Depression, anxiety, psychotropic drugs, and acute myocardial infarction: large prospective study of United Kingdom women.

BACKGROUND: Reported associations between depression and myocardial infarction in some studies might be explained by use of psychotropic drugs, residual confounding, and/or reverse causation (whereby heart disease precedes depression). We investigated these hypotheses in a large prospective study of UK women with no previous vascular disease. METHODS: At baseline in median year 2001 (IQR 2001-2003), Million Women Study participants reported whether or not they were currently being treated for depression or anxiety, their self-rated health, and medication use during the previous 4 weeks. Follow-up was through linkage to national hospital admission and mortality databases. Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the first myocardial infarction event in those reporting treatment for depression or anxiety (subdivided by whether or not the treatment was with psychotropic drugs) v. not, and stratified by self-reported health and length of follow-up. RESULTS: During mean follow-up of 13.9 years of 690 335 women (mean age 59.8 years) with no prior heart disease, stroke, transient ischaemic attack, or cancer, 12 819 had a first hospital admission or death from myocardial infarction. The aHRs for those reporting treatment for depression or anxiety with, and without, regular use of psychotropic drugs were 0.96 (95% CI 0.89-1.03) and 0.99 (0.89-1.11), respectively. No associations were found separately in women who reported being in good/excellent or poor/fair health or by length of follow-up. CONCLUSION: The null findings in this large prospective study are consistent with depression not being an independent risk factor for myocardial infarction.

Cognitive and social activities and long-term dementia risk: the prospective UK Million Women Study.

BACKGROUND: Although dementia is associated with non-participation in cognitive and social activities, this association might merely reflect the consequences of dementia, rather than any direct effect of non-participation on the subsequent incidence of dementia. Because of the slowness with which dementia can develop, unbiased assessment of any such direct effects must relate non-participation in such activities to dementia detection rates many years later. Prospective studies with long-term follow-up can help achieve this by analysing separately the first and second decade of follow-up. We report such analyses of a large, 20-year study. METHODS: The UK Million Women Study is a population-based prospective study of 1·3 million women invited for National Health Service (NHS) breast cancer screening in median year 1998 (IQR 1997-1999). In median year 2001 (IQR 2001-2003), women were asked about participation in adult education, groups for art, craft, or music, and voluntary work, and in median year 2006 (IQR 2006-2006), they were asked about reading. All participants were followed up through electronic linkage to NHS records of hospital admission with mention of dementia, the first mention of which was the main outcome. Comparing non-participation with participation in a particular activity, we used Cox regression to assess fully adjusted dementia risk ratios (RRs) during 0-4, 5-9, and 10 or more years, after information on that activity was obtained. FINDINGS: In 2001, 851 307 women with a mean age of 60 years (SD 5) provided information on participation in adult education, groups for art, craft, or music, and voluntary work. After 10 years, only 9591 (1%) had been lost to follow-up and 789 339 (93%) remained alive with no recorded dementia. Follow-up was for a mean of 16 years (SD 3), during which 31 187 (4%) had at least one hospital admission with mention of dementia, including 25 636 (3%) with a hospital admission with dementia mentioned for the first time 10 years or more after follow-up began. Non-participation in cognitive or social activities was associated with higher relative risks of dementia detection only during the first decade after participation was recorded. During the second decade, there was little association. This was true for non-participation in adult education (RR 1·04, 99% CI 0·98-1·09), in groups for art, craft, or music (RR 1·04, 0·99-1·09), in voluntary work (RR 0·96, 0·92-1·00), or in any of these three (RR 0·99, 0·95-1·03). In 2006, 655 118 women provided information on reading. For non-reading versus any reading, there were similar associations with dementia, again with strong attenuation over time since reading was recorded, but longer follow-up is needed to assess this reliably. INTERPRETATION: Life has to be lived forwards, but can be understood only backwards. Long before dementia is diagnosed, there is a progressive reduction in various mental and physical activities, but this is chiefly because its gradual onset causes inactivity and not because inactivity causes dementia. FUNDING: UK Medical Research Council, Cancer Research UK.

