Plasma level of human epididymis protein 4 and risk of recurrence after first venous thromboembolism – The HUNT Study

Background: Patients with incident venous thromboembolism (VTE) have a high risk of recurrence. Recent studies have shown that plasma levels of human epidydimis protein 4 (HE4) are associated with increased risk of future incident VTE. Aims: To investigate whether plasma HE4 levels are associated with risk of recurrent VTE. Methods: Patients with first-lifetime VTE (n=896) derived from the Trøndelag Health Study (HUNT3; 2006-2019) were followed from the VTE date. Symptomatic and objectively confirmed VTE recurrences were recorded during the study period. Plasma HE4 levels were measured by Somascan at time of inclusion in the source cohort (HUNT3, prior to incident VTE). Cox regression models were used to estimate hazard ratios (HRs) for VTE recurrence across quartiles of plasma HE4 levels adjusted for age, sex and body mass index. Subgroup analyses by type of incident VTE were also performed. Results: During follow-up, 116 patients developed recurrent VTE. We found no significant association between quartiles of plasma HE4 levels and absolute or relative risk of recurrent VTE. The HR for recurrence in individuals with elevated plasma HE4 levels (Q4) versus low HE4 levels (Q1) was HR 0.82 (95% CI 0.46-1.49). Similarly, no association was found between plasma HE4 levels and recurrent VTE in any subgroup analyses (index DVT, PE, provoked VTE, or unprovoked VTE). Conclusions: Our results suggest that inherent plasma HE4 levels are not useful as a risk biomarker for recurrent VTE.