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The prevalence of atrial fibrillation (AF) is increasing as the population ages. AF treatment-related complications also increase markedly in older adults (defined as ≥75 years of age for this review). The older AF population has a high risk of stroke, bleeding, and death. Syncope and fall-related injuries are the most common reasons for nonprescription of oral anticoagulation (OAC), and are more common in older adults when OACs are used with antiarrhythmic drugs. Digoxin may be useful for rate control, but associations with increased mortality limit its use. Beyond rate and rhythm control considerations, stroke prophylaxis is critical to AF management, and the benefits of direct OACs, compared with warfarin, extend to older adults. Invasive procedures such as AF catheter ablation, pacemaker implantation/atrioventricular junction ablation, and left atrial appendage occlusion may be useful in appropriately selected cases. However, older adults have generally been under-represented in clinical trials.

The e-cigarette or vaping product-use-associated lung injury outbreak in the United States has raised concerns about the potential health effects of cannabis vaping, a method of cannabis use that is becoming increasingly popular. We used 2017–2019 Behavioral Risk Factor Surveillance System data to estimate yearly prevalence and trends of past-30-day cannabis use and vaping among US adults. We used multivariable logistic regression to evaluate the associations of cannabis vaping with high-risk behaviors, asthma, and other respiratory symptoms. Our sample size was 160,209 (53,945–2017; 55,475–2018; and 50,789–2019). Past-30-day cannabis use prevalence increased from 10.0% (95% CI, 9.4%–10.7%) in 2017 to 13.4% (12.8%–12.0%) in 2019. Similarly, past-30-day cannabis vaping prevalence increased from 1.0% (0.8%–1.2%) to 2.0% (1.7%–2.2%) over the same period, with the greatest increase, 1.2% to 3.9%, observed among young adults (18-24 years). Individuals who vaped cannabis were more likely to concurrently vape nicotine. Cannabis vaping was associated with increased odds of heavy alcohol use (aOR, 1.95; 95% CI, 1.45–2.63), binge drinking (aOR, 2.82; 95% CI, 2.25–3.54), and other high-risk behaviors (aOR, 2.47; 95% CI, 1.89–3.24). In analyses adjusting for sociodemographic characteristics and body mass index, cannabis vaping was not associated with asthma (aOR, 1.03; 95% CI, 0.64–1.64) or other respiratory symptoms (aOR, 1.08; 95% CI, 0.44–2.63). Adjusting for nicotine vaping did not substantively alter these associations. The prevalence of past-30-day cannabis vaping has increased, particularly among young adults, and was associated with high-risk behaviors. Although there was no association between cannabis vaping and asthma or other respiratory symptoms, the increasing trends of cannabis vaping, particularly among young adults, raise concern and underscore the need for continued surveillance.

Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) provide evidence for variant pathogenicity. Effect sizes are associated with pathogenic ClinVar assertions (P

Background: Atrial fibrillation (AF) risk estimation using clinical factors with or without genetic information may identify AF screening candidates more accurately than the guideline-based age threshold of ≥65 years. Methods: We analyzed 4 samples across the United States and Europe (derivation: UK Biobank; validation: FINRISK, Geisinger MyCode Initiative, and Framingham Heart Study). We estimated AF risk using the CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology AF) score and a combination of CHARGE-AF and a 1168-variant polygenic score (Predict-AF). We compared the utility of age, CHARGE-AF, and Predict-AF for predicting 5-year AF by quantifying discrimination and calibration. Results: Among 543 093 individuals, 8940 developed AF within 5 years. In the validation sets, CHARGE-AF (C index range, 0.720–0.824) and Predict-AF (0.749–0.831) had largely comparable discrimination, both favorable to continuous age (0.675–0.801). Calibration was similar using CHARGE-AF (slope range, 0.67–0.87) and Predict-AF (0.65–0.83). Net reclassification improvement using Predict-AF versus CHARGE-AF was modest (net reclassification improvement range, 0.024–0.057) but more favorable among individuals aged Conclusions: AF risk estimation using clinical factors may prioritize individuals for AF screening more precisely than the age threshold endorsed in current guidelines. The additional value of genetic predisposition is modest but greatest among younger individuals.

Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) are proxies for variant pathogenicity. Effect sizes were associated with pathogenic ClinVar assertions (P

There has been sustained focus on the secondary prevention of coronary heart disease and heart failure; yet, apart from stroke prevention, the evidence base for the secondary prevention of atrial fibrillation (AF) recurrence, AF progression, and AF‐related complications is modest. Although there are multiple observational studies, there are few large, robust, randomized trials providing definitive effective approaches for the secondary prevention of AF. Given the increasing incidence and prevalence of AF nationally and internationally, the AF field needs transformative research and a commitment to evidenced‐based secondary prevention strategies. We report on a National Heart, Lung, and Blood Institute virtual workshop directed at identifying knowledge gaps and research opportunities in the secondary prevention of AF. Once AF has been detected, lifestyle changes and novel models of care delivery may contribute to the prevention of AF recurrence, AF progression, and AF‐related complications. Although benefits seen in small subgroups, cohort studies, and selected randomized trials are impressive, the widespread effectiveness of AF secondary prevention strategies remains unknown, calling for development of scalable interventions suitable for diverse populations and for identification of subpopulations who may particularly benefit from intensive management. We identified critical research questions for 6 topics relevant to the secondary prevention of AF: (1) weight loss; (2) alcohol intake, smoking cessation, and diet; (3) cardiac rehabilitation; (4) approaches to sleep disorders; (5) integrated, team‐based care; and (6) nonanticoagulant pharmacotherapy. Our goal is to stimulate innovative research that will accelerate the generation of the evidence to effectively pursue the secondary prevention of AF.