Health impacts and environmental footprints of diets that meet the Eatwell Guide recommendations: analyses of multiple UK studies.

OBJECTIVES: To assess the health impacts and environmental consequences of adherence to national dietary recommendations (the Eatwell Guide (EWG)) in the UK. DESIGN AND SETTING: A secondary analysis of multiple observational studies in the UK. PARTICIPANTS: Adults from the European Prospective Investigation into Cancer - Oxford(EPIC-Oxford), UK Biobank and Million Women Study, and adults and children aged 5 and over from the National Diet and Nutrition Survey (NDNS).Primary and secondary outcome measures risk of total mortality from Cox proportional hazards regression models, total greenhouse gas emissions (GHGe) and blue water footprint (WF) associated with 'very low' (0-2 recommendations), 'low' (3-4 recommendations) or 'intermediate-to-high' (5-9 recommendations) adherence to EWG recommendations. RESULTS: Less than 0.1% of the NDNS sample adhere to all nine EWG recommendations and 30.6% adhere to at least five recommendations. Compared with 'very low' adherence to EWG recommendations, 'intermediate-to-high adherence' was associated with a reduced risk of mortality (risk ratio (RR): 0.93; 99% CI: 0.90 to 0.97) and -1.6 kg CO2eq/day (95% CI: -1.5 to -1.8), or 30% lower dietary GHGe. Dietary WFs were similar across EWG adherence groups. Of the individual Eatwell guidelines, adherence to the recommendation on fruit and vegetable consumption was associated with the largest reduction in total mortality risk: an RR of 0.90 (99% CI: 0.88 to 0.93). Increased adherence to the recommendation on red and processed meat consumption was associated with the largest decrease in environmental footprints (-1.48 kg CO2eq/day, 95% CI: -1.79 to 1.18 for GHGe and -22.5 L/day, 95% CI: -22.7 to 22.3 for blue WF). CONCLUSIONS: The health and environmental benefits of greater adherence to EWG recommendations support increased government efforts to encourage improved diets in the UK that are essential for the health of people and the planet in the Anthropocene.

Body mass index, diet, physical inactivity, and the incidence of dementia in 1 million UK women.

OBJECTIVE: To help determine whether midlife obesity is a cause of dementia and whether low body mass index (BMI), low caloric intake, and physical inactivity are causes or merely consequences of the gradual onset of dementia by recording these factors early in a large 20-year prospective study and relating them to dementia detection rates separately during follow-up periods of <5, 5 to 9, 10 to 14, and 15+ years. METHODS: A total of 1,136,846 UK women, mean age 56 (SD 5) years, were recruited in 1996 to 2001 and asked about height, weight, caloric intake, and inactivity. They were followed up until 2017 by electronic linkage to National Health Service records, detecting hospital admissions with mention of dementia. Cox regression yielded adjusted rate ratios (RRs) for first dementia detection during particular follow-up periods. RESULTS: Fifteen years after the baseline survey, only 1% were lost to follow-up, and 89% remained alive with no detected dementia, of whom 18,695 had dementia detected later, at a mean age of 77 (SD 4) years. Dementia detection during years 15+ was associated with baseline obesity (BMI 30+ vs 20-24 kg/m2: RR 1.21, 95% confidence interval 1.16-1.26, p < 0.0001) but not clearly with low BMI, low caloric intake, or inactivity at baseline. The latter 3 factors were associated with increased dementia rates during the first decade, but these associations weakened substantially over time, approaching null after 15 years. CONCLUSIONS: Midlife obesity may well be a cause of dementia. In contrast, behavioral changes due to preclinical disease could largely or wholly account for associations of low BMI, low caloric intake, and inactivity with dementia detection during the first decade of follow-up.

Diet and risk of glioma: combined analysis of 3 large prospective studies in the UK and USA.

