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Background: New models of scalable population-based data collection that integrate digital and mobile health (mHealth) data are necessary. Objective: The aim of this study was to describe a cardiovascular digital and mHealth electronic cohort (e-cohort) embedded in a traditional longitudinal cohort study, the Framingham Heart Study (FHS). Methods: We invited eligible and consenting FHS Generation 3 and Omni participants to download the electronic Framingham Heart Study (eFHS) app onto their mobile phones and co-deployed a digital blood pressure (BP) cuff. Thereafter, participants were also offered a smartwatch (Apple Watch). Participants are invited to complete surveys through the eFHS app, to perform weekly BP measurements, and to wear the smartwatch daily. Results: Up to July 2017, we enrolled 790 eFHS participants, representing 76% (790/1044) of potentially eligible FHS participants. eFHS participants were, on average, 53±8 years of age and 57% were women. A total of 85% (675/790) of eFHS participants completed all of the baseline survey and 59% (470/790) completed the 3-month survey. A total of 42% (241/573) and 76% (306/405) of eFHS participants adhered to weekly digital BP and heart rate (HR) uploads, respectively, over 12 weeks. Conclusions: We have designed an e-cohort focused on identifying novel cardiovascular disease risk factors using a new smartphone app, a digital BP cuff, and a smartwatch. Despite minimal training and support, preliminary findings over a 3-month follow-up period show that uptake is high and adherence to periodic app-based surveys, weekly digital BP assessments, and smartwatch HR measures is acceptable.

BACKGROUND New models of scalable population-based data collection that integrate digital and mobile health (mHealth) data are necessary. OBJECTIVE The aim of this study was to describe a cardiovascular digital and mHealth electronic cohort (e-cohort) embedded in a traditional longitudinal cohort study, the Framingham Heart Study (FHS). METHODS We invited eligible and consenting FHS Generation 3 and Omni participants to download the electronic Framingham Heart Study (eFHS) app onto their mobile phones and co-deployed a digital blood pressure (BP) cuff. Thereafter, participants were also offered a smartwatch (Apple Watch). Participants are invited to complete surveys through the eFHS app, to perform weekly BP measurements, and to wear the smartwatch daily. RESULTS Up to July 2017, we enrolled 790 eFHS participants, representing 76% (790/1044) of potentially eligible FHS participants. eFHS participants were, on average, 53±8 years of age and 57% were women. A total of 85% (675/790) of eFHS participants completed all of the baseline survey and 59% (470/790) completed the 3-month survey. A total of 42% (241/573) and 76% (306/405) of eFHS participants adhered to weekly digital BP and heart rate (HR) uploads, respectively, over 12 weeks. CONCLUSIONS We have designed an e-cohort focused on identifying novel cardiovascular disease risk factors using a new smartphone app, a digital BP cuff, and a smartwatch. Despite minimal training and support, preliminary findings over a 3-month follow-up period show that uptake is high and adherence to periodic app-based surveys, weekly digital BP assessments, and smartwatch HR measures is acceptable.

The electronic Framingham Heart Study (eFHS) is a mobile health cardiovascular monitoring system deployed at the current in-person exam. We developed a smartphone app which includes an electronic consent, health questionnaires, and integrates with a wireless blood pressure (BP) cuff and Apple Watch. We have deployed the app in 1927 FHS participants (mean age 52.8, range 32-80 years, 57% women, 7% multi-ethnic) who owned a compatible smartphone (iPhone or Android). We have observed high rates of initial survey adherence (85% completed baseline surveys). Preliminary results demonstrate about 76% of participants who transmit data from the Apple Watch continued to transmit data 12 weeks following enrollment. Our experience highlights the capacity of FHS participants to transmit meaningful mHealth data. We plan to identify factors associated with long-term use and to compare digital data to data collected in the Research Center to understand the value of this novel means of data collection.