Community-based studies have evaluated cross-sectional age relations of aortic stiffness measures, which are not often recapitulated in longitudinal studies. We examined baseline and longitudinal change in aortic stiffness in 5491 participants (mean age, 49.5±14.5 years; 54% women) who attended 2 sequential examinations (6.0±0.6 years apart) of the Framingham Heart Study. Cross-sectional relations of central hemodynamics (mean arterial pressure, central pulse pressure, carotid-femoral pulse wave velocity, and characteristic impedance) with age and risk factors were assessed at visits 1 and 2 (models 1 and 2). We used model 1 coefficients (M 1 ), visit 1 risk factor levels (R 1 ), and age at each visit (A 1 , A 2 ) to estimate values at visits 1 (M 1 R 1 A 1 ) and 2 (M 1 R 1 A 2 ). While using model 1 coefficients, we accounted for age and risk factor level (R 2 ) changes to predict values at visit 2 (M 1 R 2 A 2 ). Using model 2 coefficients (M 2 ) and visit 2 age and risk factor levels, we predicted visit 2 values (M 2 R 2 A 2 ). We calculated predicted change 3 ways: delta1=M 1 R 1 A 2 −M 1 R 1 A 1 , delta2=M 1 R 2 A 2 −M 1 R 1 A 1 , and delta3=M 2 R 2 A 2 −M 1 R 1 A 1 . Delta1 values were biased and correlated poorly with actual changes ( r =−0.02–0.14). For mean arterial pressure, delta1=1.9±0.8 mm Hg ( r =0.14), observed change=−3.3±10.3 mm Hg, and discrepancy=5.2±10.2 mm Hg ( P 5 ( r =0.07), observed change=20.5±68.2 dyne×sec/cm 5 , and discrepancy=−13.3±68.7 dyne×sec/cm 5 ( P r =0.17–0.54) but remained biased whereas delta3 values were moderately correlated with change with no bias. Projected change in hemodynamic measures extrapolated from cross-sectional age relations may differ substantially from actual change, particularly for variables with nonlinear age relations.

Physical activity is favorable to health but the relations with human disease and causal effects are poorly quantified. Previous studies have largely relied on self-reported estimates1–3 which are subject to recall bias, confounding, and reverse causality. Using wrist-worn accelerometer measurements from the UK Biobank, we tested associations between moderate-to-vigorous physical activity (MVPA) – both total MVPA minutes and whether MVPA was above a guideline-based threshold of ≥150 minutes/week4–6 – and incidence of over 1,200 diseases. In 96,466 adults who wore accelerometers for one week (mean age 62±8 years), MVPA was associated with 401 (33%) tested diseases at a false discovery rate of 1% during a median of 6.2 years follow-up. Greater MVPA was overwhelmingly associated with reduced disease risk (98% of associations) with hazard ratios (HRs) ranging from 0.10-0.95 per standard deviation (SD) and associations spanning all 18 disease categories tested. A similar pattern of associations was observed when assessing the guideline-based threshold of ≥150 MVPA minutes/week. We examined a polygenic risk score for MVPA as an instrumental variable for activity within a separate UK Biobank sample (N=392,058, mean age 57±8 years). Greater genetically inferred MVPA was associated with reduced risk of 182 (14%) incident diseases (HR range 0.74-0.97 per 1 SD), and included strong associations conferring reduced risks of obstructive bronchitis, peripheral vascular disease, type 2 diabetes, and gastritis/duodenitis. Objective physical activity is broadly associated with lower disease incidence and many associations are consistent with a causal effect.

There are large knowledge gaps regarding the global epidemiology of atrial fibrillation (AF), in part due to the paucity of informative community-based or population-based studies representative of the world’s population. The 2019 global burden of AF is estimated at 59.7 million (95% confidence interval: 45.7 to 75.3 million), double the number of estimated cases in 1990.1 Low-income nations—and one could argue entire continents such as South America, Africa and parts of Asia—face the multiple public health challenges of limited economic resources, progressively ageing populations, and increasing prevalence of common AF risk factors such as hypertension and obesity. Unfortunately, most of the literature describing the epidemiology of AF is from high-income countries, such as the USA, Western European countries and Australia. This literature has consistently described the prevalence of the condition, its significant medical and societal costs, and its priority as the most commonly encountered cardiovascular arrhythmia. In contrast, data from much of Asia, Africa and South America are less available. A Web of Science search for AF articles published over the past 5 years conducted on 14th December 2020 (figure 1) reinforces marked imbalances in the country of origin of the AF literature with regards to the number of publications versus the population. The bottom line is a literature that is hardly representative; a small percentage of the world’s population has produced a large quantity of the literature on a condition that is increasingly common and prevalent across the globe. To develop a more comprehensive picture of AF will require investigations that represent the socioeconomic and geographical complexities across multiple nations and continents. Figure 1 Atrial fibrillation (AF) research distribution according to the country within the last 5 years. The figure presents a Web of Science search for AF scientific papers published over the past 5 years conducted on 14th December 2020. In total, 43 509 …

BACKGROUND The prevalence of obesity is rising. Most previous studies that examined the relations between BMI and physical activity (PA) measured BMI at a single timepoint. The association between BMI trajectories and habitual PA remains unclear. OBJECTIVE This study assesses the relations between BMI trajectories and habitual step-based PA among participants enrolled in the electronic cohort of the Framingham Heart Study (eFHS). METHODS We used a semiparametric group-based modeling to identify BMI trajectories from eFHS participants who attended research examinations at the Framingham Research Center over 14 years. Daily steps were recorded from the smartwatch provided at examination 3. We excluded participants with RESULTS We identified 3 trajectory groups for the 837 eFHS participants (mean age 53 years; 57.8% [484/837] female). Group 1 included 292 participants whose BMI was stable (slope 0.005; P=.75), group 2 included 468 participants whose BMI increased slightly (slope 0.123; PP CONCLUSIONS In this community-based eFHS, participants whose BMI trajectory increased greatly over time took significantly fewer steps, compared with participants with stable BMI trajectories. Our findings suggest that greater weight gain may correlate with lower levels of step-based physical activity.

Introduction: Prior data suggest associations between hearing loss, cardiovascular (CV) risk factors, and CV disease. Whether specific hearing loss patterns, including a strial pattern associated with inner ear vascular disease, are associated with systemic endothelial dysfunction and carotid intima–media thickness (IMT) remains unclear. Methods: We evaluated participants without prevalent CVD in the Framingham Offspring Study who underwent formal audiogram testing and brachial and carotid artery ultrasounds. Audiograms were categorized as normal or as belonging to one of four abnormal patterns: cochlear-conductive, low-sloping, sensorineural, or strial. Endothelial function as measured by brachial artery flow-mediated dilation (FMDmm and FMD%). Internal and common intima–media thicknesses (icIMT and ccIMT, respectively) were compared between audiogram patterns. Results: We studied 1672 participants (mean age 59 years, 57.6% women). The prevalence of each hearing pattern was as follows: 43.7% normal; 20.3% cochlear-conductive; 20.3% sensorineural; 7.7% low-sloping; and 8.0% strial. Strial pattern hearing loss was nearly twice as prevalent ( p = 0.001) in those in the highest quartile of ccIMT and nearly 50% higher in those in the highest icIMT quartile ( p = 0.04). There were no statistically significant differences between the prevalence of the strial pattern comparing the lowest quartiles of FMDmm and FMD% with the upper three quartiles. Age- and sex-adjusted linear regression models did not show significant associations between the vascular measures and hearing patterns. Conclusion: Abnormal hearing patterns were not significantly associated with impaired brachial FMD and increased carotid IMT after adjusting for age and sex effects, which may reflect age and sex-related distributional differences based on hearing loss pattern.

