Person:

Buring, Julie

Objectives: To examine the association between migraine and migraine aura status with risk of haemorrhagic stroke. Design: Prospective cohort study. Setting: Women’s Health Study, United States. Participants: 27 860 women aged ≥45 who were free from stroke or other major disease at baseline and had provided information on self reported migraine, aura status, and lipid values. Main outcome measures: Time to first haemorrhagic stroke and subtypes of haemorrhagic stroke. Results: At baseline, 5130 (18%) women reported any history of migraine; of the 3612 with active migraine (migraine in the previous year), 1435 (40%) described having aura. During a mean of 13.6 years of follow-up, 85 haemorrhagic strokes were confirmed after review of medical records. Compared with women without a history of migraine, there was no increased risk of haemorrhagic stroke in those who reported any history of migraine (adjusted hazard ratio 0.98, 95% confidence interval 0.56 to 1.71, P=0.93). In contrast, risk was increased in women with active migraine with aura (2.25, 1.11 to 4.54, P=0.024). The age adjusted increased risk was stronger for intracerebral haemorrhage (2.78, 1.09 to 7.07, P=0.032) and for fatal events (3.56, 1.23 to 10.31, P=0.02). Four additional haemorrhagic stroke events were attributable to migraine with aura per 10 000 women per year. Women who reported active migraine without aura had no increased risk for haemorrhagic stroke. Conclusion: Migraine with aura might, in addition to ischaemic events, also be a risk factor for haemorrhagic stroke. The relatively low number of events and attributable risk should caution against definitive conclusions and call for further confirmation of these observations.

Background: Better information on lung cancer occurrence in lifelong nonsmokers is needed to understand gender and racial disparities and to examine how factors other than active smoking influence risk in different time periods and geographic regions. Methods and Findings: We pooled information on lung cancer incidence and/or death rates among self-reported never-smokers from 13 large cohort studies, representing over 630,000 and 1.8 million persons for incidence and mortality, respectively. We also abstracted population-based data for women from 22 cancer registries and ten countries in time periods and geographic regions where few women smoked. Our main findings were: (1) Men had higher death rates from lung cancer than women in all age and racial groups studied; (2) male and female incidence rates were similar when standardized across all ages 40+ y, albeit with some variation by age; (3) African Americans and Asians living in Korea and Japan (but not in the US) had higher death rates from lung cancer than individuals of European descent; (4) no temporal trends were seen when comparing incidence and death rates among US women age 40–69 y during the 1930s to contemporary populations where few women smoke, or in temporal comparisons of never-smokers in two large American Cancer Society cohorts from 1959 to 2004; and (5) lung cancer incidence rates were higher and more variable among women in East Asia than in other geographic areas with low female smoking. Conclusions: These comprehensive analyses support claims that the death rate from lung cancer among never-smokers is higher in men than in women, and in African Americans and Asians residing in Asia than in individuals of European descent, but contradict assertions that risk is increasing or that women have a higher incidence rate than men. Further research is needed on the high and variable lung cancer rates among women in Pacific Rim countries.

Introduction: Rheumatoid arthritis (RA) is more common in females than males and sex steroid hormones may in part explain this difference. We conducted a case–control study nested within two prospective studies to determine the associations between plasma steroid hormones measured prior to RA onset and polymorphisms in the androgen receptor (AR), estrogen receptor 2 (ESR2), aromatase (CYP19) and progesterone receptor (PGR) genes and RA risk. Methods: We genotyped AR, ESR2, CYP19, PGR SNPs and the AR CAG repeat in RA case–control studies nested within the Nurses' Health Study (NHS), NHS II (449 RA cases, 449 controls) and the Women's Health Study (72 cases, and 202 controls). All controls were matched on cohort, age, Caucasian race, menopausal status, and postmenopausal hormone use. We measured plasma dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone binding globulin in 132 pre-RA samples and 396 matched controls in the NHS cohorts. We used conditional logistic regression models adjusted for potential confounders to assess RA risk. Results: Mean age of RA diagnosis was 55 years in both cohorts; 58% of cases were rheumatoid factor positive at diagnosis. There was no significant association between plasma DHEAS, total testosterone, or calculated free testosterone and risk of future RA. There was no association between individual variants or haplotypes in any of the genes and RA or seropositive RA, nor any association for the AR CAG repeat. Conclusions: Steroid hormone levels measured at a single time point prior to RA onset were not associated with RA risk in this study. Our findings do not suggest that androgens or the AR, ESR2, PGR, and CYP19 genes are important to RA risk in women.

