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Background: High alcohol intake has many negative health effects, but its association with venous thromboembolism (VTE) is based on self-reported consumption and is unclear. This study aimed to investigate the association between alcohol consumption measured by the biomarker phosphatidylethanol (PEth) and risk of first-ever VTE.

Methods: We conducted a population-based nested case-referent study in northern Sweden. The study is based on the Västerbotten Intervention Programme VIP which includes health examinations and prospective blood sampling. Cases of objectively verified first-ever VTE between 1985 and 2014 were registered. Referents were matched for age, sex, health examination date, geographical area, and sample freeze-thaw cycles. In 2024, PEth concentrations were measured using a liquid chromatography tandem-mass spectrometry method with a limit of quantification of 0.01 μmol/L.

Results: The study included 1410 cases with objectively verified VTE and 1410 matched referents. The median age of cases at the health examination was 50.2 years, and 55.2 % of cases were men. We found an association between the highest PEth concentration category (>0.30 μmol/L) and risk of VTE (odds ratio 1.44 [95 % confidence interval 1.05–1.98]) compared to the lowest concentration category (PEth <0.01 μmol/L) in a model adjusted for education level, body mass index, smoking, hypertension, and cancer at inclusion.

Conclusions: A high PEth concentration was independently associated with an increased risk of first-ever VTE. Furthermore, the study highlights the benefits of PEth as a biomarker to identify individuals with high alcohol consumption that are at an increased risk of adverse medical outcomes.