Background When studied in community-based samples, the association of physical activity with blood pressure (BP) remains controversial and is perhaps dependent on the intensity of physical activity. Prior studies have not explored the association of smartwatch-measured physical activity with home BP. Objective We aimed to study the association of habitual physical activity with home BP. Methods Consenting electronic Framingham Heart Study (eFHS) participants were provided with a study smartwatch (Apple Watch Series 0) and Bluetooth-enabled home BP cuff. Participants were instructed to wear the watch daily and transmit BP values weekly. We measured habitual physical activity as the average daily step count determined by the smartwatch. We estimated the cross-sectional association between physical activity and average home BP using linear mixed effects models adjusting for age, sex, wear time, antihypertensive drug use, and familial structure. Results We studied 660 eFHS participants (mean age 53 years, SD 9 years; 387 [58.6%] women; 602 [91.2%] White) who wore the smartwatch 5 or more hours per day for 30 or more days and transmitted three or more BP readings. The mean daily step count was 7595 (SD 2718). The mean home systolic and diastolic BP (mmHg) were 122 (SD 12) and 76 (SD 8). Every 1000 increase in the step count was associated with a 0.49 mmHg lower home systolic BP (P=.004) and 0.36 mmHg lower home diastolic BP (P=.003). The association, however, was attenuated and became statistically nonsignificant with further adjustment for BMI. Conclusions In this community-based sample of adults, higher daily habitual physical activity measured by a smartwatch was associated with a moderate, but statistically significant, reduction in home BP. Differences in BMI among study participants accounted for the majority of the observed association.

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: Atrial fibrillation (AF) may be asymptomatic and remain undiagnosed until the development of complications, which precludes primary prevention efforts. We aimed to quantify racial and rural-urban disparities in the frequency of incident AF presenting with ischemic stroke in a nationally representative sample of Medicare beneficiaries. Hypothesis: Black patients have higher frequency of stroke as the first presentation with AF than White patients. Methods: We used a 5% random sample of Medicare claims data to identify patients newly diagnosed with AF in 2016. The primary outcome was stroke as first AF manifestation, and was defined by inpatient diagnosis of ischemic stroke within 7 days prior to the first AF diagnosis. We computed age- and sex-adjusted proportion of AF diagnosis manifesting as stroke and used multivariable logistic regression to quantify the association of race and urban/rural residence with the outcome, adjusting for demographic and clinical characteristics. Results: Among 39,437 patients newly diagnosed with AF, 2,821 (7.2%) had ischemic stroke as the first AF manifestation. In urban areas, age- and sex-adjusted proportions of AF diagnosis manifesting as stroke were 7.2(95%CI: 6.8,7.4)% for White and 9.5(8.4,10.8)% for Black, compared to 5.9(5.4,6.4)% and 8.1(5.8,11.1)% in rural areas ( Figure ). After adjusting for age, sex, CHA 2 DS 2 -VASc score, Alzheimer's disease, Medicaid enrollment, and receipt of low-income subsidy, Black race (adjusted OR [95%CI]: 1.21 [1.05, 1.40], vs. White) and urban residence (1.16 [1.06, 1.28], vs. rural) were associated with increased risk of stroke as first AF manifestation. Conclusion: We observed uneven distributions in the frequency of stroke as first manifestation of AF between White and Black patients and between rural and urban residents. Further research is needed to evaluate the effectiveness of AF screening efforts in reducing inequities in health outcomes associated with AF.

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: Telemedicine facilitates continued access to care for management of chronic diseases while preventing exposure to health care facilities; however, reliance on telemedicine may exacerbate disparities based on the persistent digital divide. Documenting racial variation in the uptake of telemedicine is crucial to understand the potential aggravation of health care access inequities in the era of COVID-19. We used a nationally representative sample of Medicare beneficiaries with atrial fibrillation (AF) to quantify racial disparities in telehealth utilization before the COVID-19 pandemic. Hypothesis: Black patients are less likely to be engaged with telehealth services than White patients. Methods: Using a 5% random sample of Medicare claims data, we extracted telehealth visits in 2016 using modifiers GT, 95, and GQ and place of service code 2 in medical claims. We used multivariate Poisson models to estimate incidence rate ratios (IRR) comparing the number of telehealth visits across White, Black, and patients of other races. Results: Among 135,164 patients with AF, 404 (0.3%) had a total of 1420 telehealth visits in 2016. After adjusting for age, sex, AF duration, rurality, CHA2DS2-VASc score, Alzheimer's disease, use of direct oral anticoagulants and warfarin, and receipt of low-income subsidy, Black were 60% less likely than White to receive telehealth services (IRR 0.4 [0.3, 0.5]), and the ‘others’ group were 70% less likely to receive telehealth services (0.3 [0.2, 0.5]). Among rural residents, however, the racial difference in telehealth use was only seen in Black (0.4 [0.2, 0.6]) but not in the ‘others’ group (0.9 [0.6, 1.4]). The gap in telehealth use between White and Black was larger among those with higher CHA2DS2-VASc scores ( Figure) . Conclusion: Before the COVID-19 pandemic, telehealth service use was rare overall in patients with AF. However, Black patients, especially those with increased stroke risk, were still significantly less likely to have access to telemedicine than White patients.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia and a leading cause of stroke. Blood pressure (BP) responses to submaximal exercise are associated with incident cardiovascular disease and mortality. The association of BP responses to submaximal exercise with incident AF in the community is unknown. Hypothesis: We hypothesized that higher BP during and slower BP recovery after submaximal exercise are associated with a higher risk of incident AF. Methods: We evaluated Framingham Offspring Study participants who attended examination cycle 7, were free of AF, and underwent submaximal treadmill exercise testing. Systolic BP (SBP) and diastolic BP (DBP) were obtained pre-exercise (standing), during exercise (second stage, 2.5 mph at 12% grade), and 3-minutes post-exercise (supine). ΔBP during exercise was defined as exercise BP minus pre-exercise BP. ΔBP during recovery was defined as peak exercise BP minus 3-minutes post-exercise BP. We related exercise BP variables to risk of AF using Cox proportional hazards regression, adjusting for age, sex, height, weight, resting heart rate, resting SBP, resting DBP, use of antihypertensive medication, current smoking status, and diabetes. Results: We studied 2,002 participants (mean age 58 years; 53% women). During a median follow-up of 15 years, 236 participants (39% women) developed AF. We observed a positive association of exercise DBP and ΔDBP during exercise with risk of AF (Hazards Ratio [HR] per standard deviation [SD] increase 1.28, 95% CI 1.12-1.47 and HR 1.22, 95% CI 1.07-1.39, respectively). There was also a positive association between 3 minutes post-exercise SBP and AF risk (HR per SD-increase 1.31, 95% CI 1.07-1.60) and an inverse relation between ΔSBP during recovery and AF risk (HR per SD-increase 0.79, 95% CI 0.66-0.94, Table ) Conclusions: BP responses to submaximal exercise during midlife may serve as a marker for AF risk in later life.

