Body mass index and incident coronary heart disease in women: a population-based prospective study

BACKGROUND A high body mass index (BMI) is associated with an increased risk of mortality from coronary heart disease (CHD); however, a low BMI may also be associated with an increased mortality risk. There is limited information on the relation of incident CHD risk across a wide range of BMI, particularly in women. We examined the relation between BMI and incident CHD overall and across different risk factors of the disease in the Million Women Study. METHODS 1.2 million women (mean age=56 years) participants without heart disease, stroke, or cancer (except non-melanoma skin cancer) at baseline (1996 to 2001) were followed prospectively for 9 years on average. Adjusted relative risks and 20-year cumulative incidence from age 55 to 74 years were calculated for CHD using Cox regression. RESULTS After excluding the first 4 years of follow-up, we found that 32,465 women had a first coronary event (hospitalization or death) during follow-up. The adjusted relative risk for incident CHD per 5 kg/m2 increase in BMI was 1.23 (95% confidence interval (CI) 1.22 to 1.25). The cumulative incidence of CHD from age 55 to 74 years increased progressively with BMI, from 1 in 11 (95% CI 1 in 10 to 12) for BMI of 20 kg/m2, to 1 in 6(95% CI 1 in 5 to 7) for BMI of 34 kg/m2. A 10 kg/m2 increase in BMI conferred a similar risk to a 5-year increment in chronological age. The 20 year cumulative incidence increased with BMI in smokers and non-smokers, alcohol drinkers and non-drinkers, physically active and inactive, and in the upper and lower socioeconomic classes. In contrast to incident disease, the relation between BMI and CHD mortality (n=2,431) was J-shaped. For the less than 20 kg/m2 and ≥35 kg/m2 BMI categories, the respective relative risks were 1.27 (95% CI 1.06 to 1.53) and 2.84 (95% CI 2.51 to 3.21) for CHD deaths, and 0.89 (95% CI 0.83 to 0.94) and 1.85 (95% CI 1.78 to 1.92) for incident CHD. CONCLUSIONS CHD incidence in women increases progressively with BMI, an association consistently seen in different subgroups. The shape of the relation with BMI differs for incident and fatal disease.The Million Women Study is funded by Cancer Research UK, the Medical Research Council, and the NHS Breast Screening Programme. The funding organizations were not involved in the study design or conduct, data analysis or interpretation, manuscript preparation or review, final version approval, or decision to submit the manuscript

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/m2 and 35 + kg/m2 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/m2 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/m2). 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 ag

Vascular disease in women: comparison of diagnoses in hospital episode statistics and general practice records in England

BACKGROUND Electronic linkage to routine administrative datasets, such as the Hospital Episode Statistics (HES) in England, is increasingly used in medical research. Relatively little is known about the reliability of HES diagnostic information for epidemiological studies. In the United Kingdom (UK), general practitioners hold comprehensive records for individuals relating to their primary, secondary and tertiary care. For a random sample of participants in a large UK cohort, we compared vascular disease diagnoses in HES and general practice records to assess agreement between the two sources. METHODS Million Women Study participants with a HES record of hospital admission with vascular disease (ischaemic heart disease [ICD-10 codes I20-I25], cerebrovascular disease [G45, I60-I69] or venous thromboembolism [I26, I80-I82]) between April 1st 1997 and March 31st 2005 were identified. In each broad diagnostic group and in women with no such HES diagnoses, a random sample of about a thousand women was selected for study. We asked each woman's general practitioner to provide information on her history of vascular disease and this information was compared with the HES diagnosis record. RESULTS Over 90% of study forms sent to general practitioners were returned and 88% of these contained analysable data. For the vast majority of study participants for whom information was available, diagnostic information from general practice and HES records was consistent. Overall, for 93% of women with a HES diagnosis of vascular disease, general practice records agreed with the HES diagnosis; and for 97% of women with no HES diagnosis of vascular disease, the general practitioner had no record of a diagnosis of vascular disease. For severe vascular disease, including myocardial infarction (I21-22), stroke, both overall (I60-64) and by subtype, and pulmonary embolism (I26), HES records appeared to be both reliable and complete. CONCLUSION Hospital admission data in England provide diagnostic information for vascular disease of sufficient reliability for epidemiological analyses.The Million Women Study is funded by Cancer Research UK and the UK Medical Research Council. The study is registered with the NHS National Institute of Health Research Portfolio (study number 6862). General practices were reimbursed for conducting the data collection through NHS Service Support Cost funding of the National Institute of Health Research

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 VTEThis study was funded by Cancer Research UK, the UK Medical Research Council, and Lifebloo

Relationship between body mass index and length of hospital stay for gallbladder disease.

