Multivitamin use and risk of stroke incidence and mortality amongst women.

BACKGROUND AND PURPOSE: Few studies have examined the association between multivitamin use and the risk of stroke incidence and mortality, and the results remain inconclusive as to whether multivitamins are beneficial. METHODS: The associations between multivitamin use and the risk of incident stroke and stroke mortality were prospectively examined in 86 142 women in the Nurses' Health Study, aged 34-59 years and free of diagnosed cardiovascular disease at baseline. Multivitamin use and covariates were updated every 2 years and strokes were documented by review of medical records. Hazard ratios of total, ischaemic and hemorrhagic strokes were calculated across categories of multivitamin use (non-user, past, current user) and duration (years), using Cox proportional hazards models. RESULTS: During 32 years of follow-up from 1980 to 2012, 3615 incident strokes were documented, including 758 deaths from stroke. In multivariate analyses, women who were current multivitamin users did not have a lower risk of incident total stroke compared to non-users [relative risk (RR) 1.02, 95% confidence interval (CI) 0.93-1.11], even those with longer durations of 15 or more years of use (RR 1.08, 95% CI 0.97-1.20) or those with a lower quality diet (RR 0.96, 95% CI 0.80-1.15). There was also no indication of benefit from multivitamin use for incident ischaemic or hemorrhagic strokes or for total stroke mortality. CONCLUSIONS: Long-term multivitamin use was not associated with reduced risk of stroke incidence or mortality amongst women in the study population, even amongst those with a lower diet quality. An effect in a less well-nourished population cannot be ruled out.

Plasma uric acid concentrations and risk of ischaemic stroke in women.

BACKGROUND AND PURPOSE: Elevated plasma uric acid has been inconsistently associated with an increased risk of total stroke; however, data are sparse amongst women. The association between plasma uric acid concentrations and ischaemic stroke amongst women was examined and the effect modification by key cardiovascular risk factors was evaluated. METHODS: A nested case-control design with matching by age, race/ethnicity, smoking status, menopausal status, postmenopausal hormone therapy use, date of blood draw and fasting status was utilized amongst female participants of the Nurses' Health Study who provided blood samples between 1989 and 1990. Plasma uric acid was measured on stored blood samples. The National Survey of Stroke criteria were utilized to confirm 460 incident cases of ischaemic stroke by medical records from 1990 to 2006. Multivariable conditional logistic regression models were estimated. RESULTS: In matched analysis, risk of ischaemic stroke increased by 15% for each 1 mg/dl increase in plasma uric acid [95% confidence interval (CI) 3%-28%], but was no longer significant after adjustment for cardiovascular risk factors, particularly history of hypertension. The highest quartile of uric acid was significantly associated with greater risk of ischaemic stroke (relative risk 1.56; 95% CI 1.06-2.29, extreme quartiles) in matched analysis, but estimates were no longer significant after adjustment for cardiovascular risk factors (relative risk 1.43; 95% CI 0.93-2.18). Significant effect modification by key cardiovascular risk factors was not observed. CONCLUSIONS: Plasma uric acid levels were not independently associated with increased risk of ischaemic stroke in this cohort of women. Whilst plasma uric acid was associated with stroke risk factors, it was not independently associated with stroke risk.

Calcium supplement intake and risk of cardiovascular disease in women.

