International Journal of COPD (Mar 2017)
Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function
Abstract
Benjamin Waschki,1–3 Henrik Watz,2,3 Olaf Holz,4,5 Helgo Magnussen,2,3 Beata Olejnicka,6 Tobias Welte,5,7 Klaus F Rabe,1,3 Sabina Janciauskiene5,7 1Pneumology, LungenClinic Grosshansdorf, Grosshansdorf, Germany; 2Pulmonary Research Institute at LungenClinic Grosshansdorf, Grosshansdorf, Germany; 3Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany; 4Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany; 5Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany; 6Department of Medicine, Trelleborg Hospital, Trelleborg, Sweden; 7Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany Introduction: Plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD). The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear. Methods: In this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV) and 18 controls without lung disease. In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP), adiponectin, ankle–brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined. Results: The serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction. A multivariate regression analysis revealed triglyceride and hs-CRP levels to be the best predictors of PAI-1 within COPD. GOLD Stages II and III remained independently associated with higher PAI-1 levels in a final regression analysis. Conclusion: The data from the present study showed that the serum levels of PAI-1 are higher in patients with COPD and that moderate-to-severe airflow limitation, hypertriglyceridemia, and systemic inflammation are independent predictors of an elevated PAI-1 level. PAI-1 may be a potential biomarker candidate for COPD-specific and extra-pulmonary manifestations. Keywords: plasminogen activator inhibitor-1, chronic obstructive pulmonary disease, cardiovascular disease, inflammation, hypertriglyceridemia, ankle-brachial index, N-terminal pro-B-type natriuretic peptide