12931-017-0521-1
[Indexed for MEDLINE]
Free PMC Article

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