Fibrin degradation products and survival in patients with chronic obstructive pulmonary disease: a protocolized prospective observational study

Abstract

Background: Patients with chronic obstructive pulmonary disease (COPD) have a high incidence of cardiovascular disease including thromboembolisms. Fibrin degradation products, like D-dimer, have been associated with death from all causes in healthy individuals and COPD patients. We aimed to determine the (i) association between D-dimer levels and all-cause mortality and time being alive and out of a hospital, (ii) possible modifying effect of anticoagulant treatment,, and (iii) distribution of D-dimer in patients with moderate to severe COPD.

Methods: Results of routinely measured stable phase D-dimer samples from COPD-outpatients at Copenhagen University Hospital - Herlev and Gentofte, COPD-outpatient clinic were collected using the Danish registries. These were used to examine whether COPD-patients with a D-dimer level in the upper quartile, had a higher risk of death from all causes within 365 days.

Results: In the unadjusted Cox proportional hazards regression we found an association between high D-dimer and all-cause mortality: Hazard ratio (HR): 2.3 (95% Confidence Interval (CI) 1.1-4.7). In the fully adjusted regression, the HR was 1.8 (CI 0.8-3.9). We did not find any interaction between D-dimer and anticoagulant or antiplatelet therapy. For the secondary outcome, proportion of days alive and out of hospital in 365 days (pDAOH), the unadjusted multiple linear regression had an association between high D-dimer level and pDAOH: -2.7% points (pp) (CI -3.9 pp - -1.5 pp), which was attenuated to -1,7pp (-2.9pp - -0.4pp) in the fully adjusted regression.

Conclusions: In patients with moderate to severe COPD, patients with a high level of D-dimer were more likely to die; however, the signal was not strong in the adjusted analyses and our results do not support unselected risk stratification with D-dimer in COPD-outpatients.

Keywords: All-cause mortality; Biomarker; COPD; Cohort; D-dimer.

Fig. 1

Study flowchart. (Study flowchart. VTE: Venous thromboembolism, FEU: Fibrin equivalent units, n: Number)

Fig. 2

Cumulated incidence for all-cause mortality in high and low levels of D-dimer. (Aalen-Johansen estimator for 365-day cumulated incidence in high (upper quartile) and low (lower three quartiles) D-dimer levels. P-value from log-rank test. FEU: Fibrin equivalent units)

Fig. 3

D-dimer levels compared to smoking status. (Box and whiskers plot showing D-dimer levels across smoking status. IQR: Interquartile range. FEU: Fibrin equivalent units. *Kruskal-Wallis test)

Fig. 4

D-dimer levels in users of antiplatelet and anticoagulant treatment. (Box and whiskers plots showing D-dimer levels between users of antiplatelet (A-P) and anticoagulant (A-C) treatment. IQR: Interquartile range, FEU: Fibrin equivalent units. *Wilcoxon Rank-Sum test)