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Hiroyasu Iso, MD,PhD; Kathryn M. Rexrode, MD,MPH; Meir J. Stampfer, MD,DrPH; JoAnn E. Manson, MD,DrPH; Graham A. Colditz, MD,DrPH; Frank E. Speizer, MD; Charles H. Hennekens, MD,DrPH; Walter C. Willett, MD,DrPH

JAMA. 2001;285:304-312.

Context  Some prospective studies have shown an inverse association between fish intake and risk of stroke, but none has examined the relationship of fish and omega-3 polyunsaturated fatty acid intake with risk of specific stroke subtypes.

Objective  To examine the association between fish and omega-3 polyunsaturated fatty acid intake and risk of stroke subtypes in women.

Design, Setting, and Subjects  Prospective cohort study of women in the Nurses' Health Study cohort, aged 34 to 59 years in 1980, who were free from prior diagnosed cardiovascular disease, cancer, and history of diabetes and hypercholesterolemia and who completed a food frequency questionnaire including consumption of fish and other frequently eaten foods. The 79 839 women who met our eligibility criteria were followed up for 14 years.

Main Outcome Measure  Relative risk of stroke in 1980-1994 compared by category of fish intake and quintile of omega-3 polyunsaturated fatty acid intake.

Results  After 1 086 261 person-years of follow-up, 574 incident strokes were documented, including 119 subarachnoid hemorrhages, 62 intraparenchymal hemorrhages, 303 ischemic strokes (264 thrombotic and 39 embolic infarctions), and 90 strokes of undetermined type. Among thrombotic infarctions, 90 large-artery occlusive infarctions and 142 lacunar infarctions were identified. Compared with women who ate fish less than once per month, those with higher intake of fish had a lower risk of total stroke: the multivariate relative risks (RRs), adjusted for age, smoking, and other cardiovascular risk factors, were 0.93 (95% confidence interval [CI], 0.65-1.34) for fish consumption 1 to 3 times per month, 0.78 (95% CI, 0.55-1.12) for once per week, 0.73 (95% CI, 0.47-1.14) for 2 to 4 times per week, and 0.48 (95% CI, 0.21-1.06) for 5 or more times per week (P for trend = .06). Among stroke subtypes, a significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93). Women in the highest quintile of intake of long-chain omega-3 polyunsaturated fatty acids had reduced risk of total stroke and thrombotic infarction, with multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95% CI, 0.42-1.07), respectively. When stratified by aspirin use, fish and omega-3 polyunsaturated fatty acid intakes were inversely associated with risk of thrombotic infarction, primarily among women who did not regularly take aspirin. There was no association between fish or omega-3 polyunsaturated fatty acid intake and risk of hemorrhagic stroke.

Conclusions  Our data indicate that higher consumption of fish and omega-3 polyunsaturated fatty acids is associated with a reduced risk of thrombotic infarction, primarily among women who do not take aspirin regularly, but is not related to risk of hemorrhagic stroke.

Author Affiliations: Channing Laboratory (Drs Iso, Rexrode, Stampfer, Manson, Colditz, Speizer, and Willett) and the Division of Preventive Medicine, Department of Medicine (Drs Rexrode and Manson), Brigham and Women's Hospital and Harvard Medical School and Departments of Epidemiology (Drs Stampfer, Manson, Colditz, and Willett) and Nutrition (Drs Stampfer and Willett), Harvard School of Public Health, Boston, Mass; and Department of Medicine, Epidemiology and Public Health, University of Miami School of Medicine, Miami, Fla (Dr Hennekens).

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