UNLABELLED: Some recent reports suggest that calcium supplement use may increase risk of cardiovascular disease. In a prospective cohort study of 74,245 women in the Nurses' Health Study with 24 years of follow-up, we found no independent associations between supplemental calcium intake and risk of incident coronary heart disease (CHD) and stroke. INTRODUCTION: Some recent reports suggest that calcium supplements may increase cardiovascular disease (CVD) risk. The objective was to examine the independent associations between calcium supplement use and risk of CVD. METHODS: We conducted a prospective cohort study of supplemental calcium use and incident CVD in 74,245 women in the Nurses' Health Study (1984-2008) free of CVD and cancer at baseline. Calcium supplement intake was assessed every 4 years. Outcomes were incident CHD (nonfatal or fatal MI) and stroke (ischemic or hemorrhagic), confirmed by medical record review. RESULTS: During 24 years of follow-up, 4,565 cardiovascular events occurred (2,709 CHD and 1,856 strokes). At baseline, women who took calcium supplements had higher levels of physical activity, smoked less, and had lower trans fat intake compared with those who did not take calcium supplements. After multivariable adjustment for age, body mass index, dietary calcium, vitamin D intake, and other CVD risk factors, the relative risk of CVD for women taking >1,000 mg/day of calcium supplements compared with none was 0.82 (95% confidence interval [CI] 0.74 to 0.92; p for trend <0.001). For women taking >1,000 mg/day of calcium supplements compared with none, the multivariable-adjusted relative risk for CHD was 0.71 (0.61 to 0.83; p for trend < 0.001) and for stroke was 1.03 (0.87 to 1.21; p for trend = 0.61). The relative risks were similar in analyses limited to non-smokers, women without hypertension, and women who had regular physical exams. CONCLUSIONS: Our findings do not support the hypothesis that calcium supplement intake increases CVD risk in women.

Telomere length and ischaemic stroke in women: a nested case-control study.

BACKGROUND AND PURPOSE: Telomere shortening has been implicated in cardiovascular disease (CVD). However, prospective data on the association between relative telomere length (RTL) and ischaemic stroke are scarce and inconclusive. METHODS: We used a nested case-control design among women participating in the prospective Nurses' Health Study. Participants provided blood samples in 1990 and were followed till 2006. Women with confirmed incident ischaemic stroke were matched to controls by age, smoking, postmenopausal status and postmenopausal hormone use. Quantitative polymerase chain reaction was used to determine RTL in genomic DNA extracted from peripheral blood leukocytes. Conditional logistic regression was used to determine the risk of ischaemic stroke associated with RTL, using RTL quartiles and as dichotomous according to the median. RESULTS: Data on RTL were available from 504 case-control pairs. Results did not suggest an association between RTL and ischaemic stroke. The odds ratio (OR) for ischaemic stroke was 0.82 [95% confidence interval (CI) 0.52-1.32] comparing lowest with the highest RTL quartile and 0.90 (95% CI 0.65-1.24) comparing RTL below the median with RTL above the median. Associations were unchanged after additional adjustment for cardiovascular risk factors. Further analyses suggested an association between RTL and fatal ischaemic stroke (54 case-control pairs; lowest versus highest quartile OR = 1.99, 95%CI 0.26-14.9); however, results were statistically insignificant. CONCLUSION: In this large nested case-control study among women RTL was not associated with ischaemic stroke. In light of the varying study results in the literature on the association between telomere length and stroke, additional research is warranted.

Psoriasis and risk of nonfatal cardiovascular disease in U.S. women: a cohort study.

BACKGROUND: Psoriasis has been linked to cardiovascular comorbidities in cross-sectional studies, but evidence regarding the association between psoriasis and incident cardiovascular disease (CVD) is limited. OBJECTIVES: To make a prospective evaluation of the association between psoriasis and risk of incident nonfatal CVD. METHODS: Participants (n = 96, 008) were included from the Nurses' Health Study II, and followed for 18 years. Information on physician-diagnosed psoriasis was obtained by self-report and diagnosis was confirmed by supplementary questionnaires. We included 2463 individuals with self-reported psoriasis and a subsample of 1242 with validated psoriasis. The main outcome was incident nonfatal CVD events [nonfatal myocardial infarction (MI) and nonfatal stroke], ascertained by biennial questionnaires and confirmed. RESULTS: During 1 709 069 person-years of follow-up, 713 incident nonfatal CVD events were confirmed. Psoriasis was associated with a significantly increased multivariate-adjusted hazard ratio (HR) of nonfatal CVD, 1·55 [95% confidence interval (CI): 1·04-2·31]. HRs for nonfatal MI and stroke were 1·70 (95% CI: 1·01-2·84) and 1·45 (95% CI: 0·80-2·65), respectively. The association remained consistent in a sensitivity analysis of confirmed psoriasis (HR: 2·06, 95% CI: 1·31-3·26). For individuals with concomitant psoriatic arthritis, the risk of nonfatal CVD was even higher (HR: 3·47; 95% CI: 1·85-6·51). Women diagnosed with psoriasis at < 40 years of age or with duration of psoriasis ≥ 9 years had substantial elevations in CVD risk: HR: 3·26 (95% CI: 1·21-8·75) and 3·09 (95% CI: 1·15-8·29), respectively. CONCLUSIONS: Psoriasis is an independent predictor for nonfatal CVD among women, with particularly high risk for those with longer duration of psoriasis and concomitant psoriatic arthritis.