BACKGROUND: Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimize possible differential dietary recall between those with and without glioma, we present findings from 3 large prospective studies. METHODS: Participants included 692 176 from the UK Million Women Study, 470 780 from the US National Institutes of Health-AARP study, and 99 148 from the US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cox regression yielded study-specific adjusted relative risks for glioma in relation to 15 food groups, 14 nutrients, and 3 dietary patterns, which were combined, weighted by inverse variances of the relative risks. Separate analyses by <5 and ≥5 years follow-up assessed potential biases related to changes of diet before glioma diagnosis. RESULTS: The 1 262 104 participants (mean age, 60.6 y [SD 5.5] at baseline) were followed for 15.4 million person-years (mean 12.2 y/participant), during which 2313 incident gliomas occurred, at mean age 68.2 (SD 6.4). Overall, there was weak evidence for increased glioma risks associated with increasing intakes of total fruit, citrus fruit, and fiber and healthy dietary patterns, but these associations were generally null after excluding the first 5 years of follow-up. There was little evidence for heterogeneity of results by study or by sex. CONCLUSIONS: The largest prospective evidence to date suggests little, if any, association between major food groups, nutrients, or common healthy dietary patterns and glioma incidence. With the statistical power of this study and the comprehensive nature of the investigation here, it seems unlikely we have overlooked major effects of diet on risk of glioma that would be of public health concern.

Foods, macronutrients and breast cancer risk in postmenopausal women: a large UK cohort.

BACKGROUND: The role of diet in breast cancer aetiology is unclear; recent studies have suggested associations may differ by estrogen receptor status. METHODS: Baseline diet was assessed in 2000-04 using a validated questionnaire in 691 571 postmenopausal UK women without previous cancer, who had not changed their diet recently. They were followed by record linkage to national cancer and death databases. Cox regression yielded adjusted relative risks for breast cancer for 10 food items and eight macronutrients, subdivided mostly into five categories of baseline intake. Trends in risk across the baseline categories were calculated, assigning re-measured intakes to allow for measurement error and changes in intake over time; P-values allowed for multiple testing. RESULTS: Women aged 59.9 (standard deviation (SD 4.9)) years at baseline were followed for 12 (SD 3) years; 29 005 were diagnosed with invasive breast cancer. Alcohol intake had the strongest association with breast cancer incidence: relative risk (RR) 1.08 [99% confidence interval (CI) 1.05-1.11] per 10 g/day higher intake, P = 5.8 × 10-14. There were inverse associations with fruit: RR 0.94 (99% CI 0.92-0.97) per 100 g/day higher intake, P = 1.1 × 10-6, and dietary fibre: RR 0.91 (99% CI 0.87-0.96) per 5 g/day increase, P = 1.1 × 10-4. Fruit and fibre intakes were correlated (ρ = 0.62) and were greater among women who were not overweight, so residual confounding cannot be excluded. There was no heterogeneity for any association by estrogen receptor status. CONCLUSIONS: By far the strongest association was between alcohol intake and an increased risk of breast cancer. Of the other 17 intakes examined, higher intakes of fruit and fibre were associated with lower risks of breast cancer, but it is unclear whether or not these associations are causal.

Differences in risk factors for 3 types of stroke: UK prospective study and meta-analyses.