Background: New “e-Cohort” study designs provide resource-effective methods for collecting participant data. It is unclear if implementing an e-cohort without direct, in-person participant contact can achieve successful participation rates. The FHS-HeH randomized pilot study compared two distinct implementation strategies for co-enrolling participants from the Framingham Heart Study (FHS) into the Health eHeart Study, a digital cohort with infrastructure for collecting mHealth data. Methods: FHS participants who had an email address and smartphone were randomized to one of two approaches: remote vs. on-site support. In the remote arm, participants received an email containing an enrollment URL, and, upon enrollment, were sent four Bluetooth sensor devices. Participants in the on-site arm were invited to visit FHS and were provided in-person support for enrollment and connecting the devices. Results: Compared to participants that declined, individuals that accepted an invitation to participate in our pilot study (n=101 remote , n=101 on-site ) were more often women, highly educated, and younger (Figure 1). All on-site participants completed the consent, compared to 93% of the remote arm. Of participants who consented to participate, connection and initial use of devices was also higher in the on-site arm (100% connected the activity monitor, 94% the blood pressure cuff and scale, and 84% the electrocardiogram) compared to the remote arm (74%, 75%, 80%, and 42%). Roughly 75-78% of those that initially connected in both arms were still using the devices by the 3 rd month and 58-60% were still participating by the 6 th month. Conclusions: Our pilot study demonstrated that 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 to offering only remote support. Once connected, drop-off rates were similar in both groups.

Each chapter listed in the Table of Contents (see next page) is a hyperlink to that chapter. The reader clicks the chapter name to access that chapter. Each chapter listed here is a hyperlink. Click on the chapter name to be taken to that chapter. Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together in a single document the most up-to-date statistics related to heart disease, stroke, and the cardiovascular risk factors listed in the AHA’s My Life Check - Life’s Simple 7 (Figure1), which include core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure [BP], and glucose control) that contribute to cardiovascular health. The Statistical Update represents …

The matching of vascular supply to neuronal metabolic demand during cognitive engagement is known as neurovascular coupling (NVC). Arterial stiffness is a prominent determinant of pulsatility in the systemic circulation and may thus indirectly impact NVC. In this pilot investigation, we explored changes in carotid artery stiffness and cerebrovascular hemodynamic pulsatiltiy during cognitive engagement in healthy adults.Twenty-seven adults (age 39 ± 3 years, BMI 24 ± 1 kg/m(2)) underwent Doppler ultrasonography of the common carotid artery (CCA) combined with applanation tonometry to derive (i) CCA elastic modulus (Ep) and β-stiffness index; (ii) CCA flow pulsatility index (PI); (iii) CCA pulse pressure, (iv) CCA augmentation index (AIx). Cerebral PI was assessed using transcranial Doppler at the middle cerebral artery (MCA). All measures were made at rest and during an incongruent Stroop task.CCA PI was reduced (1.75 ± 0.06 to 1.57 ± 0.06, P0.05) while MCA PI was unchanged (0.75 ± 0.02 to 0.75 ± 0.02, P0.05) during Stroop. Brachial pulse pressure increased during Stroop (43 ± 1 to 46 ± 1 mm Hg, P0.05) while CCA pulse pressure was unchanged (36 ± 1 to 35 ± 1 mm Hg, P0.05). Similarly, CCA Ep (54.5 ± 5.5 to 53.8 ± 4.9 kPa, P0.05) and β-stiffness index (4.4 ± 0.4 to 4.2 ± 0.3 aU, P0.05) were unchanged. CCA AIx increased (1 ± 4 to 13 ± 4%, P0.05).Carotid pressure pulsatility is unaltered while carotid flow pulsatility is reduced during cognitive engagement. Carotid artery stiffness does not change suggesting that factors other than the dynamic elastic properties of the CCA buffer cerebrovascular hemodynamic pulsatility during cognitive engagement.

Background Low body mass index (BMI) is associated with COPD, but temporal relationships between airflow obstruction (AO) development and emphysematous change are unclear. We investigated longitudinal changes in BMI, AO, and lung density throughout adulthood using data from the Framingham Offspring Cohort (FOC). Methods BMI trajectories were modelled throughout adulthood in 4587 FOC participants from Exam 2 (mean age = 44), through Exam 9 (mean age = 71), in AO participants and non-AO participants (AO n = 1036), determined by spirometry, using fractional polynomial growth curves. This process was repeated for low lung density (LLD) and non LLD participants (LLD n = 225) determined by Computed Tomography. Spirometry decline was compared separately between tertiles of BMI in those aged Results The BMI trajectory from 30 years of age was visually lower in the AO group than both non-AO smokers (non-1/FVC ratio in both sexes. Conclusion Mean BMI is lower throughout adulthood in AO and LLD participants. Lower BMI is associated with a steeper decline in the ratio of FEV1/FVC. These findings suggest body mass may precede and potentially have a role in the development of COPD lung pathophysiology.

