Soluble Urokinase-Type Plasminogen Activator Receptor and Arterial Stiffness in Patients with COPD

Bocskei, R.; Benczúr, Béla; Losonczy, György; Illyés, Miklós; Cziráki, Attila; Müller, Veronika; Bohács, Anikó; Bikov, András

doi:10.1007/s00408-019-00211-w

Cited by 14 publications

(20 citation statements)

References 44 publications

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“…Still, our results should be interpreted carefully, especially considering the exclusion of the two outliers which resulted in differences between the two groups. The sample size calculations were based on our previous study [25], showing higher suPAR levels in COPD. Although the number of participants may seem low, it may not be the likely reason for the lack of differences between OSA and controls considering the wide overlap of suPAR values between the two groups and the lack of significant relationship between markers of OSA severity and suPAR levels.…”

Section: Discussionmentioning

confidence: 99%

“…Within 30 minutes, blood samples were centrifuged at 4 • C for 10 min at 1500 rpm, and the plasma was stored at −80 • C until further analysis. Plasma suPAR levels were measured using a commercially available ELISA kit (ViroGates A/S, Birkerød, Denmark) as described previously [25]. The samples were measured in duplicates, and the mean concentration was used.…”

Section: Supar Measurementsmentioning

confidence: 99%

“…The minimal sample size was estimated to detect differences in plasma suPAR levels between the OSA and control groups with an effect size of 0.80, power of 0.80 and alpha of 0.05 [26]. These numbers were based on a distribution of plasma suPAR values in control subjects [25]. Post-hoc sensitivity analyses ensured it was possible to detect correlations between suPAR and clinical variables within −0.23 and 0.23, minimal and maximal critical r values, statistical power of 0.80 and alpha of 0.05 [26].…”

Section: Statistical Analysesmentioning

confidence: 99%

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Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea

et al. 2020

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Background and Objectives: Obstructive sleep apnoea (OSA) is associated with heightened systemic inflammation and a hypercoagulation state. Soluble urokinase-type plasminogen activator receptor (suPAR) plays a role in fibrinolysis and systemic inflammation. However, suPAR has not been investigated in OSA. Materials and Methods: A total of 53 patients with OSA and 15 control volunteers participated in the study. Medical history was taken and in-hospital sleep studies were performed. Plasma suPAR levels were determined by ELISA. Results: There was no difference in plasma suPAR values between patients with OSA (2.198 ± 0.675 ng/mL) and control subjects (2.088 ± 0.976 ng/mL, p = 0.62). Neither was there any difference when patients with OSA were divided into mild (2.134 ± 0.799 ng/mL), moderate (2.274 ± 0.597 ng/mL) and severe groups (2.128 ± 0.744 ng/mL, p = 0.84). There was no significant correlation between plasma suPAR and indices of OSA severity, blood results or comorbidities, such as hypertension, diabetes, dyslipidaemia or cardiovascular disease. Plasma suPAR levels were higher in women when all subjects were analysed together (2.487 ± 0.683 vs. 1.895 ± 0.692 ng/mL, p < 0.01), and also separately in controls (2.539 ± 0.956 vs. 1.411 ± 0.534 ng/mL, p = 0.02) and patients (2.467 ± 0.568 vs. 1.991 ± 0.686 ng/mL, p < 0.01). Conclusions: Our results suggest that suPAR does not play a significant role in the pathophysiology of OSA. The significant gender difference needs to be considered when conducting studies on circulating suPAR.Medicina 2020, 56, 77 2 of 10 Soluble urokinase-type plasminogen activator receptor (suPAR) is a molecule which plays a role in both inflammation and coagulation. It is produced upon cleavage of the membrane-bound urokinase-type plasminogen activator receptor (uPAR). The cleavage is facilitated by urokinase-type plasminogen activator (uPA), plasmin, matrix metalloproteases, neutrophil elastase and cathepsin G [11]. The urokinase receptor (also known as uPAR) is expressed by endothelial cells, macrophages, monocytes, neutrophils, lymphocytes, smooth muscle cells and fibroblasts [12,13]. It is upregulated under infections and as an effect of pro-inflammatory cytokines [11,[13][14][15], while suPAR contributes to plasminogen activation, cell adhesion, chemotaxis and immune cell activation [16]. However, uPAR also acts as a scavenger receptor for uPA, inhibiting its actions [17]. In large studies, plasma suPAR was elevated in coronary artery disease and cerebrovascular disease and correlated with their severity and cardiovascular mortality [18][19][20]. Higher suPAR levels were also observed in obesity [21], which is the main etiological factor for OSA in the Western population [22].Only one study has investigated suPAR in probable OSA so far [23]. Patients were categorised to high and low-risk OSA based on the Berlin questionnaire and neck circumferences; however, no objective sleep tests were performed. In this study, there was a tendency for higher suPAR levels in the high-risk group, but...

