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Introduction: Depression is a common and serious medical illness world-wide. Studies have demonstrated a protective effect of physical activity on depression, but few studies have examined the prospective association between depressive symptoms and objectively measured physical activity. Objective: To investigate if antecedent depressive symptoms predict subsequent daily step counts among participants enrolled in the electronic Framingham Heart Study (eFHS). We hypothesize that the trajectory group with a larger proportion of participants having depressive symptoms and antidepressant use is associated with a lower level of physical activity. Methods: We used group-based multi-trajectory modeling to construct depressive symptom trajectory patterns using both depressive symptoms and antidepressant use collected from eFHS participants who attended three FHS health exams over fourteen years. The presence of depressive symptoms was defined at each exam with a Center for Epidemiological Studies-Depression (CES-D) score > 16. At the final exam, participants were provided with a study smartwatch to measure daily step counts. We excluded: a) person-day records with less than 5 hours of wear-time, or less than 1000 steps recorded in a day; b) participants who failed to return data for ≥1 day per week in the first month. We performed linear mixed effects models to examine the association between depressive symptom trajectories and average daily step counts during the first 30 days of smartwatch use and one-year of follow-up adjusting for age, sex, wear-hour, BMI, and smoking status. We used p Results: We identified two depressive symptom trajectory groups for the 724 eFHS participants (mean age 53 years, 60% women). The “low-stable” group (n=578; mean follow-up 286±110 days) consisted of n = 146; 269±114 days) consisted of >21% of participants with depressive symptoms and >46% of those with antidepressant medication use across the three exams. Compared to the low-stable trajectory group, the participants in the high-increasing depressive symptoms group walked 475 (95% CI: 24-927) fewer daily steps during the first 30 days of smartwatch use ( p = 0.04) and walked 550 (95% CI: 109-991) fewer daily steps during one-year of follow-up ( p = 0.01). Conclusion: Participants in the group with a larger proportion of antecedent depression and anti-depressant use walked significantly fewer steps compared to the group with a smaller proportion of antecedent depression and anti-depressant use. Our findings suggest that interventions via mHealth technologies that target mood may play an important role in promoting physical activity.

Introduction: Depressive symptoms are common and share many biopsychosocial mechanisms with hypertension, but cross-sectional studies on their association have produced inconsistent results. The emergence of digital home blood pressure (BP) measurements may provide additional insight into the relationship. Hypothesis: We hypothesized that depressive symptoms would be modestly associated with higher home BP and hypertension prevalence in participants of the electronic Framingham Heart Study (eFHS). Methods: FHS participants who attended research exam 3 (2016-2019) were invited to enroll in eFHS. They downloaded a smartphone app and were provided a digital BP cuff to measure their weekly BP for up to 1 year. Participants who had at least 3 home BPs were included. Depressive symptoms were measured at the exam using the Center for Epidemiological Studies Depression Scale (CES-D) scored 0-60. We used linear mixed regression models to test the association of CES-D score (independent) with home SBP and DBP (dependent) and a logistic regression model to evaluate the association of depressive symptoms (defined as CES-D ≥16) with prevalent hypertension, adjusting for age, sex, cohort, lifestyle factors, diabetes, and CVD. Results: The study sample included 855 eFHS participants (mean age 53 years, 59% women, 9% multi-ethnic). The prevalence of depressive symptoms was 7% (CES-D score mean±SD, 5.7±6.6). The mean SBP and DBP were 119 and 76 mmHg; the prevalence of hypertension was 48%. CES-D score was modestly associated with home BP; a 1 SD higher CES-D corresponded with 0.9 and 0.6 mmHg higher mean SBP and DBP respectively (Table). Depressive symptoms were not significantly associated with home BP or hypertension prevalence (OR=3.16, 95% CI, 0.96-10.43). Antidepressant use attenuated the relationship. Conclusion: CES-D score had a small positive association with digital home BP, but it was not clinically substantive. The association of depression and hypertension risk warrants more data, which may be supported by mobile health.