Author(s): Tan, Zaldy S; Spartano, Nicole L; Beiser, Alexa S; DeCarli, Charles; Auerbach, Sanford H; Vasan, Ramachandran S; Seshadri, Sudha | Abstract: BackgroundSeveral longitudinal studies found an inverse relationship between levels of physical activity and cognitive decline, dementia, and/or Alzheimer's disease (AD), but results have been inconsistent. We followed an older, community-based cohort for over a decade to examine the association of physical activity with the risk of incident dementia and subclinical brain MRI markers of dementia.MethodsThe physical activity index (PAI) was assessed in the Framingham Study Original and Offspring cohorts, aged 60 years or older. We examined the association between PAI and risk of incident all-cause dementia and AD in participants of both cohorts who were cognitively intact and had available PAI (n = 3,714; 54% women; mean age = 70±7 years). We additionally examined the association between PAI and brain MRI in the Offspring cohort (n = 1,987).ResultsOver a decade of follow-up, 236 participants developed dementia (188 AD). Participants in the lowest quintile of PAI had an increased risk of incident dementia compared with those in higher quintiles (hazard ratio [HR] = 1.50, 95% confidence interval [CI] = 1.04-1.97, p = .028) in a multivariable-adjusted model. Secondary analysis revealed that this relation was limited to participants who were apolipoprotein (APO)E e4 allele noncarriers (HR = 1.58, 95% CI = 1.08-2.32; p = .018) and strongest in participants aged 75 years or older. PAI was also linearly related to total brain and hippocampal volumes (β ± SE = 0.24±0.06; p l .01 and 0.004±0.001; p = .003, respectively).ConclusionLow physical activity is associated with a higher risk for dementia in older individuals, suggesting that a reduced risk of dementia and higher brain volumes may be additional health benefits of maintaining physical activity into old age.

Background: Recent evidence suggests that dementia appears linked to subclinical vascular changes, which may be attenuated by physical activity. The Physical Activity Guidelines for Americans (PA-Guidelines) are currently set at 150 min of moderate-to-vigorous physical activity (MVPA) per week, as a target for adults to achieve favorable health outcomes, but make no specific recommendations for prevention of dementia. Many Americans fall well below the PA-Guidelines. The aim of this investigation was to determine whether there is a continuum of lower intensities and volumes of physical activity associated with healthy brain aging even in individuals not meeting the PA-Guidelines. Methods: We included Framingham Heart Study (FHS) participants who wore an Actical accelerometer for ≥3 valid days (>10 h wear time per day) on their right hip during the most recent cohort examinations and completed brain magnetic resonance imaging (MRI) an average of 1.7 (±0.9) years later (n=2534): Offspring exam 9, Third Generation exam 2, and corresponding examinations of the Omni cohorts. Participants were excluded from this analysis if they had prevalent stroke or dementia (n=63) or met the 150 min MVPA per week PA-Guidelines (n=1158). Non-wear time (defined as 60 min of zero-counts, with two interruptions allowed) was removed. Sedentary time (1486 counts/min, ≥3 METs) and steps were accumulated at any time of day. The relations of physical activity measures to brain MRI measures were assessed using multivariable linear regression. Results: More than 53% of FHS participants did not meet the PA-Guidelines for MVPA during their last exam, and were thus included in this investigation (n=1313, 56 [±14] years old, 60% women). These participants took an average of 6149 [±3079] steps, spent 10.5 [±6.1] min MVPA, 13 h 36 min [±48 min] sedentary and 2 h 14 min [±48 min] in light activities per day. Each additional 40 min of light activity (spent in 1.5-3 METs) or 42 min less time spent sedentary was associated with 0.22% [±0.07%] greater total cerebral brain volume (TCBV), after adjusting for age, sex, body mass index, smoking, diabetes mellitus, and cardiovascular disease (p=0.001), equivalent to approximately 1.1 years less brain aging. Greater light activity and lower sedentary time were also associated with greater hippocampal volume (p Conclusions: Our investigation demonstrates, in a community setting, that there may be a negative association of light physical activity with brain aging even among individuals not meeting the PA-Guidelines for MVPA.

