Clinical study
Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE)

https://doi.org/10.1016/S0002-9343(02)01345-1Get rights and content

Abstract

Purpose

We sought to assess prospectively whether higher levels of blood coagulation factors and inflammation markers are risk factors for venous thromboembolism.

Subjects and methods

In two pooled population-based cohort studies, we measured levels of factor VII, factor VIII, von Willebrand factor, fibrinogen, and C-reactive protein, and white blood cell count, in samples obtained from 19,237 adults with no baseline history of venous thromboembolism, cancer, or warfarin use. The endpoint was validated venous thromboembolism during follow-up (median, 7.8 years).

Results

A total of 159 venous thromboembolism events occurred. Factor VIII and von Willebrand factor were linearly associated with increased risk of venous thromboembolism (P for trend <0.0001). As compared with those in the lowest quartile, the multivariate-adjusted hazard ratio (HR) of venous thromboembolism was 2.6 (95% confidence interval [CI]: 1.6 to 4.3) for factor VIII levels in the highest quartile and 3.8 (95% CI: 2.0 to 7.2) for the highest fifth percentile. For von Willebrand factor, the hazard ratios in middle-aged subjects were 4.6 (95% CI: 2.2 to 9.2) for the highest quartile and 7.6 (95% CI: 3.1 to 18) for the highest fifth percentile. Factor VII levels above the 95th percentile, as compared with the lowest quartile, also conveyed a higher risk of venous thromboembolism (HR = 2.4; 95% CI: 1.2 to 4.8). In contrast, there was no association of venous thromboembolism with fibrinogen or C-reactive protein levels, or white cell count.

Conclusion

In this prospective study, elevated factor VIII and von Willebrand factor levels were common, independent, and dose-dependent risk factors for venous thromboembolism, and an elevated factor VII level was a possible risk factor. Venous thromboembolism, unlike arterial disease, was not related to inflammatory markers.

Section snippets

Study sample

The LITE study combined the established cohorts from the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk In Communities (ARIC) study. The Cardiovascular Health Study examined the elderly (aged ≥65 years at entry) and ARIC examined adults aged 45 to 64 years 17, 18, 19. Information about cardiovascular risk factors was collected at the baseline examinations conducted from 1987 to 1989 in ARIC and from 1989 to 1990 in CHS. An additional cohort of 687 African Americans was recruited

Sample characteristics

A total of 159 incident cases of venous thromboembolism were ascertained (94 in ARIC, 65 in CHS) during 147,784 person-years of follow-up. The crude incidence rate per 1000 person-years was 0.80 in ARIC, 2.15 in CHS, and 1.08 in the combined cohort. Approximately half of the events had no obvious cause such as trauma or surgery.

Half of the participants who developed incident venous thromboembolism were women, and 72% were white (Table 1). Mean baseline levels of factor VII, factor VIII, and

Discussion

We found that levels of factor VIII, von Willebrand factor, and factor VII were positively and independently associated with the incidence of venous thromboembolism in this population-based cohort study. Hazard ratios tended to be larger in the middle-aged ARIC sample than in the older CHS sample. Fibrinogen and C-reactive protein levels, and white blood cell count—all markers of inflammation—were not associated with the incidence of venous thromboembolism.

Factor VIII has received much

Acknowledgements

The authors thank the staff and participants of CHS and the ARIC study for their important contributions over many years.

References (30)

  • C.M. Schambeck et al.

    Venous thromboembolism and associated high plasma factor VIII levelslinked to cytomegalovirus infection?

    Thromb Haemost

    (2000)
  • G.D. Lowe et al.

    Prediction of deep vein thrombosis after elective hip replacement surgery by preoperative clinical and haemostatic variablesthe ECAT DVT Study. European Concerted Action on Thrombosis

    Thromb Haemost

    (1999)
  • T. Koster et al.

    Factor VII and fibrinogen levels as risk factors for venous thrombosis. A case-control study of plasma levels and DNA polymorphisms—the Leiden Thrombophilia Study (LETS)

    Thromb Haemost

    (1994)
  • F. Haverkate et al.

    Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen

    Thromb Haemost

    (1995)
  • G. Lowe et al.

    Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years. Relationships to hormone replacement therapy

    Thromb Haemost

    (2000)
  • Cited by (333)

    • Renal transplant and hemostasis: early postoperative changes in recipients and donors

      2023, Research and Practice in Thrombosis and Haemostasis
    • Thrombophilia and outcomes of venous thromboembolism in older patients

      2023, Research and Practice in Thrombosis and Haemostasis
    View all citing articles on Scopus

    The LITE study was funded by grant R01 HL59367 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. The Atherosclerosis Risk In Communities (ARIC) study was funded by contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 from the National Heart, Lung, and Blood Institute. The Cardiovascular Health Study (CHS) was funded by contracts N01-HC-85079 to N01-HC-85086 from the National Heart, Lung, and Blood Institute.

    View full text