OBJECTIVE: To compare associations of behavioral and related factors for incident subarachnoid hemorrhage and intracerebral hemorrhage and ischemic stroke. METHODS: A total of 712,433 Million Women Study participants without prior stroke, heart disease, or cancer reported behavioral and related factors at baseline (1999-2007) and were followed up by record linkage to national hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) by type of stroke. Heterogeneity was assessed with χ2 tests. When appropriate, meta-analyses were done of published prospective studies. RESULTS: After 12.9 (SD 2.6) years of follow-up, 8,128 women had an incident ischemic stroke, 2,032 had intracerebral hemorrhage, and 1,536 had subarachnoid hemorrhage. In women with diabetes mellitus, the risk of ischemic stroke was substantially increased (RR 2.01, 95% confidence interval [CI] 1.84-2.20), risk of intracerebral hemorrhage was increased slightly (RR 1.31, 95% CI 1.04-1.65), but risk of subarachnoid hemorrhage was reduced (RR 0.43, 95% CI 0.26-0.69) (heterogeneity by stroke type, p < 0.0001). Stroke incidence was greater in women who rated their health as poor/fair compared to those who rated their health as excellent/good (RR 1.36, 95% CI 1.30-1.42). Among 565,850 women who rated their heath as excellent/good, current smokers were at an increased risk of all 3 stroke types, (although greater for subarachnoid hemorrhage [≥15 cigarettes/d vs never smoker, RR 4.75, 95% CI 4.12-5.47] than for intracerebral hemorrhage [RR 2.30, 95% CI 1.94-2.72] or ischemic stroke [RR 2.50, 95% CI 2.29-2.72]; heterogeneity p < 0.0001). Obesity was associated with an increased risk of ischemic stroke and a decreased risk of hemorrhagic stroke (heterogeneity p < 0.0001). Meta-analyses confirmed the associations and the heterogeneity across the 3 types of stroke. CONCLUSION: Classic risk factors for stroke have considerably different effects on the 3 main pathologic types of stroke.

Antidepressants, Depression, and Venous Thromboembolism Risk: Large Prospective Study of UK Women.

BACKGROUND: Some investigators have reported an excess risk of venous thromboembolism (VTE) associated with depression and with use of antidepressant drugs. We explored these associations in a large prospective study of UK women. METHODS AND RESULTS: The Million Women Study recruited 1.3 million women through the National Health Service Breast Screening Programme in England and Scotland. Three years after recruitment, women were sent a second questionnaire that enquired about depression and regular use of medications in the previous 4 weeks. The present analysis included those who responded and did not have prior VTE, cancer, or recent surgery. Follow-up for VTE was through linkage to routinely collected National Health Service statistics. Cox regression analyses yielded adjusted hazard ratios and 95% CIs. A total of 734 092 women (mean age 59.9 years) were included in the analysis; 6.9% reported use of antidepressants, 2.7% reported use of other psychotropic drugs, and 1.8% reported being treated for depression or anxiety but not use of psychotropic drugs. During follow-up for an average of 7.3 years, 3922 women were hospitalized for and/or died from VTE. Women who reported antidepressant use had a significantly higher risk of VTE than women who reported neither depression nor use of psychotropic drugs (hazard ratio, 1.39; 95% CI, 1.23-1.56). VTE risk was not significantly increased in women who reported being treated for depression or anxiety but no use of antidepressants or other psychotropic drugs (hazard ratio, 1.19; 95% CI, 0.95-1.49). CONCLUSIONS: Use of antidepressants is common in UK women and is associated with an increased risk of VTE.

Comparison of dementia recorded in routinely collected hospital admission data in England with dementia recorded in primary care.

BACKGROUND: Electronic linkage of UK cohorts to routinely collected National Health Service (NHS) records provides virtually complete follow-up for cause-specific hospital admissions and deaths. The reliability of dementia diagnoses recorded in NHS hospital data is not well documented. METHODS: For a sample of Million Women Study participants in England we compared dementia recorded in routinely collected NHS hospital data (Hospital Episode Statistics: HES) with dementia recorded in two separate sources of primary care information: a primary care database [Clinical Practice Research Datalink (CPRD), n = 340] and a survey of study participants' General Practitioners (GPs, n = 244). RESULTS: Dementia recorded in HES fully agreed both with CPRD and with GP survey data for 85% of women; it did not agree for 1 and 4%, respectively. Agreement was uncertain for the remaining 14 and 11%, respectively; and among those classified as having uncertain agreement in CPRD, non-specific terms compatible with dementia, such as 'memory loss', were recorded in the CPRD database for 79% of the women. Agreement was significantly better (p < 0.05 for all comparisons) for women with HES diagnoses for Alzheimer's disease (95 and 94% agreement with any dementia for CPRD and GP survey, respectively) and for vascular dementia (88 and 88%, respectively) than for women with a record only of dementia not otherwise specified (70 and 72%, respectively). Dementia in the same woman was first mentioned an average 1.6 (SD 2.6) years earlier in primary care (CPRD) than in hospital (HES) data. Age-specific rates for dementia based on the hospital admission data were lower than the rates based on the primary care data, but were similar if the delay in recording in HES was taken into account. CONCLUSIONS: Dementia recorded in routinely collected NHS hospital admission data for women in England agrees well with primary care records of dementia assessed separately from two different sources, and is sufficiently reliable for epidemiological research.

