Effect of vitamin D and/or omega-3 fatty acid supplementation on stroke outcomes: A randomized trial.

BACKGROUND AND PURPOSE: Among stroke patients, low serum 25-hydroxyvitamin D predicts poor outcomes. In mice, higher omega-3 (n-3) fatty acid intake diminishes brain damage after stroke. In this study, we tested whether vitamin D or n-3 fatty acids supplementation prior to stroke reduces the risk of functional limitations and physical disability after stroke. METHODS: We used data from VITAL (the VITamin D and OmegA-3 TriaL) which randomized middle-aged and older men and women without cardiovascular disease to vitamin D3 (2000 IU/day) and/or marine n-3 fatty acids (1 g/day) and followed them for incident stroke events. Individuals experiencing a non-fatal stroke were mailed questionnaires assessing functional limitations (the physical performance scale adapted from Nagi) and physical disability (the modified Katz Activities of Daily Living and Rosow-Breslau Functional Health scales). We used logistic regression to analyze associations between randomized treatment and limitations on each scale. RESULTS: A total of 290 individuals experienced their first stroke during the trial, of whom 197 stroke survivors completed the stroke outcomes questionnaire a median of 1.4 years after diagnosis. We observed no associations between randomized treatment to vitamin D and functional limitations (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.52, 1.97) or physical disability (Rosow-Breslau scale: OR 0.92, 95% CI 0.50, 1.67; Katz scale: OR 1.03, 95% CI 0.31, 3.42). Those randomized to n-3 fatty acids had a non-significantly lower risk of functional limitations (OR 0.55, 95% CI 0.28, 1.09) and physical disability (Rosow-Breslau scale: OR 0.56, 95% CI 0.31, 1.02; Katz sclae: OR 0.32, 95% CI 0.50, 1.67). CONCLUSION: Vitamin D or omega-3 fatty acid supplementation prior to stroke did not result in significantly improved post-stroke outcomes.

Circulating Very-Long-Chain SFA Concentrations Are Inversely Associated with Incident Type 2 Diabetes in US Men and Women.

BACKGROUND: Very-long-chain SFAs (VLCSFAs), such as arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have demonstrated inverse associations with cardiometabolic conditions, although more evidence is needed to characterize their relation with risk of type 2 diabetes (T2D). In addition, little is known regarding their potential dietary and lifestyle predictors. OBJECTIVE: We aimed to examine the association of plasma and erythrocyte concentrations of VLCSFAs with incident T2D risk. METHODS: We used existing measurements of fatty acid concentrations in plasma and erythrocytes among 2854 and 2831 participants in the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS), respectively. VLCSFAs were measured using GLC, and individual fatty acid concentrations were expressed as a percentage of total fatty acids. Incident T2D cases were identified by self-reports and confirmed by a validated supplementary questionnaire. Cox proportional hazards regression was used to evaluate the association between VLCSFAs and T2D, adjusting for demographic, lifestyle, and dietary variables. RESULTS: During 39,941 person-years of follow-up, we documented 243 cases of T2D. Intakes of peanuts, peanut butter, vegetable fat, dairy fat, and palmitic/stearic (16:0-18:0) fatty acids were significantly, albeit weakly, correlated with plasma and erythrocyte VLCSFA concentrations (|rs| ≤ 0.19). Comparing the highest with the lowest quartiles of plasma concentrations, pooled HRs (95% CIs) were 0.51 (0.35, 0.75) for arachidic acid, 0.43 (0.28, 0.64) for behenic acid, 0.40 (0.27, 0.61) for lignoceric acid, and 0.41 (0.27, 0.61) for the sum of VLCSFAs, after multivariate adjustments for demographic, lifestyle, and dietary factors. For erythrocyte VLCSFAs, only arachidic acid and behenic acid concentrations were inversely associated with T2D risk. CONCLUSIONS: Our findings suggest that, in US men and women, higher plasma concentrations of VLCSFAs are associated with lower risk of T2D. More research is needed to understand the mechanistic pathways underlying these associations.

Dietary fats and mortality among patients with type 2 diabetes: analysis in two population based cohort studies.