Objective To investigate the influence of prestroke physical activity (PA) on acute stroke severity. Methods Data from patients with first stroke were retrieved from registries with a cross-sectional design. The variables were PA, age, sex, smoking, diabetes, hypertension and statin treatment, stroke severity, myocardial infarction, new stroke during hospital stay, and duration of inpatient care at stroke unit. PA was assessed with Saltin-Grimby's 4-level Physical Activity Level Scale, and stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Logistic regression was used to predict stroke severity, and negative binomial regression was used to compare the level of PA and stroke severity. Results The study included 925 patients with a mean age of 73.1 years, and 45.2% were women. Patients who reported light or moderate PA levels were more likely to present a mild stroke (NIHSS score 0 to 5) compared with physically inactive patients in a model that also included younger age as a predictor (odds ratio = 2.02 for PA and odds ratio = 0.97 for age). The explanatory value was limited at 6.8%. Prestroke PA was associated with less severe stroke, and both light PA such as walking at least 4 h/wk and moderate PA 2–3 h/wk appear to be beneficial. Physical inactivity was associated with increased stroke severity. Conclusions This study suggests that PA and younger age could result in a less severe stroke. Both light PA such as walking at least 4 h/wk and moderate PA 2–3 h/wk appear to be beneficial.

Cardiovascular dysfunction and vascular aging are systemic conditions that affect all major target organs, including the brain.1 It follows that cardiovascular disease (CVD), subclinical cardiovascular conditions, and cardiovascular risk factors are associated with an elevated risk for developing dementia. These associations are important because they reveal a potential opportunity to prevent dementia through management and treatment of CVD and its risk factors with both pharmaceutical options (such as promising examples from antihypertension medication trials)1 and lifestyle interventions that improve cardiovascular health.

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 ≥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 ≥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.

ObjectiveTo examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality.DesignSystematic review and harmonised meta-analysis.Data sourcesPubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018.Eligibility criteriaProspective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals.Data extraction and analysisGuidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis.Main outcome measureAll cause mortality.Results39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56).ConclusionHigher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults.Systematic review registrationPROSPERO CRD42018091808.

Importance Dementia risk may be attenuated by physical activity (PA); however, the specific activity levels optimal for dementia prevention are unclear. Moreover, most older adults are unable to meet the nationally recommended PA guidelines, set at 150 minutes of moderate to vigorous PA per week. Objective To assess the association of total steps walked per day and total dose (intensity × duration) of PA with brain volumes on magnetic resonance imaging (MRI) among Framingham Heart Study participants. Design, Setting, and Participants This cross-sectional, community-based cohort study of the association of accelerometry-determined PA with brain MRI measures in Framingham, Massachusetts, included the Framingham Heart Study third-generation (examination 2, 2008-2011) and offspring (examination 9, 2011-2014) cohorts. Of 4021 participants who agreed to wear an accelerometer and had valid data (≥10 hours/day for ≥3 days), 1667 participants who did not undergo brain MRI (n = 1604) or had prevalent dementia or stroke (n = 63) were excluded. Data analysis began in 2016 and was completed in February 2019. Exposures Physical activity achieved using accelerometry-derived total activity (steps per day) and 2 intensity levels (light intensity and moderate to vigorous intensity). Main Outcomes and Measures Differences in total brain volume and other MRI markers of brain aging. Results The study sample of 2354 participants had a mean (SD) age of 53 (13) years, 1276 (54.2%) were women, and 1099 (46.7%) met the PA guidelines. Incremental light-intensity PA was associated with higher total brain volume; each additional hour of light-intensity PA was associated with approximately 1.1 years less brain aging (β estimate, 0.22; SD, 0.07;P = .003). Among individuals not meeting the PA guidelines, each hour of light-intensity PA (β estimate, 0.28; SD, 0.11;P = .01) and achieving 7500 steps or more per day (β estimate, 0.44; SD, 0.18;P = .02) were associated with higher total brain volume, equivalent to approximately 1.4 to 2.2 years less brain aging. After adjusting for light-intensity PA, neither increasing moderate to vigorous PA levels nor meeting the threshold moderate to vigorous PA level recommended by the PA guidelines were significantly associated with total brain volume. Conclusions and Relevance Every additional hour of light-intensity PA was associated with higher brain volumes, even among individuals not meeting current PA guidelines. These data are consistent with the notion that the potential benefits of PA on brain aging may accrue at a lower, more achievable level of intensity or duration.