Introduction: The prevalence of obesity is rising. Most previous studies that examined the relationship between body mass index (BMI) and physical activity measured BMI at a single time-point, ignoring the time-varying nature of BMI. The relationship between BMI trajectories and habitual physical activity in community settings remains unclear. Objective: To assess the relationship between BMI trajectories and habitual physical activity measured by daily steps from a smartwatch, among participants enrolled in the electronic Framingham Heart Study (eFHS). We hypothesized that participants whose BMI trajectories increased over a 14-year period prior to the step assessment take fewer daily steps, compared to participants who maintained stable BMI trajectories during the same time period. Methods: We used a semiparametric group-based modelling method to identify BMI trajectory patterns. Participants who attended exams 1, 2, and 3 were included in building the trajectories. Daily steps were recorded from the smartwatch provided at exam 3 with “active days” defined as days with ≥ 5watch wear-hours. We excluded participants with Results: We identified three trajectory groups for the 837 eFHS participants. Group 1 included 292 participants (mean age 54 years, 57% women) whose BMI was stable (slope: 0.005, p=0.75); Group 2 included 468 participants (mean age 53 years, 56% women) whose BMI increased slightly (slope: 0.123, p Conclusion: Participants whose BMI trajectory increased over time took significantly fewer steps compared to participants with more stable BMI trajectories. Our findings suggest that levels of physical activity may correlate with greater weight gain during adulthood.

Introduction: Long-term use is critical for successful clinical or research applications of digital devices, but digital health studies are challenged by significant early discontinuation of use. Hypothesis: We sought to identify factors associated with long-term use of a smartwatch among participants enrolled in the electronic Framingham Heart Study (eFHS). We hypothesized that sociodemographic and health variables are associated with watch use. Methods: Participants were provided with a study smartwatch and were asked to wear the watch daily. We examined watch use over 12 months. Weekly watch use was defined as a binary response (yes=watch wear for ≥1 days for ≥ 5 hours per day, vs. no). We considered 19 different predictors including sociodemographic, health behaviors, and family relationship. We selected an individual predictor for watch use ( P Results: Among 1243 participants (mean age 53 years, 59% women), watch use was highest in the age-group ≥65 years, and decreased linearly over time in all participants (Figure). In GLMM adjusted for age, sex, and weeks, we found that self-reported health status (excellent vs good, fair or poor) (OR=2.7; 95%CI, 1.6-4.8), BMI (OR=0.9; 95%CI, 0.9-1.0) per 1 kg/m 2 increase, and depressive symptoms (OR=0.5; 95%CI, 0.3-0.8) were associated with watch use. In the model with all selected predictors, age-group > 65 (OR=4.0; 95%CI, 1.4 -11.6), excellent health (OR=2.3; 95%CI, 1.3-4.1), and depressive symptoms (OR=0.5; 95%CI, 0.3-0.9) remained significant. Conclusions: Older age, lack of depressive symptoms, and self-reported excellent health were associated with greater use of the smartwatch over the 12-month follow-up. Consideration of these factors in planning future digital studies may improve participation.

Introduction: The electronic Framingham Heart Study (eFHS) is an ongoing study nested within the Framingham Heart Study. eFHS examines associations between health data measured by mobile devices and cardiovascular risk and disease. We aim to describe the eFHS app design and deployment methodology, report the characteristics of the eFHS app users, and describe usability of the app. Hypothesis: We hypothesize that eFHS participants will find the app highly usable. Methods: Participants were eligible if they were part of FHS, had a mobile phone, and were willing to share data with the research center. After consent, they received a smartwatch, digital blood pressure (BP) cuff, and the eFHS smartphone app through which surveys were administered. Three years later, the app was enhanced to include an interactive health dashboard to promote participant engagement and facilitate survey completion. We assessed usability of the new app with the Mobile App Rating Scale (MARS) (specifically app functionality and aesthetics), and survey completion rates at baseline (measures include socio-demographics, self-reported health and health behaviors, and medical history) and 3 months (physical activity). Results: A total of 196 participants were recruited using the enhanced eFHS app. Of these, 97 (49.5%) completed the MARS. The average age of survey respondents was 53 years, 51.5% were women, 93.8% were white. At least one instrument of the baseline survey was completed by 86% of participants, and 50% completed the 3-month assessment. The mean score on the “overall impression” subscale of the MARS was 4.2 (SD 0.74) on a scale of 1 to 5, with all sub-domains scoring > 4.0. Of those who shared their health data with others, 46% shared their BP data, and 7.7% shared their physical activity data with a healthcare provider. Conclusion: Participants rated the new, enhanced eFHS app positively overall. Mobile app survey completion rates were moderate, suggesting that mHealth-delivered cardiovascular research is feasible.

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.

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.

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.