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Section: Discussionmentioning

confidence: 99%

Section: Supar Measurementsmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

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Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea

et al. 2020

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“…Five studies included participants from the outpatient department, 12 , 22 , 25 , 27 , 28 and four included participants from the respiratory medicine. 23 , 26 , 29 , 31 In terms of pulmonary function, six studies included patients with predicted FEV1% ⩾80%, 12 , 22 , 23 , 26 – 28 and another five studies reported patients with the predicted FEV1% < 80%. 12 , 25 , 29 – 31 The studies reported that the smoking status of patients ranged from 28 to 53 packs per year.…”

Section: Resultsmentioning

confidence: 99%

The clinical value of suPAR in diagnosis and prediction for patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

Huang

Xiong

Shuai

et al. 2020

Ther Adv Respir Dis

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Background: Soluble urokinase-type plasminogen activator receptor (suPAR) is positively correlated with immune system activity. Inflammation can promote the development of chronic obstructive pulmonary disease (COPD). Therefore, this study conducted a systematic review and meta-analysis to assess the association between suPAR levels and the pathogenesis of COPD, and further assess the exact clinical value of suPAR in COPD. Methods: PubMed, Excerpt Medica Database (Embase), Web of Science (WOS), and Cochrane Library databases were searched for studies that reported the value of suPAR diagnosis for adult COPD patients. Results: A total of 11 studies were included, involving 4520 participants. Both COPD patients with predicted forced expiratory volume in 1 s (FEV1)⩾80% [weighted mean difference (WMD) = 320.25; 95% confidence interval (CI): 99.79–540.71] and FEV1 < 80% (WMD = 2950.74; 95% CI: 2647.06–3254.43) showed higher suPAR level. The sensitivity and specificity of suPAR for diagnosis of COPD were 87% and 79%, respectively, and AUC was 84%. This can not only effectively identify acute exacerbation of COPD (AECOPD) in a healthy population (WMD = 3114.77; 95% CI: 2814.66–3414.88), but also has the potential to distinguish AECOPD from stable COPD (WMD = 351.40; 95% CI: 215.88–486.93). There was a significant decrease of suPAR level after treatment [WMD = –1226.97; 95% CI: –1380.91– (–1073.03)]. Conclusion: suPAR as a novel biomarker has potential for early diagnosis of COPD and prediction of AECOPD. There is a potential correlation between the level of suPAR and the state of COPD, which may also indicate the early state and severity of COPD. When the suPAR level of COPD patients is further increased, the risk of acute exacerbation increases and should be highly valued. This also shows potential as a measure of treatment response, and as a guide to the clinical management in COPD. The reviews of this paper are available via the supplemental material section.

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“…27 A recent study has shown that suPAR concentrations in COPD patients correlate with forced expiratory volume in 1 second (FEV 1 ), Tiffeneau Index as well as Medical Research Council Dyspnea Score. 28 Of note, suPAR was further elevated in patients with more than two exacerbations per year. 28 Several intrinsic risk factors for COPD readmission are known, including low FEV 1 , hypoxia and comorbidities.…”

Section: Discussionmentioning

confidence: 98%

<p>High suPAR and Low Blood Eosinophil Count are Risk Factors for Hospital Readmission and Mortality in Patients with COPD</p>

Håkansson

Ulrik

Godtfredsen

et al. 2020

COPD

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Introduction:The biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with increased mortality in chronic obstructive pulmonary disease (COPD), while elevated blood eosinophils have been associated with better survival. We hypothesized that suPAR and blood eosinophil count are independent risk factors for readmission and mortality after an acute admission in patients with COPD. Methods: This retrospective cohort study comprised 4022 patients with prevalent COPD acutely admitted to Hvidovre Hospital, Denmark. Irrespective of cause of admission, suPAR and blood eosinophils were measured, and patients were followed up to 365 days. Associations with 365-day respiratory readmission, all-cause readmission and all-cause mortality were investigated by Cox regression analyses adjusted for age, sex, Charlson score and C-reactive protein.Results: suPAR was significantly elevated in patients who later experienced readmission or died. At 365 days, hazard ratios (HRs) for all-cause readmission and mortality reached 1.61 (95% CI 1.40-1.85; p<0.0001) and 3.40 (95% CI 2.64-4.39; p<0.0001), respectively, for COPD patients in the fourth suPAR quartile compared to patients in the first suPAR quartile. High blood eosinophils (>300 cells/μL) were associated with lower risk of mortality (HR 0.49, 95% CI 0.39-0.62; p<0.0001) compared with patients with <150 cells/μL. When stratifying patients by suPAR quartiles and blood eosinophil counts, the highest relative mortality rate was found in patients belonging to both the fourth suPAR quartile and the low blood eosinophil (<150 cells/μL) group. Conclusion:In this cohort of COPD patients acutely admitted to a hospital, elevated suPAR concentrations were associated with both higher risk of all-cause readmission and mortality, whereas higher blood eosinophil count was associated with lower risk of mortality.

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Soluble Urokinase-Type Plasminogen Activator Receptor and Arterial Stiffness in Patients with COPD

Cited by 14 publications

References 44 publications

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea

The clinical value of suPAR in diagnosis and prediction for patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

<p>High suPAR and Low Blood Eosinophil Count are Risk Factors for Hospital Readmission and Mortality in Patients with COPD</p>

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