Night Shift Work and Breast Cancer Incidence: Three Prospective Studies and Meta-analysis of Published Studies.

BACKGROUND: It has been proposed that night shift work could increase breast cancer incidence. A 2007 World Health Organization review concluded, mainly from animal evidence, that shift work involving circadian disruption is probably carcinogenic to humans. We therefore aimed to generate prospective epidemiological evidence on night shift work and breast cancer incidence. METHODS: Overall, 522 246 Million Women Study, 22 559 EPIC-Oxford, and 251 045 UK Biobank participants answered questions on shift work and were followed for incident cancer. Cox regression yielded multivariable-adjusted breast cancer incidence rate ratios (RRs) and 95% confidence intervals (CIs) for night shift work vs no night shift work, and likelihood ratio tests for interaction were used to assess heterogeneity. Our meta-analyses combined these and relative risks from the seven previously published prospective studies (1.4 million women in total), using inverse-variance weighted averages of the study-specific log RRs. RESULTS: In the Million Women Study, EPIC-Oxford, and UK Biobank, respectively, 673, 28, and 67 women who reported night shift work developed breast cancer, and the RRs for any vs no night shift work were 1.00 (95% CI = 0.92 to 1.08), 1.07 (95% CI = 0.71 to 1.62), and 0.78 (95% CI = 0.61 to 1.00). In the Million Women Study, the RR for 20 or more years of night shift work was 1.00 (95% CI = 0.81 to 1.23), with no statistically significant heterogeneity by sleep patterns or breast cancer risk factors. Our meta-analysis of all 10 prospective studies included 4660 breast cancers in women reporting night shift work; compared with other women, the combined relative risks were 0.99 (95% CI = 0.95 to 1.03) for any night shift work, 1.01 (95% CI = 0.93 to 1.10) for 20 or more years of night shift work, and 1.00 (95% CI = 0.87 to 1.14) for 30 or more years. CONCLUSIONS: The totality of the prospective evidence shows that night shift work, including long-term shift work, has little or no effect on breast cancer incidence.

The role of health-related behavioural factors in accounting for inequalities in coronary heart disease risk by education and area deprivation: prospective study of 1.2 million UK women.

BACKGROUND: Some recent research has suggested that health-related behaviours, such as smoking, might explain much of the socio-economic inequalities in coronary heart disease (CHD) risk. In a large prospective study of UK women, we investigated the associations between education and area deprivation and CHD risk and assessed the contributions of smoking, alcohol consumption, physical activity and body mass index (BMI) to these inequalities. METHODS: After excluding women with heart disease, stroke or cancer at recruitment, 1,202,983 women aged 56 years (SD 5 years) on average, were followed for first coronary event (hospital admission or death) and for CHD mortality. Relative risks of CHD were estimated by Cox regression, and the extent to which any association could be accounted for by smoking, alcohol, physical inactivity, and BMI was assessed by calculating the percentage reduction in the relevant likelihood-ratio (LR) statistic after adjustment for these factors, separately and together. RESULTS: A total of 71,897 women had a first CHD event (hospital admission or death) and 6032 died from CHD during 12 years follow-up. In analyses adjusted by age, birth cohort and region of residence only, lower levels of education and greater deprivation were associated with higher risks of CHD (P heterogeneity < 0.0001 for each); associations for education were found within every level of deprivation and for deprivation were found within every level of education. Smoking, alcohol consumption, physical inactivity and BMI accounted for most of the associations (adjustment for all four factors together reduced the LR statistics for education and for deprivation by 76 % and 71 %, respectively, for first CHD event; and by 87 % and 79 %, respectively, for CHD mortality). Of these four factors, adjustment for smoking resulted in the largest reduction in the LR statistic. Given the large reduction in the predictive values of education and deprivation after adjustment for only four health-related behavioural factors recorded just at recruitment, residual confounding might plausibly account for the remaining associations. CONCLUSIONS: Most of the association between CHD risk and education and area deprivation in UK women is accounted for by health-related behaviours, particularly by smoking and to a lesser extent by alcohol consumption, physical inactivity and BMI.

