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Authors: H Iso, KM Rexrode, MJ Stampfer, JE Manson, et al.

Reference: JAMA 2001; 285: 304-312, http://jama.ama-assn.org/cgi/content/abstract/285/3/304

Reviewer: Carlos Mendoza Montano, PhD, APRECOR, Guatemala

Mini-abstract
This investigation was a prospective cohort study that analyzed the association between fish and omega-3 fatty intake and risk of stroke subtypes in women. Compared with women who ate fish less than once per month, those with higher intake of fish had a lower risk of total stroke. Among stroke subtypes, a significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week. Women in the highest quintile of intake of omega-3 fatty acids had reduced risk of total stroke and thrombotic infarction. There was no association between fish or omega-3 fatty acid intake and risk of hemorrhagic stroke.

Introduction
The role of fat intake as a risk factor for stroke remains uncertain, whereas the association between stroke and cholesterol has more convincingly been demostrated by the recent intervention trials using statins. 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. Therefore, this study examined the association between fish and omega-3 polyunsaturated fatty acid intake and risk of stroke subtypes in women.

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

The main outcome measure was relative risk of stroke compared by category of fish intake and quintile of omega-3 polyunsaturated fatty acid intake.

Results
During the follow-up period, 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. 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.

Discussion
In this large prospective study, frequent fish consumption in women was associated with significant reduced risk of stroke. Women who consumed fish 5 or more times per week had about 50% lower risk than those women who rarely ate fish. In addition, women in the highest quintile of intake of long-chain omega-3 fatty acids had a reduced risk of total stroke and thrombotic infarction. Therefore, this research supports the hypothesis that the salutary effect of fish on cardiovascular health is in part due to the presence of omega-3 fatty acids.

It was considered the possibility that confounding may explain the observed inverse association because women who frequently consumed fish had a healthier lifestyle and diet than those who rarely ate fish. However, the detailed analyses performed in this study, took the differences in these factors into account. Another potential concern is inaccurate assessment of fish consumption. However, fish intake was reported on dietary questionnaires with reasonable accuracy.

In conclusion, these 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.

Commentary
This article reports results of the association between the consumption of fish and omega-3 fatty acids and the risk of specific stroke subtypes. The reduced risk of thrombotic stroke observed in this study is consistent with the effects of fish and omega-3 fatty acids on several atherogenic process. Studies have shown that fish oil intake reduces blood pressure in those hypertensive individual, improves the blood lipoprotein profile, and prevents thrombosis by reducing platelet aggegation. These effects may explain the findings of epidemiological studies that indicate that populations with high fish consumption have low incidence of cardiovascular diseases.

However, when considering cardiovascular health, it seems premature to recommend general usage of fish oil supplements before compelling evidence for their beneficial action is obtained from clinical trials. This will require the continued support of cardiovascular research on fish and omega-3 fatty acids. In the mean time, inclusion of fish rich in omega-3 fatty acids in the diet seems reasonable because they are good sources of protein without the accompanying high saturated fat contained in fatty meat products.