| 1. |
- Hodges, Gethin W., et al.
(author)
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Effect of simvastatin and ezetimibe on suPAR levels and outcomes
- 2018
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In: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 272, s. 129-136
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Journal article (peer-reviewed)abstract
- Background and aims: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown.& para;& para;Methods: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE).& para;& para;Results: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (p<0.001). In a multivariate 1-year analysis, 1-year suPAR was strongly associated with all-cause mortality, hazard ratio (HR) = 2.05 (1.17-3.61); MCE 1.40 (1.01-1.92); and AVE 1.42 (1.02-1.99) (all p<0.042) for each doubling of suPAR; but was not associated with ICE.& para;& para;Conclusions: Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677). (C) 2018 Elsevier B.V. All rights reserved.
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| 2. |
- Hodges, Gethin W., et al.
(author)
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SuPAR Predicts Cardiovascular Events and Mortality in Patients With Asymptomatic Aortic Stenosis
- 2016
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In: Canadian Journal of Cardiology. - : Elsevier. - 0828-282X .- 1916-7075. ; 32:12, s. 1462-1469
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Journal article (peer-reviewed)abstract
- Background: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with subclinical cardiovascular damage and cardiovascular events. Whether suPAR is of prognostic value in asymptomatic patients with aortic stenosis (AS) remains unknown. Methods: Plasma suPAR levels were measured in 1503 patients with a mean age of 68 years who were recruited in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox regression analysis was performed to evaluate associations between suPAR and the composite end points of ischemic cardiovascular events (ICEs), aortic valve events (AVEs), cardiovascular and all-cause mortality after adjusting for traditional cardiovascular risk factors, and allocation to treatment. Results: The multivariate adjusted hazard ratio (HR) (95% confidence interval [CI]) per unit log2 ng/mL increase in suPAR was HR, 1.5; 95% CI, 1.2-1.9; P = 0.002 for ICEs; HR, 1.2; 95% CI, 0.9-1.5; P = 0.071) for AVEs; HR, 2.0; 95% CI, 1.2-3.3; P = 0.007) for cardiovascular mortality, and HR, 2.0; 95% CI, 1.4-2.9; P < 0.001 for all-cause mortality. Conclusions: In patients with mild-moderate AS, suPAR is independently associated with the incidence of ICEs, cardiovascular mortality, and all-cause mortality.
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| 3. |
- Hodges, Gethin W., et al.
(author)
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SuPAR predicts postoperative complications and mortality in patients with asymptomatic aortic stenosis
- 2018
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In: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 5:1
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Journal article (peer-reviewed)abstract
- Background We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery.Methods Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period.Results Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively.Conclusion Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted.
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| 4. |
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| 5. |
- Hindy, George, et al.
(author)
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Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis
- 2022
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In: Journal of Clinical Investigation. - 0021-9738. ; 132:24, s. 1-14
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Journal article (peer-reviewed)abstract
- People with kidney disease are disproportionately affected by atherosclerosis for unclear reasons. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived mediator of kidney disease, levels of which are strongly associated with cardiovascular outcomes. We assessed suPAR’s pathogenic involvement in atherosclerosis using epidemiologic, genetic, and experimental approaches. We found serum suPAR levels to be predictive of coronary artery calcification and cardiovascular events in 5,406 participants without known coronary disease. In a genome-wide association meta-analysis including over 25,000 individuals, we identified a missense variant in the plasminogen activator, urokinase receptor (PLAUR) gene (rs4760), confirmed experimentally to lead to higher suPAR levels. Mendelian randomization analysis in the UK Biobank using rs4760 indicated a causal association between genetically predicted suPAR levels and atherosclerotic phenotypes. In an experimental model of atherosclerosis, proprotein convertase subtilisin/kexin–9 (Pcsk9) transfection in mice overexpressing suPAR (suPARTg) led to substantially increased atherosclerotic plaques with necrotic cores and macrophage infiltration compared with those in WT mice, despite similar cholesterol levels. Prior to induction of atherosclerosis, aortas of suPARTg mice excreted higher levels of CCL2 and had higher monocyte counts compared with WT aortas. Aortic and circulating suPARTg monocytes exhibited a proinflammatory profile and enhanced chemotaxis. These findings characterize suPAR as a pathogenic factor for atherosclerosis acting at least partially through modulation of monocyte function.
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| 6. |
- Iversen, Anne Kristine Servais, et al.