Hypertension in pregnancy and risk of coronary heart disease and stroke: A prospective study in a large UK cohort.

BACKGROUND: Many studies investigating long-term vascular disease risk associated with hypertensive pregnancies examined risks in relatively young women among whom vascular disease is uncommon. We examined the prospective relation between a history of hypertension during pregnancy and coronary heart disease (CHD) and stroke in middle-aged UK women. METHODS: In 1996-2001, 1.1 million parous women (mean age=56years) without vascular disease at baseline reported their history of hypertension during pregnancy and other factors. They were followed for incident CHD and stroke (hospitalisation or death). Adjusted relative risks (RRs) were calculated using Cox regression. RESULTS: Twenty-six percent (290,008/1.1 million) reported having had a hypertensive pregnancy; 27% (79,163/290,008) of women with hypertensive pregnancy, but only 10% (82,145/815,560) of those without hypertensive pregnancy, reported being treated for hypertension at baseline. Mean follow-up was 11.6years (mean ages at diagnosis/N of events: CHD=65years/N=68,161, ischaemic stroke=67years/N=8365, haemorrhagic stroke=64years/N=5702). Overall, the RRs (95% confidence interval [CI]) of incident disease in women with hypertensive pregnancy versus those without such history were: CHD=1.29 (1.27-1.31), ischaemic stroke=1.29 (1.23-1.35), and haemorrhagic stroke=1.14 (1.07-1.21). However, among women with hypertensive pregnancy who were not taking hypertension treatment at baseline, their RRs (95% CI) were only modestly increased: CHD=1.17 (1.14-1.19), ischaemic stroke=1.18 (1.11-1.25), and haemorrhagic stroke=1.09 (1.02-1.18). CONCLUSION: Hypertension during pregnancy was associated with increased CHD and stroke incidence in middle age, largely because such women also had hypertension in their 50s and 60s, which has a substantially greater effect on vascular disease risk than hypertension during pregnancy without hypertension later in life.

Body size from birth to middle age and the risk of hip and knee replacement.

BACKGROUND: Information regarding the effects of body size in childhood and early adulthood on the risk of hip and knee replacement in later life is inconsistent. We aimed to assess their effect, taking into account body mass index (BMI) in middle-age. METHODS: Prospective cohort (Million Women Study) of 791,034 women with information on birth weight, body size at age 10 and age 20, and current BMI (at mean age 59.5 years) were followed for 6.82 million person-years. Adjusted relative risks (RRs) and absolute risks of hospitalisations for hip or knee replacement surgery for osteoarthritis were estimated. RESULTS: After a mean of 8.6 years follow-up, 17,402 women had a hip replacement and 18,297 a knee replacement. Between the ages of 50 and 79 years, absolute risks for women with current BMIs of <22.5 kg/m(2) and 35 + kg/m(2) were respectively 5.6 and 13.2 % for hip replacement; and 2.6 and 35.1 % for knee replacement. Within each category of current BMI, increasing body size at age 10 and at age 20 had comparatively small effects; there were no significant associations with birth weight. We estimate that 40 % of UK women with a BMI 35 + kg/m(2) have either a hip or knee replacement between the ages of 50-79 years; this compares to just 10 % of UK women with a healthy BMI (<25 kg/m(2)). CONCLUSIONS: The effects of body size in childhood and early adulthood on the absolute risks of either a hip or knee replacement are minimal compared to the effect of adiposity in middle age.