Background: Obesity increases the risk of hospital admission for gallbladder disease but its impact on the length of hospital stay is largely unknown. Methods: Prospective population-based study of 1.3 million women aged 56 years on average, recruited from 1996 to 2001 in England and Scotland and followed-up through NHS hospital admission record databases for gallbladder disease (cholelithiasis, cholecystitis, cholecystectomy) over a total of 7.8 million person-years. Results: During follow-up, 24 953 women were admitted with gallbladder disease, 87% who had a cholecystectomy. After adjusting for age, socioeconomic status and other factors, women with higher BMI at recruitment to the study were more likely to be admitted and spend more days in hospital. For 1000 person-years of follow-up, women in BMI categories of 18.5-24.9, 25-29.9, 30-39.9, 40+ kg/m2 spent, respectively, 16.5[16.0-17.0], 28.6[28.3-28.8], 44.0[43.4-44.5] and 49.4[45.7-53.0] days in hospital for gallbladder disease. Conclusion: On the basis of these estimates, over a quarter of all the days in hospital for gallbladder disease in middle-aged women can be attributed to obesity

Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency

Context: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases. Objective: A locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified. Design: The study design comprised single-nucleotide polymorphism genotyping and mutation detection. Setting: The study was conducted at secondary and tertiary referral centers. Patients: Eighty probands from families referred for investigation of the genetic cause of FGD participated in the study. Interventions: There were no interventions. Results: Analysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families. Conclusions: Mutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD

Market outlook for satellite-based RE index insurance in agribusiness

In the current report a market outlook for satellite-based RE index insurance is elaborated on. Special thanks for the contributions of Andries Rosema of EARS Earth Environment Monitoring BV and Erik Klaassens of ECORYS Nederland BV. Also the views of experts who were consulted are acknowledged (see for the list of experts Appendix I)

Scoping workshop 3 on next generation of mixed fisheries advice (WKMIXFISH3)

WKMIXFISH are a series of workshops bringing together scientists, advice recipients, and stakeholders to identify future research and advisory priorities for mixed fisheries science. The third scoping workshop on the next generation of mixed fisheries advice (WKMIXFISH3) met to review changes to mixed fisheries considerations and progress on method development since the last workshop in March 2023. The workshop focused on three areas of development. First, it reviewed changes and clarifications to mixed fisheries considerations that were incorporated to improve communication around the purpose of and assumptions in the advice. Second, it reviewed the substantial methodological development that has been undertaken by WGMIXFISH-METHODS and EU and UK research projects. The focus of this work was to address an EU/UK joint request to ICES on mixed fisheries science. Third, it discussed the outcome of a workshop on fleet and métier definitions (WKMIXFLEET) that took place the preceding two days. Methodological developments included evaluation of uncertainty in mixed fisheries models, analyses of sensitivity to model assumptions, including fleet and métier structure, and creating new ways to explore mixed fisheries data. It was noted that these, in combination with new tools, guidance, and visualizations, helped to provide greater understanding of the models and advice. While these endeavours are ongoing, there was general support for continued development; in particular, the deployment of a mixed fisheries online app to provide end-users and stakeholders with the ability to interact with the multifaceted outputs from mixed fisheries models. Support for, and engagement with, developments on using the Regional Database Estimation System (RDBES) data to make improvements to fleet and métier definitions was also highlighted. Next steps identified were for WGMIXFISH-ADVICE and WGMIXFISH-METHODS to use the valuable feedback obtained to continue to develop the tools, and implement and receive feedback on them as part of an iterative process. It was noted that further research and dedicated time for scientists was necessary to support the ongoing improvements to mixed fisheries advice and data products, and that this should be a priority.info:eu-repo/semantics/publishedVersio

Differences in risk factors for three 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

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy