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

Abstract

<p><i>Background</i> 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. <p><i>Objectives</i> To investigate the association between plasma D-dimer levels and risk of future incident VTE. <p><i>Methods</i> A population-based nested case-control study, comprising 414 VTE patients and 843 randomly selected age- and sex-matched controls, was derived from the Tromsø 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. <p><i>Results</i> 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. <p><i>Conclusion</i> 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 D-dimer partly reflects underlying conditions associated with obesity and an inflammatory state.