Background: Social networks can influence individual health behaviors, but interventions that leverage social incentives within these networks to change health behaviors have not been well examined. The objective of this study was to test the effectiveness of a social incentive-based gamification intervention to increase physical activity in the community. Methods: The Behavioral Economics Framingham Incentive Trial (BE FIT) was a randomized clinical trial that recruited 206 adults comprising 97 groups of two or three family members in the Framingham Heart Study and occurred between December 2015 and August 2016. Participants used a wearable device or smartphone application to establish a baseline step count and selected a step goal increase for a 12-week primary intervention period and a 12-week follow-up period. Participants in both the control and intervention arms received daily feedback on their performance for 24 weeks. During the first 12 weeks, participants in the intervention arm played a game (including points, levels, and lifelines) with their family members that was designed using insights from behavioral economics to enhance social incentives such as peer support, accountability, and collaboration. The primary outcome was the mean proportion of participant-days the step goal was achieved during the primary intervention period. Secondary outcomes included the mean proportion of participant-days the step goal was achieved during the follow-up period and mean daily steps during the intervention and follow-up periods. Results: Participants in the intervention arm achieved step goals on a greater proportion of participant-days and had greater mean daily steps than the control arm during the intervention and follow-up periods (TABLE). Conclusions: Among groups of family members in a community, a social incentive-based gamification intervention was effective at increasing physical activity during the 12-week intervention period and effects were sustained during the 12-week follow-up period.

Background: Biological age ( BA ) may reflect an individual’s aging process better than chronological age ( CA ). The objective of our study was to construct BA measures from different types of biomarkers and test their associations with mortality and age-related disease in a community-based sample. Methods: We selected 6 clinical predictors that capture pulmonary, vascular, atherosclerosis, insulin sensitivity, inflammatory, and kidney domains of aging, and 9 inflammatory biomarkers measured in Framingham Heart Study Offspring cohort participants at exams 7 (1998-2001, N=3539, mean age 62±10) and 8 (2005-2008, N=3021, mean age 67±9). We used the Klemera-Doubal method to calculate a clinical variable BA and an inflammatory marker BA. We computed BA using DNA methylation (DNAm) data at exam 8 using Horvath’s method. For each of the measures we computed the difference ( ΔAge ) between BA and CA and modeled the effects of ΔAge after accounting for CA. We followed participants through 2014 for all-cause mortality (N=713), cardiovascular disease (CVD, N=412), coronary heart disease (CHD, N=223), stroke (N=129), and cancer (N=509). Results: Inflammatory and clinical ΔAge were correlated (=0.35, =0.33, for exams 7 and 8 respectively), and also across exams (inflammatory ΔAge exam 7 vs 8: =0.61; clinical ΔAge: =0.76). DNAm ΔAge was not significantly correlated with exam 8 inflammatory or clinical ΔAge. After adjusting for CA and sex, larger inflammatory and clinical ΔAge, corresponding to older BA than CA, was associated with significantly increased hazards of all-cause mortality, CVD, and CHD (Table). The clinical and inflammatory ΔAge were significant (p Conclusions: Our findings suggest the three BA measures may be complementary in predicting risk for age-related disease.

Background— The American Heart Association Cardiovascular Health score (CVH score) is inversely associated with cardiovascular disease (CVD) incidence, but the mechanisms underlying this association warrant exploration. Methods and Results— We related the CVH score to circulating biomarkers and prevalent subclinical CVD (defined as ≥1 of the following: increased carotid intima-media thickness or stenosis, left ventricular hypertrophy [by ECG or echocardiography], left ventricular systolic dysfunction, microalbuminuria, and a reduced ankle-brachial index) in 2680 Framingham Study participants (mean age, 58 years; 55% women). After adjustment for age and sex, an ideal CVH score (nonsmoking status, ideal body mass index, regular physical activity, healthy diet, and an optimal profile of serum cholesterol, blood pressure, and glucose; 1 point for each) was associated with higher circulating concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide and B-type natriuretic peptide) and lower blood concentrations of plasminogen activator inhibitor-1, aldosterone, C-reactive protein, D-dimer, fibrinogen, homocysteine, and growth differentiation factor-15 levels ( P Conclusion— In our prospective community-based study, the inverse association between an ideal cardiovascular health score and CVD incidence was partly attributable to its favorable impact on CVD biomarker levels and subclinical disease.

