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BMI is correlated with circulating metabolites, but few studies discuss other adiposity measures, and little is known about metabolomic correlates of BMI from early life. We investigated associations between different adiposity measures, BMI from childhood through adulthood, and metabolites quantified from serum using 1H NMR spectroscopy in 900 British men and women aged 60–64. We assessed BMI, waist-to-hip ratio (WHR), android-to-gynoid fat ratio (AGR), and BMI from childhood through adulthood. Linear regression with Bonferroni adjustment was performed to assess adiposity and metabolites. Of 233 metabolites, 168; 126; and 133 were associated with BMI, WHR, and AGR at age 60–64, respectively. Associations were strongest for HDL, particularly HDL particle size—e.g., there was 0.08 SD decrease in HDL diameter (95% CI: 0.07–0.10) with each unit increase in BMI. BMI-adjusted AGR or WHR were associated with 31 metabolites where there was no metabolome-wide association with BMI. We identified inverse associations between BMI at age 7 and glucose or glycoprotein at age 60–64 and relatively large LDL cholesteryl ester with postadolescent BMI gains. In summary, we identified metabolomic correlates of central adiposity and earlier-life BMI. These findings support opportunities to leverage metabolomics in early prevention of cardiovascular risk attributable to body fatness.

Summary: Background: Early menopause is linked to an increased risk of cardiovascular disease mortality; however, the association between early menopause and incidence and timing of cardiovascular disease is unclear. We aimed to assess the associations between age at natural menopause and incidence and timing of cardiovascular disease. Methods: We harmonised and pooled individual-level data from 15 observational studies done across five countries and regions (Australia, Scandinavia, the USA, Japan, and the UK) between 1946 and 2013. Women who had reported their menopause status, age at natural menopause (if postmenopausal), and cardiovascular disease status (including coronary heart disease and stroke) were included. We excluded women who had hysterectomy or oophorectomy and women who did not report their age at menopause. The primary endpoint of this study was the occurrence of first non-fatal cardiovascular disease, defined as a composite outcome of incident coronary heart disease (including heart attack and angina) or stroke (including ischaemic stroke or haemorrhagic stroke). We used Cox proportional hazards models to estimate multivariate hazard ratios (HRs) and 95% CIs for the associations between age at menopause and incident cardiovascular disease event. We also adjusted the model to account for smoking status, menopausal hormone therapy status, body-mass index, and education levels. Age at natural menopause was categorised as premenopausal or perimenopausal, younger than 40 years (premature menopause), 40–44 years (early menopause), 45–49 years (relatively early), 50–51 years (reference category), 52–54 years (relatively late), and 55 years or older (late menopause). Findings: Overall, 301 438 women were included in our analysis. Of these 301 438 women, 12 962 (4·3%) had a first non-fatal cardiovascular disease event after menopause, of whom 9369 (3·1%) had coronary heart disease and 4338 (1·4%) had strokes. Compared with women who had menopause at age 50–51 years, the risk of cardiovascular disease was higher in women who had premature menopause (age

High impact physical activity (PA) is thought to benefit bone. We examined associations of lifetime walking and weight bearing exercise with accelerometer-measured high impact and overall PA in later life. Data were from 848 participants (66.2% female, mean age=72.4years) from the Cohort for Skeletal Health in Bristol and Avon, Hertfordshire Cohort Study and MRC National Survey of Health and Development. Acceleration peaks from seven-day hip-worn accelerometer recordings were used to derive counts of high impact and overall PA. Walking and weight bearing exercise up to age 18, between 18–29, 30–49 and since age 50 were recalled using questionnaires. Responses in each age category were dichotomised and cumulative scores derived. Linear regression was used for analysis. Greater lifetime walking was related to higher overall, but not high impact PA, whereas greater lifetime weight bearing exercise was related to higher overall and high impact PA. For example, fully-adjusted differences in log-overall and log-high impact PA respectively for highest versus lowest lifetime scores were: walking [0.224 (0.087, 0.362) and 0.239 (−0.058, 0.536)], and weight bearing exercise [0.754 (0.432, 1.076) and 0.587 (0.270, 0.904)]. For both walking and weight bearing exercise, associations were strongest in the ‘since age 50’ category. Those reporting the most walking and weight bearing exercise since age 50 had highest overall and high impact PA, e.g. fully-adjusted difference in log-high impact PA versus least walking and weight bearing exercise=0.588 (0.226, 0.951). Promoting walking and weight bearing exercise from midlife may help increase potentially osteogenic PA levels in later life. Keywords: Accelerometer, Exercise, Life course, Physical activity

