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

Academic Article

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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    Keywords

  • Adult, Biomarkers, Coronary Artery Disease, Cross-Sectional Studies, Multivariate Analysis, Risk Factors, Aged, Asymptomatic Diseases, Biomarkers, Causality, Comorbidity, Coronary Artery Disease, Female, Growth Differentiation Factor 15, Humans, Incidence, Male, Michigan, Middle Aged, Pulmonary Disease, Chronic Obstructive, Reproducibility of Results, Risk Factors, Sensitivity and Specificity
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    Author List

  • Martinez CH; Freeman CM; Nelson JD; Murray S; Wang X; Budoff MJ; Dransfield MT; Hokanson JE; Kazerooni EA; Kinney GL
  • Start Page

  • 42
  • Volume

  • 18
  • Issue

  • 1