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— Although mortality after myocardial infarction (MI) has declined in the United States in recent decades, there have been few community-based investigations of the long-term trends in the incidence of heart failure after MI, and their results appear to be conflicting. Methods and Results— We evaluated 676 Framingham Heart Study participants between 45 and 85 years of age (mean age 67 years, 34% women) who developed a first MI between 1970 and 1999. We assessed the incidence rates of heart failure and of death without heart failure in each of 3 decades (1970 to 1979, 1980 to 1989, and 1990 to 1999). We estimated the multivariable-adjusted risk of events in the latter 2 decades, with the period 1970 to 1979 serving as the referent. The 30-day incidence of heart failure after MI rose from 10% in 1970 to 1979 to 23.1% in 1990 to 1999 ( P for trend 0.003), whereas 30-day mortality after MI declined from 12.2% (1970 to 1979) to 4.1% (1990 to 1999). The 5-year incidence of heart failure after MI rose from 27.6% in 1970 to 1979 to 31.9% in 1990 to 1999 ( P for trend 0.02), whereas 5-year mortality after MI declined from 41.1% (1970 to 1979) to 17.3% (1990 to 1999). In multivariable analyses, compared with the period 1970 to 1979, we observed higher 30-day (risk ratio 2.05, 95% confidence interval 1.25 to 3.36) and 5-year (risk ratio 1.74, 95% confidence interval 1.07 to 2.84) risks of heart failure in the decade 1990 to 1999. These trends were accompanied by lower 30-day (risk ratio 0.21, 95% confidence interval 0.09 to 0.47) and 5-year (risk ratio 0.31, 95% confidence interval 0.18 to 0.54) mortality rates in 1990 to 1999. Conclusions— In the present community-based sample, we observed an increase in the incidence of heart failure in recent decades that paralleled the decrease in mortality after MI.

Background— The burden and prognostic importance of subclinical cardiovascular disease (CVD) in obesity has not been investigated systematically. Methods and Results— We examined prevalence of subclinical disease in 1938 Framingham Study participants (mean age, 57 years; 59% women) by use of 5 tests (electrocardiography, echocardiography, carotid ultrasound, ankle-brachial pressure, and urinary albumin excretion) and stratified by body mass index (BMI) (normal, 2 ) and waist circumference (WC) (increased, ≥88 cm for women or ≥102 cm for men). We investigated risk of overt CVD associated with adiposity according to presence versus absence of subclinical disease on any of the 5 tests. Prevalence of subclinical disease was higher in overweight (40.0%; adjusted odds ratio, 1.68) and obese individuals (49.7%; odds ratio, 2.82) compared with individuals with normal BMI (29.3%) and in individuals with increased WC (44.9%; odds ratio, 1.67) compared with normal WC (31.9%). On follow-up (mean 7.2 years), 139 participants had developed overt CVD. Presence of subclinical disease was associated with >2-fold risk of overt CVD in all BMI and WC strata, with no evidence of an interaction between BMI and subclinical disease. CVD risk was attenuated in participants with obesity or increased WC but without subclinical disease (adjusted hazard ratio for obesity, 1.57; 95% confidence interval, 0.74 to 3.33; adjusted hazard ratio for increased WC, 1.22; 95% confidence interval, 0.69 to 2.15), compared with individuals with normal BMI or WC and no subclinical disease, respectively. Conclusions— In our community-based sample, overweight and obesity were associated with high prevalence of subclinical disease, which partly contributed to the increased risk of overt CVD in these strata.

Background —Intermittent claudication (IC) is associated with an increased risk of cardiovascular disease morbidity and mortality. The relation of alcohol consumption to the risk of IC remains controversial. The purpose of this study was to assess the relation of alcohol consumption and type of beverage to the development of IC among participants in the Framingham Heart Study. Methods and Results —Alcohol consumption was categorized as 0, 1 to 6, 7 to 12, 13 to 24, and ≥25 g/d. During a mean follow-up of 6.8 years, 414 subjects developed IC. From the lowest to the highest category of alcohol intake, the age-standardized incidence rates of IC were 5.3, 4.1, 4.2, 3.2, and 4.6 cases/1000 person-years for men and 3.4, 2.5, 1.5, 1.9, and 2.5, respectively, for women. A multivariate Cox regression model demonstrated an inverse relation, with the lowest IC risk at levels of 13 to 24 g/d for men and 7 to 12 g/d for women compared with nondrinkers; the hazard ratio (95% CI) was 0.67 (0.42 to 0.99) for men and 0.44 (0.23 to 0.80) for women. This protective effect was seen mostly with wine and beer consumption. Conclusions —Our data are consistent with a protective effect of moderate alcohol consumption on IC risk, with lowest risk observed in men consuming 13 to 24 g/d (1 to 2 drinks/d) and in women consuming 7 to 12 g/d (0.5 to 1 drink/d).