Use of antidepressant medication and risk of type 2 diabetes: results from three cohorts of US adults.

AIMS/HYPOTHESIS: The results of several studies have suggested a potential positive association between use of antidepressant medication (ADM) and incident type 2 diabetes mellitus. We examined this association in three cohorts of US adults. METHODS: We followed 29,776 men in the Health Professionals Follow-up Study (HPFS, 1990-2006), 61,791 women in the Nurses' Health Study I (NHS I, 1996-2008) and 76,868 women in NHS II (1993-2005), who were free of diabetes mellitus, cardiovascular disease or cancer at baseline. The mean baseline ages for participants from the HPFS and NHS I and II were 56.4, 61.3 and 38.1 years, respectively. ADM use and other covariates were assessed at baseline and updated every 2 years. A time-dependent Cox proportional hazards model was used, and HRs were pooled together across the three cohorts. RESULTS: During 1,644,679 person-years of follow-up, we documented 6,641 new cases of type 2 diabetes. ADM use was associated with an increased risk of diabetes in all three cohorts in age-adjusted models (pooled HR 1.68 [95% CI 1.27, 2.23]). The association was attenuated after adjustment for diabetes risk factors and histories of high cholesterol and hypertension (1.30 [1.14, 1.49]), and further attenuated by controlling for updated BMI (1.17 [1.09, 1.25]). Use of selective serotonin reuptake inhibitors and other antidepressants (mainly tricyclic antidepressants) were both associated with an elevated risk of diabetes, with pooled multivariate-adjusted HRs of 1.10 (1.00, 1.22) and 1.26 (1.11, 1.42), respectively. CONCLUSIONS/INTERPRETATION: The results suggest that ADM users had a moderately elevated risk of type 2 diabetes mellitus compared with non-users, even after adjustment for BMI.

Association of estrogen receptor 2 gene polymorphisms with obesity in women (obesity and estrogen receptor 2 gene).

OBJECTIVE: Few studies have examined the association between genetic variants of the estrogen receptor beta (ESR2) and obesity in postmenopausal women. METHODS: The relationship of three polymorphisms (rs1271572, rs1256049 and rs4986938) and their associated haplotypes in the ESR2 gene with obesity and overweight were evaluated in 561 apparently healthy women (median age 63 years) from the Women's Health Study. Most of the women were postmenopausal (99.1%). The associations between genotypes and haplotypes with obesity (BMI> or =30kg/m(2)) and overweight (BMI> or =25kg/m(2)) were evaluated by logistic regression, assuming an additive model. RESULTS: No association was observed for any of the three polymorphisms with BMI, overweight or obesity. In haplotype analyses, one haplotype (major allele for all polymorphisms) was associated with a borderline inverse association with overweight but not obesity (OR=0.62, 95% CI=0.39-0.98). CONCLUSIONS: An inverse and borderline significant association was found between the ESR2 G-G-G haplotype and overweight in postmenopausal women. Further investigation regarding the association between ESR2 and adiposity should be performed to confirm these findings.

Polymorphisms in advanced glycosylation end product-specific receptor (AGER) gene, insulin resistance, and type 2 diabetes mellitus.