OBJECTIVE: To assess the association of dietary fatty acids with cardiovascular disease mortality and total mortality among patients with type 2 diabetes. DESIGN: Prospective, longitudinal cohort study. SETTING: Health professionals in the United States. PARTICIPANTS: 11 264 participants with type 2 diabetes in the Nurses' Health Study (1980-2014) and Health Professionals Follow-Up Study (1986-2014). EXPOSURES: Dietary fat intake assessed using validated food frequency questionnaires and updated every two to four years. MAIN OUTCOME MEASURE: Total and cardiovascular disease mortality during follow-up. RESULTS: During follow-up, 2502 deaths including 646 deaths due to cardiovascular disease were documented. After multivariate adjustment, intake of polyunsaturated fatty acids (PUFAs) was associated with a lower cardiovascular disease mortality, compared with total carbohydrates: hazard ratios comparing the highest with the lowest quarter were 0.76 (95% confidence interval 0.58 to 0.99; P for trend=0.03) for total PUFAs, 0.69 (0.52 to 0.90; P=0.007) for marine n-3 PUFAs, 1.13 (0.85 to 1.51) for α-linolenic acid, and 0.75 (0.56 to 1.01) for linoleic acid. Inverse associations with total mortality were also observed for intakes of total PUFAs, n-3 PUFAs, and linoleic acid, whereas monounsaturated fatty acids of animal, but not plant, origin were associated with a higher total mortality. In models that examined the theoretical effects of substituting PUFAs for other fats, isocalorically replacing 2% of energy from saturated fatty acids with total PUFAs or linoleic acid was associated with 13% (hazard ratio 0.87, 0.77 to 0.99) or 15% (0.85, 0.73 to 0.99) lower cardiovascular disease mortality, respectively. A 2% replacement of energy from saturated fatty acids with total PUFAs was associated with 12% (hazard ratio 0.88, 0.83 to 0.94) lower total mortality. CONCLUSIONS: In patients with type 2 diabetes, higher intake of PUFAs, in comparison with carbohydrates or saturated fatty acids, is associated with lower total mortality and cardiovascular disease mortality. These findings highlight the important role of quality of dietary fat in the prevention of cardiovascular disease and total mortality among adults with type 2 diabetes.

Dietary glutamine, glutamate and mortality: two large prospective studies in US men and women.

Background: Emerging studies have related circulating glutamine metabolites to various chronic diseases such as cardiovascular disease and cancer; diet is the major source of nutrients involved in glutamine metabolism. However, it remains unknown whether dietary intakes of glutamine, glutamate,and their ratio are related to total and cause-specific mortality. Methods: We followed 74 082 women from the Nurses' Health Study (1984-2012) and 42 303 men from the Health Professionals Follow-up Study (1986-2012), who were free of cardiovascular disease and cancer at baseline. Diet was updated every 2 to 4 years by using validated food frequency questionnaires. The content of glutamine and glutamate in foods was calculated based on protein fractions generated from gene sequencing methods and adjusted for total energy intake. Results: We documented 30 424 deaths during 2 878 344 person-years of follow-up. After adjustment for potential confounders including lifestyle and dietary factors, higher intakes of glutamine and glutamine-to-glutamate ratio were associated with significantly lower risk of total and cause-specific mortality. Compared with people in the lowest quintile of dietary glutamine-to-glutamate ratio, the pooled hazard ratio (HR) in the highest quintile was 0.87 [95% confidence interval (CI): 0.84, 0.91; P for trend < 0.001) for total mortality, 0.81 (95% CI: 0.75, 0.88; P for trend < 0.001) for cardiovascular mortality, and 0.93 (95% CI: 0.87, 0.99; P for trend = 0.01) for cancer mortality. Conclusions: We found dietary glutamine and glutamine-to-glutamate ratio were inversely related to risk of mortality, particularly cardiovascular mortality, independent of other dietary and lifestyle factors, in US men and women.

Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts.

BACKGROUND AND PURPOSE: The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke. METHODS: We measured circulating phospholipid fatty acids at baseline in 3 separate US cohorts: CHS (Cardiovascular Health Study), NHS (Nurses' Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis. RESULTS: A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.58-0.92) and DHA (HR, 0.80; 95% CI, 0.64-1.00) but not eicosapentaenoic acid (HR, 0.94; 95% CI, 0.77-1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95% CI, 0.34-0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95% CI, 0.37-0.92). Findings in each individual cohort were consistent with pooled results. CONCLUSIONS: In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid.

Dairy fat and risk of cardiovascular disease in 3 cohorts of US adults.