Background Intermittent claudication identifies persons at increased risk for death and disability. Methods and Results Using 38-year follow-up data for the original cohort in the Framingham Heart Study, we developed an intermittent claudication risk profile. Intermittent claudication occurred in a total of 381 men and women. Age, sex, serum cholesterol, hypertension, cigarette smoking, diabetes, and coronary heart disease were associated with an increased risk for claudication and were included in the profile. A pooled logistic regression model was used to compute the probability of intermittent claudication for specified levels of risk factors. Conclusions The intermittent claudication risk profile allows physicians to identify high-risk individuals during a routine office visit and can be used to educate patients about modifiable risk factors, particularly smoking and blood pressure. Improved compliance with risk factor modification strategies may result in a beneficial impact on survival.

The goal of this American Heart Association Guide for Improving Cardiovascular Health at the Community Level (AHA Community Guide) is to provide a comprehensive inventory of evidence-based goals, strategies, and recommendations for cardiovascular disease (CVD) and stroke prevention that can be implemented on a community level. This guide advances the 2003 AHA Community Guide1 and the 2005 AHA statement on guidance for implementation2 by incorporating new evidence for community interventions gained over the past decade, expanding the target audience to include a broader range of community advocates, aligning with the concepts and terminology of the AHA 2020 Impact Goals, and recognizing the contributions of new public and private sector programs involving community interventions. In recent years, expanding arrays of programs and policies have been implemented in increasingly diverse communities to provide tools, strategies, and other best practices to potentially reduce the incidence of initial and recurrent cardiovascular events. The AHA Community Guide complements the AHA statement entitled “Population Approaches to Improve Diet, Physical Activity, and Smoking Habits”3 and supports the AHA 2020 goal4 to “improve the cardiovascular health of all Americans by 20%, while reducing deaths from CVDs and stroke by 20%.” The present AHA Community Guide supports the AHA 2020 goal by identifying exemplary regional or national programs that encourage cardiovascular health behaviors and health factors (formerly addressing risk behaviors and risk factors) from which communities might acquire proven strategies, expertise, and technical assistance for improving cardiovascular health. The AHA Community Guide seeks to prevent the onset of disease (primary prevention) and to maintain optimal cardiovascular health (primordial prevention) among broader segments of the population. Prior research indicates that using public health strategies such as sodium reduction in processed foods to lower blood pressure,5–8 tobacco laws to promote smoking cessation,9–11 and modification of …

Introduction: Ectopic fat depots may play a role in obesity-mediated cardiovascular disease (CVD). We tested the association of several distinct fat depots and incident CVD in an asymptomatic community-based sample. Methods: Participants from the Framingham Heart Study (n=3086, 49% women, mean age 50.2 years, free of CVD at baseline) underwent volumetric assessment of multiple fat depots using multidetector computed tomography from 2002–2005, and were followed longitudinally for CVD events. Fat depots included subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), pericardial adipose tissue, intra-thoracic adipose tissue and thoracic periaortic adipose tissue (TAT). Adipose volumes were standardized within sex to a mean of 0 and a standard deviation of 1. Cardiovascular events included coronary heart disease (myocardial infarction, coronary insufficiency or angina), cerebrovascular disease (stroke or transient ischemic attack), intermittent claudication, heart failure or CVD death. Using Cox proportional hazards regression models, we examined the association of each fat depot with the risk of CVD after adjustment for age, sex, systolic blood pressure, hypertension treatment, diabetes, total cholesterol, high-density lipoprotein cholesterol, smoking, and then additionally for BMI. We additionally examined the association of pericardial fat and incident coronary heart disease. Results: During a mean follow-up of 4.7 years, 90 CVD events occurred. After multivariable adjustment, VAT, VAT/SAT ratio, intra-thoracic fat and TAT were significantly associated with incident CVD events. The hazard ratios (95% confidence intervals) per each standard deviation higher were 1.37 (1.10–1.71, p=0.006 [VAT]), 1.30 (1.05–1.60, p=0.02 [VAT/SAT ratio]), 1.28 (1.03–1.59, p=0.03 [intra-thoracic fat]), and 1.30 (1.03–1.67, p=0.03 [TAT]), respectively. We observed no association between BMI (HR 1.15, 0.92–1.43, p=0.21), SAT (HR 1.13, 0.90–1.42, p=0.28) or pericardial fat (HR 1.14, 0.95–1.37, p=0.15) and incident CVD. After additional adjustment for BMI, VAT, VAT/SAT ratio and TAT remained significantly associated with incident CVD events [HR 1.44 (1.08–1.92, p=0.01 [VAT]), 1.34 (1.08–1.65, p=0.007 [VAT/SAT ratio]), and 1.31 (1.03–1.67, p=0.03 [TAT])], respectively. Pericardial fat was also not associated with incident coronary heart disease, even when limiting our events to myocardial infarction or coronary heart disease death (HR 0.97, p=0.81). Conclusion: Several distinct ectopic fat depots, including VAT, VAT/SAT ratio, intra-thoracic fat, and TAT, but not generalized obesity, are significantly associated with CVD events after adjustment for risk factors in our community-based sample. These findings support the growing recognition of several potentially pathogenic ectopic fat depots.

