There is a need for biomarkers in patients with multiple medical diseases Chronic Acute Complications Morbidity and Mortality
supar = soluble form of upar D1 D1 upar D1 D2 D3 D3 D2 D3 D2 Immune cells Endothelial cells Siemens BEP 2000 suparnostic ELISA (CE/IVD)
Diagnosis Treatment supar HOSPITAL Pre-Diagnosis How sick is the patient? Monitor Is treatment working? Post-Treatment Home free?
15+ supar and Risk Sepsis, TB, HIV, Other acute Infections High risk of mortality 10.0 Critical Illness 5.5 Low Grade Inflammation? Increased 10 year risk of developing CVD, Type II Diabetes and Mortality 3.0 Low inflammatory state Healthy 0.1
Positive predictive value and Negative predictive value
Severety of various diseases What elevates supar Organ failure Cancer Infectious diseases Inflammatory diseases Life style diseases Unhealthy living (smoking etc)
Fase 1: supar analysen etableres på analyserobot (BEP2000) som en ELISA metode. Batch-analyse Fase 2: supar udvikles til KBAs analyseplatform (Cobas 6000) som en particle-enhanced immunoturbidimetrisk metode. Løbende analyse døgnet rundt med svar indenfor 3 timer efter prøvetagning.
Praksis fra 18. november Separat 4 ml EDTA til supar foruden glas til AMA -pakke supar prøven centrifugeres ved ankomst til KBA plasma afpipetteres og stilles i køleskab indtil batch analyse: Mandag, onsdag, fredag: kl. 10 Tirsdag og torsdag: kl. 8 Svar kl. 13:30 over LABKA Kan bestilles som rutine ikke som fremskyndet eller haste supar vil indgå i AMA pakken
supar levels in healthy Danish blood donors Age categories Women Median (q1-q3) N Men Median (q1-q3) N < 30 2.43 (2.05 2.79) 1672 31-40 2.59 (2.16 2.04) 1028 41-50 2.62 (2.18 3.12) 978 >50 2.71 (2.25 3.23) 786 2.08 (1.76-2.44) 1257 2,17 (1.85 2.57) 1416 2.25 (1.90 2.69) 1112 2.40 (2.02 2.90) 1056 supar (ng/ml)measured in 9305 participants (4464 women and 4841 men) Haastrup E. et al, under revision
N=2602 1984 1994 2005 Start of Population Survey Single Blood Measurement Follow-up
supar (ng/ml) supar (ng/ml) Lifestyle influence biomarker levels supar levels of Non-Smokers vs. smokers 9 Men Women 9 8 8 7 7 6 6 5 5 4 4 3 3 2 2 1 1 41 51 Age 61 71 41 51 Age 61 71 41 51 Age 61 71 Eugen-Olsen, Andersen et al, JIM 2010
Cancer CVD T2D Mortality
Patients admitted during daytime to Acute Care Medical Unit, Copenhagen University Hospital at Hvidovre from 4 th august till 4 th October 2010.
SuPAR i Charlson-grupperne Charlson Score 0 Cardiovascular disease Dementia Chronic pulmonary disease Rheumatic disease Diabetes Liver disease Cancer n 342 50 10 81 6 54 8 17 SuPAR (s.d.) 4.70 (2.84) 5.88 (3.39) 4.53 (2.38) 4.96 (2.77) 5.98 (1.16) 6.06 (2.91) 11.8 (8.31) 8.12 (2.79) P-value 0.0081 0.85 0.47 0.28 0.0013 0.046 <0.0001 -Tendens til at supar er høj ved inflammatoriske sygdomme lav ved degenerative sygdomme
What does supar levels reflect? < 3 ng/ml Normal 3 5.5 ng/ml Slightly elevated, expected? 5.5 10 ng/ml Somethings going on. > 10 ng/ml Critical, organ failure
supar-data fra AMA-studiet i 2010 sorteret efter referenceintervaller supar (ng/ml) n (%) 90 days mortality cases (%) 0 3 120 (22.1) 2 (1.7) 1.8 days 3 5.5 255 (47.0) 17 (6.7) 3.3 days 5.5 10 133 (24.5) 18 (13.5) 7.4 days 10 35 (6.5) 11 (31.4) 8.9 days Mean admission time Haupt et al. Critical Care 2012
Cardiovascular risk prediction in the general population with use of supar, CRP and Framingham Risk Score S Lyngbæk, J Marott, T Sehestedt,T Hansen, MH. Olsen, O Andersen, A Linneberg, SB. Haugaard J Eugen-Olsen, P Hansen, J Jeppesen The inflammatory biomarkers soluble urokinase plasminogen activator receptor (supar) and C-reactive protein (CRP) independently predict cardiovascular disease (CVD). The prognostic implications of supar and CRP combined with Framingham Risk Score (FRS) have not been determined. From 1993 to 1994, baseline levels of supar and CRP were obtained from 2315 generally healthy Danish individuals (mean age: 53.9 years) who were followed for the composite outcome of ischemic heart disease, stroke and CVD mortality. Results During a median follow-up of 12.7 years, 302 events were recorded. After adjusting for FRS, women with supar levels in the highest tertile had a 1.74-fold and men a 2.09-fold increase in risk compared to the lowest tertile. Including supar and CRP together resulted in stronger risk prediction with a 3.30-fold increase for women and a 3.53-fold increase for men when both biomarkers were in the highest compared to the lowest tertile. The combined extreme tertiles of supar and CRP reallocated individuals predicted to an intermediate 10-year risk of CVD of 10 20% based on FRS, to low (< 10%) or high (> 20%) risk categories, respectively. Conclusions supar provides prognostic information of CVD risk beyond FRS and improves risk prediction substantially when combined with CRP. Journal of Cardiology 2013
Low supar
High supar
Is triaging now supar easy? supar is not a miracle. Clinical assessment is Number 1. In most cases, supar will add no further value. In some cases, a high or low supar value may aid in deciding -whether to examine the patient further -whether to hospitalize a patient or not.