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

Albert W. Tsai, Mary Cushman, Wayne D. Rosamond, Susan R. Heckbert, Russell P. Tracy, Nena Aleksic, Aaron R. Folsom

Research output: Contribution to journalArticlepeer-review

283 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)636-642
Number of pages7
JournalAmerican Journal of Medicine
Volume113
Issue number8
DOIs
StatePublished - Dec 1 2002

Bibliographical note

Funding Information:
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.

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