Aims Little is known about the impact of daily physical activity timing (here referred to as 'chronoactivity') on cardiovascular disease (CVD) risk. We aimed to examined the associations between chronoactivity and multiple CVD outcomes in the UK Biobank. Methods and results physical activity data were collected in the UK-Biobank through triaxial accelerometer over a 7-day measurement period. We used K-means clustering to create clusters of participants with similar chronoactivity irrespective of the mean daily intensity of the physical activity. Multivariable-adjusted Cox-proportional hazard models were used to estimate hazard ratios (HRs) comparing the different clusters adjusted for age and sex (model 1), and baseline cardiovascular risk factors (model 2). Additional stratified analyses were done by sex, mean activity level, and self-reported sleep chronotype. We included 86 657 individuals (58% female, mean age: 61.6 [SD: 7.8] years, mean BMI: 26.6 [4.5] kg/m2). Over a follow-up period of 6 years, 3707 incident CVD events were reported. Overall, participants with a tendency of late morning physical activity had a lower risk of incident coronary artery disease (HR: 0.84, 95%CI: 0.77, 0.92) and stroke (HR: 0.83, 95%CI: 0.70, 0.98) compared to participants with a midday pattern of physical activity. These effects were more pronounced in women (P-value for interaction=0.001). We did not find evidence favouring effect modification by total activity level and sleep chronotype. Conclusion Irrespective of total physical activity, morning physical activity was associated with lower risks of incident cardiovascular diseases, highlighting the potential importance of chronoactivity in CVD prevention.

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Background: Little is known about the impact of timing as opposed to frequency and intensity of daily physical activity on metabolic health. Therefore, we assessed the association between accelerometery-based daily timing of physical activity and measures of metabolic health in sedentary older people. Methods: Hourly mean physical activity derived from wrist-worn accelerometers over a 6-day period was collected at baseline and after 3 months in sedentary participants from the Active and Healthy Ageing study. A principal component analysis (PCA) was performed to reduce the number of dimensions (e.g. define periods instead of separate hours) of hourly physical activity at baseline and change during follow-up. Cross-sectionally, a multivariable-adjusted linear regression analysis was used to associate the principal components, particularly correlated with increased physical activity in data-driven periods during the day, with body mass index (BMI), fasting glucose and insulin, HbA1c and the homeostatic model assessment for insulin resistance (HOMA-IR). For the longitudinal analyses, we calculated the hourly changes in physical activity and change in metabolic health after follow-up. Results: We included 207 individuals (61.4% male, mean age: 64.8 [SD 2.9], mean BMI: 28.9 [4.7]). Higher physical activity in the early morning was associated with lower fasting glucose (−2.22%, 95% CI: −4.19, −0.40), fasting insulin (−13.54%, 95%CI: −23.49, −4.39), and HOMA-IR (−16.07%, 95%CI: −27.63, −5.65). Higher physical activity in the late afternoon to evening was associated with lower BMI (−2.84%, 95% CI: −4.92, −0.70). Higher physical activity at night was associated with higher BMI (2.86%, 95% CI: 0.90, 4.78), fasting glucose (2.57%, 95% CI: 0.70, 4.30), and HbA1c (2.37%, 95% CI: 1.00, 3.82). Similar results were present in the prospective analysis. Conclusion: Specific physical activity timing patterns were associated with more beneficial metabolic health, suggesting particular time-dependent physical activity interventions might maximise health benefits.

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Scope: Abdominal obesity is one of the main modifiable risk factors of age-related cardiometabolic disease. Cardiometabolic disease risk and its associated high abdominal fat mass, cholesterol, and glucose concentrations can be reduced by a healthier lifestyle. Hence, the aim is to understand the relation between lifestyle-induced changes in body composition, and specifically abdominal fat, and accompanying changes in circulating metabolic biomarkers. Methods and results: Data from the Growing Old Together (GOTO) study was used, which is a single arm lifestyle intervention in which 164 older adults (mean age 63 years, BMI 23–35 kg/m²) changed their lifestyle during 13 weeks by 12.5% caloric restriction plus 12.5% increase in energy expenditure. It is shown here that levels of circulating metabolic biomarkers, even after adjustment for body mass index, specifically associate with abdominal fat mass. The applied lifestyle intervention mainly reduces abdominal fat mass (−2.6%, SD = 3.0) and this reduction, when adjusted for general weight loss, is highly associated with decreased circulating glycerol concentrations and increased HDL diameter. Conclusion: The lifestyle-induced reduction of abdominal fat mass is particularly associated, independent of body mass index or general weight loss, with decreased circulating glycerol concentrations and increased HDL diameter.

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Animal studies suggest the involvement of natriuretic peptides (NP) in several brain functions that are known to be disturbed during Alzheimer's disease (AD). However, it remains unclear whether such findings extend to humans. In this study, we aimed to: (1) map the gene expression and localization of NP and their receptors (NPR) in human post-mortem brain tissue; (2) compare the relative amounts of NP and NPR between the brain tissue of AD patients and non-demented controls, and (3) compare the relative amounts of NP between the cerebrospinal fluid (CSF) of AD patients and non-demented controls. Using the publicly available Allen Human Brain Atlas dataset, we mapped the gene expression of NP and NPR in healthy humans. Using immunohistochemistry, we visualized the localization of NP and NPR in the frontal cortex of AD patients (n = 10, mean age 85.8 ± 6.2 years) and non-demented controls (mean age = 80.2 ± 9.1 years). Using Western blotting and ELISA, we quantified the relative amounts of NP and NPR in the brain tissue and CSF of these AD patients and non-demented controls. Our results showed that NP and NPR genes were ubiquitously expressed throughout the brain in healthy humans. NP and NPR were present in various cellular structures including in neurons, astrocyte-like structures, and cerebral vessels in both AD patients and non-demented controls. Furthermore, we found higher amounts of NPR type-A in the brain of AD patients (p = 0.045) and lower amounts of NP type-B in the CSF of AD patients (p = 0.029). In conclusion, this study shows the abundance of NP and NPR in the brain of humans suggesting involvement of NP in various brain functions. In addition, our findings suggest alterations of NP levels in the brain of AD patients. The role of NP in the development and progression of AD remains to be elucidated.@en