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Background:Obesity and sedentary lifestyles are known risk factors for atrial fibrillation (AF). Wearable devices such as smartwatches present an opportunity to investigate relations between daily step count and AF risk.Hypothesis:Higher daily step count, as measured by wearable devices, will be associated with a smaller five-year risk of AF, as predicted by CHARGE-AF score.Methods:Participants from the electronic Framingham Heart Study (eFHS) utilized an AppleWatch. Individuals with diagnosed AF were excluded. Daily step count, watch wear time (hours, days), and self-reported physical activity were collected. Individual five-year risk of AF was estimated using The Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) score. Relation between daily step counts and five-year predicted AF risk was examined with linear regression adjusted for age, sex, and wear time. Secondary analyses examined effect modification by sex and obesity (body mass index ≥30 kg/m2), as well as relation between self-reported physical activity and predicted 5-year AF risk.Results:We examined 932 eFHS participants (mean age 53±9 years, 61% female) with a median daily step of 7360 (25th-75thpercentile 5841-9060). Most participants (89.2%) had <2.5% CHARGE-AF risk. Every 1000 steps were associated with 0.08% lower CHARGE-AF risk (P<0.001). A stronger association was observed in men and individuals with obesity. In contrast, self-reported physical activity was not associated with CHARGE-AF risk.Conclusion:Higher daily step count was associated with lower predicted 5-year risk of AF, and this relation was stronger in men and participants with obesity. The utility of a wearable daily step counter for risk reduction for AF merits further investigation.

Introduction:Resting heart rate (HR) is an established predictor of cardiorespiratory fitness. Commercial smartwatches permit remote HR monitoring in real world settings over long periods of time, but the relations of smartwatch measured HR and cardiorespiratory fitness in the general public remain uncharacterized. ObjectiveWe aimed to examine the associations of resting HR measured with a smartwatch in the electronic Framingham Heart Study (eFHS) with multi-dimensional fitness assessment via cardiopulmonary exercise test (CPET). We hypothesized that participants with lower resting HR would have greater cardiorespiratory fitness.Methods:eFHS participants were enrolled at an FHS research exam (2016-2019) and provided with a study smartwatch that collected longitudinal HR data for up to 3 years. We identified participants’ HR measures in the sedentary state through a classification algorithm to calculate the average resting HR for each participant. At the same exam, participants underwent CPET performed on a cycle ergometer. Multivariable linear models were used to test the association of resting HR with CPET indices. We used P<0.05 for significance.Results:We included 1,051 participants (mean age 52±8 years, 59% women, mean resting HR 77±6 beats/min) with a median of 27,655 HR records for each individual, and median of 266 watch-wearing days. Higher individual resting HR was associated with a lower peak oxygen uptake (VO2; both in ml/kg/min and % predicted), lower VO2at the ventilatory anaerobic threshold (VAT), higher (adverse) ventilatory efficiency (VE/VCO2), and unfavorable blood pressure response to exercise (higher mean arterial pressure at 75 watts) (Table).Conclusions:Our findings suggest the feasibility of smartwatch-based HR assessment as an indicator of a broad array of cardiorespiratory fitness responses in the community, including measures of global fitness (peak VO2), ventilatory efficiency, and blood pressure response to exercise.

Introduction:Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies examined associations between arterial stiffness and digital home BPV over an intermediate time span.Objective:We investigated if antecedent arterial stiffness was associated with home BPV among participants in the electronic Framingham Heart Study (eFHS). We hypothesize that higher arterial stiffness predicts higher intermediate-term home BPV over one-year follow-up.Methods:At an FHS research exam (2016-2019), participants underwent arterial tonometry to acquire mean arterial pressure (MAP) and measures of arterial stiffness (carotid femoral pulse wave velocity, CFPWV; forward pressure wave amplitude, FWA) and wave reflection (reflection coefficient, RC). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly. Participants with < 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with home average real variability (ARV) of systolic (SBP) and diastolic (DBP) BP adjusting for covariates. We obtained ARV as an average of the absolute differences of consecutive BP measurements. ARV considers not only the dispersion of the BP readings around the mean, but also the order of BP readings. We used p<0.05 for significance.Results:Among 857 eFHS participants (mean age 54 years, 59% women, mean BP 119/76, 47% hypertension, mean ARV of DBP 5.50, mean ARV of SBP 8.61), higher FWA and RC were associated with higher ARV of SBP (Table). Higher CFPWV was associated with lower ARV of DBP (Table).Conclusion:In eFHS, higher FWA and RC were associated with higher intermediate-term home BPV of SBP while higher CFPWV was associated with blunted BPV of DBP. Our findings suggest that higher aortic stiffness and wave reflection may affect day-to-day modulation of blood pressure in a home-based setting.