Nonalcoholic fatty liver disease (NAFLD) is associated with increased liver- and cardiovascular disease (CVD)-related morbidity and mortality. In cross-sectional analyses, NAFLD clusters with several cardiometabolic traits including obesity,1,2 hypertension,3 diabetes,1 and dyslipidemia.3 However, liver fat is dynamic and changes over time. Aside from limited prior studies evaluating diet or exercise interventions, little is known about the association between changes in liver fat and the incidence of CVD risk factors. Additionally, previous studies often have limited follow-up; evaluate only select populations, such as individuals with obesity4,5 or diabetes6-8; and may not account for changes in weight or body mass index (BMI). The aim of the present study was to examine, in a longitudinal cohort, the natural history of liver fat change and the association with the incidence of multiple CVD risk factors.

BACKGROUND:Cigarette smoking is known to increase the risk of atrial fibrillation (AF), and a recent cross-sectional analysis suggested that parental smoking may be an AF risk factor. OBJECTIVES:The purpose of this study was to assess if parental smoking predicts offspring AF in the Framingham Heart Study. METHODS:This study analyzed Framingham Offspring cohort participants with parents in the Original cohort with known smoking status during the offspring's childhood. Framingham participants were evaluated every 2 to 8 years and were under routine surveillance for incident AF. The authors assessed AF incidence among Offspring participants exposed to parental smoking through age 18 years and performed a mediation analysis to determine the extent to which offspring smoking might explain observed associations. RESULTS:Of 2,816 Offspring cohort participants with at least 1 parent in the Original cohort, 82% were exposed to parental smoking. For every pack/day increase in parental smoking, there was an 18% increase in offspring AF incidence (adjusted hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 1.00 to 1.39; p = 0.04). Additionally, parental smoking was a risk factor for offspring smoking (adjusted odds ratio [OR]: 1.34; 95% CI: 1.17 to 1.54; p

We studied the association between cigarette smoking and incident heart failure (HF) in a racially diverse US cohort. We included 6,792 participants from the Multi-Ethnic Study of Atherosclerosis with information on cigarette smoking at baseline, characterized by status, intensity, burden, and time since quitting. Adjudicated outcomes included total incident HF cases and HF stratified by ejection fraction (EF) into HF with reduced EF (HFrEF; EF ≤ 40%) and preserved EF (HFpEF; EF ≥ 50%). We used Cox proportional hazards models adjusted for traditional cardiovascular risk factors and accounted for competing risk of each HF type. Mean age was 62 ± 10 years; 53% were women, 61% were nonwhite, and 13% were current smokers. A total of 279 incident HF cases occurred over a median follow-up of 12.2 years. The incidence rates of HFrEF and HFpEF were 2.2 and 1.9 cases per 1000 person-years, respectively. Current smoking was associated with higher risk of HF compared with never smoking (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.36 to 3.09); this was similar for HFrEF (HR, 2.58; 95% CI, 1.27 to 5.25) and HFpEF (HR, 2.51; 95% CI, 1.15 to 5.49). Former smoking was not significantly associated with HF (HR, 1.17; 95% CI, 0.88 to 1.56). Smoking intensity, burden, and time since quitting did not provide additional information for HF risk after accounting for smoking status.

BACKGROUND & AIMS Prior studies demonstrated an association between non-alcoholic fatty liver disease and chronic kidney disease (CKD), though data are conflicting. We examined the association between liver fat and prevalent and incident CKD in the Framingham Heart Study (FHS). METHODS We included FHS participants who underwent computed tomography (CT) from 2002 to 2005 (n = 1315). After excluding heavy alcohol use (n = 211) and missing covariates (n = 117), the final sample included 987 participants. For the incident CKD analysis, we excluded 73 participants with prevalent CKD. Liver fat was measured by the average liver attenuation on CT. Estimated glomerular filtration rate (eGFR) was obtained using the CKD Epidemiology Collaboration Creatinine-Cystatin C equation, and CKD was defined as eGFR

Introduction To implement and evaluate a blended online and in-person training to help mentors of early-career researchers appreciate the complexities of Tobacco Regulatory Science (TRS), refine TRS mentoring skills, and become acquainted with resources for providing effective guidance to TRS mentees. Methods TRS mentors engaged in a two-part pilot test of the training program. Authors evaluated both the online and in-person training using retrospective pre-post evaluations, which measure learning at the conclusion of a training program, and post-program focus groups. Twenty learners completed the online training, and 16 learners attended the in-person training module. Nine participants completed evaluations for the online module, and 12 participants completed evaluations for the in-person module. Results Program assessments revealed that participants found that the training achieved its overall goals. The majority of respondents (87.5%) rated the online portion of the training as valuable. For the in-person training, participants reported statistically significant improvements regarding confidence in: helping mentees to identify skills and training to effectively pursue TRS, assisting mentees in weighing career trajectories, and guiding mentees in conducting research responsive to TRS regulatory priorities. Conclusions The novel mentoring program was well received by faculty seeking to strengthen skills for mentoring early-career TRS researchers to navigate the complex landscape of TRS, explore diverse funding opportunities, and discern potential career trajectories. It provided unique content to address issues outside the traditional tobacco research training curriculum and offered specific information on regulatory policies, priorities, and opportunities. Implications This research documents the deployment and evaluation of a blended online and in-person training program for investigators mentoring early-career researchers working in TRS. Our assessment discovered that participants found the training to be valuable to their overall mentoring objectives. The training comprises a novel curriculum for investigators engaged in mentoring early-career researchers in a unique field, thus filling a deficit in the published literature by presenting a curriculum that has been customized to the unique needs of TRS mentors.