Dietary modification alters plasma lipoprotein profiles and atherosclerotic lesion progression in humans and some animal models. Variability in response to diet induced atherosclerosis has been reported in hamsters. Assessed was the interaction between background diet composition and dietary fat type on aortic cholesterol accumulation, lipoprotein profiles, hepatic lipids and selected genes. F1B Golden Syrian hamsters (20/group) were fed (12 weeks) semi-purified or non-purified diets containing either 10 % (w/w) coconut oil or safflower oil and 0.15 % (w/w) cholesterol. The non-purified diets relative to semi-purified diets resulted in significantly higher TC (72 % [percent difference] and 38 %, coconut oil and safflower oil, respectively) and nHDL-C (84 and 61 %, coconut oil and safflower oil, respectively), and lower HDL-C (−47 and −45 %, coconut oil and safflower oil, respectively) concentrations. Plasma triacylglycerol concentrations in the hamsters fed the non-purified coconut oil-supplemented diets were three- to fourfold higher than non-purified safflower oil-supplemented, and both semi-purified diets. With the exception of HDL-C, a significant effect of fat type was observed in TC, nHDL-C and triacylglycerol (all P < 0.05) concentrations. Regardless of diet induced differences in lipoprotein profiles, there was no significant effect on aortic cholesterol accumulation. There was an inverse relationship between plasma nHDL-C and triacylglycerol, and hepatic cholesteryl ester content (P < 0.001). Diet induced differences in hepatic gene transcription (LDL receptor, apoB-100, microsomal transfer protein) were not reflected in protein concentrations. Although hamsters fed non-purified and/or saturated fatty acid-supplemented diets had more atherogenic lipoprotein profiles compared to hamsters fed semi-purified and/or polyunsaturated fatty acid-supplemented diets these differences were not reflected in aortic cholesterol accumulation.

Background Beyond their resting values, exercise responses in blood pressure ( BP ) and heart rate ( HR ) may add prognostic information for cardiovascular disease ( CVD ). In cross‐sectional studies, exercise BP and HR responses correlate with CVD risk factors; however, it is unclear which factors influence longitudinal changes in exercise responses over time, which is important for our understanding of the development of CVD . Methods and Results We assessed BP and HR responses to low‐level exercise tests (6‐minute Bruce protocol) in 1231 Framingham Offspring participants (55% women) who underwent a routine treadmill test in 1979–1983 (baseline; mean age 39±8 years) that was repeated in 1998–2001 (follow‐up; mean age 58±8 years). Adjusting for baseline exercise responses, we related the follow‐up exercise responses to baseline CVD risk factors and to their changes between examinations. Compared with men, women had greater rise in exercise systolic (S) BP and HR at 20‐year follow‐up (both P SBP and HR , and smoking status were associated with greater exercise SBP at follow‐up (all P SBP and HR at follow‐up (both P SBP (≥180 mm Hg) at follow‐up ( P Conclusion An adverse CVD risk factor profile in young adults and its worsening over time were associated with higher SBP and HR responses to low‐level exercise in midlife. Maintaining or adopting a healthy risk factor profile may favorably impact the exercise responses over time.

Objectives Cardiovascular reactivity has been associated with future hypertension and cardiovascular mortality. Higher physical activity (PA) has been associated with lower cardiovascular reactivity in adults, but little data is available in children. The purpose of this study was to examine the relationship between PA and cardiovascular reactivity to mental stress in children. Design Cross-sectional study. Methods This study sample included children from the Oswego Lead Study (n = 79, 46% female, 9–11 years old). Impedance cardiography was performed while children participated in a stress response protocol. Children were also asked to wear Actigraph accelerometers on their wrists for 3 days to measure intensity and duration of PA and sedentary time. Results In multivariable models, moderate to vigorous (MV) PA was associated with lower body mass index (BMI) percentile and lower total peripheral resistance (TPR) response to stress (beta = −0.025, p = 0.02; beta = −0.009, p = 0.05). After additional adjustment for BMI, MVPA was also associated with lower diastolic blood pressure response to stress (beta = −0.01, p = 0.03). Total PA and sedentary time were not associated with BMI or cardiovascular responses to stress. Conclusions A modest, inverse relation of PA to vascular reactivity to mental stress was observed in children. These data provide confirmatory evidence that the promotion of PA recommendations for children are important for cardiovascular health.

