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Fish and Omega-3 Fatty Acid Intake and Risk of
Coronary Heart Disease in Women

Frank B. Hu; Leslie Bronner; Walter C. Willett; et al. JAMA. 2002;287(14):1815-1821 (doi:10.1001/jama.287.14.1815) Nutritional and Metabolic Disorders; Lipids and Lipid Disorders; Women's Health;Women's Health, Other Fish and Omega-3 Fatty Acid Intake and
Risk of Coronary Heart Disease in Women
Frank B. Hu, MD
Context Higher consumption of fish and omega-3 fatty acids has been associated
with a lower risk of coronary heart disease (CHD) in men, but limited data are avail-able regarding women.
Objective To examine the association between fish and long-chain omega-3 fatty
acid consumption and risk of CHD in women.
Design, Setting, and Participants Dietary consumption and follow-up data from
84688 female nurses enrolled in the Nurses’ Health Study, aged 34 to 59 years andfree from cardiovascular disease and cancer at baseline in 1980, were compared from validated questionnaires completed in 1980, 1984, 1986, 1990, and 1994.
Main Outcome Measures Incident nonfatal myocardial infarction and CHD deaths.
Results During 16 years of follow-up, there were 1513 incident cases of CHD (484
CHD deaths and 1029 nonfatal myocardial infarctions). Compared with women who rarely ate fish (Ͻ1 per month), those with a higher intake of fish had a lower risk of CHD. After adjustment for age, smoking, and other cardiovascular risk factors, the mul- tivariable relative risks (RRs) of CHD were 0.79 (95% confidence interval [CI], 0.64- 0.97) for fish consumption 1 to 3 times per month, 0.71 (95% CI, 0.58-0.87) for once fishing villages,5,6 have suggested that fish per week, 0.69 (95% CI, 0.55-0.88) for 2 to 4 times per week, and 0.66 (95% CI, 0.50- 0.89) for 5 or more times per week (P for trend=.001). Similarly, women with a higherintake of omega-3 fatty acids had a lower risk of CHD, with multivariable RRs of 1.0, erosclerosis. Several7-9 but not all pro- 0.93, 0.78, 0.68, and 0.67 (PϽ.001 for trend) across quintiles of intake. For fish intake spective cohort studies10,11 have found an and omega-3 fatty acids, the inverse association appeared to be stronger for CHD deaths (multivariate RR for fish consumption 5 times per week, 0.55 [95% CI, 0.33-0.90] for CHD deaths vs 0.73 [0.51-1.04]) than for nonfatal myocardial infarction.
Conclusion Among women, higher consumption of fish and omega-3 fatty acids is
associated with a lower risk of CHD, particularly CHD deaths.
supplementation reduced coronary mor-tality among patients with preexisting Ascertainment of Diet
blank, those with reported total food in- Author Affiliations: Departments of Nutrition (Drs
Cardiology Division (Dr Albert), Massachusetts Gen- Hu, Willett, Stampfer, and Hunter) and Epidemiol- eral Hospital, Harvard Medical School, Boston, Mass; ogy (Drs Willett, Stampfer, Hunter, and Manson); Department of Psychiatry, Duke University Medical Harvard School of Public Health, the Channing Laboratory (Drs Hu, Willett, Stampfer, Hunter, and Corresponding Author and Reprints: Frank B. Hu, MD,
Manson); the Division of Preventive Medicine (Drs Department of Nutrition, Harvard School of Public Manson, Rexrode, and Albert); Department of Health, 665 Huntington Ave, Boston, MA 02115 Medicine, Brigham and Women’s Hospital, and the (e-mail: Frank.hu@channing.harvard.edu).
