Biomarkers of Clot Activation and Degradation and Risk of Future Major Cardiovascular Events in Acute Exacerbation of COPD: A Cohort Sub-Study in a Randomized Trial Population
Peter Kamstrup,
Jannie Marie Bülow Sand,
Charlotte Suppli Ulrik,
Julie Janner,
Christian Philip Rønn,
Sarah Rank Rønnow,
Diana Julie Leeming,
Sidse Graff Jensen,
Torgny Wilcke,
Alexander G. Mathioudakis,
Marc Miravitlles,
Therese Lapperre,
Elisabeth Bendstrup,
Ruth Frikke-Schmidt,
Daniel D. Murray,
Theis Itenov,
Apostolos Bossios,
Susanne Dam Nielsen,
Jørgen Vestbo,
Tor Biering-Sørensen,
Morten Karsdal,
Jens-Ulrik Jensen,
Pradeesh Sivapalan
Affiliations
Peter Kamstrup
Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev-Gentofte, 2900 Hellerup, Denmark
Jannie Marie Bülow Sand
Nordic Bioscience A/S, 2730 Herlev, Denmark
Charlotte Suppli Ulrik
Department of Respiratory Medicine, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark
Julie Janner
Department of Respiratory Medicine, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark
Christian Philip Rønn
Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev-Gentofte, 2900 Hellerup, Denmark
Sarah Rank Rønnow
Nordic Bioscience A/S, 2730 Herlev, Denmark
Diana Julie Leeming
Nordic Bioscience A/S, 2730 Herlev, Denmark
Sidse Graff Jensen
Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev-Gentofte, 2900 Hellerup, Denmark
Torgny Wilcke
Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev-Gentofte, 2900 Hellerup, Denmark
Alexander G. Mathioudakis
The North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester M13 9PL, UK
Marc Miravitlles
Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
Therese Lapperre
Department of Respiratory Medicine, Copenhagen University Hospital Bispebjerg, 2400 Copenhagen, Denmark
Elisabeth Bendstrup
Department Respiratory Disease and Allergy, Aarhus University Hospital, 8000 Aarhus, Denmark
Ruth Frikke-Schmidt
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Daniel D. Murray
Centre of Excellence for Health, Immunity and Infections (CHIP), Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark
Theis Itenov
Centre of Excellence for Health, Immunity and Infections (CHIP), Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark
Apostolos Bossios
Department of Respiratory Medicine and Allergy, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden
Susanne Dam Nielsen
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Jørgen Vestbo
The North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester M13 9PL, UK
Tor Biering-Sørensen
Department of Cardiology, Copenhagen University Hospital Herlev-Gentofte, 2900 Hellerup, Denmark
Morten Karsdal
Nordic Bioscience A/S, 2730 Herlev, Denmark
Jens-Ulrik Jensen
Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev-Gentofte, 2900 Hellerup, Denmark
Pradeesh Sivapalan
Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev-Gentofte, 2900 Hellerup, Denmark
Cardiovascular diseases are common in patients with chronic obstructive pulmonary disease (COPD). Clot formation and resolution secondary to systemic inflammation may be a part of the explanation. The aim was to determine whether biomarkers of clot formation (products of von Willebrand Factor formation and activation) and clot resolution (product of fibrin degeneration) during COPD exacerbation predicted major cardiovascular events (MACE). The cohort was based on clinical data and biobank plasma samples from a trial including patients admitted with an acute exacerbation of COPD (CORTICO-COP). Neo-epitope biomarkers of formation and the activation of von Willebrand factor (VWF-N and V-WFA, respectively) and cross-linked fibrin degradation (X-FIB) were assessed using ELISAs in EDTA plasma at the time of acute admission, and analyzed for time-to-first MACE within 36 months, using multivariable Cox proportional hazards models. In total, 299/318 participants had samples available for analysis. The risk of MACE for patients in the upper quartile of each biomarker versus the lower quartile was: X-FIB: HR 0.98 (95% CI 0.65–1.48), VWF-N: HR 1.56 (95% CI 1.07–2.27), and VWF-A: HR 0.78 (95% CI 0.52–1.16). Thus, in COPD patients with an acute exacerbation, VWF-N was associated with future MACE and warrants further studies in a larger population.