Background: Older adults (≥ 65 years [y]) may have difficulty meeting the Physical Activity (PA) Guidelines for Americans. Recent literature suggests that light activity is an important determinant of physical function in older adults. We hypothesized that PA (especially light activity) is associated with gait speed in older adults. Methods: Framingham Offspring Study examination 9 participants, free of mobility limitations with accelerometry and physical performance data (timed 4 meter walk), were included in this investigation (n=1449, age ≥ 50y). Sedentary time (1486 counts/min) and steps/day were also assessed. We used linear regression to relate gait speed (dependent variable) to PA levels (independent), adjusting for sex and wear time. For interactions observed between PA and age at the p≤0.1 level, regression models were stratified by age group: age 50-64 y (n=422, 55% women), age 65-44 y (n=704, 54% women), and age ≥75 y (n=323, 52% women). Results: Only 38% of adults aged 50-64 y achieved the PA Guidelines, i.e., 150 min MVPA per week. Guideline achievement dropped to 15% in participants ≥75 y. Average gait speed decreased from 1.23 to 1.08 m/s across age groups. Each 10 min increment in MVPA was associated with a 0.01 m/s higher gait speed in the full sample (p Discussion: Our cross-sectional study demonstrated an association of light-intensity PA with gait speed in adults ≥65 y. These data warrant future research on the impact of light activity on physical function and health outcomes in the elderly.

Background: Physical activity (PA) has been associated with lower cardiovascular reactivity in adults, but little data is available in children. The purpose of this study was to examine the relationship between PA and cardiovascular reactivity to stress in children. Methods: This study sample included children from the Oswego Lead Study (n=79, 46% female, 9-11 years old). Impedance cardiography was performed while children participated in a stress response protocol consisting of three stress tasks in random order, separated by 8-minute intertask rest periods. Change in heart rate (HR) and systolic and diastolic blood pressure (SBP and DBP) (from baseline to stress level) were standardized within each task, then averaged across tasks (zMean [[Unable to Display Character: ∆]]). Total peripheral resistance (TPR) was calculated using BP and cardiac output (CO); TPR = ([(SBP-DBP)/3] + DBP)/CO X 80. Percent change in TPR (from baseline to stress level) was standardized within each task, and then averaged across tasks (zMean %[[Unable to Display Character: ∆]]). Children were also asked to wear Actigraph accelerometers on their wrists for 3 days to measure intensity and duration of PA and sedentary time. Results: In multivariable regression models, moderate to vigorous (MV) PA was associated with a lower body mass index (BMI) percentile, lower resting heart rate (HR), and lower TPR response to stress (Table 1; all p < 0.05). After additional adjustment for BMI, MVPA was also associated with lower diastolic blood pressure response to stress (p < 0.05). Sedentary time was not associated with resting measures or cardiovascular responses to stress (data not shown). Conclusions: A modest relation was observed between MVPA and vascular reactivity to stress in children after accounting for the effect of BMI. These data provide confirmatory evidence that the promotion of PA recommendations for children are important for cardiovascular health.