Background: Adipokines, produced by adipose tissues, contribute to the development of obesity-related metabolic traits. It is unclear, however, if greater physical activity favorably affects cardiometabolic profiles by influencing levels of key adipokines. We related physical activity, as measured by accelerometry, to circulating levels of novel adipokines, including retinol binding protein-4 (RBP4), adipocyte-fatty acid binding protein (A-FABP), adiponectin, leptin and leptin-receptor (LEP-R), in a large community-based sample. Methods: We evaluated 2063 participants in the 3rd generation Framingham Heart Study cohort (mean age 47 years, 55% female) who underwent objective assessment of moderate-to-vigorous physical activity (MVPA) by an accelerometer. MVPA was measured in total minutes, and in bouts ≥10 minutes (MVPA10) and nonbouts (MVPA Results: On average, participants engaged in 28 minutes/day of MVPA, 19 minutes/day of nonbout MVPA and 9 minutes/day of MVPA10. Mean adipokine levels were 40.7 ± 10.7 ng/ml for RBP-4, 18.6 ± 10.3 ng/ml for A-FABP, 11.4 ± 12.9 ng/ml for leptin, 19.6 ± 8.6 ng/ml for LEP-R, and 8.7 ± 5.5 ng/ml for adiponectin. Total MVPA, as well as MVPA10 and nonbout MVPA, were inversely related to leptin and A-FABP and positively associated with levels of adiponectin (See Table). The directionality of the observed associations - positive for adiponectin and negative for leptin and A-FABP- were consistent with greater physical activity being related to a more favorable cardiometabolic profile. Conclusions: In our cross-sectional study of a large community-based sample, both bout and nonbout MVPA were significantly related to a favorable adipokine profile. Additional longitudinal observations are warranted to assess if physical activity influences cardiometabolic health through alterations in adipokine levels.

Background: Visceral abdominal tissue (VAT) is a unique pathogenic fat depot that is associated with cardiometabolic risk above and beyond overall body mass index (BMI). Higher lipid content of adipose tissue is associated with lower tissue attenuation (i.e. more negative) in computed tomography (CT) and is expressed as Hounsfield units (HU). Given this framework, we hypothesized that lower CT attenuation of adipose tissue is associated with more adverse metabolic risk. Methods: Framingham Heart Study participants (n=3198, mean age 51 years, 47% women) who participated in a computed tomography sub-study with volumetrically assessed VAT and documented HU were studied. Cardiovascular risk factors were measured using standard definitions. The association between HU and metabolic risk factors was assessed using sex-specific multivariable-adjusted regression models. Results: Mean visceral HU was −93.9 (Range −105.7 to −79.0). Mean HU were overall lower in men (−95.2) than women (−92.4). Lower HU correlated with higher BMI levels in women (age adjusted r = −0.51, p Conclusion: Lower CT attenuation of visceral fat, a marker of higher lipid content of adipose tissue, is associated with increased adverse metabolic risk above and beyond total VAT volume. These findings highlight that both quantity and quality of fat depots may provide additional information regarding cardiometabolic risk.