The Framingham Heart Study (FHS) was established in 1948 to improve understanding of the epidemiology of coronary heart disease (CHD) in the USA. In 1961, seminal work identified major risk factors for CHD (high blood pressure, high cholesterol levels and evidence on the electrocardiogram of left ventricular hypertrophy), which later formed the basis for multivariable 10-year and 30-year risk-prediction algorithms. The FHS cohorts now comprise three generations of participants (n ≈ 15,000) and two minority cohorts. The FHS cohorts are densely phenotyped, with recurring follow-up examinations and surveillance for cardiovascular and non-cardiovascular end points. Assessment of subclinical disease and physiological profiling of these cohorts (with the use of echocardiography, ambulatory electrocardiographic monitoring, exercise stress testing, cardiac CT, heart and brain MRI, serial vascular tonometry and accelerometry) have been performed repeatedly. Over the past decade, the FHS cohorts have undergone deep ‘omics’ profiling (including whole-genome sequencing, DNA methylation analysis, transcriptomics, high-throughput proteomics and metabolomics, and microbiome studies). The FHS is a rich, longitudinal, transgenerational and deeply phenotyped cohort study with a sustained focus on state-of-the-art epidemiological methods and technological advances to facilitate scientific discoveries. The Framingham Heart Study (FHS) has been collecting epidemiological data on cardiovascular risk factors and disease for >70 years. In this Timeline Perspectives article, the authors summarize the major achievements of the FHS, highlight some of the seminal publications and discuss how epidemiological research has changed and continues to evolve.

BACKGROUND: Hispanics/Latinos represent the largest ethnic minority group in the United States. Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States. OBJECTIVE: The purpose of this study was to provide data on the prevalence of AF and its correlates in a representative Hispanic/Latino population–based sample inclusive of all background groups. METHODS: Hispanic Community Health Study/Study of Latinos participants (n=16,415; 60% women; 59% age >45 years) were enrolled between March 2008 and June 2011, representing individuals of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American heritage. AF was defined by the 12-lead electrocardiogram and/or participant self-report of a physician diagnosis. Hispanic background–specific AF prevalence rates were determined. Weighted sequential logistic regression models were adjusted for demographic factors (age and sex) and clinical variables (diabetes, hypertension, body mass index, tobacco use, and estimated glomerular filtration rate). RESULTS: The overall weighted prevalence of AF was 1.0% (n=162), with the highest prevalence in Hispanics of Dominican and Puerto Rican backgrounds (1.9% and 2.5% respectively) and the lowest in those of Mexican background (0.3%). Diabetes, hypertension, renal disease, left ventricular hypertrophy determined by the electrocardiogram, alcohol use, and English language preference (greater acculturation) (P < .01 for all) were significantly associated with higher AF prevalence. Multivariate analysis by Hispanic/Latino background group showed that Hispanics of Dominican and Puerto Rican backgrounds were at a 3- to 6-fold higher risk of AF than their Mexican counterparts. CONCLUSION: In a diverse representative population of Hispanics/Latinos, overall AF prevalence was low and varied significantly across Hispanic/Latino background groups independent of clinical or demographic factors.

The global prevalence of atrial fibrillation (AF) and heart failure (HF) is rising. Population-based studies have observed that AF and HF often coexist, predispose to each other, and share risk factors. Age is the most potent risk factor for both AF and HF, but race plays an important role. Although AF and HF share common risk factors, adjusting for these risk factors does not explain the higher risk of AF patients developing HF and vice versa. Common pathophysiologic mechanisms may explain this linkage. The morbidity and mortality outcomes with combined AF and HF are substantial and warrant improved preventive strategies.

Background Short-term exposure to air pollution has been associated with cardiovascular events, potentially by promoting endothelial cell activation and inflammation. A few large-scale studies have examined the associations and have had mixed results. Methods We included 3820 non-current smoking participants (mean age 56 years, 54% women) from the Framingham Offspring cohort examinations 7 (1998–2001) and 8 (2005–2008), and Third Generation cohort examination 1 (2002–2005), who lived within 50 km of a central monitoring station. We calculated the 1- to 7-day moving averages of fine particulate matter (PM2.5), black carbon (BC), sulfate (SO42-), nitrogen oxides (NOx), and ozone before examination visits. We used linear mixed effect models for P-selectin, monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1, lipoprotein-associated phospholipase A2 activity and mass, and osteoprotegerin that were measured up to twice, and linear regression models for CD40 ligand and interleukin-18 that were measured once, adjusting for demographics, life style and clinical factors, socioeconomic position, time, and meteorology. Results We found negative associations of PM2.5 and BC with P-selectin, of ozone with MCP-1, and of SO42- and NOx with osteoprotegerin. At the 5-day moving average, a 5 µg/m3 higher PM2.5 was associated with 1.6% (95% CI: − 2.8, − 0.3) lower levels of P-selectin; a 10 ppb higher ozone was associated with 1.7% (95% CI: − 3.2, − 0.1) lower levels of MCP-1; and a 20 ppb higher NOx was associated with 2.0% (95% CI: − 3.6, − 0.4) lower levels of osteoprotegerin. Conclusions We did not find evidence of positive associations between short-term air pollution exposure and endothelial cell activation. On the contrary, short-term exposure to higher levels of ambient pollutants were associated with lower levels of P-selectin, MCP-1, and osteoprotegerin in the Framingham Heart Study.

IMPORTANCE Increased free thyroxine (FT4) and decreased thyrotropin are associated with increased risk of atrial fibrillation (AF) in observational studies, but direct involvement is unclear.OBJECTIVE To evaluate the potential direct involvement of thyroid traits on AF.DESIGN, SETTING. AND PARTICIPANTS Study-level mendelian randomization (MR) included 11 studies, and summary-level MR included 55 114 AF cases and 482 295 referents, all of European ancestry.EXPOSURES Genomewide significant variants were used as instruments for standardized FT4 and thyrotropin levels within the reference range, standardized triiodothyronine (FT3):FT4 ratio, hypothyroidism, standardized thyroid peroxidase antibody levels, and hyperthyroidism. Mendelian randomization used genetic risk scores in study-level analysis or individual single-nucleotide polymorphisms in 2-sample MR for the summary-level data.MAIN OUTCOMES AND MEASURES Prevalent and incident AF.RESULTS The study-level analysis included 7679 individuals with AF and 49 233 referents (mean age [standard error], 62 [3] years; 15 859 men [29.7%]). In study-level random-effects meta-analysis, the pooled hazard ratio of FT4 levels (nanograms per deciliter) for incident AF was 1.55 (95% CI, 1.09-2.20; P = .02; I-2= 76%) and the pooled odds ratio (OR) for prevalent AF was 2.80 (95% CI, 1.41-5.54; P = .003; I-2 = 64%) in multivariable-adjusted analyses. The FT4 genetic risk score was associated with an increase in FT(4 )by 0.082 SD (standard error, 0.007; P CONCLUSIONS AND RELEVANCE Genetically increased FT3:FT(4 )ratio and hyperthyroidism, but not FT4 within the reference range, were associated with increased AF, and increased thyrotropin within the reference range and hypothyroidism were associated with decreased AF, supporting a pathway involving the pituitary-thyroid-cardiac axis.

