Patient characteristics
In this study, we extracted 160 patients with COPD as their primary diagnosis from September 2019 to May 2022. A total of 57 patients with COPD who met the inclusion criteria were further screened, and 34 age- and sex-matched healthy physical examiners with no history of COPD or other diseases during the same period were selected as the control group. Clinical data for the control group and COPD patients are shown in Table 1, where there were no statistically significant between-group differences in general information, except for the number of non-smokers (P < 0.001) and BMI (P = 0.005), which differed between the two groups. For general coagulation function, platelet count (PLT) and activated partial thromboplastin time (APTT) were not statistically different between the control and COPD groups. Prothrombin time (PT) and fibrinogen concentration (FIB) were elevated in the COPD group, while prothrombin time (TT) was lower in the COPD group than in the control group.
Table 1
Baseline characteristics of the study population
Parameters | Control (n = 34) | COPD (n = 57) | P-value |
Age (y) | 63.12 ± 6.95 | 65.47 ± 4.90 | 0.089 |
Sex n(%) | | | 0.074 |
Male | 23.00(67.60%) | 48.00(84.20%) | |
Female | 11.00(32.40%) | 9.00(15.80%) | |
Never smokers n(%) | 27.00(79.40%) | 10.00(17.50%) | P < 0.001 |
BMI(kg/m2) | 22.38(20.44–24.17) | 20.76(17.99–22.43) | 0.005 |
Disease history n(%) | | | |
Hypertension | 9.00(26.50%) | 17.00(29.80%) | 0.813 |
Diabetes mellitus | 4.00(11.80%) | 6.00(10.50%) | 1.000 |
Coronary heart disease | 0.00(0.00%) | 1.00(1.80%) | 1.000 |
PLT (×109/l) | 230.00(190.00-282.00) | 225.00(174.00-300.00) | 0.857 |
PT (s) | 11.10(10.60–12.10) | 11.80(11.10–12.60) | 0.036 |
FIB (g/l) | 2.95(2.60–3.60) | 4.10(3.10–5.40) | 0.001 |
APTT (s) | 31.15(28.70–33.90) | 30.90(29.60–34.30) | 0.661 |
TT (s) | 15.35(14.20–16.50) | 14.00(13.40–14.70) | P < 0.001 |
VWF (ng/ml) | 327.62 ± 210.97 | 770.15 ± 325.52 | P < 0.001 |
PAI-1 (ng/ml) | 0.17(0.12–0.19) | 0.47(0.28–1.11) | P < 0.001 |
Note: Continuous variables with a normal distribution are shown as mean ±standard deviation, or expressed as median (25th percentile–75th percentile). Categorical variables are shown as percentages with numbers in brackets.
Abbreviations: COPD, chronic obstructive pulmonary disease; BMI, body mass index; PLT, platelet; PT, prothrombin time; FIB, fibrinogen; APTT, activated partial thromboplastin time; TT, thrombin time, vWF, von Willebrand factor; PAI-1, plasminogen activator inhibitor type-1.
Concentrations and diagnostic values of vWF and PAI-1 in all the participants
Figure 1 gives the comparative results of plasma vWF and PAI-1 concentrations in control and COPD patients and demonstrates the predictive value of vWF and PAI-1 in the risk of COPD development. Compared with the control group, the plasma concentrations of vWF and PAI-1 in COPD patients are higher (Figs. 1A and 1B). ROC curve analysis (Figs. 1C and 1D) shows that both vWF and PAI-1 have a high value in predicting the risk of COPD (vWF: AUC = 0.8741, P < 0.001; PAI-1: AUC = 0.8222, P < 0.001). Moreover, the elevated value of combined vWF and PAI-1 (Fig. 1E) was presented (AUC = 0.9226, P < 0.001).
Multivariate analysis
Table 2 presents a multivariate analysis of vWF and PAI-1 concentrations and COPD development, corrects for smoking history, BMI, PLT, PT, APTT, FIB, and TT. The analysis shows that a higher concentration of vWF is associated with the development of COPD and is an independent risk factor for COPD.
Table 2
Multivariate analysis for the risk factors in COPD patients.