BACKGROUND: Variants in the advanced glycosylation end product-specific receptor (AGER) gene have been associated with diabetic vasculopathy, however their role in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM) are uncertain. We investigated the relationship of 3 polymorphisms (rs1800625, rs1800624 and rs2070600) in the AGER gene and their haplotypes with T2DM as well as insulin resistance. METHODS: A case-control study from community-based population sample of the Boston metropolitan area was performed in 637 diabetic patients and 596 controls (non-diabetic). The relationships between genotypes and T2DM were evaluated by linear and logistic regression models. Associations with insulin resistance [using corrected insulin response (CIR-30), insulin sensitivity index (ISI-120) and oral glucose tolerance test] were also examined among controls. RESULTS: We found no consistent association between prevalent type 2 diabetes mellitus, and "insulin indices" (CIR-30, ISI-120 and oral glucose tolerance test) and the AGER polymorphisms. The A allele in the rs1800624 was modestly associated with a progressive decrease in CIR-30 levels only among Black controls (p=0.03). CONCLUSIONS: A suggestive association between the A allele in the rs1800624 and CIR-30 levels was found. Further large and multiethnic studies should be performed to clarify these relationships.

HbA1c measured in stored erythrocytes and mortality rate among middle-aged and older women.

AIMS/HYPOTHESIS: Diabetes is known to increase mortality rate, but the degree to which mild hyperglycaemia may be associated with the risk of death is uncertain. We examined the association between HbA1c measured in stored erythrocytes and mortality rate in women with and without diabetes. METHODS: We conducted a cohort study of 27,210 women>or=45 years old with no history of cardiovascular disease or cancer who participated in the Women's Health Study, a randomised trial of vitamin E and aspirin. RESULTS: Over a median of 10 years of follow-up, 706 women died. Proportional hazards models adjusted for age, smoking, hypertension, blood lipids, exercise, postmenopausal hormone use, multivitamin use and C-reactive protein were used to estimate the relative risk of mortality. Among women without a diagnosis of diabetes and HbA1c<5.60%, those in the top quintile (HbA1c 5.19-5.59%) had a relative risk of mortality of 1.28 (95% CI 0.98-1.69, p value for linear trend=0.14) compared with those with HbA1c 2.27-4.79%. Women with HbA1c 5.60-5.99% and no diagnosis of diabetes had a 54% increased risk of mortality (95% CI 1-136%) compared with those with HbA1c 2.27-4.79%. HbA1c was significantly associated with mortality across the range 4.50-7.00% (p value for linear trend=0.02); a test of deviation from linearity was not statistically significant (p=0.67). Diabetic women had more than twice the mortality risk of non-diabetic women. CONCLUSIONS/INTERPRETATION: This study provides further evidence that chronic mild hyperglycaemia, even in the absence of diagnosed diabetes, is associated with increased risk of mortality. ClinicalTrials.gov ID no.: NCT00000479.

Phylloquinone intake as a marker for coronary heart disease risk but not stroke in women.

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. .

Lifetime physical activity and risk of breast cancer.

We conducted a case-control study of 394 women with breast cancer and 788 control women (91% response) to investigate the association of lifetime physical activity with mainly menopausal breast cancer risk. After controlling for potential confounders, the odds ratios (95% confidence intervals) for increasing quartiles of lifetime physical activity were 1.00 (referent), 0.91 (0.60-1.37), 0.91 (0.60-1.39), and 1.10 (0.73-1.67), respectively; P, trend = 0.47. We also separately examined physical activity at ages 12-18, 19-34, 35-49 and > or =50 years; no significant trends were observed in any age group. These data do not support a role of physical activity in preventing breast cancer.

Abdominal and total adiposity and risk of coronary heart disease in men.