Rationale: Proinflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of MCP-1 (monocyte chemoattractant protein-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether circulating levels of MCP-1 are associated with risk of incident stroke in the general population. Methods and Results: We used previously unpublished data on 17 180 stroke-free individuals (mean age, 56.7±8.1 years; 48.8% men) from 6 population-based prospective cohort studies and explored associations between baseline circulating MCP-1 levels and risk of any stroke, ischemic stroke, and hemorrhagic stroke during a mean follow-up interval of 16.3 years (280 522 person-years at risk; 1435 incident stroke events). We applied Cox proportional-hazards models and pooled hazard ratios (HRs) using random-effects meta-analyses. After adjustments for age, sex, race, and vascular risk factors, higher MCP-1 levels were associated with increased risk of any stroke (HR per 1-SD increment in ln-transformed MCP-1, 1.07; 95% CI, 1.01–1.14). Focusing on stroke subtypes, we found a significant association between baseline MCP-1 levels and higher risk of ischemic stroke (HR, 1.11 [1.02–1.21]) but not hemorrhagic stroke (HR, 1.02 [0.82–1.29]). The results followed a dose-response pattern with a higher risk of ischemic stroke among individuals in the upper quartiles of MCP-1 levels as compared with the first quartile (HRs, second quartile: 1.19 [1.00–1.42]; third quartile: 1.35 [1.14–1.59]; fourth quartile: 1.38 [1.07–1.77]). There was no indication for heterogeneity across studies, and in a subsample of 4 studies (12 516 individuals), the risk estimates were stable after additional adjustments for circulating levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein). Conclusions: Higher circulating levels of MCP-1 are associated with increased long-term risk of stroke. Our findings along with genetic and experimental evidence suggest that MCP-1 signaling might represent a therapeutic target to lower stroke risk.Visual Overview: An online visual overview is available for this article.

Background: Decay products of radioactive materials may attach to ambient fine particles and form radioactive aerosol. Internal ionizing radiation source from inhaled radioactive aerosol may contribute to the fine particulate matter (PM2.5)-inflammation pathway. However, few studies in humans have examined the associations. Objectives: To examine the associations between particle radioactivity and biomarkers of oxidative stress and inflammation among participants from the Framingham Offspring and Third Generation cohorts. Methods: We included 3996 participants who were not current smokers and lived within 50 km from our central air pollution monitoring station. We estimated regional mean gross beta radioactivity from monitors in the northeastern U.S. as a surrogate for ambient radioactive particles, and calculated the 1- to 28-day moving averages. We used linear regression models for fibrinogen, tumor necrosis factor α, interleukin-6, and myeloperoxidase which were measured once, and linear mixed effect models for 8-epi-prostaglandin F2α, C-reactive protein, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), P-selectin, and tumor necrosis factor receptor-2 that were measured up to twice, adjusting for demographics, individual- and area-level socioeconomic positions, time, meteorology, and PM2.5. We also examined whether the associations differed by median age, sex, diabetes status, PM2.5 levels, and black carbon levels. Results: The mean age was 54 years and 54% were women. An interquartile range (3 × 10−3 pCi/m3) higher beta radioactivity level at the 7-day moving average was associated with 5.09% (95% CI: 0.92, 9.43), 2.65% (1.10, 4.22), and 4.71% (95% CI: 3.01, 6.44) higher levels of interleukin-6, MCP-1, and P-selectin, but with 7.01% (95% CI: −11.64, −2.15) and 2.70% (95% CI: −3.97, −1.42) lower levels of 8-epi-prostaglandin F2α and ICAM-1, respectively. Conclusions: Regional mean particle radioactivity was positively associated with interleukin-6, MCP-1, and P-selectin, but negatively with ICAM-1 and 8-epi-prostaglandin F2α among our study participants. Keywords: Gross beta radiation, Particle radioactivity, Epidemiology, Environment, Inflammation, Oxidative stress

Background: Studies of air pollution exposure and arterial stiffness have reported inconsistent results and large studies employing the reference standard of arterial stiffness, carotid-femoral pulse-wave velocity (CFPWV), have not been conducted. Aim: To study long-term exposure to ambient fine particles (PM2.5), proximity to roadway, and short-term air pollution exposures in relation to multiple measures of arterial stiffness in the Framingham Heart Study. Methods: We assessed central arterial stiffness using CFPWV, forward pressure wave amplitude, mean arterial pressure and augmentation index. We investigated long-and short-term air pollution exposure associations with arterial stiffness with linear regressions using long-term residential PM2.5 (2003 average from a spatiotemporal model using satellite data) and proximity to roadway in addition to short-term averages of PM2.5, black carbon, particle number, sulfate, nitrogen oxides, and ozone from stationary monitors. Results: We examined 5842 participants (mean age 51 ± 16, 54% women). Living closer to a major roadway was associated with higher arterial stiffness (0.11 m/s higher CFPWV [95% CI: 0.01, 0.22] living

Atrial fibrillation affects almost 60 million adults worldwide. Atrial fibrillation is associated with a high risk of cardiovascular morbidity and death as well as with social, psychological and economic burdens on patients and their families. Social determinants - such as race and ethnicity, financial resources, social support, access to health care, rurality and residential environment, local language proficiency and health literacy - have prominent roles in the evaluation, treatment and management of atrial fibrillation. Addressing the social determinants of health provides a crucial opportunity to reduce the substantial clinical and non-clinical complications associated with atrial fibrillation. In this Review, we summarize the contributions of social determinants to the patient experience and outcomes associated with this common condition. We emphasize the relevance of social determinants and their important intersection with atrial fibrillation treatment and outcomes. In closing, we identify gaps in the literature and propose future directions for the investigation of social determinants and atrial fibrillation.

Background Although Black adults are more likely to die from coronary heart disease (CHD) compared with White adults, few studies have examined the relationship between cigarette smoking and CHD risk among Black adults. We evaluated the relationship between cigarette smoking, incident CHD, and coronary artery calcification in the JHS (Jackson Heart Study). Methods and Results We classified JHS participants without a history of CHD (n=4432) by self‐reported baseline smoking status into current, former (smoked at least 400 cigarettes/life) or never smokers at baseline (2000–2004). We further classified current smokers by smoking intensity (number of cigarettes smoked per day [1–19 or ≥20]) and followed for incident CHD (through 2016). Hazard ratios (HR) for incident CHD for each smoking group compared with never smokers were estimated with adjusted Cox proportional hazard regression models. At baseline, there were 548 (12.4%) current, 782 (17.6%) former, and 3102 (70%) never smokers. During follow‐up (median, 13.8 years), 254 participants developed CHD. After risk factor adjustment, CHD risk was significantly higher in current smokers compared with never smokers (HR, 2.11; 95% CI, 1.39–3.18); the difference between former smokers and never smokers (HR, 1.37; 95% CI, 1.0–1.90) did not achieve statistical significance. Among current smokers, we did not observe a dose‐response effect for CHD risk. Additionally, in multivariable logistic regression models with a subset of our analytic cohort, current smokers had greater odds of coronary artery calcification score >0 compared with never smokers (odds ratio, 2.63; 95% CI, 1.88–3.68). Conclusions In a large prospective cohort of Black adults, current smoking was associated with a >2‐fold increased risk of CHD over a median follow‐up of greater than a decade.

