Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE).
OBJECTIVE
We sought to assess prospectively whether higher levels of blood coagulation factors and inflammation markers are risk factors for venous thromboembolism.


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.


CONCLUSIONS
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.
Tsai
Albert W
AW
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
Cushman
Mary
M
Rosamond
Wayne D
WD
Heckbert
Susan R
SR
Tracy
Russell P
RP
Aleksic
Nena
N
Folsom
Aaron R
AR
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001779:Blood Coagulation Factors / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D016001:Confidence Intervals; D005167:Factor VII / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013923:Thromboembolism / Q000175:diagnosis / Q000209:etiology*; D020246:Venous Thrombosis / Q000175:diagnosis*; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D001779:Blood Coagulation Factors; D018836:Inflammation Mediators; D014841:von Willebrand Factor; D005167:Factor VII; D005340:Fibrinogen; D002097:C-Reactive Protein