Variables | B | P | OR | 95% CI for OR | |
Min | Max |
vWF (ng/ml) | 0.01 | 0.01 | 1.01 | 1.00 | 1.01 |
PAI-1 (ng/ml) | 5.79 | 0.10 | 326.57 | 0.35 | 307643.19 |
BMI(kg/m2) | 0.16 | 0.30 | 1.18 | 0.87 | 1.60 |
Smoking history | -4.24 | 0.00 | 0.01 | 0.00 | 0.24 |
PLT (×109/l) | 0.00 | 0.96 | 1.00 | 0.98 | 1.02 |
PT (s) | -0.21 | 0.71 | 0.81 | 0.27 | 2.46 |
FIB (g/l) | 0.71 | 0.31 | 2.03 | 0.52 | 7.98 |
APTT (s) | -0.01 | 0.94 | 0.99 | 0.77 | 1.28 |
TT (s) | -0.81 | 0.15 | 0.44 | 0.15 | 1.33 |
Constant | 6.11 | 0.59 | 450.23 | | |
Note: Binary logistic regression was used. OR, odds ratio; CI, confidence interval; Max, maximum; Min, minimum; vWF, von Willebrand factor; PAI-1, plasminogen activator inhibitor type-1; BMI, body mass index; PLT, platelet; PT, prothrombin time; FIB, fibrinogen; APTT, activated partial thromboplastin time; TT, thrombin time. |
Clinical features of COPD patients
We divided COPD patients into "AB" and "E" groups based on their mMRC score, CAT score, and acute exacerbation history and compared the clinical characteristics of the two groups of patients. The results (Table 3) showed that the CAT scores of COPD patients in the "E" group are higher than those in the "AB" group (P = 0.046).
Table 3
Characteristics of the COPD “AB” and “E” groups
Parameters | “AB” group (n = 27) | “E” group `(n = 30) | P-value |
Age (y) | 64.67 ± 4.44 | 66.20 ± 5.25 | 0.242 |
Sex n(%) | | | 0.149 |
Male | 25.00(92.60%) | 2.00(7.40%) | |
Female | 23.00(76.70%) | 7.00(23.30%) | |
Smoking n(%) | | | 0.304 |
Smokers | 24.00(88.90%) | 23.00(76.70%) | |
Nonsmokers | 3.00(11.10%) | 7.00(23.30%) | |
BMI(kg/m2) | 21.04 ± 3.63 | 20.35 ± 3.99 | 0.501 |
CAT score | 19.50 ± 6.77 | 23.40 ± 7.14 | 0.046 |
SGRQ score | 38.84 ± 24.33 | 50.09 ± 21.49 | 0.086 |
mMRC score | 2.00(1.00–3.00) | 2.00(1.00–3.00) | 0.189 |
FEV1(L) | 0.90(0.62–1.42) | 1.04(0.75–1.26) | 0.523 |
FEV1/FVC(%) | 48.35(37.90–60.10) | 49.42(40.61–55.52) | 0.936 |
FEV1/Pred(%) | 34.20(21.80–53.30) | 39.80(29.10–46.50) | 0.462 |
Disease history n(%) | | | |
Hypertension | 7.00(25.90%) | 10.00(33.30%) | 0.576 |
Diabetes mellitus | 3.00(11.10%) | 3.00(10.00%) | 1.000 |
Coronary heart disease | 0.00(0.00%) | 1.00(3.30%) | 1.000 |
PLT (×109/l) | 241.30 ± 101.30 | 238.87 ± 86.09 | 0.922 |
PT (s) | 11.30(11.10-12.35) | 12.20(11.15–12.95) | 0.263 |
FIB (g/l) | 3.80(3.00-4.55) | 4.40(3.25–5.50) | 0.263 |
APTT (s) | 31.30(29.95–33.90) | 30.20(29.55–33.75) | 0.507 |
TT (s) | 14.21 ± 1.24 | 14.07 ± 1.11 | 0.635 |
vWF (ng/ml) | 552.21 ± 253.28 | 966.29 ± 251.18 | 0.000 |
PAI-1 (ng/ml) | 0.38(0.18–0.52) | 1.02(0.43–1.29) | 0.003 |
VTE | 2.00(2.00–3.00) | 2.50(2.00–3.00) | 0.245 |
Note: Continuous variables with a normal distribution are shown as mean ±standard deviation, or expressed as median (25th percentile–75th percentile). Categorical variables are shown as percentages with numbers in brackets.
Abbreviations: COPD, chronic obstructive pulmonary disease; E, exacerbation; BMI, body mass index; CAT, COPD Assessment Test; SGRQ, St.George’s Respiratory Questionnaire; mMRC, Modified British Medical Research Council; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; Pred, predicted, PLT, platelet; PT, prothrombin time; FIB, fibrinogen; APTT, activated partial thromboplastin time; TT, thrombin time, vWF, von Willebrand factor, PAI-1, plasminogen activator inhibitor type-1; VTE, venous thromboembolism.
Concentrations of vWF and PAI-1 in different COPD subgroups and predictive value of COPD exacerbation.