BACKGROUND: Few prospective studies have examined dairy fat in relation to cardiovascular disease (CVD). OBJECTIVE: We aimed to evaluate the association between dairy fat and incident CVD in US adults. DESIGN: We followed 43,652 men in the Health Professionals Follow-Up Study (1986-2010), 87,907 women in the Nurses' Health Study (1980-2012), and 90,675 women in the Nurses' Health Study II (1991-2011). Dairy fat and other fat intakes were assessed every 4 y with the use of validated food-frequency questionnaires. RESULTS: During 5,158,337 person-years of follow-up, we documented 14,815 incident CVD cases including 8974 coronary heart disease cases (nonfatal myocardial infarction or fatal coronary disease) and 5841 stroke cases. In multivariate analyses, compared with an equivalent amount of energy from carbohydrates (excluding fruit and vegetables), dairy fat intake was not significantly related to risk of total CVD (for a 5% increase in energy from dairy fat, the RR was 1.02; 95% CI: 0.98, 1.05), coronary heart disease (RR: 1.03; 95% CI: 0.98, 1.09), or stroke (RR: 0.99; 95% CI: 0.93, 1.05) (P > 0.05 for all). In models in which we estimated the effects of exchanging different fat sources, the replacement of 5% of energy intake from dairy fat with equivalent energy intake from polyunsaturated fatty acid (PUFA) or vegetable fat was associated with 24% (RR: 0.76; 95% CI: 0.71, 0.81) and 10% (RR: 0.90; 95% CI: 0.87, 0.93) lower risk of CVD, respectively, whereas the 5% energy intake substitution of other animal fat with dairy fat was associated with 6% increased CVD risk (RR: 1.06; 95% CI: 1.02, 1.09). CONCLUSIONS: The replacement of animal fats, including dairy fat, with vegetable sources of fats and PUFAs may reduce risk of CVD. Whether the food matrix may modify the effect of dairy fat on health outcomes warrants further investigation.

Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts.

BACKGROUND: In prospective studies, the relationship of self-reported consumption of dairy foods with risk of diabetes mellitus is inconsistent. Few studies have assessed dairy fat, using circulating biomarkers, and incident diabetes mellitus. We tested the hypothesis that circulating fatty acid biomarkers of dairy fat, 15:0, 17:0, and t-16:1n-7, are associated with lower incident diabetes mellitus. METHODS AND RESULTS: Among 3333 adults aged 30 to 75 years and free of prevalent diabetes mellitus at baseline, total plasma and erythrocyte fatty acids were measured in blood collected in 1989 to 1990 (Nurses' Health Study) and 1993 to 1994 (Health Professionals Follow-Up Study). Incident diabetes mellitus through 2010 was confirmed by a validated supplementary questionnaire based on symptoms, diagnostic tests, and medications. Risk was assessed by using Cox proportional hazards, with cohort findings combined by meta-analysis. During mean±standard deviation follow-up of 15.2±5.6 years, 277 new cases of diabetes mellitus were diagnosed. In pooled multivariate analyses adjusting for demographics, metabolic risk factors, lifestyle, diet, and other circulating fatty acids, individuals with higher plasma 15:0 had a 44% lower risk of diabetes mellitus (quartiles 4 versus 1, hazard ratio, 0.56; 95% confidence interval, 0.37-0.86; P-trend=0.01); higher plasma 17:0, 43% lower risk (hazard ratio, 0.57; 95% confidence interval, 0.39-0.83; P-trend=0.01); and higher t-16:1n-7, 52% lower risk (hazard ratio, 0.48; 95% confidence interval, 0.33-0.70; P-trend <0.001). Findings were similar for erythrocyte 15:0, 17:0, and t-16:1n-7, although with broader confidence intervals that only achieved statistical significance for 17:0. CONCLUSIONS: In 2 prospective cohorts, higher plasma dairy fatty acid concentrations were associated with lower incident diabetes mellitus. Results were similar for erythrocyte 17:0. Our findings highlight the need to better understand the potential health effects of dairy fat, and the dietary and metabolic determinants of these fatty acids.

Intakes of magnesium, potassium, and calcium and the risk of stroke among men.

