Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population

J Eugen-Olsen; O Andersen; A Linneberg; S Ladelund; W Hansen T; A Langkilde; Janne Petersen; T Pielak; N. L. Møller; J Jeppesen; S Lyngbæk; M Fenger; H Olsen M; K Borch-Johnsen; Torben Jørgensen; B Haugaard S; P. R.  Hildebrandt

doi:10.1111/j.1365-2796.2010.02252.x

Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population

J Eugen-Olsen, O Andersen, A Linneberg, S Ladelund, W Hansen T, A Langkilde, Janne Petersen, T Pielak, N. L. Møller, J Jeppesen, S Lyngbæk, M Fenger, H Olsen M, K Borch-Johnsen, Torben Jørgensen, B Haugaard S, P. R. Hildebrandt

Section of Biostatistics

252 Citations (Scopus)

Abstract

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. Design. This was an observational prospective cohort study. Cohort participants were included from June 1993 to December 1994 and followed until the end of 2006. Setting. General adult Caucasian population. Participants. The MONICA10 study, a population-based cohort recruited from Copenhagen, Denmark, included 2602 individuals aged 41, 51, 61 or 71 years. Measurements. 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. Limitation. Further validation in ethnic populations other than Caucasians is needed. Conclusion. 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.

Original language	English
Journal	Journal of Internal Medicine
Volume	268
Issue number	3
Pages (from-to)	296-308
Number of pages	13
ISSN	0954-6820
DOIs	https://doi.org/10.1111/j.1365-2796.2010.02252.x
Publication status	Published - Sept 2010

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Eugen-Olsen, J., Andersen, O., Linneberg, A., Ladelund, S., Hansen T, W., Langkilde, A., Petersen, J., Pielak, T., Møller, N. L., Jeppesen, J., Lyngbæk, S., Fenger, M., Olsen M, H., Borch-Johnsen, K., Jørgensen, T., Haugaard S, B., & Hildebrandt, P. R. (2010). Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. Journal of Internal Medicine, 268(3), 296-308. https://doi.org/10.1111/j.1365-2796.2010.02252.x

Eugen-Olsen, J, Andersen, O , Linneberg, A, Ladelund, S, Hansen T, W, Langkilde, A, Petersen, J, Pielak, T, Møller, NL, Jeppesen, J, Lyngbæk, S, Fenger, M, Olsen M, H, Borch-Johnsen, K, Jørgensen, T, Haugaard S, B & Hildebrandt, PR 2010, 'Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population', Journal of Internal Medicine, vol. 268, no. 3, pp. 296-308. https://doi.org/10.1111/j.1365-2796.2010.02252.x

@article{e42aac368c014591837e8d090ad38194,

title = "Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population",

abstract = "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. Design. This was an observational prospective cohort study. Cohort participants were included from June 1993 to December 1994 and followed until the end of 2006. Setting. General adult Caucasian population. Participants. The MONICA10 study, a population-based cohort recruited from Copenhagen, Denmark, included 2602 individuals aged 41, 51, 61 or 71 years. Measurements. 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. Limitation. Further validation in ethnic populations other than Caucasians is needed. Conclusion. 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.",

author = "J Eugen-Olsen and O Andersen and A Linneberg and S Ladelund and {Hansen T}, W and A Langkilde and Janne Petersen and T Pielak and M{\o}ller, {N. L.} and J Jeppesen and S Lyngb{\ae}k and M Fenger and {Olsen M}, H and K Borch-Johnsen and Torben J{\o}rgensen and {Haugaard S}, B and Hildebrandt, {P. R.}",

year = "2010",

month = sep,

doi = "10.1111/j.1365-2796.2010.02252.x",

language = "English",

volume = "268",

pages = "296--308",

journal = "Journal of Internal Medicine",

issn = "0954-6820",

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T1 - Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population

AU - Eugen-Olsen, J

AU - Andersen, O

AU - Linneberg, A

AU - Ladelund, S

AU - Hansen T, W

AU - Langkilde, A

AU - Petersen, Janne

AU - Pielak, T

AU - Møller, N. L.

AU - Jeppesen, J

AU - Lyngbæk, S

AU - Fenger, M

AU - Olsen M, H

AU - Borch-Johnsen, K

AU - Jørgensen, Torben

AU - Haugaard S, B

AU - Hildebrandt, P. R.

PY - 2010/9

Y1 - 2010/9

N2 - 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. Design. This was an observational prospective cohort study. Cohort participants were included from June 1993 to December 1994 and followed until the end of 2006. Setting. General adult Caucasian population. Participants. The MONICA10 study, a population-based cohort recruited from Copenhagen, Denmark, included 2602 individuals aged 41, 51, 61 or 71 years. Measurements. 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. Limitation. Further validation in ethnic populations other than Caucasians is needed. Conclusion. 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.

AB - 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. Design. This was an observational prospective cohort study. Cohort participants were included from June 1993 to December 1994 and followed until the end of 2006. Setting. General adult Caucasian population. Participants. The MONICA10 study, a population-based cohort recruited from Copenhagen, Denmark, included 2602 individuals aged 41, 51, 61 or 71 years. Measurements. 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. Limitation. Further validation in ethnic populations other than Caucasians is needed. Conclusion. 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.

U2 - 10.1111/j.1365-2796.2010.02252.x

DO - 10.1111/j.1365-2796.2010.02252.x

M3 - Journal article

C2 - 20561148

SN - 0954-6820

VL - 268

SP - 296

EP - 308

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

IS - 3

ER -

Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population

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