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Introduction:Physical inactivity is associated with a higher risk of dementia, and has also been associated with unfavorable brain morphology. It is also clear that cardiometabolic risk factors accelerate the brain aging process.Hypothesis:Cardiometabolic risk factors mediate the association of physical inactivity with unfavorable brain morphology.Methods:Our investigation included participants from the Third Generation (exam 2) and Offspring (exam 9) cohorts of the Framingham Heart Study who wore an accelerometer for &gte10 hours on &gte3 days (to measure moderate to vigorous physical activity [MVPA] and steps walked per day), underwent brain MRI scans, and had no dementia, stroke, or missing cardiometabolic risk factor data (n=2416, 54% women, mean age 54.1 years). Higher levels of brain peak width of skeletonized mean (white matter) diffusivity, higher free water, and lower total cerebral brain volume were measured by MRI as markers of brain aging. We examined mediation by the 2017 revised version of the Framingham Stroke Risk Profile (FSRP, using weights for age, prevalent cardiovascular disease, atrial fibrillation, diabetes and smoking status, antihypertension medications and systolic blood pressure) and the homeostatic model of insulin resistance (HOMA-IR) in models of the association of MVPA and steps with brain volume, white matter diffusivity, and free water, adjusting for age, age-squared, sex, wear time, smoking status (for HOMA-IR mediation analysis only), cohort, time from exam to MRI, and season of exam.Results:The associations of lower MVPA and steps with lower brain volume, higher white matter diffusivity, and higher free water were partially mediated through FSRP, accounting for 14.1-25.7% (p&lt0.05) of the total association of physical inactivity with brain aging. The association of fewer steps (but not MVPA) with lower brain volume was mediated by HOMA-IR (20.1% of the total association, p&lt0.05).Conclusions:Our results suggest that the associations of physical inactivity with lower brain volume, poorer white matter microstructure and aggregation of free water in the extracellular compartments of the brain are partially mediated by cardiometabolic risk factors.

Background:Smartphone apps and mHealth devices offer innovative ways to collect cardiovascular data. However, maintaining engagement is challenging. We assessed the effect of interventions to enhance remote transmission of blood pressure (BP) and heart rate (HR) data.Methods:We conducted a 2x2x2 factorial blinded randomized trial (NCT03516019). We invited eFHS participants, an e-cohort embedded in the Framingham Study, to enroll. We trained participants to wear their smartwatch (Apple Watch) daily and measure their BP (Withings) weekly. We sent weekly notifications to promote adherence. We assessed 3 notification strategies: personalized vs. standard; weekday vs. weekend; and morning vs. evening. Personalized notifications included the participant?s name and were tailored to prior week?s data transmission. Primary outcomes were adherence to HR and BP transmission in the week following the 12thnotification (3-month). Secondary outcomes were 1- and 6-month adherence.Results:We randomized 655 participants (54?9 years, 60% women). For the personalized vs. standard notification primary outcomes, there was no evidence of difference for HR data transmission (64.1% vs. 62.4%; p=0.65), but 38.7% vs. 28.8% participants sent BP data (difference, 9.9%; 95%CI 2.7-17.0%; p=0.008). Personalized notifications were associated with increased HR transmission at 6 months (59.8% vs. 49.2%, difference 10.6%; 95%CI 2.8-18.2%; p<0.01). For HR and BP primary or secondary outcomes, there was no evidence of a difference between notifications sent on weekday vs. weekend, or morning vs. evening. We did not observe two-way or three-way interactions.Conclusion:Our trial demonstrated that personalized notifications increase adherence to BP and HR transmission from mobile and digital devices among eFHS participants. Our results suggest that personalized messaging is a powerful tool to promote adherence to mHealth systems in cardiovascular research.

Introduction:Motor function in older adults is known to correlate with neurodegenerative changes and Alzheimer’s Disease (AD) pathology in the brain, however the relationship between mid-life fitness and AD pathology is unknown. AD pathology accumulates early and is difficult to measure; precise estimation requires brain imaging not accessible beyond research settings. Plasma Amyloid and Tau, on the other hand are easy to measure, and are markers of AD pathology and neuronal loss. We tested the association between physical fitness measures in mid-life (gait speed, grip strength and chair stand speed) and plasma markers of AD in the Framingham Heart Study (FHS) Offspring cohort. If these measures correlate with and predict plasma measures of AD burden, these could potentially be used to screen for risk of dementia.Hypothesis:We hypothesized that superior physical fitness will be cross-sectionally associated with higher plasma Amyloid Aβ42 and lower Tau; also, that physical fitness measures will be longitudinally associated with Tau measured at a later exam.Methods:The FHS Offspring cohort had plasma Aβ40 and Aβ42 measured at their 7th clinic exam (1998-01) and plasma total Tau measured at Exam 8 (2005-08). They had grip strength, gait speed and chair stand speed measured at Exam 7, and grip strength and gait speed measured at Exam 8. Grip strength was measured using the Jamar dynamometer, fast gait speed was measured over a 4-meter walkway and chair stand speed was assessed by asking the participants to stand up and down five times, as quickly as they can with their hands folded across their chest. Quantification of Aβ isoforms in plasma was performed using INNO-BIA assays and tau using Single Molecule Array technology.We used linear regression models to examine the association between physical fitness measures and plasma markers of AD adjusting for known confounders (diabetes, cardiovascular disease, atrial fibrillation, smoking, APOE4, systolic blood pressure, waist-to-hip ratio, total cholesterol level, physical activity index, and plasma homocysteine).Results:In this sample of 1886 community living adults (mean age 61, 54% women), hand grip strength was independently associated with plasma Aβ40 (Beta coefficient -0.28; SD 0.10; p value 0.003) and plasma Tau measured 5 years later (Beta coefficient -0.003; SD 0.001; p value 0.001). Gait speed and chair stand speed demonstrated associations with Aβ40 and total Tau which were attenuated by vascular risk factors.Conclusions:Hand grip strength is associated with AD pathology. Grip strength measurement could be a valid screening tool for identifying individuals at a higher risk for AD alongside other validated markers. Future research should examine the correlation between grip strength and AD burden measured by PET imaging.