Inflammatory Cytokines as Risk Factors for a First Venous Thrombosis: A Prospective Population-Based Study

Background In case-control studies, elevated levels of interleukins 6 and 8 have been found to be associated with an increased risk of venous thrombosis (VT). Because of the design of these studies, it remained uncertain whether these alterations were a cause or a result of the VT. In order to distinguish between the two, we set out to measure the levels of six inflammatory markers prior to thrombosis in a population-based cohort using a nested case-cohort design. Methods and Findings Between August 1995 and June 1997, blood was collected from 66,140 people in the second Norwegian Health Study of Nord-Trøndelag (HUNT2). We identified venous thrombotic events occurring between entry and 1 January 2002. By this date we had registered 506 cases with a first VT; an age- and sex-stratified random sample of 1,464 controls without previous VT was drawn from the original cohort. Levels of interleukins 1β, 6, 8, 10, 12p70, and tumour necrosis factor-α were measured in the baseline sample that was taken 2 d to 75 mo before the event (median 33 mo). Cut-off points for levels were the 80th, 90th, and 95th percentile in the control group. With odds ratios ranging from 0.9 (95% CI: 0.6–1.5) to 1.1 (95% CI: 0.7–1.8), we did not find evidence for a relationship between VT and an altered inflammatory profile. Conclusions The results from this population sample show that an altered inflammatory profile is more likely to be a result rather than a cause of VT, although short-term effects of transiently elevated levels cannot be ruled out.