Background— Whereas the prevalence of coronary heart disease risk factors has declined over the past decades in the United States, acute myocardial infarction (AMI) rates have been steady. We hypothesized that this paradox is due partly to the advent of increasingly sensitive biomarkers for AMI diagnosis. Methods and Results— In Framingham Heart Study participants over 4 decades, we compared the incidence and survival rates of initial AMI diagnosis by ECG (AMI-ECG) regardless of biomarkers with those based exclusively on infarction biomarkers (AMI-marker). We used Poisson regression to calculate annual incidence rates of first AMI over 4 decades (1960 to 1969, 1970 to 1979, 1980 to 1989, and 1990 to 1999) and compared rates of AMI-ECG with rates of AMI-marker. Cox proportional-hazards analysis was used to compare AMI case fatality over 4 decades. In 9824 persons (54% women; follow-up, 212 539 person-years; age, 40 to 89 years), 941 AMIs occurred, including 639 AMI-ECG and 302 AMI-marker events. From 1960 to 1999, rates of AMI-ECG declined by ≈50% and rates of AMI-marker increased ≈2-fold. Crude 30-day, 1-year, and 5-year case fatality rates in 1960 to 1969 and 1990 to 1999 were 0.20 and 0.14, 0.24 and 0.21, and 0.45 and 0.41, respectively. Age- and sex-adjusted 30-day, 1-year, and 5-year AMI case fatality declined by 60% in 1960 to 1999 ( P for trend Conclusions— Over the past 40 years, rates of AMI-ECG have declined by 50%, whereas rates of AMI-marker have doubled. Our findings offer an explanation for the apparently steady national AMI rates in the face of improvements in primary prevention.

Background: Public health recommendations advocate breastfeeding in infancy as a means to reducing later-life obesity. However many prior studies relating breastfeeding to cardiovascular (CVD) risk factors have been limited by lack of adjustment for maternal and participant confounding factors. Methods: In 962 Framingham Third Generation participants (mean age = 41 yrs, 54% women) we related history of breastfeeding (yes vs. no) and CVD risk factors in young-mid adulthood. Breastfeeding data was ascertained via questionnaire from mothers enrolled in the Framingham Offspring Study. Dependent variables were body mass index (BMI), HDL-cholesterol (HDL-c), total cholesterol, triglycerides, fasting blood glucose, C-reactive protein (CRP), systolic (SBP) and diastolic blood pressure (DBP). Covariates for multivariable adjustment were age, sex, hypertension medications, lipid treatment, smoking, birth order, oral contraceptives, hormone replacement, physical activity, education, maternal smoking, maternal education, and maternal BMI. Low HDL was defined as < 50 mg/dL (women) and < 40 mg/dL(men). Adiposity categories were defined by BMI normal [< 25], overweight [≥ 25 to < 30] and obese [≥ 30 kg/m 2 ]. Generalized estimating equations (GEE) were used to account for sibling correlations. Results: Overall 26% of participants were reported by their mother to have been breastfed. Compared to non-breastfed individuals, breastfed offspring had lower adult BMI [adjusted mean 26.1 kg/m 2 vs. 26.9 kg/m 2 , p = 0.04) and higher adult HDL-c levels [adjusted mean HDL 56.6 mg/dL relative to 53.7 mg/dL p = 0.01] in multivariable-adjusted models. Breastfeeding was not associated with other examined adult CVD risk factors. Upon adjustment for BMI the association between breastfeeding and HDL was attenuated (p = 0.09). Breastfeeding was associated with high versus low HDL (multivariable-adjusted OR = 1.55, p = 0.04) but not with overweight or obesity versus normal weight (p = 0.26, 0.13 respectively). Conclusions: Breastfeeding in infancy is inversely associated with adult BMI and positively associated with HDL-c. Associations between breastfeeding and BMI appear to mediate most of the association with HDL-c.

Background— Parental premature cardiovascular disease (CVD) is a risk factor for coronary heart disease (CHD). We related validated parental premature CVD with the subclinical measures of coronary artery (CAC) and abdominal aortic (AAC) calcification in the community. Methods and Results— We studied 2 generations of Framingham Heart Study subjects who underwent multidetector computed tomography measurements of CAC and AAC and who had 2 parents in the study. Subjects included 797 Framingham Offspring (mean age, 63 years; 56% women) and 1238 Third Generation (Gen3) (mean age, 46 years; 47% women) participants free of CVD. Generalized estimating equations adjusted for major CVD risk factors were used to relate validated parental premature CVD and CHD to CAC and AAC, defined by >90th percentile age- and sex-specific cut points from a healthy subsample. Parental premature CVD was associated with CAC among Gen3 (odds ratio=2.17 [1.41 to 3.33]; P P =0.12). Parental premature CHD was associated with CAC among Gen3 (odds ratio=2.22 [1.22 to 4.01]) but not Offspring. Parental premature CVD was not associated with AAC in either cohort. Parental premature CHD was associated with AAC among Gen3 (odds ratio=1.65 [0.99 to 2.75]; P =0.05) but not among Offspring. The magnitude of risk conferred was greater for paternal than maternal premature CVD. Conclusions— Parental premature CVD is associated with CAC, and premature CHD is associated with AAC, after adjustment for risk factors, particularly in younger middle-aged adults. Risk conferred by parental premature CVD on vascular calcification may be mediated through novel mechanisms not accounted for by classic CVD risk factors known to cause atherosclerosis.

