title: Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD.
abstract: Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic-femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=-0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05).In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.
authors.affiliation: Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation and Research, Queens' Medical Research Institute, Edinburgh, UK roberto.rabinovich@ed.ac.uk.
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Rabinovich
authors.affiliation: Respiratory Therapy Area Unit, GSK, King of Prussia, PA, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Miller
authors.affiliation: Medical Research Institute, School of Medicine, University of Dundee, Dundee, UK.
authors.forename: Karolina
authors.initials: K
authors.lastname: Wrobel
authors.affiliation: Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation and Research, Queens' Medical Research Institute, Edinburgh, UK.
authors.forename: Kareshma
authors.initials: K
authors.lastname: Ranjit
authors.affiliation: University/BHF Centre for Cardiovascular Science, Edinburgh, UK.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Williams
authors.affiliation: Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation and Research, Queens' Medical Research Institute, Edinburgh, UK.
authors.forename: Ellen
authors.initials: E
authors.lastname: Drost
authors.affiliation: PAREXEL International, Durham, NC, USA.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Edwards
authors.affiliation: Faculty of Medical Sciences, University College London, London, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska, Omaha, NE, USA Clinical Discovery Unit, AstraZeneca, Cambridge, UK.
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
authors.affiliation: Servei de Pneumologia, Thorax Institute, Hospital Clinic, IDIBAPS, Universitat de Barcelona and CIBER Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
authors.affiliation: Respiratory Therapy Area Unit, GSK, King of Prussia, PA, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.affiliation: Centre for Respiratory Medicine and Allergy, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.affiliation: Dept of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Emiel F M
authors.initials: EF
authors.lastname: Wouters
authors.affiliation: Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: John
authors.affiliation: Clinical Research Imaging Centre, Queens Medical Research Institute, Edinburgh, UK.
authors.forename: Edwin J R
authors.initials: EJ
authors.lastname: van Beek
authors.affiliation: Dept of Radiology, Royal Infirmary of Edinburgh, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: Murchison
authors.affiliation: Nottingham Respiratory Research Unit, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Bolton
authors.affiliation: Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation and Research, Queens' Medical Research Institute, Edinburgh, UK.
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.affiliation: Medical Research Institute, School of Medicine, University of Dundee, Dundee, UK.
authors.forename: Jeffrey T J
authors.initials: JT
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001823:Body Composition; D001993:Bronchodilator Agents / Q000494:pharmacology; D002114:Calcinosis; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications / Q000401:mortality; D016022:Case-Control Studies; D003331:Coronary Vessels / Q000473:pathology; D003895:Desmosine / Q000097:blood*; D018450:Disease Progression; D004549:Elastin / Q000097:blood / Q000378:metabolism; D004646:Emphysema / Q000097:blood* / Q000150:complications / Q000401:mortality; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications / Q000401:mortality; D011656:Pulmonary Emphysema / Q000503:physiopathology; D063177:Pulse Wave Analysis; D012129:Respiratory Function Tests; D012307:Risk Factors; D012907:Smoking / Q000378:metabolism; D059289:Vascular Stiffness
chemical_list: D015415:Biomarkers; D001993:Bronchodilator Agents; D003895:Desmosine; D004549:Elastin