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

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

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