Objectives: To evaluate whether the association between migraine with aura and increased risk of cardiovascular disease is modified by vascular risk groups as measured by the Framingham risk score for coronary heart disease. Design: Prospective cohort study. Setting: Women’s health study, United States. Participants: 27 519 women who were free from cardiovascular disease at baseline with available information on the Framingham risk score and migraine status. Main outcome measures Time to major cardiovascular disease event (non-fatal myocardial infarction, non-fatal ischaemic stroke, death from ischaemic cardiovascular disease), myocardial infarction, and ischaemic stroke. Results: At baseline, 3577 (13.0%) women reported active migraine, of whom 1418 (39.6%) reported migraine with aura. During 11.9 years of follow-up, there were 697 cardiovascular disease events. We stratified participants based on 10 year risk of coronary heart disease estimated from the Framingham risk score (≤1%, 2-4%, 5-9%, and ≥10%). Compared with women without migraine, the age adjusted hazard ratios in women with active migraine with aura were 1.93 (95% confidence interval 1.45 to 2.56) for major cardiovascular disease, 1.80 (1.16 to 2.79) for ischaemic stroke, and 1.94 (1.27 to 2.95) for myocardial infarction. When stratified by Framingham risk score, the association between migraine with aura and major cardiovascular disease was strongest in the lowest risk score group. There was a diametric association pattern for ischaemic stroke and myocardial infarction. Compared with women without migraine, the age adjusted hazard ratios in women who reported migraine with aura in the lowest Framingham risk score group were 3.88 (1.87 to 8.08) for ischaemic stroke and 1.29 (0.40 to 4.21) for myocardial infarction. Hazard ratios in women with migraine with aura in the highest Framingham risk score group were 1.00 (0.24 to 4.14) for ischaemic stroke and 3.34 (1.50 to 7.46) for myocardial infarction. Women with migraine without aura were not at increased risk of ischaemic stroke or myocardial infarction in any of the Framingham risk score groups. Conclusion: The association between migraine with aura and cardiovascular disease varies by vascular risk status. Information on history of migraine and vascular risk status might help to identify women at increased risk for specific future cardiovascular disease events. Trial registration Clinical trials NCT00000479.

OBJECTIVE—To evaluate the association between type 2 diabetes and newly reported Parkinson's disease. RESEARCH DESIGN AND METHODS—Our study included 21,841 participants in the Physicians’ Health Study, a cohort of U.S. male physicians. Diabetes and Parkinson's disease were self-reported via questionnaire. We used time-varying Cox regression to calculate adjusted relative risk (RR) for Parkinson's disease. RESULTS—Over 23 years, 556 individuals with Parkinson's disease were identified. Subjects with diabetes had an increased Parkinson's disease risk (multivariable-adjusted RR 1.34 [95% CI 1.01–1.77]). The association remained significant after exclusion of those with known vascular disease. The diagnosis of diabetes was clustered around the diagnosis of Parkinson's disease and was more apparent among men with short diabetes duration and those without complications from diabetes. CONCLUSIONS—Results of this large prospective study in men do not suggest that diabetes is a preceding risk factor for Parkinson's disease. Whether the positive association may be explained by ascertainment bias or a common underlying biological mechanism remains to be established.

OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.

Background: Ion channel transient receptor potential membrane melastatin 6 and 7 (TRPM6 and TRPM7) play a central role in magnesium homeostasis, which is critical for maintaining glucose and insulin metabolism. However, it is unclear whether common genetic variation in TRPM6 and TRPM7 contributes to risk of type 2 diabetes. Methods: We conducted a nested case-control study in the Women's Health Study. During a median of 10 years of follow-up, 359 incident diabetes cases were diagnosed and matched by age and ethnicity with 359 controls. We analyzed 20 haplotype-tagging single nucleotide polymorphisms (SNPs) in TRPM6 and 5 common SNPs in TRPM7 for their association with diabetes risk. Results: Overall, there was no robust and significant association between any single SNP and diabetes risk. Neither was there any evidence of association between common TRPM6 and TRPM7 haplotypes and diabetes risk. Our haplotype analyses suggested a significant risk of type 2 diabetes among carriers of both the rare alleles from two non-synomous SNPs in TRPM6 (Val1393Ile in exon 26 [rs3750425] and Lys1584Glu in exon 27 [rs2274924]) when their magnesium intake was lower than 250 mg per day. Compared with non-carriers, women who were carriers of the haplotype 1393Ile-1584Glu had an increased risk of type 2 diabetes (OR, 4.92, 95% CI, 1.05–23.0) only when they had low magnesium intake (less than 250 mg/day). Conclusion: Our results provide suggestive evidence that two common non-synonymous TRPM6 coding region variants, Ile1393Val and Lys1584Glu polymorphisms, might confer susceptibility to type 2 diabetes in women with low magnesium intake. Further replication in large-scale studies is warranted.