(author)
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A simple clinical assessment is superior to systematic triage in prediction of mortality in the emergency department
- 2019
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In: Emergency Medicine Journal. - : BMJ. - 1472-0213 .- 1472-0205. ; 36:2, s. 66-71
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Journal article (peer-reviewed)abstract
- Objective To compare the Danish Emergency Process Triage (DEPT) with a quick clinical assessment (Eyeball triage) as predictors of short-term mortality in patients in the emergency department (ED).Methods The investigation was designed as a prospective cohort study conducted at North Zealand University Hospital. All patient visits to the ED from September 2013 to December 2013 except minor injuries were included. DEPT was performed by nurses. Eyeball triage was a quick non-systematic clinical assessment based on patient appearance performed by phlebotomists. Both triage methods categorised patients as green (not urgent), yellow, orange or red (most urgent). Primary analysis assessed the association between triage level and 30-day mortality for each triage method. Secondary analyses investigated the relation between triage level and 48-hour mortality as well as the agreement between DEPT and Eyeball triage.Results A total of 6383 patient visits were included. DEPT was performed for 6290 (98.5%) and Eyeball triage for 6382 (~100%) of the patient visits. Only patients with both triage assessments were included. The hazard ratio (HR) for 48-hour mortality for patients categorised as yellow was 0.9 (95% CI 0.4 to 1.9) for DEPT compared with 4.2 (95% CI 1.2 to 14.6) for Eyeball triage (green is reference). For orange the HR for DEPT was 2.2 (95% CI 1.1 to 4.4) and 17.1 (95% CI 5.1 to 57.1) for Eyeball triage. For red the HR was 30.9 (95% CI 12.3 to 77.4) for DEPT and 128.7 (95% CI 37.9 to 436.8) for Eyeball triage. For 30-day mortality the HR for patients categorised as yellow was 1.7 (95% CI 1.2 to 2.4) for DEPT and 2.4 (95% CI 1.6 to 3.5) for Eyeball triage. For orange the HR was 2.6 (95% CI 1.8 to 3.6) for DEPT and 7.6 (95% CI 5.1 to 11.2) for Eyeball triage, and for red the HR was 19.1 (95% CI 10.4 to 35.2) for DEPT and 27.1 (95% CI 16.9 to 43.5) for Eyeball triage. Agreement between the two systems was poor (kappa 0.05).Conclusion Agreement between formalised triage and clinical assessment is poor. A simple clinical assessment by phlebotomists is superior to a formalised triage system to predict short-term mortality in ED patients.
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| 7. |
- Rudolf, Frauke, et al.
(author)
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TBscore II: Refining and validating a simple clinical score for treatment monitoring of patients with pulmonary tuberculosis
- 2013
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In: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 45:11, s. 825-836
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Journal article (peer-reviewed)abstract
- Background: The TBscore, based on simple signs and symptoms, was introduced to predict unsuccessful outcome in tuberculosis patients on treatment. A recent inter-observer variation study showed profound variation in some variables. Further, some variables depend on a physician assessing them, making the score less applicable. The aim of the present study was to simplify the TBscore. Methods: Inter-observer variation assessment and exploratory factor analysis were combined to develop a simplified score, the TBscore II. To validate TBscore II we assessed the association between start score and failure (i.e. death or treatment failure), responsiveness using Cohens effect size, and the relationship between severity class at treatment start and a decrease andlt; 25% in score from the start until the end of the second treatment month and subsequent mortality. Results: We analyzed data from 1070 Guinean (2003-2012) and 432 Ethiopian (2007-2012) pulmonary tuberculosis patients. For the refined score, items with less than substantial agreement (kappa andlt;= 0.6) and/or not associated with the underlying constructs were excluded. Items kept were: cough, dyspnea, chest pain, anemia, body mass index (BMI) andlt; 18 kg/m(2), BMI andlt; 16 kg/m(2), mid upper arm circumference (MUAC) andlt; 220 mm, and MUAC andlt; 200 mm. The effect sizes for the change between the start of treatment and the 2-month follow-up were 0.51 in Guinea-Bissau and 0.68 in Ethiopia, and for the change between the start of treatment and the end of treatment were 0.68 in Guinea-Bissau and 0.74 in Ethiopia. Severity class placement at treatment start predicted failure (p andlt; 0.001 Guinea-Bissau, p = 0.208 Ethiopia). Inability to decrease at least 25% in score was associated with a higher failure rate during the remaining 4 months of treatment (p = 0.063 Guinea-Bissau, p = 0.008 Ethiopia). Conclusion: The TBscore II could be a useful monitoring tool, aiding triage at the beginning of treatment and during treatment.
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