Design and rationale of a randomized clinical trial assessing the effect of inclisiran on atherosclerotic plaque in individuals without previous cardiovascular event and without flow- limiting lesions identified in an in-hospital screening: The VICTORION-PLAQUE primary prevention trial.

Background: The impact of low-density lipoprotein cholesterol (LDL-C) on atherosclerotic cardiovascular disease (ASCVD) risk is influenced by both the magnitude and duration of exposure. Patients with nonobstructive coronary artery disease (NOCAD) and a CT-adapted Leaman score (CT-LeSc) >5 have a higher risk of cardiac events. The CT-LeSc semi-quantitatively assesses total coronary atherosclerotic burden via coronary computed tomography angiography (CCTA).

Causal mediation analysis for time-to-event outcomes on the Restricted Mean Survival Time scale: A pseudo-value approach.

Causal mediation analysis decomposes the total effect of an exposure on an outcome into: 1. the indirect effect through a mediator and 2. the remaining "direct" effect through all other pathways.

Agreement Between Apple Watch and Actical Step Counts in a Community Setting: Cross-Sectional Investigation From the Framingham Heart Study.

Background: Step counting is comparable among many research-grade and consumer-grade accelerometers in laboratory settings.

Objective: The purpose of this study was to compare the agreement between Actical and Apple Watch step-counting in a community setting.

Methods: Among Third Generation Framingham Heart Study participants (N=3486), we examined the agreement of step-counting between those who wore a consumer-grade accelerometer (Apple Watch Series 0) and a research-grade accelerometer (Actical) on the same days.

Causal mediation analysis with mediator values below an assay limit.

Causal indirect and direct effects provide an interpretable method for decomposing the total effect of an exposure on an outcome into the indirect effect through a mediator and the direct effect through all other pathways. A natural choice for a mediator in a randomized clinical trial is the treatment's targeted biomarker. However, when the mediator is a biomarker, values can be subject to an assay lower limit.

Association of Physical Inactivity with MRI Markers of Brain Aging: Assessing Mediation by Cardiometabolic and Epigenetic Factors.

Introduction: Cardiometabolic risk factors and epigenetic patterns, increased in physically inactive individuals, are associated with an accelerated brain aging process.

Objective: To determine whether cardiometabolic risk factors and epigenetic patterns mediate the association of physical inactivity with unfavorable brain morphology.

Methods: We included dementia and stroke free participants from the Framingham Heart Study Third Generation and Offspring cohorts who had accelerometery and brain MRI data (n = 2,507, 53.

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.

Association of Accelerometer-Measured Physical Activity and Sedentary Time with Epigenetic Markers of Aging.

Introduction/purpose: Physical activity may influence chronic disease risk, in part, through epigenetic mechanisms. Previous studies have demonstrated that an acute bout of physical activity can influence DNA methylation status. Few studies have explored the relationship between habitual, accelerometer-measured physical activity or sedentary time with epigenetic markers of aging.

Blood-Based Fingerprint of Cardiorespiratory Fitness and Long-Term Health Outcomes in Young Adulthood.

Background Cardiorespiratory fitness is a powerful predictor of health outcomes that is currently underused in primary prevention, especially in young adults. We sought to develop a blood-based biomarker of cardiorespiratory fitness that is easily translatable across populations. Methods and Results Maximal effort cardiopulmonary exercise testing for quantification of cardiorespiratory fitness (by peak oxygen uptake) and profiling of >200 metabolites at rest were performed in the FHS (Framingham Heart Study; 2016-2019).

Predictors of incident diabetes in two populations: framingham heart study and hispanic community health study / study of latinos.

Background: Non-genetic factors contribute to differences in diabetes risk across race/ethnic and socioeconomic groups, which raises the question of whether effects of predictors of diabetes are similar across populations. We studied diabetes incidence in the primarily non-Hispanic White Framingham Heart Study (FHS, N = 4066) and the urban, largely immigrant Hispanic Community Health Study/Study of Latinos (HCHS/SOL, N = 6891) Please check if the affiliations are captured and presented correctly.

Methods: Clinical, behavioral, and socioeconomic characteristics were collected at in-person examinations followed by seven-day accelerometry.

Do Physical Therapy and Yoga Improve Pain and Disability through Psychological Mechanisms? A Causal Mediation Analysis of Adults with Chronic Low Back Pain.

Objective: To investigate whether indirect effects via psychological mechanisms explain the effects of physical therapy (PT) or yoga versus education on back-related outcomes.

Design: Mediation analyses using data from a randomized controlled trial of PT, yoga, and education interventions for chronic low back pain.

Methods: Primary outcomes were changes in back-related pain on the 11-point numeric rating scale and disability on the modified 23-point Roland-Morris Disability Questionnaire, measured at 52 weeks after randomization.

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.

The association of lung function and pulmonary vasculature volume with cardiorespiratory fitness in the community.

Background: Cardiorespiratory fitness is not limited by pulmonary mechanical reasons in the majority of adults. However, the degree to which lung function contributes to exercise response patterns among ostensibly healthy individuals remains unclear.

Methods: We examined 2314 Framingham Heart Study participants who underwent cardiopulmonary exercise testing (CPET) and pulmonary function testing.

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.

Physical activity and fitness in the community: the Framingham Heart Study.

Aims: While greater physical activity (PA) is associated with improved health outcomes, the direct links between distinct components of PA, their changes over time, and cardiorespiratory fitness are incompletely understood.

Methods And Results: Maximum effort cardiopulmonary exercise testing (CPET) and objective PA measures [sedentary time (SED), steps/day, and moderate-vigorous PA (MVPA)] via accelerometers worn for 1 week concurrent with CPET and 7.8 years prior were obtained in 2070 Framingham Heart Study participants [age 54 ± 9 years, 51% women, SED 810 ± 83 min/day, steps/day 7737 ± 3520, MVPA 22.

Feasibility, Methodology, and Interpretation of Broad-Scale Assessment of Cardiorespiratory Fitness in a Large Community-Based Sample.

Cardiorespiratory fitness (CRF) is intricately related to health status. The optimal approach for CRF quantification is through assessment of peak oxygen uptake (VO), but such measurements have been largely confined to small referral populations. Here we describe protocols and methodological considerations for peak VO assessment and determination of volitional effort in a large community-based sample.

Joint associations of accelero-meter measured physical activity and sedentary time with all-cause mortality: a harmonised meta-analysis in more than 44 000 middle-aged and older individuals.

Objectives: To examine the joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality.

Methods: We conducted a harmonised meta-analysis including nine prospective cohort studies from four countries. 44 370 men and women were followed for 4.

Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis.

Objective: To examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality.

Design: Systematic review and harmonised meta-analysis.

Data Sources: PubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018.