2002 American Medical Association. All rights reserved.
(Reprinted) JAMA, April 10, 2002—Vol 287, No. 14 1815
FATTY ACID INTAKE AND RISK OF HEART DISEASE aged 45 to 70 years and living in the Bos- ous year she had consumed that amount.
food item, ranging from “almost never” to “6 or more times per day.” In 1984, the fatty acid composition of adipose tis- ficients for the fish items between 2 ques- tionnaires administered 1 year apart were such as mackerel, salmon, sardines, blue- for which no records were available.
dish.16 The mean total fish intake was 3.7 Statistical Analyses
tion of each item by its nutrient content 0.61; PϽ.001). The energy-adjusted in- per serving and totaling the nutrient in- elsewhere.15 Briefly, to calculate intake PϽ.001).17 Information on fish oil 1990 in the Nurses’ Health Study; at that End Point Ascertainment
self-reported risk factor status. The di- signed 1.16 g of long-chain omega-3 fatty other nutrient variables (fiber, trans- other fish by using the relative consump- tion of these types of fish on the 1984 di- 1816 JAMA, April 10, 2002—Vol 287, No. 14 (Reprinted)
2002 American Medical Association. All rights reserved.
FATTY ACID INTAKE AND RISK OF HEART DISEASE which is equivalent to age in months.
(TABLE 1). In a second multivariate
were included in the propensity model.
trans-fat, fiber, and the ratio of poly- ticipant was at risk, with covariates set (quintiles), or ␣-linolenic acid did not appreciably alter the results, we did not we stratified the analysis jointly by age omega-3 fatty acids (the sum of ␣-lino- naire cycle. The time scale for the analy- lar aspirin use, and mutivitamin use.
start of the current questionnaire cycle, Table 1. Relative Risks of Coronary Heart Disease (CHD) According to the Average Frequency of Fish Intake in the Nurses’ Health Study,
1980-1996*
Average Frequency of Fish Intake
Ͻ1 per mo
1-3 Times per mo
Once per wk
2-4 Times per wk
Ն5 Times per wk
P for Trend
*Data are presented as relative risk (95% confidence interval) unless otherwise indicated. The ␹2 test was used for P values.
†Relative risk was adjusted for age (continuous), time periods, smoking status (never, past, current [1-14, 15-24, Ն25 cigarettes/d]), body mass index (Ͻ22, 22-22.9, 23-24.9, 25-28.9, Ն29 kg/m2), alcohol intake (0, Ͻ5, 5-14, Ն15 g/d), menopausal status and postmenopausal hormone use, vigorous to moderate activity (Ͻ1, 1-1.9, 2-3.9, 4-6.9, Ն7h/wk), number of times aspirin was used per week (Ͻ1, 1-2, 3-6, 7-14, and Ն15), multivitamin use (yes vs no), vitamin E supplement use (yes vs no) and history of hypertension(yes vs no), hypercholesterolemia (yes vs no), diabetes (yes vs no).
‡Also adjusted for intake of trans-fat, the ratio of polyunsaturated fat to saturated fat, and dietary fiber (all in quintiles).
2002 American Medical Association. All rights reserved.
(Reprinted) JAMA, April 10, 2002—Vol 287, No. 14 1817
FATTY ACID INTAKE AND RISK OF HEART DISEASE ciated with intake of chicken, fruits and groups. As shown in TABLE 4, omega-3
nificantly lower risk of CHD in both low- and high-ratio omega-6/omega-3 groups.
(TABLE 3), but tests for interaction did
not reach statistical significance (P for test for interaction was not statistically and aspirin use = .14; P for interaction tors (P for trend Ͻ.001). After further factors, the association was still signifi- cant (P for trend = .001). Further ad- 0.42-1.09; P for trend = .008), not 0.82; P for trend Ͻ.001). The multi- 0.59-1.16; P for trend = .15).
fatty acid intake was 0.75 (95% CI, 0.67- with a lower risk of CHD (TABLE 2) (P
for trend Ͻ.001). Further adjustment for oleic) to omega-3 (the sum of ␣-linole- dietary factors did not materially change nic acid and fish oil) fatty acid intake.
In this analysis, we used the mean of the Table 2. Relative Risk of Coronary Heart Disease (CHD) According to Quintiles of Omega-3 Fatty Acid Intake in the Nurses’ Health Study,
1980-1996*
Quintiles of Average Omega-3 Fatty Acids
P for Trend
*Data are presented as relative risk (95% confidence interval) unless indicated otherwise.
†See the corresponding footnote in Table 1.