BACKGROUND: Intakes of magnesium, potassium, and calcium have been inversely associated with the incidence of hypertension, a known risk factor for stroke. However, only a few studies have examined intakes of these cations in relation to risk of stroke. AIM: The aim of this study was to investigate whether high intake of magnesium, potassium, and calcium is associated with reduced stroke risk among men. METHODS: We prospectively examined the associations between intakes of magnesium, potassium, and calcium from diet and supplements, and the risk of incident stroke among 42 669 men in the Health Professionals Follow-up Study, aged 40 to 75 years and free of diagnosed cardiovascular disease and cancer at baseline in 1986. We calculated the hazard ratio of total, ischemic, and haemorrhagic strokes by quintiles of each cation intake, and of a combined dietary score of all three cations, using multivariate Cox proportional hazard models. RESULTS: During 24 years of follow-up, 1547 total stroke events were documented. In multivariate analyses, the relative risks and 95% confidence intervals of total stroke for men in the highest vs. lowest quintile were 0·87 (95% confidence interval, 0·74-1·02; P, trend = 0·04) for dietary magnesium, 0·89 (95% confidence interval, 0·76-1·05; P, trend = 0·10) for dietary potassium, and 0·89 (95% confidence interval, 0·75-1·04; P, trend = 0·25) for dietary calcium intake. The relative risk of total stroke for men in the highest vs. lowest quintile was 0·74 (95% confidence interval, 0·59-0·93; P, trend = 0·003) for supplemental magnesium, 0·66 (95% confidence interval, 0·50-0·86; P, trend = 0·002) for supplemental potassium, and 1·01 (95% confidence interval, 0·84-1·20; P, trend = 0·83) for supplemental calcium intake. For total intake (dietary and supplemental), the relative risk of total stroke for men in the highest vs. lowest quintile was 0·83 (95% confidence interval, 0·70-0·99; P, trend = 0·04) for magnesium, 0·88 (95% confidence interval, 0·75-4; P, trend = 6) for potassium, and 3 (95% confidence interval, 79-09; P, trend = 84) for calcium. Men in the highest quintile for a combined dietary score of all three cations had a multivariate relative risk of 0·79 (95% confidence interval, 0·67-0·92; P, trend = 0·008) for total stroke, compared with those in the lowest. CONCLUSIONS: A diet rich in magnesium, potassium, and calcium may contribute to reduced risk of stroke among men. Because of significant collinearity, the independent contribution of each cation is difficult to define.

Dietary flavonoids and risk of stroke in women.

BACKGROUND AND PURPOSE: To date, few studies have examined associations between the wide range of flavonoid subclasses and risk of ischemic, hemorrhagic, and total stroke. METHODS: We conducted a prospective study among 69 622 women from the Nurses' Health Study. Total flavonoid and subclass intakes were calculated from semiquantitative food frequency questionnaires collected every 4 years using an updated and extended US Department of Agriculture flavonoid database. RESULTS: During 14 years of follow-up, 1803 incident strokes were confirmed. After adjusting for potential confounders, women in the highest compared with the lowest quintile of flavanone intake had a relative risk of ischemic stroke of 0.81 (95% CI, 0.66-0.99; P=0.04). Citrus fruits/juices, the main dietary source of flavanones, tended to be associated with a reduced risk for ischemic stroke (relative risk, 0.90; 95% CI, 0.77-1.05) comparing extreme quintiles. CONCLUSIONS: Total flavonoid intake was not inversely associated with risk of stroke; however, increased intake of the flavanone subclass was associated with a reduction in the risk of ischemic stroke. Citrus fruit consumption may be associated with a reduction in stroke risk, and experimental data support these epidemiological associations that the flavanone content of citrus fruits may potentially be cardioprotective. Further prospective studies are needed to confirm these associations.

Vitamin D and calcium supplementation and one-year change in mammographic density in the women's health initiative calcium and vitamin D trial.

BACKGROUND: Calcium and vitamin D may be inversely related to breast cancer risk, in part by affecting mammographic density. However, results from previous, mostly cross-sectional studies have been mixed, and there have been few randomized clinical trials of the effect of calcium and vitamin D supplementation on change in mammographic density. METHODS: We assessed the effect of one year of supplementation on mammographic density in 330 postmenopausal women enrolled in the Women's Health Initiative hormone therapy (HT) and calcium and vitamin D (CaD) trials. Women were randomized to receive 1,000 mg/d of elemental calcium carbonate plus 400 IU/d of vitamin D(3) or placebo. RESULTS: After approximately one year, mammographic density decreased 2% in the CaD supplementation group and increased 1% in the placebo group (ratio of means = 0.97; 95% CI = 0.81-1.17). Results suggested potential interaction by HT use (P = 0.08). Among women randomized to HT placebo, the ratio of mean density comparing CaD supplementation and placebo groups was 0.82 (95% CI = 0.61-1.11) vs. 1.16 (95% CI = 0.92-1.45) in women randomized to active HT. In sensitivity analyses limited to women taking ≥ 80% of study supplements, ratios were 0.67 (95% CI = 0.41-1.07) in women not assigned to HT and 1.07 (95% CI = 0.79-1.47) women assigned to HT. CONCLUSIONS: We observed no overall effect of vitamin D and calcium supplementation on mammographic density after one year. IMPACT: Potential interaction between these nutrients and estrogen as related to mammographic density warrants further study.