BACKGROUND: Waist circumference is a simpler measure of abdominal adiposity than waist/hip ratio (WHR), but few studies have directly compared the two measures as predictors of coronary heart disease (CHD) in men. In addition, whether the association of abdominal adiposity is independent of total adiposity as measured by body mass index (BMI) in men remains uncertain. OBJECTIVE: To compare waist circumference and WHR as predictors of CHD in men, and to determine whether the association is independent of BMI. DESIGN: Prospective cohort study. METHODS: We compared WHR, waist circumference and BMI with risk of CHD (myocardial infarction or coronary revascularization) among men in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among 22 071 apparently healthy US male physicians, aged 40-84 y at baseline in 1982. Men reported height at baseline, and weight, waist and hip measurements on the 9 y follow-up questionnaire. RESULTS: Among the 16 164 men who reported anthropometric measurements and were free from prior CHD, stroke or cancer, a total of 552 subsequent CHD events occurred during an average follow-up of 3.9 y. After adjusting for age, randomized study agent, smoking, physical activity, parental history of myocardial infarction, alcohol intake, multivitamin and aspirin use, men in the highest WHR quintile (>or=0.99) had a relative risk (RR) for CHD of 1.50 (95% CI 1.14-1.98) compared with those in the lowest quintile (<0.90). Men in the highest waist circumference quintile (>or=103.6 cm) had a RR of 1.60 (CI, 1.21-2.11) for CHD compared with men in the lowest quintile (<88.4 cm). Further adjustment for BMI substantially attenuated these associations: men in the highest WHR and waist circumference quintiles had relative risks for CHD of 1.23 (CI, 0.92-1.66) and 1.06 (CI, 0.74-1.53), respectively. Men in the highest BMI quintile (>or=27.6 kg/m(2)) had a multivariate RR of CHD of 1.73 (CI, 1.29-2.32), after adjustment for WHR. No significant effect modification by age of the relationship between either measure of abdominal adiposity and risk of CHD was observed. CONCLUSIONS: These data support a modest relationship between abdominal adiposity, as measured by either WHR or waist circumference, and risk of CHD both in middle-aged and older men. However, abdominal adiposity did not remain an independent predictor of CHD after adjustment for BMI.

Analgesic use and renal function in men.

CONTEXT: Several case-control studies suggest an association between analgesic use and increased risk of chronic renal disease, but few cohort studies have examined this association. OBJECTIVE: To determine whether analgesic use is associated with risk of renal dysfunction. DESIGN AND SETTING: Cohort study of analgesic use data from the Physicians' Health Study, which lasted 14 years from September 1982 to December 1995 with annual follow-up. PARTICIPANTS: A total of 11 032 initially healthy men who provided blood samples and self-report of analgesic use. MAIN OUTCOME MEASURES: Elevated creatinine level defined as 1.5 mg/dL (133 micromol/L) or higher and a reduced creatinine clearance defined as 55 mL/min (0.9 mL/s) or less, and self-reported use of acetaminophen, aspirin, and other nonsteroidal anti-inflammatory drugs (never [<12 pills]; 12-1499 pills; 1500-2499 pills; and >/=2500 pills). RESULTS: A total of 460 men had elevated creatinine levels (4.2%) and 1258 had reduced creatinine clearance (11.4%). Mean creatinine levels and creatinine clearances were similar among men who did not use analgesics and those who did, even at total intakes of 2500 or more pills. In multivariable analyses adjusted for age; body mass index; history of hypertension, elevated cholesterol, and diabetes; occurrence of cardiovascular disease; physical activity; and use of other analgesics, the relative risks of elevated creatinine level associated with intake of 2500 or more pills were 0.83 (95% confidence interval [CI], 0.50-1.39; P for trend =.05) for acetaminophen, 0.98 (95% CI, 0.53-1.81; P for trend =.96) for aspirin, and 1.07 (95% CI, 0.71-1.64; P for trend =.86) for other nonsteroidal anti-inflammatory drugs. No association was observed between analgesic use and reduced creatinine clearance. CONCLUSIONS: Moderate analgesic use in this cohort study of initially healthy men was not associated with increased risk of renal dysfunction.

Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women.