Introduction: Blood pressure (BP) and heart rate (HR) responses to exercise may add prognostic information beyond their resting values. Many cardiovascular disease (CVD) risk factors are associated with exercise BP and HR cross-sectionally, but factors influencing exercise hemodynamics over the life-course are unknown. Methods: We assessed BP and HR in response to treadmill tests (6 minutes of the Bruce protocol) in a sample of 1231 Framingham Offspring participants who performed the treadmill test during two routine examinations: 1979-1983 (baseline) and 1998-2001 (follow-up). We included participants (55% women, mean age 39±8 years at baseline, 58±8 years at follow up) free of CVD and not taking beta-blockers or anti-hypertension medications at either exam. Baseline diabetes mellitus (DM) cases and individuals taking lipid-lowering medications at baseline were excluded due to small numbers. We related exercise hemodynamics at follow-up to baseline CVD risk factors and their interim changes, also adjusting for baseline exercise hemodynamics. Results: Compared with men, women experienced greater change in exercise hemodynamics at 20 y follow-up, relative to baseline exercise hemodynamics (see Table 1). Baseline blood lipid levels, resting SBP and HR, and smoking status were associated with greater exercise SBP at follow-up. Baseline BMI did not independently influence follow-up exercise hemodynamics, but weight gain across exams (the effect of 1 kg/m2 increase in BMI) was associated with higher exercise SBP and higher exercise HR. New-onset DM was associated with ~6 mm Hg higher exercise SBP, independent of weight gain, compared to those who remained free of DM across exams. Conclusions: CVD risk factors and their worsening over time were associated with higher exercise SBP and HR on follow-up. Our findings suggest that maintaining an optimal risk factor profile over the lifecourse will favorably impact exercise hemodynamic responsesover time.

Background: Exaggerated blood pressure (BP) and vascular stiffness have been associated with lower cognitive performance and brain atrophy in older age. The brain is a high-flow, low impedance organ that is susceptible to fluctuation in BP. Poor cardiovascular (CV) fitness is also emerging as a factor associated with cognitive decline in older age. The BP and heart rate (HR) response to exercise are impacted by CV fitness; and exercise BP is also highly determined by vascular stiffness. The objective of this investigation was to examine whether poor fitness and exaggerated BP and HR response to exercise in midlife are associated with worse brain morphology in later life. Methods: A subset of Framingham Offspring Study participants (n=1340, 54.5% F) free from dementia and CV disease underwent an exercise treadmill test (the modified Bruce protocol) in midlife [mean age of 41±9 y] and continued until exhaustion or until 85% HR maximum (age- and sex- predicted) was reached. Exercise test duration was used to estimate VO2max. BP and HR were measured during stage 2. MRI scans of the brain and neurocognitive tests (Trail Making Tests [Trails] B-A) were administered in later life [mean age of 59±9 y]. Results: A greater exercise systolic (S)BP and HR response at midlife was associated with smaller total cerebral brain volume (TCBV) in later life (β=-0.09 ±0.04, p=0.042; β=-0.10 ±0.05, p=0.033) after adjustment models including resting SBP and HR; an effect equal to approximately 0.5 y brain aging for every 11.1 mm Hg increase in SBP or 10 beats per min increase in HR. Higher estimated VO2max at midlife was associated with larger TCBV in later life (β=0.03 ±0.01, p=0.014). Additionally, greater exercise HR response at midlife was associated with smaller frontal lobe volume in later life (β=-0.012 ±0.05, p=0.002). Exercise diastolic (D)BP at midlife was associated with poorer performance on Trails B-A in later life (β=-0.009 ±0.004, p=0.017) and the achievement of target HR during exercise was associated with better performance on Trails B-A in later life (β=0.03 ±0.01, p=0.044). Resting SBP at midlife was associated with greater white matter hyperintensity volume in later life (β=0.05 ±0.02, p=0.031); and resting SBP and DBP at midlife were also associated with smaller frontal lobe volume in later life (β=-0.17 ±0.07, p=0.011; β=-0.21 ±0.10, p=0.030). Conclusion: Our investigation provides new evidence that lower midlife fitness and worse exercise BP and HR responses are associated with smaller brain volumes and poorer cognitive performance nearly two decades later. Promotion of midlife physical fitness may be an important step towards ensuring healthy brain aging in the population.

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 log e left ventricular mass (estimate 0.006 log e [g/m 2 ]; 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 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.