Vitamin D intake and risk of cardiovascular disease in US men and women.

BACKGROUND: Although studies have linked vitamin D deficiency to an increased risk of cardiovascular disease (CVD), evidence regarding whether vitamin D intake from foods or supplements is prospectively associated with lower CVD risk in healthy humans is limited and inconclusive. OBJECTIVE: The objective was to comprehensively evaluate the associations between both dietary and supplemental vitamin D and CVD risk. DESIGN: In the Nurses' Health Study (1984-2006) and the Health Professionals Follow-Up Study (1986-2006)-consisting of 74,272 women and 44,592 men, respectively, who were free of CVD and cancer at baseline-we prospectively examined the association between vitamin D intake and incident CVD. RESULTS: Over a total of 2,280,324 person-years of follow-up, we identified 9886 incident cases of coronary heart disease and stroke. After multivariate adjustment for age and other CVD risk factors, a higher total vitamin D intake (from foods and supplements) was associated with a decreased risk of CVD in men but not in women; the relative risks (95% CIs) for a comparison of participants who met the Dietary Reference Intake of vitamin D (≥600 IU/d) with participants whose vitamin D intake was <100 IU/d were 0.84 (0.72, 0.97; P for trend = 0.009) for men and 1.02 (0.89, 1.17; P for trend = 0.12) for women. CONCLUSIONS: These observations suggest that a higher intake of vitamin D is associated with a lower risk of CVD in men but not in women. Further research is needed to confirm these findings and to elucidate a biological basis for potential sex differences.

Dietary vitamin D and calcium intake and mammographic density in postmenopausal women.

OBJECTIVE: Dietary intake of vitamin D and calcium may be related to risk of breast cancer, possibly by affecting mammographic density. However, the few studies that have evaluated the association between these nutrients and mammographic density in postmenopausal women have had inconsistent results. METHODS: We conducted a cross-sectional analysis in 808 participants of the Mammogram Density Ancillary Study of the Women's Health Initiative. Mammographic percent density was measured using baseline mammograms taken before randomization of participants in the intervention trials. Vitamin D and calcium intake was assessed with a validated food frequency questionnaire and an inventory of current supplement use, both completed at baseline. RESULTS: After adjustment for age, body mass index, regional solar irradiance, and other factors, we did not find a relationship between vitamin D or calcium intake and mammographic density. Mean mammographic percent densities in women reporting total vitamin D intakes of less than 100, 100 to 199, 200 to 399, 400 to 599, and 600 or greater IU/day were 5.8%, 10.4%, 6.2%, 3.8%, and 5.1%, respectively (P trend = 0.67). Results in women reporting a total calcium intake of less than 500, 500 to 749, 750 to 999, 1,000 to 1,199, and 1,200 or greater mg/day were 7.3%, 4.9%, 7.3%, 6.9%, and 7.11%, respectively (P trend = 0.51). We did not observe any effect modification by overall level of mammographic density or solar irradiance, but supplemental vitamin D use was associated with lower density in younger women (P interaction = 0.009). CONCLUSIONS: These findings do not support a relationship between dietary vitamin D or calcium intake and mammographic density in postmenopausal women. Additional studies should explore these associations in women of different ages and in relation to serum vitamin D levels.

Coffee consumption and risk of stroke in women.

