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Objectives: To review the contributions of the Nurses' Health Studies (NHSs) to the understanding of cardiovascular disease etiology in women., Methods: We performed a narrative review of the publications of the NHS and NHS II between 1976 and 2016., Results: Diets low in trans fat, saturated fat, refined carbohydrates, and sugar-sweetened beverages and rich in fruits and vegetables, whole grains, and sources of unsaturated fats are associated with reduced risk of cardiovascular disease. Healthy lifestyle choices include smoking avoidance, regular physical activity, maintaining a normal body mass index, and moderate alcohol consumption. Adherence to a combination of these healthy diet and lifestyle behaviors may prevent most vascular events. Studies also covered oral contraceptive use, postmenopausal hormone therapy, shift work, sleep duration, psychosocial factors, and various biomarkers and genetic factors. Findings, such as the association of trans fat with cardiovascular disease, have helped shaped medical guidelines and government policies., Conclusions: The NHS has provided compelling evidence that the majority of vascular events may be prevented by avoiding smoking, participating in regular physical activity, maintaining normal body mass index, and eating a healthy diet.

Objective: Diabetes-related metabolic abnormality may aggravate the adverse effects of iron overload on cardiovascular health. However, little is known about whether iron consumption affects coronary heart disease (CHD) risk in diabetes., Research Design and Methods: We prospectively assessed the associations of long-term intakes of dietary iron and red meat with CHD risk among 6,161 women who reported a diagnosis of type 2 diabetes., Results: During 54,455 person-years of follow-up from 1980 through 2000, we documented 550 incident cases of CHD. After adjustment for age and BMI, high intakes of both heme iron and red meat were associated with a significantly increased risk of fatal CHD (P for trend = 0.003 and 0.018), coronary revascularization (P for trend = 0.02 and 0.06), and total CHD (P for trend = 0.0009 and 0.007). Women with the highest intake of heme iron had 50% (6-94%) increased risk of total CHD compared with those with the lowest intake. Further adjustment for other lifestyle and dietary factors did not appreciably change the associations. The positive association between heme iron and red meat intakes and CHD was more evident among postmenopausal women compared with premenopausal women., Conclusions: Our data indicate that higher consumption of heme iron and red meat may increase CHD risk among women with type 2 diabetes.

Objective: To examine the feasibility of using phylloquinone intake as a marker for coronary heart disease (CHD) and stroke risk in women., Design and Setting: Nurses' Health Study, a prospective cohort study during 1984-2000. Dietary data were collected in 1984, 1986, 1990, and 1994 using a validated semiquantitative food frequency questionnaire., Subjects: A total of 72 874 female nurses, aged 38-65 y, without previously diagnosed angina, myocardial infarction (MI), stroke, or cancer at baseline., Main Outcome Measures: Incidence of nonfatal MI, CHD deaths, total CHD events, ischemic, and total strokes., Results: There were 1679 CHD events (1201 nonfatal) and 1009 strokes (567 ischemic). After adjustment for age and lifestyle factors associated with cardiovascular disease risk, the multivariate relative risks (RR) (95% CI) of total CHD from the lowest to the highest quintile category of phylloquinone intake were 1 (reference), 0.80 (0.69-0.94), 0.86 (0.74-1.00), 0.77 (0.66-0.99), and 0.79 (0.68-0.92), P for trend=0.01. Further adjustment for dietary intakes of saturated fat, polyunsaturated fat, trans fatty acids, eicosapentaenoic, and docosahexaenoic acids, cereal fiber, and folate attenuated the association (RR comparing extreme quintiles 0.84 [0.71-1.00], P for trend=0.12). Incidence rates of total or ischemic strokes were not associated with phylloquinone intake., Conclusion: The data suggest that high phylloquinone intake may be a marker for low CHD risk. Dietary and lifestyle patterns associated with phylloquinone intakes, rather than intake of the nutrient itself, might account for all or part of the weak association. .

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.

Context: Although increased intake of grain products has been recommended to prevent cardiovascular disease (CVD), prospective data examining the relation of whole grain intake to risk of ischemic stroke are sparse, especially among women., Objective: To examine the hypothesis that higher whole grain intake reduces the risk of ischemic stroke in women., Design, Setting, and Participants: A prospective cohort of 75,521 US women aged 38 to 63 years without previous diagnosis of diabetes mellitus, coronary heart disease, stroke, or other CVDs in 1984, who completed detailed food frequency questionnaires (FFQs) in 1984, 1986, 1990, and 1994, and were followed up for 12 years as part of the Nurses' Health Study., Main Outcome Measure: Incidence of ischemic stroke, confirmed by medical records, by quintile of whole grain intake according to FFQ responses., Results: During 861,900 person-years of follow-up, 352 confirmed incident cases of ischemic stroke occurred. We observed an inverse association between whole grain intake and ischemic stroke risk. The age-adjusted relative risks (RRs) from the lowest to highest quintiles of whole grain intake were 1.00 (referent), 0.68 (95% confidence interval [CI], 0.49-0.94), 0.69 (95% CI, 0.51-0.95), 0.49 (95% CI, 0.35-0.69), and 0.57 (95% CI, 0.42-0.78; P =.003 for trend). Adjustment for smoking modestly attenuated this association (RR comparing extreme quintiles, 0.64; 95% CI, 0.47-0.89). This inverse association remained essentially unchanged with further adjustment for known CVD risk factors, including saturated fat and transfatty acid intake (multivariate-adjusted RR comparing extreme quintiles, 0.69; 95% CI, 0.50-0.98). The inverse relation between whole grain intake and risk of ischemic stroke was also consistently observed among subgroups of women who never smoked, did not drink alcohol, did not exercise regularly, or who did not use postmenopausal hormones. No significant association was observed between total grain intake and risk of ischemic stroke., Conclusions: In this cohort, higher intake of whole grain foods was associated with a lower risk of ischemic stroke among women, independent of known CVD risk factors. These prospective data support the notion that higher intake of whole grains may reduce the risk of ischemic stroke.