Social participation and coronary heart disease risk in a large prospective study of UK women.

BACKGROUND: Participation in social activities is thought to prevent heart disease, but evidence is inconclusive. DESIGN: We assessed whether participating in social activities reduces the risk of coronary heart disease (CHD) in a large prospective study of 735,159 middle-aged UK women. METHODS: Women reported their participation in eight social activities (religious group, voluntary work, adult education, art/craft/music, dancing, sports club, yoga, bingo) and were followed for first CHD event (hospital admission or death) over the next 8.6 years. Cox regression models were used to estimate relative risks for CHD incidence by participation in each and in any of the social activities. RESULTS: After adjustment for age and region only, every activity except bingo was associated with a reduced risk of CHD (n = 30,756 cases in total). However, after additional adjustment for 11 factors (deprivation, education, smoking, physical activity, body mass index, alcohol, marital status, self-rated health, happiness, hypertension, diabetes), every relative risk estimate moved close to 1.0. For example, for participation in any of the activities compared with none, the relative risk adjusted for age and region only was 0.83 (99% confidence interval 0.81-0.86), but changed to 1.06 (99% confidence interval 1.02-1.09) after additional adjustment. Adjustment for education, self-rated health, smoking and physical activity attenuated the associations most strongly. Residual confounding and other unmeasured factors may well account for any small remaining associations. CONCLUSIONS: Associations between participation in various social activities and CHD risk appear to be largely or wholly due to confounding by personal characteristics of the participants.

Effects of obesity and hormone therapy on surgically-confirmed fibroids in postmenopausal women.

To examine the association between body mass index (BMI), use of menopausal hormone therapy (HT), and incidence of uterine fibroids in postmenopausal women, 610,604 postmenopausal women without prior hysterectomy or diagnosis of fibroids were followed as part of a large United Kingdom prospective cohort study. We used Cox regression models to calculate adjusted relative risks (RRs) of surgically-confirmed fibroids (defined as a hospital admission with uterine fibroids as a primary diagnosis with a related surgical procedure), in relation to BMI and use of HT. During an average of 11.4 years of follow-up, 3561 women were admitted to hospital with surgically-confirmed fibroids. Five-year incidence rates decreased with age, from 0.50% (1 in 200 women) at age 50-54, to 0.11% (1 in 1000 women) at age 75-79. The 5-year rate in postmenopausal women aged 50-54 was about a quarter that seen in premenopausal women of the same age (1 in 200 vs. 1 in 50). Compared with normal weight women, obese women had a RR of surgically-detected fibroids of 1.46 (95% CI 1.33-1.59; p < 0.0001). HT use was associated with a RR of 2.33 (95% CI 2.18-2.49; p < 0.0001) in ever versus never users. When we analysed HT use and BMI together, obese vs. normal weight never users had a RR of 2.00 (95% CI 1.77-2.26): the highest risks were seen in women who were obese and had ever used HT, RR = 3.30 (95% CI 2.88-3.79). Uterine fibroids continue to occur in postmenopausal women; obesity and hormone therapy use are important modifiable risk factors.

The association of plasma IGF-I with dietary, lifestyle, anthropometric, and early life factors in postmenopausal women.

