Physical Function, Cognitive Function, and Aortic Stiffness in Older Adults

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Objective physical activity and physical performance in middle-aged and older adults

Background: Older adults may have difficulty meeting the Physical Activity (PA) Guidelines. A favorable balance between PA and sedentary time (SED) is an important determinant of physical performance in older adults. Our objective was to explore associations of PA/SED with physical performance across mid-older age in adults without overt mobility disability. Methods: Framingham Offspring Study participants free of mobility disability with accelerometry and physical performance data (gait speed, chair stand time, and handgrip strength), were studied in cross-sectional analysis (n = 1352). We regressed physical performance on PA level, measured using steps, moderate to vigorous (MV)PA and SED. We stratified by age groups, adjusted for covariates, and modelled MVPA and SED separately and together as predictors. Results: Only 38% of adults 50–64 years and 15% of adults ≥75 years met the PA Guidelines (i.e., 150 min MVPA per week). Individuals achieving at least 5 min/day of MVPA had 0.062 ± 0.013 m/s greater gait speed and better chair stands and handgrip strength (in women) than those with 0.05). For adults ≥75 years, every 5000 more steps/day related to ~0.045 m/s greater gait speed (p = 0.006). Conclusion: Our cross-sectional study demonstrated that, across mid-older adulthood, MVPA related to better physical performance, but in adults ≥75 years, total steps walked associated with better gait speed. These data warrant future research on the impact of PA on physical performance and health outcomes in older age

Comparison of On-Site Versus Remote Mobile Device Support in the Framingham Heart Study Using the Health eHeart Study for Digital Follow-up: Randomized Pilot Study Set Within an Observational Study Design

BACKGROUND: New electronic cohort (e-Cohort) study designs provide resource-effective methods for collecting participant data. It is unclear if implementing an e-Cohort study without direct, in-person participant contact can achieve successful participation rates. OBJECTIVE: The objective of this study was to compare 2 distinct enrollment methods for setting up mobile health (mHealth) devices and to assess the ongoing adherence to device use in an e-Cohort pilot study. METHODS: We coenrolled participants from the Framingham Heart Study (FHS) into the FHS-Health eHeart (HeH) pilot study, a digital cohort with infrastructure for collecting mHealth data. FHS participants who had an email address and smartphone were randomized to our FHS-HeH pilot study into 1 of 2 study arms: remote versus on-site support. We oversampled older adults (age \u3e /=65 years), with a target of enrolling 20% of our sample as older adults. In the remote arm, participants received an email containing a link to enrollment website and, upon enrollment, were sent 4 smartphone-connectable sensor devices. Participants in the on-site arm were invited to visit an in-person FHS facility and were provided in-person support for enrollment and connecting the devices. Device data were tracked for at least 5 months. RESULTS: Compared with the individuals who declined, individuals who consented to our pilot study (on-site, n=101; remote, n=93) were more likely to be women, highly educated, and younger. In the on-site arm, the connection and initial use of devices was \u3e /=20% higher than the remote arm (mean percent difference was 25% [95% CI 17-35] for activity monitor, 22% [95% CI 12-32] for blood pressure cuff, 20% [95% CI 10-30] for scale, and 43% [95% CI 30-55] for electrocardiogram), with device connection rates in the on-site arm of 99%, 95%, 95%, and 84%. Once connected, continued device use over the 5-month study period was similar between the study arms. CONCLUSIONS: Our pilot study demonstrated that the deployment of mobile devices among middle-aged and older adults in the context of an on-site clinic visit was associated with higher initial rates of device use as compared with offering only remote support. Once connected, the device use was similar in both groups

Deregulated expression of the imprinted DLK1-DIO3 region in glioblastoma stemlike cells: Tumor suppressor role of lncRNA MEG3

Background: Glioblastoma (GBM) stemlike cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted delta-like homolog 1 gene type III iodothyronine deiodinase gene (DLK-DIO3) region on chromosome 14q32 in GBM pathogenesis. Methods: Real-time PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression, and reverse-phase protein array profiles were used to investigate the tumor suppressor function of the maternally expressed 3 gene (MEG3). Results: Loss of expression of genes and noncoding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared with normal brain. This downregulation is mainly mediated by epigenetic silencing. Kaplan-Meier analysis indicated that low expression of MEG3 and MEG8 long noncoding (lnc)RNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration, and colony formation and decreases in vivo tumor growth, reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and epithelial-to-mesenchymal transition (EMT). Conclusion: In GBM, MEG3 acts as a tumor suppressor mainly regulating cell adhesion, EMT, and cell proliferation, thus providing a potential candidate for novel GBM therapies

Physical activity measured by accelerometry and its associations with cardiac structure and vascular function in young and middle-aged adults

