Prognostic value of suPAR and hs-CRP on cardiovascular disease

Diederichsen, Marie Zöga; Diederichsen, Søren Zöga; Mickley, Hans; Steffensen, Flemming Hald; Lambrechtsen, Jess; Sand, Niels Peter Rønnow; Christensen, Kent Lodberg; Olsen, Michael Hecht; Diederichsen, Axel Cosmus Pyndt; Grønhøj, Mette Hjortdal

doi:10.1016/j.atherosclerosis.2018.01.029

Cited by 33 publications

(34 citation statements)

References 28 publications

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“…It has been shown that plasma suPAR levels are higher in women [20] and related to BMI and waist circumference only in females [20]. In addition, plasma suPAR levels were prognostic for cardiovascular events only in women [19] and more strongly related to coronary artery calcification in women than in men [31]. Our results are in line with the previous findings [20], namely that suPAR was higher in women in both OSA and controls.…”

Section: Discussionsupporting

confidence: 91%

“…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].…”

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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: Discussionsupporting

confidence: 91%

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confidence: 99%

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

et al. 2020

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“…4,5 These biomarkers include high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR). 6–11 Accordingly, the aim of this study was to examine whether these three circulating biomarkers carried incremental prognostic value in predicting cardiovascular events beyond traditional cardiovascular risk factors in apparently healthy individuals.…”

Section: Introductionmentioning

confidence: 99%

Circulating biomarkers for long-term cardiovascular risk stratification in apparently healthy individuals from the MONICA 10 cohort

Frary

Blicher

Olesen

et al. 2019

Eur J Prev Cardiolog

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Aims The aim of this study was to examine whether high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR) carried incremental prognostic value in predicting cardiovascular morbidity and mortality beyond traditional risk factors in apparently healthy individuals. Methods and results This was a prospective population-based cohort study comprising 1951 subjects included in the 10-year follow-up of the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, between 1993 and 1994. The principal endpoint was death from cardiovascular causes. Secondary endpoints were death from any cause, coronary artery disease, heart failure, and cerebrovascular disease. Predictive capabilities of each of the three biomarkers were tested using Cox proportional-hazards regression, Harrell’s concordance index (C-index), and net reclassification improvement (NRI). Study participants were aged 41, 51, 61, or 71 years, and equally distributed between the two sexes. During a median follow-up of 18.5 years (interquartile range: 18.1–19.0), 177 (9.1%) subjects died from a cardiovascular cause. Hs-CRP (adjusted standardized hazard ratio (HR): 1.37, 95% confidence interval (CI): 1.17–1.60), NT-proBNP (HR: 1.90, 95% CI: 1.58–2.29), and suPAR (HR: 1.35, 95% CI: 1.17–1.57) were all significantly associated with cardiovascular deaths after adjustment for age, sex, smoking status, systolic blood pressure, and total cholesterol ( p < 0.001 for all). Furthermore, all three biomarkers were significantly associated with significant NRI. However, only NT-proBNP significantly raised the C-index in predicting death from cardiovascular causes when added to the risk factors (C-index 0.860 versus 0.847; p = 0.02). Conclusions Hs-CRP, suPAR, and particularly NT-proBNP predicted cardiovascular death and may enhance prognostication beyond traditional risk factors in apparently healthy individuals.

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“…They studied a large cohort of 1179 participants older than 50 years of age (49% of the study cohort, males and females (52,4%) at moderate to high CV risk or with a history of previous CV event (61,9%) of the study cohort reported MACE at enrollment. [49]. At unadjusted analysis suPAR as well as hsCRP was significantly associated with MACE.…”

Section: Suparmentioning

confidence: 91%

“…Recently, Diedrichsen and coworkers examined the association and prognostic role of a systemic marker named soluble urokinase Plasminogen Activator Receptor (suPAR) in major cardiovascular event (MACE)- [49,50]. They studied a large cohort of 1179 participants older than 50 years of age (49% of the study cohort, males and females (52,4%) at moderate to high CV risk or with a history of previous CV event (61,9%) of the study cohort reported MACE at enrollment.…”

Section: Suparmentioning

confidence: 99%

New Insights into Inflammation in Atherosclerosis

Naafs¹

2018

GJEM

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In this mini-review recent developments in the pathogenesis, pathophysiology, biomarkers and therapeutics in residual inflammation of atherosclerosis are discussed. New cellular pathways are discovered raise new interest in old therapeutics as colchicine and niacin. Biomarker studies call for more specific and sensitive markers. The recent CANTOS trial provided clinicians evidence that directly targeting inflammation by canakinumab is beneficial for the secondary prevention of cardiovascular disease. Whole genome and exome studies will lead to the discovery of new cellular pathways and treatments of residual atherosclerotic inflammation.

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Prognostic value of suPAR and hs-CRP on cardiovascular disease

Cited by 33 publications

References 28 publications

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

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

Circulating biomarkers for long-term cardiovascular risk stratification in apparently healthy individuals from the MONICA 10 cohort

New Insights into Inflammation in Atherosclerosis

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