OBJECTIVE: Higher circulating concentrations of insulin like growth factor (IGF-I) are associated with an increased risk of breast cancer. The objective of this study was to investigate associations between circulating IGF-I concentrations and dietary factors (intakes of protein, dairy protein, and alcohol), lifestyle factors (smoking and HT use), anthropometric indices (height and adiposity) and factors in early life (birth weight, having been breastfed, body size at age 10, and at age 20) in postmenopausal women in the UK. DESIGN: An analysis of plasma IGF-I concentrations (measured by immunoassay) in 1883 postmenopausal women. Multivariate analysis was used to examine correlates of plasma IGF-I concentrations. RESULTS: Women in the highest quintile of total protein and dairy protein intakes had, respectively, 7.6% and 5.5% higher plasma IGF-I concentrations than women in the lowest quintile (p trend <0.05 for both). Other factors significantly (p<0.05) associated with reduced IGF-I concentrations were: consuming 14 or more vs 3-7 alcoholic drinks per week (8.8% lower IGF-I); current vs non-current HT users (9.9% lower IGF-I); current use of oestrogen alone vs oestrogen+progestagen (16.9% lower IGF-I); obese vs overweight (6.8% lower IGF-I); and women who reported wearing larger vs smaller clothes sizes at age 20 (4.9% lower IGF-I). CONCLUSIONS: This study in post-menopausal women identified several potentially modifiable determinants of circulating IGF-I concentrations. There is now strong evidence from this and other studies that IGF-I concentrations are associated with dietary protein intakes.

Age at menarche and risks of coronary heart and other vascular diseases in a large UK cohort.

BACKGROUND: Early menarche has been associated with increased risk of coronary heart disease (CHD), but most studies were relatively small and could not assess risk across a wide range of menarcheal ages; few have examined associations with other vascular diseases. We examined CHD, cerebrovascular disease, and hypertensive disease risks by age at menarche in a large prospective study of UK women. METHODS AND RESULTS: In 1.2 million women (mean±SD age, 56±5 years) without previous heart disease, stroke, or cancer, menarcheal age was reported to be 13 years by 25%, ≤10 years by 4%, and ≥17 years by 1%. After 11.6 years of follow-up, 73 378 women had first hospitalization for or death from CHD, 25 426 from cerebrovascular disease, and 249 426 from hypertensive disease. Using Cox regression, we calculated relative risks for each vascular outcome by single year of menarcheal age. The relationship was U-shaped for CHD. Compared with women with menarche at 13 years, the adjusted relative risk for CHD for menarche at ≤10 years of age was 1.27 (95% confidence interval, 1.22-1.31; P<0.0001) and for menarche at ≥17 years of age was 1.23 (95% confidence interval, 1.16-1.30; P<0.0001). U-shaped relationships were also seen for cerebrovascular and hypertensive disease, although the magnitudes of these risks for early and late menarche were smaller than those for CHD. CONCLUSIONS: In this cohort, the relation of age at menarche to vascular disease risk was U shaped, with both early and late menarche being associated with increased risk. Associations were weaker for cerebrovascular and hypertensive disease than for CHD.

Variations in vascular mortality trends, 2001-2010, among 1.3 million women with different lifestyle risk factors for the disease.

AIMS: Vascular disease mortality has declined rapidly in most Western countries, against a background of improved treatments and falling prevalence of smoking, but rising obesity. We examined whether this decline differed by lifestyle risk factors for vascular disease. METHODS AND RESULTS: During 2001-2010, there were 9241 vascular disease deaths in a prospective study of 1.3 million women in middle age, about one-quarter of all UK women in the eligible age range (50-64 years in 1996-2001). We estimated percentage declines in mortality from coronary heart disease, cerebrovascular disease and other vascular diseases, overall and by age, smoking, alcohol consumption, adiposity, physical activity, socioeconomic status and age at leaving school. Over 10 years, coronary heart disease mortality fell by half (52%), cerebrovascular disease mortality by two-fifths (42%) and other vascular disease mortality by one-fifth (22%). Lean women experienced greater declines in coronary heart disease mortality than overweight or obese women (70%, 48% and 26%, respectively; P < 0.001 for heterogeneity) and women in the highest and middle thirds of socioeconomic status experienced greater declines in other (non-coronary, non-cerebrovascular) vascular disease mortality than women in the lowest third (41% and 42% and -9%, respectively; P = 0.001). After accounting for multiple testing, there were no other significant differences in vascular mortality trends by any lifestyle risk factor, including by smoking status. CONCLUSION: Vascular disease mortality trends varied in this cohort by adiposity and socioeconomic status, but not by smoking status or other lifestyle risk factors. Prevention and treatment of vascular disease appear not to have been equally effective in all subgroups of UK women.