Background— Excess adiposity is associated with greater systemic inflammation. Whether visceral adiposity is more proinflammatory than subcutaneous abdominal adiposity is unclear. Methods and Results— We examined the relations of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), assessed by multidetector computerized tomography, to circulating inflammatory and oxidative stress biomarkers in 1250 Framingham Heart Study participants (52% women; age 60±9 years). Biomarkers were examined in relation to increments of SAT and VAT after adjustment for age, sex, smoking, physical activity, menopause, hormone replacement therapy, alcohol, and aspirin use; additional models included body mass index and waist circumference. SAT and VAT were positively and similarly (with respect to strength of association) related to C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, P-selectin, and tumor necrosis factor receptor-2 (multivariable model R 2 0.06 to 0.28 [SAT] and 0.07 to 0.29 [VAT]). However, compared with SAT, VAT was more highly associated with urinary isoprostanes and monocyte chemoattractant protein-1 (SAT versus VAT comparison: isoprostanes, R 2 0.07 versus 0.10, P =0.002; monocyte chemoattractant protein-1, R 2 0.07 versus 0.08, P =0.04). When body mass index and waist circumference were added to the models, VAT remained significantly associated with only C-reactive protein ( P =0.0003 for women; P =0.006 for men), interleukin-6 ( P =0.01), isoprostanes ( P =0.0002), and monocyte chemoattractant protein-1 ( P =0.008); SAT only remained associated with fibrinogen ( P =0.01). Conclusions— The present cross-sectional data support an association between both SAT and VAT with inflammation and oxidative stress. The data suggest that the contribution of visceral fat to inflammation may not be completely accounted for by clinical measures of obesity (body mass index and waist circumference).

Background— Visceral adipose tissue (VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting. Methods and Results— Participants (n=3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005. Metabolic risk factors were examined in relation to increments of SAT and VAT after multivariable adjustment. Heritability was calculated using variance-components analysis. Among both women and men, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus, and metabolic syndrome ( P range P for difference between SAT and VAT P ≤0.01). Among overweight and obese individuals, the prevalence of hypertension, impaired fasting glucose, and metabolic syndrome increased linearly and significantly across increasing VAT quartiles. Heritability values for SAT and VAT were 57% and 36%, respectively. Conclusions— Although both SAT and VAT are correlated with metabolic risk factors, VAT remains more strongly associated with an adverse metabolic risk profile even after accounting for standard anthropometric indexes. Our findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot. Measurement of VAT may provide a more complete understanding of metabolic risk associated with variation in fat distribution.

Background— Atrial fibrillation (AF) and congestive heart failure (CHF) frequently occur together, but there is limited information regarding their temporal relations and the combined influence of these conditions on mortality. Methods and Results— We studied participants in the Framingham Study with new-onset AF or CHF. Multivariable Cox proportional hazards models with time-dependent variables were used to evaluate whether mortality after AF or CHF was affected by the occurrence and timing of the other condition. Hazard ratios (HRs) were adjusted for time period and cardiovascular risk factors. During the study period, 1470 participants developed AF, CHF, or both. Among 382 individuals with both conditions, 38% had AF first, 41% had CHF first, and 21% had both diagnosed on the same day. The incidence of CHF among AF subjects was 33 per 1000 person-years, and the incidence of AF among CHF subjects was 54 per 1000 person-years. In AF subjects, the subsequent development of CHF was associated with increased mortality (men: HR 2.7; 95% CI, 1.9 to 3.7; women: HR 3.1; 95% CI, 2.2 to 4.2). Similarly, in CHF subjects, later development of AF was associated with increased mortality (men: HR 1.6; 95% CI, 1.2 to 2.1; women: HR 2.7, 95% CI, 2.0 to 3.6). Preexisting CHF adversely affected survival in individuals with AF, but preexisting AF was not associated with adverse survival in those with CHF. Conclusions— Individuals with AF or CHF who subsequently develop the other condition have a poor prognosis. Additional studies addressing the pathogenesis, prevention, and optimal management of the joint occurrence of AF and CHF appear warranted.