‡See the corresponding footnote in Table 1.
1818 JAMA, April 10, 2002—Vol 287, No. 14 (Reprinted)
2002 American Medical Association. All rights reserved.
FATTY ACID INTAKE AND RISK OF HEART DISEASE points.10 In the Health Professionals Fol- take and the risk of coronary disease, but tablished cardiovascular risk factors and had a 40% lower risk of fatal CHD. In the trans-fatty acids, and the ratio of poly- US Physicians’ Health Study, Albert et al9 unsaturated to saturated fats. It was also than nonfatal MI. Notably, previous stud- not explained by differences in intake of 0.96) but was not related to risks of non- Table 3. Relative Risk (RR) of Coronary Heart Disease According to Fish and Omega-3 Fatty Acid Intakes, Stratified by Aspirin Use
in the Nurses’ Health Study, 1980-1996
Average Frequency of Fish Intake
Aspirin Use
Ͻ1 per mo
1-3 Times per mo
2-4 Times per wk
Ն5 Times per wk
P for Trend
Quintiles of Omega-3 Fatty Acids
*See the corresponding footnote in Table 1. Aspirin use was not adjusted for. CI indicates confidence interval. The number of cases does not add to 1513 because of missing data.
Table 4. Relative Risk (RR) of Coronary Heart Disease According to Quintiles of Omega-3 Fatty Acid Intake, Stratified by Omega-6/Omega-3
Ratio in the Nurses’ Health Study, 1980-1996*
Quintiles of Omega-3 Fatty Acid Intake
Low omega-6/omega-3 ratio (median = 5.9)† High omega-6/omega-3 ratio (median = 9.2) *All trend comparisons, calculated with the ␹2 test, were significant (PϽ.001). The number of cases does not add to 1513 because of missing data.
†The mean of omega-6/omega-3 ratio (7.6) was used as a cutoff point to define low- and high-ratio groups. Omega-3 included ␣-linolenic acid and fish omega-3 fatty acids. CI ‡See the first footnote in Table 1. Aspirin use was not adjusted for.
2002 American Medical Association. All rights reserved.
(Reprinted) JAMA, April 10, 2002—Vol 287, No. 14 1819
FATTY ACID INTAKE AND RISK OF HEART DISEASE nary mortality among patients after MI.
allocated to 3 dietary interventions, sub- fish had a significantly lower (29%) total mortality during 2 years of follow-up.
sclerosis.33,34 In vitro studies have con- actions.33 Additionally, clinical experi- fatty acids may lower the risk of CHD.
tion.34,35 The beneficial effects of omega-3 Because a higher intake of linoleic acid20 consistent with those in other trials.
in endothelial cells.37 The result is re- the active agent primarily responsible for the apparent protective effect of fish.
variation.21 Finally, we were able to ad- aspirin is a more potent inhibitor of cy- rum triglycerides,26 platelet aggregabil- ity,27 and antiarrhythmic effects.28 Ani- mal studies have established that fish oil potential dietary and lifestyle confound- 1820 JAMA, April 10, 2002—Vol 287, No. 14 (Reprinted)
2002 American Medical Association. All rights reserved.
FATTY ACID INTAKE AND RISK OF HEART DISEASE dent effect of fish and omega-3 fatty ac- Author Contributions: Study concept and design: Hu,
Bronner, Willett, Manson.
Acquisition of data: Willett, Stampfer, Manson.
Analysis and interpretation of data: Hu, Bronner, Wil-lett, Stampfer, Rexrode, Albert, Hunter, Manson.
Drafting of the manuscript: Hu.
Critical revision of the manuscript for important in-tellectual content: Hu, Bronner, Willett, Stampfer, plausibility of a causal relationship be- Statistical expertise: Hu, Bronner, Rexrode, Albert,Hunter.
Obtained funding: Willett, Stampfer, Manson.
Administrative, technical, or material support: Wil-lett, Manson.
oil, as well as the consistency of the pres- Funding/Support: This work was supported by re-
search grants HL24074, HL34594, and CA87969 from
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(Reprinted) JAMA, April 10, 2002—Vol 287, No. 14 1821

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