BACKGROUND: Data on the association between coffee consumption and risk of stroke are sparse. We assessed the association between coffee consumption and the risk of stroke over 24 years of follow-up in women. METHODS AND RESULTS: We analyzed data from a prospective cohort of 83,076 women in the Nurses' Health Study without history of stroke, coronary heart disease, diabetes, or cancer at baseline. Coffee consumption was assessed first in 1980 and then repeatedly every 2 to 4 years, with follow-up through 2004. We documented 2280 strokes, of which 426 were hemorrhagic, 1224 were ischemic, and 630 were undetermined. In multivariable Cox regression models with adjustment for age, smoking status, body mass index, physical activity, alcohol intake, menopausal status, hormone replacement therapy, aspirin use, and dietary factors, the relative risks (RRs) of stroke across categories of coffee consumption (<1 cup per month, 1 per month to 4 per week, 5 to 7 per week, 2 to 3 per day, and >or=4 per day) were 1, 0.98 (95% CI, 0.84 to 1.15), 0.88 (95% CI, 0.77 to 1.02), 0.81 (95% CI, 0.70 to 0.95), and 0.80 (95% CI, 0.64 to 0.98) (P for trend=0.003). After further adjustment for high blood pressure, hypercholesterolemia, and type 2 diabetes, the inverse association remained significant. The association was stronger among never and past smokers (RR for >or=4 cups a day versus <1 cup a month, 0.57; 95% CI, 0.39 to 0.84) than among current smokers (RR for >or=4 cups a day versus <1 cup a month, 0.97; 95% CI, 0.63 to 1.48). Other drinks containing caffeine such as tea and caffeinated soft drinks were not associated with stroke. Decaffeinated coffee was associated with a trend toward lower risk of stroke after adjustment for caffeinated coffee consumption (RR for >or=2 cups a day versus <1 cup a month, 0.89; 95% CI, 0.73 to 1.08; P for trend=0.05). CONCLUSIONS: Long-term coffee consumption was not associated with an increased risk of stroke in women. In contrast, our data suggest that coffee consumption may modestly reduce risk of stroke.

Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial infarction.

BACKGROUND: Whereas dietary intake of long-chain n-3 fatty acids has been associated with risk of nonfatal myocardial infarction (MI), few studies have examined the relation for blood concentrations. OBJECTIVE: We aimed to investigate the effect of long-chain n-3 fatty acids in blood on the risk of nonfatal MI. DESIGN: Baseline blood samples were collected from 32 826 participants of the Nurses' Health Study in 1989-1990, among whom 146 incident cases of nonfatal MI were ascertained during 6 y of follow-up and matched with 288 controls. RESULTS: After multivariate adjustment, the relative risks (95% CI) comparing the highest with the lowest quartiles in plasma were 0.23 (0.09, 0.55; P for trend = 0.001) for eicosapentaenoic acid (EPA), 0.40 (0.20, 0.82; P for trend = 0.004) for docosapentaenoic acid (DPA), and 0.46 (0.18, 1.16; P for trend = 0.07) for docosahexaenoic acid (DHA). The associations for these fatty acids in erythrocytes were generally weaker and nonsignificant. In contrast to EPA and DHA, blood concentrations of DPA were not correlated with dietary consumption of n-3 fatty acids. Higher plasma concentrations of EPA, DPA, and DHA were associated with higher plasma concentrations of HDL cholesterol and lower concentrations of triacylglycerol and inflammatory markers. CONCLUSIONS: Higher plasma concentrations of EPA and DPA are associated with a lower risk of nonfatal MI among women. These findings may partly reflect dietary consumption but, particularly for DPA, may indicate important risk differences based on metabolism of long-chain n-3 fatty acids.

Coffee consumption and coronary heart disease in men and women: a prospective cohort study.

BACKGROUND: We examined the association between long-term habitual coffee consumption and risk of coronary heart disease (CHD). METHODS AND RESULTS: We performed a prospective cohort study with 44,005 men and 84,488 women without history of cardiovascular disease or cancer. Coffee consumption was first assessed in 1986 for men and in 1980 for women and then repeatedly every 2 to 4 years; the follow-up continued through 2000. We documented 2173 incident cases of coronary heart disease (1449 nonfatal myocardial infarctions and 724 fatal cases of CHD) among men and 2254 cases (1561 nonfatal myocardial infarctions and 693 fatal cases of CHD) among women. Among men, after adjustment for age, smoking, and other CHD risk factors, the relative risks (RRs) of CHD across categories of cumulative coffee consumption (<1 cup/mo, 1 cup/mo to 4 cups/wk, 5 to 7 cups/wk, 2 to 3 cups/d, 4 to 5 cups/d, and > or =6 cups/d) were 1.0, 1.04 (95% confidence interval 0.91 to 1.17), 1.02 (0.91 to 1.15), 0.97 (0.86 to 1.11), 1.07 (0.88 to 1.31), and 0.72 (0.49 to 1.07; P for trend=0.41); among women, the RRs were 1.0, 0.97 (0.83 to 1.14), 1.02 (0.90 to 1.17), 0.84 (0.74 to 0.97), 0.99 (0.83 to 1.17), and 0.87 (0.68 to 1.11; P for trend=0.08). Stratification by smoking status, alcohol consumption, history of type 2 diabetes mellitus, and body mass index gave similar results. Similarly, we found no effect when the most recent coffee consumption was examined. RRs for quintiles of caffeine intake varied from 0.97 (0.84 to 1.10) in the second quintile to 0.97 (0.84 to 1.11) in the highest quintile (P for trend=0.82) in men and from 1.02 (0.90 to 1.16) to 0.97 (0.85 to 1.11; P for trend=0.37) in women. CONCLUSIONS: These data do not provide any evidence that coffee consumption increases the risk of CHD.