Individuals with type 2 diabetes mellitus are at increased risk of developing atherosclerosis. This may be partially attributable to suppression of macrophage ATP-binding cassette (ABC) transporter mediated cholesterol efflux by sustained elevated blood glucose concentrations. 2 models were used to assess this potential relationship: human monocytes/leukocytes and murine bone marrow-derived macrophages (BMDM).10 subjects (4 F/6 M, 50-85 years, BMI 25-35 kg/m²) underwent an oral glucose challenge. Baseline and 1- and 2-h post-challenge ABC-transporter mRNA expression was determined in monocytes, leukocytes and peripheral blood mononuclear cells (PBMC). In a separate study, murine-BMDM were exposed to 5 mmol/L D-glucose (control) or additional 20 mmol/L D- or L-glucose and 25 ug/mL oxidized low density lipoprotein (oxLDL). High density lipoprotein (HDL)-mediated cholesterol efflux and ABC-transporter (ABCA1 and ABCG1) expression were determined.Baseline ABCA1and ABCG1 expression was lower (>50%) in human monocytes and PBMC than leukocytes (p

Individuals with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease (CVD), possibly associated with elevated plasma free fatty acid concentrations. Paradoxically, evidence suggests that unsaturated, compared to saturated fatty acids, suppress macrophage cholesterol efflux, favoring cholesterol accumulation in the artery wall. Murine bone marrow-derived macrophages (BMDM) were used to further explore the relationship between saturated and unsaturated fatty acids, and cholesterol efflux mediated by ATP-binding cassette transporters (ABCA1 and ABCG1) through transcription factors liver-x-receptor-alpha (LXR-α) and sterol receptor element binding protein (SREBP)-1. BMDM isolated from C57BL/6 mice were exposed to 100 μM linoleic acid (18:2) or palmitic acid (16:0) for 16 h, and 25 μg/mL oxidized low density lipoprotein for an additional 24 h. ABCA1 and ABCG1 mRNA expression was suppressed to a greater extent by 18:2 (60 % and 54 %, respectively) than 16:0 (30 % and 29 %, respectively) relative to the control (all p

Background: Sex differences in arterial stiffness and wave reflections may lead to disproportionate increases in afterload and myocardial work in women. We examined sex differences in arterial stiffness, pressure from wave reflections, measures of left ventricular (LV) energetics and myocardial work. Methods: 99 Healthy adults participated in this study 84 were selected (42 females, 42 males) to be matched for potential confounders of central hemodynamic burden such as age, BMI, and mean arterial pressure. Aortic pressure waves were derived from the radial artery using a generalized transfer function. Pulse contour analysis and wave separation analysis were used to obtain: pulse wave velocity (PWV) as a measure of aortic stiffness, augmentation index (AIx) and reflection index (RIx) as measures of global wave reflections, LV pressure effort (ΔEw) as a measure of LV energy required to overcome wave reflections and the subendocardial viability ratio (SEVR) as a proxy of myocardial work. Results: Women exhibited higher ΔEw (p < 0.05), heart rate corrected AIx (p < 0.05) and RIx (p < 0.01), and lower PWV (p < 0.001) compared to men. Pressure from wave reflections (Pb) was significantly associated with ΔEw in women (r = 0.81, p < 0.001), but not in men (r = 0.14, p > 0.05). There were no sex differences for SEVR (p = 0.4). Conclusion: Women had higher pressure from wave reflections which was associated with greater LV pressure effort compared to men. Although women had increased LV pressure effort, proxies of myocardial perfusion and work were not affected.

The primary prevention of cardiovascular (CV) disease is hindered by the inadequacy of traditional risk factors to stratify CV risk. The presence of cardiac target organ damage (cTOD), as detected by measures of left ventricular (LV) hypertrophy and dysfunction, is associated with future CV outcomes, but is not currently assessed in asymptomatic individuals. Arterial stiffness contributes to cTOD and may represent a biomarker that can detect vascular dysfunction before the clinical manifestations of cTOD. Measurement of arterial stiffness may provide insight into premature risk for cTOD and afford opportunity for early intervention to prevent further damage. The purpose of this review is to examine the utility of arterial stiffness as a noninvasive biomarker of subclinical cTOD. To this end, we will examine the evidence sup- porting the association between arterial stiffness and measures of cTOD. We will then explore the developmental origins of arterial stiffness and cTOD and outline the progression of CV damage that occurs with age. We discuss the mechanistic role of pressure from wave reflections as a crucial link between arterial stiffness and cTOD. Finally, we examine these associations in context by exploring sex and racial differences in arterial stiffness as related to cTOD. Our comprehensive examination of the literature suggests that early identification of arterial stiffness would be a useful biomarker of future cTOD risk.