BACKGROUND: Few studies have examined the effects of paternal and maternal history of myocardial infarction (MI), including age at MI, on cardiovascular disease (CVD) risk, particularly among women. METHODS AND RESULTS: We prospectively studied 22 071 men from the Physicians' Health Study and 39 876 women from the Women's Health Study with data on parental history and age at MI. Among men, 2654 CVD cases developed over 13.0 years; among women, 563 CVD cases occurred over 6.2 years. Compared with men with no parental history, only maternal, only paternal, and both maternal and paternal history of MI conferred relative risks (RRs) of CVD of 1.71, 1.40, and 1.85; among women, the respective RRs were 1.46, 1.15, and 2.05. For men, maternal age at MI of <50, 50 to 59, 60 to 69, 70 to 79, and >/=80 years had RRs of 1.00, 1.88, 1.88, 1.67, and 1.17; for women, the RRs for maternal age at MI of <50, 50 to 59, and >/=60 years were 2.57, 1.33, and 1.52. Paternal age at MI of <50, 50 to 59, 60 to 69, 70 to 79, and >/=80 years in men had RRs of 2.19, 1.64, 1.42, 1.16, and 0.92; in women, for paternal age at MI of <50, 50 to 59, and >/=60 years, the RRs were 1.63, 1.33, and 1.13. CONCLUSIONS: An early history of parental MI (<60 years) conferred a greater risk of CVD than did MI at older ages. However, an increased risk of CVD remained for maternal age at MI of 70 to 79 years in men and >/=60 years in women, which suggests that any maternal history of MI may be important.

Physical activity and coronary heart disease in women: is "no pain, no gain" passé?

CONTEXT: Physically active women have lower coronary heart disease (CHD) rates than inactive women. However, whether the association differs by intensity of activity or in women at high risk for CHD is unclear. OBJECTIVE: To examine the relation between physical activity, specifically investigating walking (a light-to-moderate activity depending on pace), and CHD among women, including those at high risk for CHD. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 39 372 healthy female health professionals aged 45 years or older, enrolled throughout the United States between September 1992 and May 1995, with follow-up to March 1999. Recreational activities, including walking and stair climbing, were reported at study entry. MAIN OUTCOME MEASURE: Correlation of CHD with energy expended on all activities, vigorous activities, and walking. RESULTS: A total of 244 cases of CHD occurred. Adjusting for potential confounders, the relative risks (RRs) of CHD for less than 200, 200-599, 600-1499, and 1500 or more kcal/wk expended on all activities were 1.00 (referent), 0.79 (95% confidence interval [CI], 0.56-1.12), 0.55 (95% CI, 0.37-0.82), and 0.75 (95% CI, 0.50-1.12), respectively (P for linear trend =.03). Vigorous activities were associated with lower risk (RR, 0.63; 95% CI, 0.38-1.04 comparing highest and lowest categories). Walking also predicted lower risk among women without vigorous activities. Among these women, the multivariate RRs for walking 1 to 59 min/wk, 1.0 to 1.5 h/wk, and 2 or more h/wk, compared with no regular walking, were 0.86 (95% CI, 0.57-1.29), 0.49 (95% CI, 0.28-0.86), and 0.48 (95% CI, 0.29-0.78), respectively. For walking paces of less than 3.2 km/h (2.0 mph), 3.2 to 4.7 km/h (2.0-2.9 mph), and 4.8 km/h (3.0 mph) or more, compared with no regular walking, RRs were 0.56 (95% CI, 0.32-0.97), 0.71 (95% CI, 0.47-1.05), and 0.52 (95% CI, 0.30-0.90), respectively. When analyzed simultaneously, time spent walking (P for linear trend =.01) but not walking pace (P for linear trend =.55) predicted lower risk. The inverse association between physical activity and CHD risk did not differ by weight or cholesterol levels (P for interaction =.95 and.71, respectively), but there were significant interactions by smoking and hypertension status. Physical activity was inversely related to risk in current smokers but not hypertensive women (P for interaction =.01 and.001, respectively). CONCLUSIONS: These data indicate that even light-to-moderate activity is associated with lower CHD rates in women. At least 1 hour of walking per week predicted lower risk. The inverse association with physical activity was also present in women at high risk for CHD, including those who were overweight, had increased cholesterol levels, or were smokers.