Folate intake and risk of stroke among women.

BACKGROUND AND PURPOSE: Few studies have examined the association between folate intake and risk of stroke, although numerous studies have suggested that high levels of homocysteine are positively related to stroke. We aim to assess the relation between folate intake and stroke incidence among women participating in the Nurses' Health Study. METHODS: 83,272 female nurses aged 34 to 59 years in 1980 and residing in 11 US states were followed-up for 18 years. Follow-up questionnaires were sent biennially to update information on diet and to identify newly diagnosed cases of stroke and other illnesses. RESULTS: During 1,379614 person-years of follow-up from 1980 to 1998, we identified 1140 incident cases of stroke. Using age-adjusted and multivariable-adjusted models, no appreciable association between the intake of folate and total incidence of stroke was observed [relative risk in the multivariable-adjusted model for the highest quintile of folate intake (median=696 microg/d) compared with the lowest quintile (median=158 microg/d) was 1.01 (95% confidence interval [CI]: 0.79 to 1.29), P for trend=0.8]. Similar null results were found in secondary analyses on stroke subtypes (ischemic, thrombotic, embolic, subarachnoid hemorrhage, intraparenchymal hemorrhage) and in analyses that separately assessed dietary folate (excluding supplement users) and folate supplement intake. CONCLUSIONS: Folate intake was not associated with incident stroke among women participating in the Nurses' Health Study.

Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women.

BACKGROUND: Although several prospective cohort studies have found an inverse association between fish consumption and risk of coronary heart disease (CHD) or sudden cardiac death in the general population, limited data are available among diabetic patients. METHODS AND RESULTS: We examined prospectively the association between intake of fish and omega-3 fatty acids and risk of CHD and total mortality among 5103 female nurses with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline. Between 1980 and 1996 (45 845 person-years of follow-up), we documented 362 incident cases of CHD (141 CHD deaths and 221 nonfatal myocardial infarctions) and 468 deaths from all causes. Compared with women who seldom consumed fish (<1 serving/mo), the relative risks (RRs) (95% CI) of CHD adjusted for age, smoking, and other established coronary risk factors were 0.70 (0.48 to 1.03) for fish consumption 1 to 3 times per month, 0.60 (0.42 to 0.85) for once per week, 0.64 (0.42 to 0.99) for 2 to 4 times per week, and 0.36 (0.20 to 0.66) for 5 or more times per week (P for trend=0.002). Higher consumption of fish was also associated with a significantly lower total mortality (multivariate RR=0.48 [0.29 to 0.80] for > or =5 times per week [P for trend=0.005]). Higher consumption of long-chain omega-3 fatty acids was associated with a trend toward lower incidence of CHD (RR=0.69 [95% CI 0.47 to 1.03], P for trend=0.10) and total mortality (RR=0.63 [95% CI, 0.45 to 0.88], P for trend=0.02). CONCLUSIONS: A higher consumption of fish and long-chain omega-3 fatty acids was associated with a lower CHD incidence and total mortality among diabetic women.

Fish and omega-3 fatty acid intake and risk of coronary heart disease in women.

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 available 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 84 688 female nurses enrolled in the Nurses' Health Study, aged 34 to 59 years and free 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 (<1 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 multivariable 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 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 higher intake of omega-3 fatty acids had a lower risk of CHD, with multivariable RRs of 1.0, 0.93, 0.78, 0.68, and 0.67 (P<.001 for trend) across quintiles of intake. For fish intake 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.