OBJECTIVE—Subclinical inflammation is linked with the development of type 2 diabetes, and epidemiologic data suggest that this association may be stronger in women. Although small clinical studies have shown a prominent hypoglycemic effect of short-term high-dose aspirin, no randomized trials have directly evaluated the efficacy of aspirin in diabetes prevention at doses acceptable for use in routine clinical practice. We evaluated whether chronic low-dose aspirin prevents the development of clinical diabetes among initially healthy American women. RESEARCH DESIGN AND METHODS—Subjects were enrolled in the Women's Health Study, a 10-year randomized double-blind, placebo-controlled trial of aspirin and vitamin E for primary prevention of cardiovascular disease and cancer. Between 1992 and 1995, 38,716 women aged ≥45 years and free of clinical diabetes were randomly assigned to either low-dose aspirin or placebo (median follow-up 10.2 years). Documented clinical type 2 diabetes was prospectively evaluated throughout the trial. RESULTS—Among women randomly assigned to receive aspirin (n = 19,326) or placebo (n = 19,390), there was no statistically significant difference in the incidence of type 2 diabetes. There were 849 cases of diabetes in the aspirin group and 847 in the placebo group (rate ratio 1.01 [95% CI 0.91–1.11]). Stratification by diabetes risk factors including age, BMI, family history of diabetes, physical activity, A1C, and high-sensitivity C-reactive protein did not support a modulating effect of these variables. Analyses accounting for treatment duration and adherence similarly found no beneficial effects. CONCLUSIONS—These data suggest that long-term low-dose aspirin does not prevent the development of clinical type 2 diabetes in initially healthy women.

Objective: To evaluate the association between migraine and cognitive decline among women. Design Prospective cohort study. Setting Women’s Health Study, United States. Participants 6349 women aged 65 or older enrolled in the Women’s Health Study who provided information about migraine status at baseline and participated in cognitive testing during follow-up. Participants were classified into four groups: no history of migraine, migraine with aura, migraine without aura, and past history of migraine (reports of migraine history but no migraine in the year prior to baseline). Main outcome measures Cognitive testing was carried out at two year intervals up to three times using the telephone interview for cognitive status, immediate and delayed recall trials of the east Boston memory test, delayed recall trial of the telephone interview for cognitive status 10 word list, and a category fluency test. All tests were combined into a global cognitive score, and tests assessing verbal memory were combined to create a verbal memory score. Results: Of the 6349 women, 853 (13.4%) reported any migraine; of these, 195 (22.9%) reported migraine with aura, 248 (29.1%) migraine without aura, and 410 (48.1%) a past history of migraine. Compared with women with no history of migraine, those who experienced migraine with or without aura or had a past history of migraine did not have significantly different rates of cognitive decline in any of the cognitive scores: values for the rate of change of the global cognitive score between baseline and the last observation ranged from −0.01 (SE 0.04) for past history of migraine to 0.08 (SE 0.04) for migraine with aura when compared with women without any history of migraine. Women who experienced migraine were also not at increased risk of substantial cognitive decline (worst 10% of the distribution of decline). When compared with women without a history of migraine, the relative risks for the global score ranged from 0.77 (95% confidence interval 0.46 to 1.28) for women with migraine without aura to 1.17 (0.84 to 1.63) for women with a past history of migraine. Conclusion: In this prospective cohort of women, migraine status was not associated with faster rates of cognitive decline.

Objectives: To evaluate the association between restless legs syndrome (RLS) and incident cardiovascular disease (CVD). Design: Prospective cohort study. Setting: Women's Health Study (WHS) and Physicians' Health Study (PHS), USA. Participants: 29,756 female health professionals aged ( \geq 45) years and 19,182 male physicians aged ( \geq 40) years at baseline. Main outcome measures: Main outcome was incidence of major CVD; secondary outcomes were first incidence of myocardial infarction, stroke, death due to CVD or coronary revascularisation. Results: 3487 (11.7%) women and 1373 (7.2%) men met International Restless Legs Study Group criteria for RLS. In the WHS 450 major CVD events occurred and 1064 major CVD events were confirmed in the PHS. In both cohorts, RLS was not associated with increased risk of major CVD, stroke, myocardial infarction, CVD death or coronary revascularisation. After adjustment for major vascular risk factors, the HRs (95% CI) for major CVD were 1.15 (0.88 to 1.50) in women and 1.01 (0.81 to 1.25) in men. Highest multivariable-adjusted HRs were 1.29 (0.91 to 1.82) for total stroke in women and 1.22 (0.87 to 1.70) for CVD death in men. Excluding participants with comorbidities potentially leading to RLS did not substantially change the effect estimates. Conclusions: In these large prospective studies of female and male health professionals, RLS was not associated with an increased risk of any incident CVD event. The data do not support the hypothesis that RLS is a marker of increased risk of vascular disease.