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

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

Associations between pre-pregnancy obesity and asthma symptoms in adolescents

Background: The high prevalence of children's asthma symptoms, worldwide, is unexplained. We examined the relation between maternal pre-pregnancy weight and body mass index (BMI), and asthma symptoms in adolescents. Methods: Data from 6945 adolescents born within the Northern Finland Birth Cohort 1986 were used. Prospective antenatal and birth outcome data, including maternal pre-pregnancy weight and BMI, and asthma symptoms in adolescent offspring at age 15–16 years, were employed. Logistic regression analyses were performed to examine the associations between relevant prenatal factors and asthma symptoms during adolescence. Results: Current wheeze (within the past year) was reported by 10.6% of adolescents, and physician-diagnosed asthma by 6.0%. High maternal pre-pregnancy BMI was a significant predictor of wheeze in the adolescents (increase per kilogram per square metre unit; 2.7%, 95% CI 0.9 to 4.4 for ever wheeze; 3.5%, 95% CI 1.3 to 5.8 for current wheeze), and adjusting for potential confounders further increased the risk (2.8%, 95% CI 0.5 to 5.1; 4.7%, 95% CI 1.9 to 7.7, respectively). High maternal pre-pregnancy weight, in the top tertile, also significantly increased the odds of current wheeze in the adolescent by 20% (95% CI 4 to 39), and adjusting for potential confounders further increased the risk (OR=1.52, 95% CI 1.19 to 1.95). Results were similar for current asthma. Furthermore, these significant associations were observed only among adolescents without parental history of atopy but not among those with parental history of atopy. Conclusions: The association demonstrated here between maternal pre-pregnancy overweight and obesity, and asthma symptoms in adolescents suggests that increase in asthma may be partly related to the rapid rise in obesity in recent years

An explainable Transformer-based deep learning model for the prediction of incident heart failure

Predicting the incidence of complex chronic conditions such as heart failure is challenging. Deep learning models applied to rich electronic health records may improve prediction but remain unexplainable hampering their wider use in medical practice. We developed a novel Transformer deep-learning model for more accurate and yet explainable prediction of incident heart failure involving 100,071 patients from longitudinal linked electronic health records across the UK. On internal 5-fold cross validation and held-out external validation, our model achieved 0.93 and 0.93 area under the receiver operator curve and 0.69 and 0.70 area under the precision-recall curve, respectively and outperformed existing deep learning models. Predictor groups included all community and hospital diagnoses and medications contextualised within the age and calendar year for each patient's clinical encounter. The importance of contextualised medical information was revealed in a number of sensitivity analyses, and our perturbation method provided a way of identifying factors contributing to risk. Many of the identified risk factors were consistent with existing knowledge from clinical and epidemiological research but several new associations were revealed which had not been considered in expert-driven risk prediction models

Spousal concordance in adverse childhood experiences and the association with depressive symptoms in middle-aged and older adults: findings across China, the US, and Europe

BackgroundAdverse childhood experiences (ACEs) are associated with higher depressive risks in adulthood. Whether respondents’ ACEs are associated with their own depressive symptoms in adulthood and whether this association extends to their spouses’ depressive symptoms remain unexplored.MethodsData were from China Health and Retirement Longitudinal Study (CHARLS), the Health and Retirement Study (HRS), and the Survey of Health, Ageing and Retirement in Europe (SHARE). ACEs were categorized into overall, intra-familial, and extra-familial ACEs. Correlations of couples’ ACEs were calculated using Cramer’s V and partial Spearman’s correlation. Associations of respondents’ ACEs with spousal depressive symptoms were assessed using logistic regression, and mediation analyses were conducted to explore the mediating role of respondents’ depressive symptoms.ResultsSignificant associations between husbands’ ACEs and wives’ depressive symptoms, with odds ratios (ORs) and 95% confidence intervals (CIs) of 2.09 (1.36–3.22) for 4 or more ACEs in CHARLS, and 1.25 (1.06–1.48) and 1.38 (1.06–1.79) for 2 or more ACEs in HRS and SHARE. However, wives’ ACEs were associated with husbands’ depressive symptoms only in CHARLS and SHARE. Findings in intra-familial and extra-familial ACEs were consistent with our main results. Additionally, respondents’ depressive symptoms mediated more than 20% of the effect of respondents’ ACEs on spousal depressive symptoms.ConclusionWe found that ACEs were significantly correlated between couples. Respondents’ ACEs were associated with spousal depressive symptoms, with respondents’ depressive symptoms mediating the association. The bidirectional implications of ACEs on depressive symptoms should be considered within household and effective interventions are warranted

Genetic susceptibility, elevated blood pressure and risk of atrial fibrillation:A Mendelian randomization study

Background: Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual’s genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk. Methods: First, causality of association was assessed through two-sample Mendelian randomization, using data from two independent genome-wide association studies that included a total of one million European population. Second, the UK Biobank data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with major BP-lowering drug classes on AF risk was predicted through genetic variants in genes encode the therapeutic targets of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists. Results: The two-sample Mendelian randomization analysis indicated that, on average, exposure to a higher systolic BP increased the risk of AF by 19% (odds ratio per each 10-mm Hg [OR]: 1.19 [1.12 to 1.27]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF. The comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers and calcium channel blockers) suggested similar average effects for the prevention of atrial fibrillation and coronary heart disease. Conclusions: The effect of elevated BP on the risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility risk for AF