Background Frailty occurs in 10-15% of community-living older adults and inflammation is a key determinant of frailty. Though diet is a modulator of inflammation, there are few prospective studies elucidating the role of diet-associated inflammation on frailty. Objective To determine whether a pro-inflammatory diet was associated with increased odds of frailty in adults from the Framingham Heart Study (FHS). Design and methods This study is nested in a prospective cohort that included individuals without frailty. Diet was assessed in 1998-2001 using a valid food frequency questionnaire (FFQ) and frailty was measured in 2011-2014. FFQ-derived energy-adjusted dietary inflammatory index (E-DII®) scores were computed, with higher E-DII scores indicating a more pro-inflammatory diet. Frailty was defined as fulfilling ≥3 of 5 Fried Phenotype criteria. Information on potential mediators, serum interleukin-6 and C-reactive protein was obtained in 1998-2001. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (95% CI) for E-DII (as continuous and in quartiles) and frailty onset adjusting for relevant confounders. Results Of 1,701 individuals without frailty at baseline (mean age = 58 years, SD = 8, range: 33-81; 55% female), 224 developed frailty (13% incidence) over ∼12 years. Mean E-DII score was -1.95 (SD = 2.20; range: -6.71 to +5.40). After adjusting for relevant confounders, a one-unit higher E-DII score was associated with 16% increased odds of developing frailty (95% CI = 1.07, 1.25). In categorical analyses, participants in the highest (pro-inflammatory) vs. lowest quartile of E-DII had >2-fold increased odds of frailty (ORquartile4vs.1 = 2.22, 95% CI = 1.37, 3.60, Ptrend Conclusions In this cohort of middle-aged and older adults, a pro-inflammatory diet was associated with increased odds of frailty over ∼12 years of follow-up. Trials designed to increase consumption of anti-inflammatory foods for frailty prevention are warranted.Clinical registry number and website: Not applicable.

BACKGROUND Daily routines (eg, physical activity and sleep patterns) are important for diabetes self-management. Traditional research methods are not optimal for documenting long-term daily routine patterns in participants with glycemic conditions. Mobile health offers an effective approach for collecting users’ long-term daily activities and analyzing their daily routine patterns in relation to diabetes status. OBJECTIVE This study aims to understand how routines function in diabetes self-management. We evaluate the associations of daily routine variables derived from a smartwatch with diabetes status in the electronic Framingham Heart Study (eFHS). METHODS The eFHS enrolled the Framingham Heart Study participants at health examination 3 between 2016 and 2019. At baseline, diabetes was defined as fasting blood glucose level ≥126 mg/dL or as a self-report of taking a glucose-lowering medication; prediabetes was defined as fasting blood glucose level of 100-125 mg/dL. Using smartwatch data, we calculated the average daily step counts and estimated the wake-up times and bedtimes for the eFHS participants on a given day. We compared the average daily step counts and the intraindividual variability of the wake-up times and bedtimes of the participants with diabetes and prediabetes with those of the referents who were neither diabetic nor prediabetic, adjusting for age, sex, and race or ethnicity. RESULTS We included 796 participants (494/796, 62.1% women; mean age 52.8, SD 8.7 years) who wore a smartwatch for at least 10 hours/day and remained in the study for at least 30 days after enrollment. On average, participants with diabetes (41/796, 5.2%) took 1611 fewer daily steps (95% CI 863-2360; PPP=.005) in the variation of their estimated bedtimes compared with the referents (546/796, 68.6%) without diabetes or prediabetes. Participants with prediabetes (209/796, 26.2%) also walked fewer daily steps (P=.04) and had a larger variation in their estimated wake-up times (P=.04) compared with the referents. CONCLUSIONS On average, participants with diabetes at baseline walked significantly fewer daily steps and had larger variations in their wake-up times and bedtimes than the referent group. These findings suggest that modifying the routines of participants with poor glycemic health may be an important approach to the self-management of diabetes. Future studies should be designed to improve the remote monitoring and self-management of diabetes. CLINICALTRIAL

Background:The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).Methods:The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year’s worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year’s edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease.Results:Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.Conclusions:The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Background and aimsNAFLD is increasing in prevalence and will soon be the most common chronic liver disease. Liver stiffness, as assessed by vibration-controlled transient elastography (VCTE), correlates with hepatic fibrosis, an important predictor of liver-related and all-cause mortality. Although liver fat is associated with cardiovascular risk factors, the association between hepatic fibrosis and cardiovascular risk factors is less clear.Approach and resultsWe performed VCTE, assessing controlled attenuation parameter (CAP; measure of steatosis) and liver stiffness measurement (LSM) in 3,276 Framingham Heart Study adult participants (53.9% women, mean age 54.3±9.1years) presenting for a routine study visit. We performed multivariable-adjusted logistic regression models to determine the association between LSM and obesity-related, vascular-related, glucose-related, and cholesterol-related cardiovascular risk factors. The prevalence of hepatic steatosis (CAP≥290dB/m) was 28.8%, and 8.8% had hepatic fibrosis (LSM≥ 8.2kPa). Hepatic fibrosis was associated with multiple cardiovascular risk factors, including increased odds of obesity (OR, 1.82; 95% CI, 1.35-2.47), metabolic syndrome (OR, 1.49; 95% CI 1.10-2.01), diabetes (OR, 2.67; 95% CI, 1.21-3.75), hypertension (OR, 1.52; 95% CI, 1.15-1.99), and low high-density lipoprotein cholesterol (OR, 1.47; 95% CI, 1.09-1.98), after adjustment for age, sex, smoking status, alcohol drinks/week, physical activity index, aminotransferases, and CAP.ConclusionsIn our community-based cohort, VCTE-defined hepatic fibrosis was associated with multiple cardiovascular risk factors, including obesity, metabolic syndrome, diabetes, hypertension, and high-density lipoprotein cholesterol, even after accounting for covariates and CAP. Additional longitudinal studies are needed to determine if hepatic fibrosis contributes to incident cardiovascular disease risk factors or events.

