Intake of Marine n-3 Polyunsaturated Fatty Acids and Risk of Hemorrhagic Stroke and Its Subtypes: A Danish Follow-Up Study

INTRODUCTION: A diet rich in marine n-3 polyunsaturated fatty acids (PUFAs) may lower the risk of coronary heart disease and ischemic stroke. However, the association between intake of marine n-3 PUFAs and risk of hemorrhagic stroke has only been sparsely explored. We aimed to investigate the associations between intake of the major marine n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and their sum, in relation to incident hemorrhagic stroke and its subtypes, intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). METHODS: We analyzed data from the Danish Diet, Cancer and Health Cohort, which was established between 1993 and 1997. Information on dietary intake of marine n-3 PUFAs was obtained through a validated food frequency questionnaire. Potential hemorrhagic stroke cases were identified by linkage to the Danish National Patient Register and subsequently validated. Hazard ratios obtained by Cox proportional hazard regression analyses were used as measures of association. RESULTS: A total of 394 subjects among 55,519 individuals developed hemorrhagic stroke during a median follow-up period of 13.5 years. In multivariable analyses including adjustment for established risk factors, we observed weak and statistically nonsignificant inverse associations between intake of EPA, DHA, and EPA + DHA and the rate of incident hemorrhagic stroke. In analyses of hemorrhagic stroke subtypes, we found indications of lower rates of ICH among participants in the highest quartile of EPA, DHA, and EPA + DHA compared with those in the lowest quartile and indications of lower rates of SAH in the highest quartile of EPA intake compared to the lowest quartile, but the findings were statistically nonsignificant. CONCLUSIONS: Inversely statistically nonsignificant associations were found between EPA, DHA, and EPA + DHA and hemorrhagic stroke.