Elevated plasma D-dimer levels are associated with risk of future incident venous thromboembolism

Background: D-dimer, a global biomarker for activation of the coagulation and fibrinolysis systems, is useful in assessing individual risk of venous thromboembolism (VTE) recurrence. However, there is limited information on the association between D-dimer and risk of a first lifetime VTE event. Objectives: To investigate the association between plasma D-dimer levels and risk of future incident VTE. Methods: A population-based nested case-control study, comprising 414 VTE patients and 843 randomly selected age- and sex-matched controls, was derived from the Tromso Study (1994-2007). D-dimer was measured in plasma samples collected at cohort baseline (1994-95). Odds ratios (ORs) for VTE with 95% confidence intervals (CIs) were estimated according to quartile cut-offs of D-dimer levels determined in controls. Results: The risk of VTE increased across quartiles of D-dimer levels (P-trend = 0.014) in the age- and sex-adjusted model. Participants with plasma D-dimer levels in the highest quartile (>= 152 ng/mL) had an OR for VTE of 1.65 (95% CI 1.14-2.40) compared with those in the lowest quartile (<94 ng/mL). The ORs were marginally attenuated after additional adjustment for body mass index (BMI) (OR 1.51, 95% CI 1.04-2.20) and C-reactive protein (CRP) (OR 1.34, 95% CI 0.90-1.98). Similar results were obtained for VTE subgroups, i.e. deep vein thrombosis, pulmonary embolism, and provoked/unprovoked events. Conclusion: Our results indicate that elevated plasma D-dimer levels are associated with increased risk of incident VTE. However, the attenuation of risk estimates upon additional adjustment for BMI and CRP suggests that Ddimer partly reflects underlying conditions associated with obesity and an inflammatory state.