Abstract
BACKGROUND: Studies on the association between long-chained n-3 polyunsaturated fatty acids (n-3 PUFAs) and risk of venous thromboembolism (VTE) are conflicting, potentially due to challenges related to assessment of n-3 PUFA intake and changes in diet during follow-up. OBJECTIVES: To investigate whether dietary intake of marine n-3 PUFAs was associated with risk of incident VTE in a population-based cohort with repeated assessments of n-3 PUFA intake. METHODS: We recruited 21 970 participants (after excluding 7570 with incomplete data) from the fourth (1994-1995) and sixth (2007-2008) surveys of the Tromsø Study, and recorded incident VTEs up to 2016. Intake of n-3 PUFAs was computed from self-reported consumption of fat and lean fish, fish spread, and supplements. Cox proportional hazards regression models with n-3 PUFA intake as a time-varying variable were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE across quartiles (Q) of n-3 PUFA intake. RESULTS: There were 541 incident VTEs during follow-up. Compared to Q1, subjects in Q2-4 had 22%-26% lower risk of VTE (HR Q2 0.74, 95% CI 0.57-0.96; HR Q3 0.77, 95% CI 0.59-0.99; HR Q4 0.78, 95% CI 0.61-1.00). The association was most pronounced for provoked VTE, particularly provoked pulmonary embolism (PE), with risk estimates of 0.42 (95% CI 0.25-0.72), 0.40 (95% CI 0.23-0.68), and 0.61 (95% CI 0.38-0.96) for Q2-4, respectively. CONCLUSIONS: Dietary intake of marine n-3 PUFAs was associated with a lower risk of VTE, particularly provoked PE. The association displayed a threshold pattern and suggested a protective effect of an n-3 PUFA intake ≥4.7 g/week.