Summary: Background: Evidence of the possible health benefits of social connectedness is increasing. We aimed to examine poor social connectedness as a possible barrier to participation in preventive health services among older people (aged 53–69 years). Methods: We analysed data from a prospective cohort study of 5362 socially stratified births from the Medical Research Council National Survey of Health and Development enrolled in England, Scotland, and Wales in March 1946. At ages 68–69 years, participants reported participation in blood pressure and cholesterol measurement, eyesight and dental check-ups, influenza immunisation, and bowel and breast cancer screening. Our primary outcome measure summed participation across all these tests and services at ages 68–69 years. We tested associations between structural and functional social connectedness from ages 53 years to 69 years and total count of participation in these preventive services in Poisson models controlling for sex, education, occupational class, employment, chronic illnesses, and general practitioner consultations for health problems. Findings: 940 (44%) of 2132 participants attended all preventive services within the recommended timeframes. At ages 68–69 years, being unmarried or not cohabiting (incident rate ratio [IRR] 1·33, 95% CI 1·20–1·47) and small personal social networks (IRR 1·51, 1·32–1·71) were independently associated with non-participation in more services, with associations consistent across most services. High social relationship quality at ages 68–69 years (IRR 0·91, 95% CI 0·87–0·95) and increasing social relationship quality from ages 53 years to 69 years (IRR 0·93, 0·89–0·97) were associated with low risk of non-participation. Interpretation: Individuals with poor social connectedness appear to be at greater risk of not engaging in the full range of preventive services than individuals with good social connectedness. Improvement of access to social contacts and networks in older ages is already recommended for the maintenance of good mental health. This study suggests that social connectedness could also improve participation in a wide range of preventive health services, and hence could improve use of the health-care system and population health. Funding: UK Medical Research Council.

Summary: Background: Socioeconomic inequalities in childhood body-mass index (BMI) have been documented in high-income countries; however, uncertainty exists with regard to how they have changed over time, how inequalities in the composite parts (ie, weight and height) of BMI have changed, and whether inequalities differ in magnitude across the outcome distribution. Therefore, we aimed to investigate how socioeconomic inequalities in childhood and adolescent weight, height, and BMI have changed over time in Britain. Methods: We used data from four British longitudinal, observational, birth cohort studies: the 1946 Medical Research Council National Survey of Health and Development (1946 NSHD), 1958 National Child Development Study (1958 NCDS), 1970 British Cohort Study (1970 BCS), and 2001 Millennium Cohort Study (2001 MCS). BMI (kg/m2) was derived in each study from measured weight and height. Childhood socioeconomic position was indicated by the father's occupational social class, measured at the ages of 10–11 years. We examined associations between childhood socioeconomic position and anthropometric outcomes at age 7 years, 11 years, and 15 years to assess socioeconomic inequalities in each cohort using gender-adjusted linear regression models. We also used multilevel models to examine whether these inequalities widened or narrowed from childhood to adolescence, and quantile regression was used to examine whether the magnitude of inequalities differed across the outcome distribution. Findings: In England, Scotland, and Wales, 5362 singleton births were enrolled in 1946, 17 202 in 1958, 17 290 in 1970, and 16 404 in 2001. Low socioeconomic position was associated with lower weight at childhood and adolescent in the earlier-born cohorts (1946–70), but with higher weight in the 2001 MCS cohort. Weight disparities became larger from childhood to adolescence in the 2001 MCS but not the earlier-born cohorts (pinteraction=0·001). Low socioeconomic position was also associated with shorter height in all cohorts, yet the absolute magnitude of this difference narrowed across generations. These disparities widened with age in the 2001 MCS (pinteraction=0·002) but not in the earlier-born cohorts. There was little inequality in childhood BMI in the 1946–70 cohorts, whereas inequalities were present in the 2001 cohort and widened from childhood to adolescence in the 1958–2001 cohorts (pinteraction

Abstract Objective: To explore endocrine‐related and general symptoms among three groups of middle‐aged women defined by country of birth and country of residence, in the context of debates about biological, cultural and other factors in menopause. Methods: British‐born women participating in a British birth cohort study (n=1,362) and age‐matched Australian‐born (n=1,724) and British‐born (n=233) Australian women selected from the Australian Longitudinal Study on Women's Health (ALSWH) responded to two waves of surveys at ages 48 and 50. Results: Australian‐Australian and British‐Australian women report reaching menopause later than British‐British women, even after accounting for smoking status and parity. Hormone replacement therapy (HRT) use was lower and hysterectomy was more common among both Australian groups, probably reflecting differences in health services between Britain and Australia. The Australian‐Australian and British‐Australian groups were more likely to report endocrine‐related symptoms than the British‐British group, even after adjusting for menopausal status. British‐British women were more likely to report some general symptoms. Conclusions: Symptom reporting is high among Australian and British midlife women and varies by country of residence, country of birth and menopausal status. Implications: The data do not support either a simple cultural or a simple biological explanation for differences in menopause experience.