AIMS: To determine the prevalence and incidence of AF among HF subtypes in a biracial community-based cohort. METHODS: We studied 6,496 participants in the Atherosclerosis Risk in Community study (mean age, 75.8±5.3, 59% women, 23% black) who attended the 2011–2013 visit. HF was identified from physician adjudicated diagnosis, hospital discharges, and self-report. HF subtypes were based on echocardiography. A left ventricular ejection fraction

Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci associated with another trait. A typical approach to address this issue is to perform an additional analysis adjusting for the confounder. However, obtaining conditional results can be time-consuming. We propose an approximate conditional phenotype analysis based on GWAS summary statistics, the covariance between outcome and confounder, and the variant minor allele frequency (MAF). GWAS summary statistics and MAF are taken from GWAS meta-analysis results while the traits covariance may be estimated by two strategies: (i) estimates from a subset of the phenotypic data; or (ii) estimates from published studies. We compare our two strategies with estimates using individual level data from the full GWAS sample (gold standard). A simulation study for both binary and continuous traits demonstrates that our approximate approach is accurate. We apply our method to the Framingham Heart Study (FHS) GWAS and to large-scale cardiometabolic GWAS results. We observed a high consistency of genetic effect size estimates between our method and individual level data analysis. Our approach leads to an efficient way to perform approximate conditional analysis using large-scale GWAS summary statistics.

Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute’s virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF.

BackgroundeCohort studies offer an efficient approach for data collection. However, eCohort studies are challenged by volunteer bias and low adherence. We designed an eCohort embedded in the Framingham Heart Study (eFHS) to address these challenges and to compare the digital data to traditional data collection.ObjectiveThe aim of this study was to evaluate adherence of the eFHS app-based surveys deployed at baseline (time of enrollment in the eCohort) and every 3 months up to 1 year, and to compare baseline digital surveys with surveys collected at the research center.MethodsWe defined adherence rates as the proportion of participants who completed at least one survey at a given 3-month period and computed adherence rates for each 3-month period. To evaluate agreement, we compared several baseline measures obtained in the eFHS app survey to those obtained at the in-person research center exam using the concordance correlation coefficient (CCC).ResultsAmong the 1948 eFHS participants (mean age 53, SD 9 years; 57% women), we found high adherence to baseline surveys (89%) and a decrease in adherence over time (58% at 3 months, 52% at 6 months, 41% at 9 months, and 40% at 12 months). eFHS participants who returned surveys were more likely to be women (adjusted odds ratio [aOR] 1.58, 95% CI 1.18-2.11) and less likely to be smokers (aOR 0.53, 95% CI 0.32-0.90). Compared to in-person exam data, we observed moderate agreement for baseline app-based surveys of the Physical Activity Index (mean difference 2.27, CCC=0.56), and high agreement for average drinks per week (mean difference 0.54, CCC=0.82) and depressive symptoms scores (mean difference 0.03, CCC=0.77).ConclusionsWe observed that eFHS participants had a high survey return at baseline and each 3-month survey period over the 12 months of follow up. We observed moderate to high agreement between digital and research center measures for several types of surveys, including physical activity, depressive symptoms, and alcohol use. Thus, this digital data collection mechanism is a promising tool to collect data related to cardiovascular disease and its risk factors.

Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. Objective: To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population. Data Sources and Selection: Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points. Data Extraction and Synthesis: Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses. Main Outcomes and Measures: Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes). Results: The meta-analysis included 7 cohort studies involving 21401 individuals (mean [SD] age, 53.7 [10.2] years; 10012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P =.01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P =.02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P

Introduction: Excess alcohol intake and inherited predisposition may increase risk of atrial fibrillation (AF). We sought to characterize the association between alcohol intake and incident AF and determine whether the effect of alcohol is modified by inherited predisposition to AF. Methods: We analyzed UK Biobank participants without prevalent AF and with complete alcohol consumption, genomic, and clinical data collected between 2006-2010. Exposures included alcohol consumption (stratified by an acceptable range of ≤98 grams/week for women or ≤196 grams/week for men and analyzed as a continuous variable) and an AF polygenic risk score (PRS). Cox proportional hazard models were adjusted for established AF risk factors. The cumulative incidence of AF was assessed at 5 years. Results: Among 376,776 participants (47.5% male, mean age 56.9 years), 6,293 developed AF during a median of 6.9 years of follow-up. Alcohol consumption was associated with AF (hazard ratio [HR] 1.10; 95% CI 1.05-1.16 for intake above an acceptable range; HR 1.04 per 100 grams/week; 95% CI 1.02-1.06). An AF PRS was associated with AF (HR 1.38 per standard deviation [SD]; 95% CI 1.35-1.41). In models including both alcohol intake and the AF PRS, each remained associated with AF. The 5-year cumulative incidence of AF for individuals with alcohol intake above an acceptable range and in the highest decile of polygenic risk was 2.33% (95% CI 2.07-2.59), compared to 0.69% (95% CI 0.58-0.80) for those with alcohol intake within acceptable range and in the lowest decile of polygenic risk. Conclusions: Alcohol consumption is associated with risk of incident AF across a range of polygenic predisposition to AF. Preventive counseling regarding alcohol intake may reduce the risk of AF regardless of the degree of risk conferred by inherited predisposition.

Introduction: Cigarette smoking is associated with peripheral artery disease (PAD) in African Americans (AA), but the association between cigarette constituents and PAD remain inadequately studied. We evaluated the effect of volatile organic compounds (VOC) acrolein and crotonaldehyde on ankle-brachial index (ABI) as well as related biomarkers in AA participants of the Jackson Heart Study. Methods: Urinary VOC concentrations were measured in a subset of participants at baseline including 345 self-reported current smokers and 718 never smokers. Multivariable linear regression assessed the association between ABI and VOC concentrations after adjustment for acute (cotinine) and chronic (pack-years) smoking measures in models 1 and 2, respectively. The degree of association was assessed after adjusting for possible mediation (Baron & Kenny procedure) by C-reactive protein (CRP), fibrinogen, and homocysteine (HCY) concentrations. VOC concentrations were natural log transformed for normal distribution and all models adjusted for relevant covariates. Results: The mean age of included participants was 52 years and 49% women. Individuals who smoked were more likely to be men, less educated, have prevalent cardiovascular disease, and lower mean ABI. In model 1, ABI was inversely associated with urinary acrolein and crotonaldehyde concentrations. Model 2 retained the inverse ABI association for both VOC. Crotonaldehyde was directly associated with CRP and HCY in models 1 and 2. In model 1, acrolein was associated with HCY (Table). Biomarker mediation of the VOC-ABI relationship was insignificant. Conclusions: Acrolein and crotonaldehyde concentrations are associated with lower ABI and higher measures of inflammation and thrombosis in a community-based sample of AA. These findings suggest reduction in VOC exposure may reduce the risk of PAD in AA who smoke cigarettes.