Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population.
BACKGROUND
Low-grade inflammation is thought to contribute to the development of cardiovascular disease (CVD), type-2 diabetes mellitus (T2D), cancer and mortality. Biomarkers of inflammation may aid in risk prediction and enable early intervention and prevention of disease.


OBJECTIVE
The aim of this study was to investigate whether plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) are predictive of disease and mortality in the general population.


METHODS
This was an observational prospective cohort study. Cohort participants were included from June 1993 to December 1994 and followed until the end of 2006.


METHODS
General adult Caucasian population.


METHODS
The MONICA10 study, a population-based cohort recruited from Copenhagen, Denmark, included 2602 individuals aged 41, 51, 61 or 71 years.


METHODS
Blood samples were analysed for suPAR levels using a commercially available enzyme-linked immunosorbent assay. Risk of cancer (n = 308), CVD (n = 301), T2D (n = 59) and mortality (n = 411) was assessed with a multivariate proportional hazards model using Cox regression.


RESULTS
Elevated baseline suPAR level was associated with an increased risk of cancer, CVD, T2D and mortality during follow-up. suPAR was more strongly associated with cancer, CVD and mortality in men than in women, and in younger compared with older individuals. suPAR remained significantly associated with the risk of negative outcome after adjustment for a number of relevant risk factors including C-reactive protein levels.


CONCLUSIONS
Further validation in ethnic populations other than Caucasians is needed.


CONCLUSIONS
The stable plasma protein suPAR may be a promising biomarker because of its independent association with incident cancer, CVD, T2D and mortality in the general population.
Eugen-Olsen
J
J
Clinical Research Centre, Copenhagen University, Hvidovre Hospital, Hvidovre, Denmark. jeo@biobase.dk
Andersen
O
O
Linneberg
A
A
Ladelund
S
S
Hansen
T W
TW
Langkilde
A
A
Petersen
J
J
Pielak
T
T
Møller
L N
LN
Jeppesen
J
J
Lyngbaek
S
S
Fenger
M
M
Olsen
M H
MH
Hildebrandt
P R
PR
Borch-Johnsen
K
K
Jørgensen
T
T
Haugaard
S B
SB
D000328:Adult; D017677:Age Distribution; D000368:Aged; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000453:epidemiology; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000453:epidemiology; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis* / Q000453:epidemiology; D011379:Prognosis; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D017678:Sex Distribution
D015415:Biomarkers; D014408:Biomarkers, Tumor; D055293:Receptors, Urokinase Plasminogen Activator; D002097:C-Reactive Protein