Soluble urokinase plasminogen activator receptor (suPAR) in acute care: a strong marker of disease presence and severity, readmission and mortality. A retrospective cohort study

Abstract

ObjectiveSoluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker associated with presence and progression of disease and with increased risk of mortality. We aimed to evaluate the unspecific biomarker suPAR as a prognostic marker in patients admitted to acute care.MethodsThis registry-based retrospective cohort study included 4343 consecutively admitted patients from the Acute Medical Unit at a large Danish university hospital. Time to readmission and death were analysed by multiple Cox regression. Results were reported as HRs for 30-day and 90-day follow-up.ResultsDuring 30-day follow-up, 782 patients (18.0%) were readmitted and 224 patients (5.2%) died. Comparing 30-day readmission and mortality between patients in the highest and lowest suPAR quartiles yielded HRs of 2.11 (95% CI 1.70 to 2.62) and 4.11 (95% CI 2.46 to 6.85), respectively, when adjusting for age, sex, Charlson score and C reactive protein. Area under the curve for receiver operating characteristics curve analysis of suPAR for 30-day mortality was 0.84 (95% CI 0.81 to 0.86). Furthermore, in the entire cohort, women had slightly higher suPAR compared with men, and suPAR was associated with age, admission time, admission to intensive care unit and Charlson score.ConclusionsIn this large unselected population of acute medical patients, suPAR is strongly associated with disease severity, readmission and mortality after adjusting for all other risk factors, indicating that suPAR adds information to established prognostic indicators. While patients with low suPAR levels have low risk of readmission and mortality, patients with high suPAR levels have a high risk of adverse events.

Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood

“…This applies to acute as well as chronic diseases and infectious as well as noncommunicable diseases, including clinical conditions investigated in children (Schaefer et al, 2017;S ßirino glu et al, 2017;Wittenhagen et al, 2011;Wrotek, Jackowska, & Pawlik, 2015). suPAR appears to reflect the health status or inflammatory burden of an individual, and chronic multimorbid patients have higher suPAR levels than patients with fewer chronic diseases (Rasmussen et al, 2016), while healthy people have low suPAR levels (Haupt et al, 2014). In the general population, suPAR has been found to increase with age and unhealthy lifestyle, with smoking and morbid obesity being major drivers of increased suPAR levels (Haupt et al, 2014).…”

“…The resulting suPAR is a stable circulating molecule with intrinsic chemotactic properties (Resnati et al, 2002), and the level of suPAR is thought to reflect the overall immune activity of an individual (Desmedt et al, 2017). suPAR levels are elevated across a wide range of diseases (Rasmussen et al, 2016), including cardiovascular disease (Persson et al, 2014), type 2 diabetes (Guthoff et al, 2017), cancer (Sorio et al, 2011;Tarpgaard et al, 2015), renal disease (Hayek et al, 2015), and infections (Donadello et al, 2014). In addition, suPAR predicts mortality, both in the general population and in patient populations (Eugen-Olsen et al, 2010;Rasmussen et al, 2016).…”

“…suPAR levels are elevated across a wide range of diseases (Rasmussen et al, 2016), including cardiovascular disease (Persson et al, 2014), type 2 diabetes (Guthoff et al, 2017), cancer (Sorio et al, 2011;Tarpgaard et al, 2015), renal disease (Hayek et al, 2015), and infections (Donadello et al, 2014). In addition, suPAR predicts mortality, both in the general population and in patient populations (Eugen-Olsen et al, 2010;Rasmussen et al, 2016). However, to date, suPAR has not been incorporated into studies of early-life origins of poor latelife health, and it is relatively unknown in pediatric medical practice or research.…”

Plasma levels of intact and cleaved urokinase plasminogen activator receptor (uPAR) in men with clinically localised prostate cancer

“…Rasmussen et al 35 found that the total plasma uPAR level in acutely admitted patients was strongly associated with 30-day mortality after admission. Also, the total plasma uPAR level in the general population may be associated with an increased risk of developing cancer, cardiovascular disease and type 2 diabetes later on in life,36 which links plasma uPAR levels to the Charlson comorbidity scores demonstrated in the present study as well as in previous studies 5.…”

Soluble urokinase plasminogen activator receptor is linearly associated with dietary quality and predicts mortality

“…However, since stroke was included as a composite endpoint in the present study, we were unable to test whether suPAR only explained the difference in the risk of ischaemic and not haemorrhagic stroke or whether suPAR also predicts haemorrhagic stroke independently of blood pressure. Association between suPAR and IHD risk has been shown earlier in a large population cohort (36) , and since suPAR is highly predictive of mortality (3)(4)(5)(6)(7) , we speculate that the association between suPAR and IHD risk may be driven by high case fatality rates in historic cohorts (37)(38)(39) . Missing values regarding survival analyses generally seem to produce a slight underestimation of effect of diet on IHD risk and a slight overestimation of the effect of diet on stroke risk.…”