For all the parameters relevant to hypercoagulabilities, such as PLT, APTT, PT, TT, fibrinogen, and VTE scores, they had no significance in the two subgroups. As shown in Figs. 2A and 2B, the plasma concentrations of vWF (P < 0.001) and PAI-1 (P = 0.003) were significantly increased in the "E" group. To verify the predictive effect of vWF and PAI-1 on the exacerbation risk of COPD, we plotted ROC curves for vWF and PAI-1, as shown in Fig. 2C. Among them, the area under the curve (AUC) of vWF is 0.8802, P < 0.001; The AUC of PAI-1 is 0.7914, P < 0.001.Then the predictive effect of combined vWF and PAI-1 was demonstrated simultaneously (AUC = 0.8593, P < 0.001).
Correlation analysis of vWF and PAI-1 with clinical data
We analyzed the correlation of vWF and PAI-1 with COPD-related clinical data such as CAT score, SGRQ score, mMRC, and spirometry variables. The results showed that vWF positively correlated with patients' CAT and SGRQ scores, with r of 0.37 and 0.34, respectively, with a P value of 0.01 (Table 4 and Fig. 2D-E). We also evaluated the correlation between vWF and PAI-1. We found that the level of PAI-1 was positively associated with the concentration of vWF(r = 0.518, P < 0.001 in analysis in COPD and controls shown in Fig. 1F; r = 0.374, P = 0.004 in COPD ABE groups presented in Fig. 2F).
Table 4
Correlations of vWF and PAI-1 with symptom and spirometry of COPD patients
Variables | | CAT score | SGRQ score | mMRC score | FEV1 | FEV1 /pred | FEV1 /FVC | |
vWF (ng/ml) | r | 0.37 | 0.34 | 0.24 | -0.05 | 0.02 | -0.04 |
| P | 0.01 | 0.01 | 0.07 | 0.69 | 0.87 | 0.78 |
PAI-1 ng/ml) | r | 0.23 | 0.09 | 0.02 | -0.05 | 0.05 | -0.10 |
| p | 0.11 | 0.53 | 0.90 | 0.71 | 0.74 | 0.44 |
Note: Spearman correlation analysis was used.
Abbreviations: vWF, von Willebrand factor, PAI-1, plasminogen activator inhibitor type-1; COPD, chronic obstructive pulmonary disease; CAT, COPD Assessment Test; SGRQ, St.George’s Respiratory Questionnaire; mMRC, Modified British Medical Research Council; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; Pred, predicted,.
Multivariate analysis of COPD patients
Table 5 presents a multivariate analysis of vWF and PAI-1 concentrations and COPD exacerbation risk, corrects for PLT, PT, FIB, APTT, TT, CAT score, SGRQ score, mMRC score, and VTE scores. The results show that vWF could be an independent risk factor for the exacerbation of COPD.
Table 5
Multivariate analysis for risk of exacerbations in ECOPD patients
Variables | B | P-value | OR | 95% CI for OR |
Min | Max |
vWF (ng/ml) | 0.01 | 0.01 | 1.01 | 1.00 | 1.01 |
PAI-1 (ng/ml) | 1.86 | 0.07 | 6.41 | 0.89 | 46.34 |
PLT (×109/l) | 0.00 | 0.94 | 1.00 | 0.99 | 1.01 |
PT (s) | 0.95 | 0.20 | 2.58 | 0.61 | 10.91 |
FIB (g/l) | -0.18 | 0.74 | 0.84 | 0.29 | 2.41 |
APTT (s) | -0.24 | 0.12 | 0.79 | 0.58 | 1.07 |
TT (s) | -0.26 | 0.65 | 0.77 | 0.26 | 2.33 |
CAT score | 0.25 | 0.15 | 1.29 | 0.91 | 1.82 |
SGRQ score | -0.06 | 0.20 | 0.94 | 0.86 | 1.03 |
mMRC score | -0.05 | 0.94 | 0.95 | 0.22 | 4.07 |
VTE score | -0.11 | 0.88 | 0.90 | 0.23 | 3.50 |
Constant | -6.56 | 0.57 | 0.00 | | |
Note: Binary logistic regression was used. E, exacerbation; OR, odds ratio; CI, confidence interval; Max, maximum; Min, minimum; vWF, von Willebrand factor; PAI-1, plasminogen activator inhibitor type-1; BMI, body mass index; PLT, platelet; PT, prothrombin time; FIB, fibrinogen; APTT, activated partial thromboplastin time; TT, thrombin time; CAT, COPD Assessment Test; SGRQ, St.George’s Respiratory Questionnaire; mMRC, Modified British Medical Research Council; VTE, venous thromboembolism. |