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Individual changes in fibrinolytic factors, von Willebrand factor, and C-reactive protein over a nine-year period.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. (Skellefteå Reserach Unit)
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. (Sunderby Research Unit)
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Intra-individual changes in haemostatic factor concentrations over time are unknown, in the general population.

Objective: To describe intra-individual longitudinal changes in tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), tPA/PAI-1 complex, von Willebrand factor (VWF), and C-reactive protein (CRP) over nine years, in different age groups, stratified for sex.

Methods: The MONICA survey in 1990 examined randomly selected men and women in four age groups (25–64 years) who were re-examined in 1999. A total of 309 individuals donated venous blood samples in Stabilyte tubes for both surveys during the morning hours, after an overnight fast. We analysed tPA activity and antigens of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP.

Results: Over nine years, in both men and women, we found significant intra-individual increases in the antigen levels of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP (P < 0.001). PAI-1 antigen levels increased by 75% for men and 95% for women. Compared to men, women had a significantly higher CRP increase (0.92 vs. 0.22 mg/L; P = 0.044). The P for trend for mean Δ1999–1990 across age groups showed a significant linear trend for VWF (P = 0.001 for men; P < 0.001 for women), but not for the other studied variables.

Conclusions: There were intra-individual longitudinal increases in the antigen levels of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP over nine years in both men and women, with PAI-1 showing the highest relative increase. VWF increased significantly across age groups; however, fibrinolytic variables did not.

Keyword [en]
fibrinolysis, haemostasis, longitudinal studies, tissue plasminogen activator, plasminogen activator inhibitor -1
National Category
Hematology
Research subject
Medicine, cardiovascular disease
Identifiers
URN: urn:nbn:se:umu:diva-86358OAI: oai:DiVA.org:umu-86358DiVA: diva2:698565
Available from: 2014-02-24 Created: 2014-02-24 Last updated: 2014-02-28Bibliographically approved
In thesis
1. Fibrinolytic factors in relation to anthropometry and incident type 2 diabetes.
Open this publication in new window or tab >>Fibrinolytic factors in relation to anthropometry and incident type 2 diabetes.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Fibrinolysfaktorer i relation till antropometri och incident typ 2 diabetes.
Abstract [en]

Fibrinolytic imbalance is associated with cardiovascular disease and its risk factors. The longitudinal changes in the fibrinolytic factors tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and tPA/PAI-1 complex have been inadequately studied in the general population and in relation to incident type 2 diabetes mellitus (T2DM). The measurements, questionnaires and blood samples prospectively collected in the World Health Organisation-project MONItoring trends and determinants in CArdiovascular disease (MONICA) and in the Västerbotten Intervention Programme (VIP) enable such studies. The samples have been stored since 1985, at the Northern Sweden Medical Research Biobank. However, it is unknown how these factors are affected by long-term storage.

The aims of this thesis were to evaluate the effects of long-term storage on fibrinolytic factors, and to determine how these factors are related to incident T2DM, how these factors change over time and how these factors are related to changes in anthropometric measurements.

Storage time was shown to have a negligible impact on plasma antigen levels of fibrinolytic factors. After adjustments for traditional diabetic and cardiovascular risk markers the fibrinolytic factors tPA, PAI-1 and tPA/PAI-1 complex were associated with incident T2DM. PAI-1 was associated with incident T2DM in subjects with normal fasting and 2-hour plasma glucose levels. In MONICA-Västerbotten, tPA, PAI-1 and tPA/PAI-1 complex increased over 9 years in both men and women. PAI-1 appears to interact in a complex manner with anthropometric, inflammatory, glycaemic and lipidemic measurements, but the pattern of components correlating with the changes in PAI-1 differed markedly between the sexes.

In conclusion, PAI-1 is a potential risk marker of incident T2DM. PAI-1 increased markedly over nine years, but the pathophysiological background to these findings needs to be further investigated, separately for each sex.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2014. 81 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1626
National Category
Endocrinology and Diabetes Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public health; Medicine, cardiovascular disease
Identifiers
urn:nbn:se:umu:diva-86360 (URN)978-91-7459-796-7 (ISBN)
Public defence
2014-03-21, Forumsalen, Campus, Skellefteå, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2014-02-28 Created: 2014-02-24 Last updated: 2014-03-17Bibliographically approved

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