Physical activity and breast cancer risk: the Women's Health Study (United States).

OBJECTIVE: It is biologically plausible for physical activity to decrease breast cancer risk; however, epidemiologic studies have yielded inconsistent findings. We therefore examined physical activity and breast cancer risk in the Women's Health Study. METHODS: We assessed physical activity among 39,322 apparently healthy women, aged > or = 45 years, and prospectively followed them for an average of 48 months. Four hundred eleven women developed breast cancer, with 222 positive for both estrogen and progesterone receptors. RESULTS: Among all women the multivariate relative risks of all breast cancer associated with < 840, 840-2519, 2520-6299, and > or = 6300 kJ/week expended on recreational activities and stair climbing were 1.00 (referent), 1.04 (95% confidence interval, 0.77-1.40), 0.86 (0.64-1.17), and 0.80 (0.58-1.12), respectively; p-trend = 0.11. However, among postmenopausal women there was a significant inverse trend for all breast cancer; the corresponding relative risks were 1.0 (referent), 0.97 (0.68-1.4), 0.78 (0.54-1.1), and 0.67 (0.44-1.0), respectively; p-trend = 0.03. Physical activity was unrelated to breast cancers positive for both estrogen and progesterone receptors either among all or postmenopausal women (p-trend = 0.50 and 0.26, respectively). When we assessed only vigorous recreational activity, requiring > or = 6 METs or multiples of resting metabolic rate, we observed no significant associations with all or steroid hormone receptor positive breast cancer, either among all or postmenospausal women. CONCLUSIONS: These data suggest that physical activity during middle age and older is not uniformly associated with decreased breast cancer risk. Among postmenopausal women only, higher levels of physical activity may decrease the risk of breast cancer. This study, however, had limited statistical power to detect small effects.

Intake of fish and omega-3 fatty acids and risk of stroke in women.

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.

Prospective study of fat and protein intake and risk of intraparenchymal hemorrhage in women.

BACKGROUND: -Dietary animal fat and protein have been inversely associated with a risk of intraparenchymal hemorrhage in ecological studies. METHODS AND RESULTS: In 1980, 85 764 women in the Nurses' Health Study cohort, who were 34 to 59 years old and free of diagnosed cardiovascular disease and cancer, completed dietary questionnaires. From these questionnaires, we calculated fat and protein intake. By 1994, after 1.16 million person-years of follow-up, 690 incident strokes, including 74 intraparenchymal hemorrhages, had been documented. Multivariate-adjusted risk of intraparenchymal hemorrhage was higher among women in the lowest quintile of energy-adjusted saturated fat intake than at all higher levels of intake (relative risk [RR], 2.36; 95% CI, 1.10 to 5.09; P:=0.03). For trans unsaturated fat, the corresponding RR was 2.50 (95% CI, 1.35 to 4.65; P:=0.004). Animal protein intake was inversely associated with risk (RR in the highest versus lowest quintiles, 0.32; 95% CI, 0.10 to 1.00; P:=0.04). The excess risk associated with low saturated fat intake was observed primarily among women with a history of hypertension (RR, 3.66; 95% CI, 1.09 to 12.3; P=0.04), but such an interaction was not seen for trans unsaturated fat or animal protein. These nutrients were not related to risk of other stroke subtypes. Dietary cholesterol and monounsaturated and polyunsaturated fat were not related to risk of any stroke subtype. CONCLUSIONS: Low intake of saturated fat and animal protein was associated with an increased risk of intraparenchymal hemorrhage, which may help to explain the high rate of this stroke subtype in Asian countries. The increased risk with low intake of saturated fat and trans unsaturated fat is compatible with the reported association between low serum total cholesterol and risk.

Whole grain consumption and risk of ischemic stroke in women: A prospective study.

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.