Background Physical activity is associated with several health benefits, including lower cardiovascular disease risk. The independent influence of physical activity on cardiac and vascular function in the community, however, has been sparsely investigated. Measures and Results We related objective measures of moderate‐ to vigorous‐intensity physical activity (MVPA, assessed by accelerometry) to cardiac and vascular indices in 2376 participants of the Framingham Heart Study third generation cohort (54% women, mean age 47 years). Using multivariable regression models, we related MVPA to the following echocardiographic and vascular measures: left ventricular mass, left atrial and aortic root sizes, carotid–femoral pulse wave velocity, augmentation index, and forward pressure wave. Men and women engaged in MVPA 29.9±21.4 and 25.5±19.4 min/day, respectively. Higher values of MVPA (per 10‐minute increment) were associated with lower carotid–femoral pulse wave velocity (estimate −0.53 ms/m; P=0.006) and lower forward pressure wave (estimate −0.23 mm Hg; P=0.03) but were not associated with augmentation index (estimate 0.13%; P=0.25). MVPA was associated positively with loge left ventricular mass (estimate 0.006 loge [g/m2]; P=0.0003), left ventricular wall thickness (estimate 0.07 mm; P=0.0001), and left atrial dimension (estimate 0.10 mm; P=0.01). MVPA also tended to be positively associated with aortic root dimension (estimate 0.05 mm; P=0.052). Associations of MVPA with cardiovascular measures were similar, in general, for bouts lasting <10 versus ≥10 minutes. Conclusions In our community‐based sample, greater physical activity was associated with lower vascular stiffness but with higher echocardiographic left ventricular mass and left atrial size. These findings suggest complex relations of usual levels of physical activity and cardiovascular remodeling

Device-measured physical activity, adiposity and mortality: a harmonised meta-analysis of eight prospective cohort studies.

BACKGROUND: The joint associations of total and intensity-specific physical activity with obesity in relation to all-cause mortality risk are unclear. METHODS: We included 34 492 adults (72% women, median age 62.1 years, 2034 deaths during follow-up) in a harmonised meta-analysis of eight population-based prospective cohort studies with mean follow-up ranging from 6.0 to 14.5 years. Standard body mass index categories were cross-classified with sample tertiles of device-measured total, light-to-vigorous and moderate-to-vigorous physical activity and sedentary time. In five cohorts with waist circumference available, high and low waist circumference was combined with tertiles of moderate-to-vigorous physical activity. RESULTS: There was an inverse dose-response relationship between higher levels of total and intensity-specific physical activity and mortality risk in those who were normal weight and overweight. In individuals with obesity, the inverse dose-response relationship was only observed for total physical activity. Similarly, lower levels of sedentary time were associated with lower mortality risk in normal weight and overweight individuals but there was no association between sedentary time and risk of mortality in those who were obese. Compared with the obese-low total physical activity reference, the HRs were 0.59 (95% CI 0.44 to 0.79) for normal weight-high total activity and 0.67 (95% CI 0.48 to 0.94) for obese-high total activity. In contrast, normal weight-low total physical activity was associated with a higher risk of mortality compared with the obese-low total physical activity reference (1.28; 95% CI 0.99 to 1.67). CONCLUSIONS: Higher levels of physical activity were associated with lower risk of mortality irrespective of weight status. Compared with obesity-low physical activity, there was no survival benefit of being normal weight if physical activity levels were low

Prospective Association of Daily Steps with Cardiovascular Disease: A Harmonized Meta-Analysis

Background: Taking fewer than the widely promoted “10 000 steps per day” has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose–response relationship between steps per day and CVD can help inform clinical and public health guidelines. Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance–weighted random effects models. Results: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. Conclusions: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician–patient communication and population health to reduce the risk of CVD

Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts

Background Although 10000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. Methods In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose– response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inversevariance weighted random effects models. Findings We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3–9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51–0·71) for quartile 2, 0·55 (0·49–0·62) for quartile 3, and 0·47 (0·39–0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000–8000 steps per day and among adults younger than 60 years until 8000–10000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56–0·83]) and a peak of 60 min (0·67 [0·50–0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96–1·32]) and 100 steps per min or faster (0·86 [0·58–1·28]). Interpretation Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity

Prospective Association of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis.

BACKGROUND: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines. METHODS: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models. RESULTS: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. CONCLUSIONS: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD

Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts.

BACKGROUND: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3-9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51-0·71) for quartile 2, 0·55 (0·49-0·62) for quartile 3, and 0·47 (0·39-0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56-0·83]) and a peak of 60 min (0·67 [0·50-0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96-1·32]) and 100 steps per min or faster (0·86 [0·58-1·28]). INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. FUNDING: US Centers for Disease Control and Prevention