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

Ellen-Sofie Hansen; Fridtjof B Rinde; Magnus S Edvardsen; Kristian Hindberg; Nadezhda Latysheva; Pål Aukrust; Thor Ueland; Annika E Michelsen; John-Bjarne Hansen; Sigrid K Brækkan; Vânia M Morelli

doi:10.1016/j.thromres.2021.10.020

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

Thromb Res. 2021 Dec:208:121-126. doi: 10.1016/j.thromres.2021.10.020. Epub 2021 Oct 26.

Affiliations

¹ Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway. Electronic address: ellen-sofie.hansen@uit.no.
² Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway.
³ Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁴ Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo, Norway.
⁵ Faculty of Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo, Norway.
⁶ Thrombosis Research Center, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.

PMID: 34763296
DOI: 10.1016/j.thromres.2021.10.020

Abstract

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 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.

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 D-dimer partly reflects underlying conditions associated with obesity and an inflammatory state.

Keywords: D-dimer; Deep vein thrombosis; Inflammation; Obesity; Venous thromboembolism.

MeSH terms

Case-Control Studies
Fibrin Fibrinogen Degradation Products
Humans
Venous Thromboembolism* / epidemiology

Substances

Fibrin Fibrinogen Degradation Products
fibrin fragment D