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Abstract Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021. We tested the association of time-to-LTME and HT subtype (parenchymal, petechial) using Cox regression, controlling for age, mean arterial pressure, glucose, tissue plasminogen activator, mechanical thrombectomy, National Institute of Health Stroke Scale, antiplatelets, anticoagulation, temperature, and stroke side. Secondary and exploratory outcomes included mass effect-related death, all-cause death, disposition, and decompressive hemicraniectomy. Of 840 patients, 358 (42.6%) had no HT, 403 (48.0%) patients had petechial HT, and 79 (9.4%) patients had parenchymal HT. LTME occurred in 317 (37.7%) and 100 (11.9%) had mass effect-related deaths. Parenchymal (HR 8.24, 95% CI 5.46–12.42, p

Background: Exhaled carbon monoxide (eCO) is associated with subclinical and overt cardiovascular disease and stroke. The association between eCO with left atrial size, prevalent, or incident atrial fibrillation (AF) are uncertain. Methods: eCO was measured using an Ecolyzer instrument among Framingham Heart Study Offspring and Omni participants who attended an examination from 1994 to 1998. We analyzed multivariable-adjusted (current smoking, and other covariates including age, race, sex, height, weight, systolic blood pressure, diastolic blood pressure, diabetes, hypertension treatment, prevalent myocardial infarction [MI], and prevalent heart failure [HF]). Cox and logistic regression models assessed the relations between eCO and incident AF (primary model), and prevalent AF and left atrial (LA) size (pre-specified secondary analyses). We also conducted secondary analyses adjusting for biomarkers, and interim MI and interim HF. Results: Our study sample included 3814 participants (mean age 58 ± 10 years; 54.4 % women, 88.4 % White). During an average of 18.8 ± 6.5 years follow-up, 683 participants were diagnosed with AF. eCO was associated with incident AF after adjusting for established AF risk factors (HR, 1.31 [95 % CI, 1.09–1.58]). In secondary analyses the association remained significant after additionally adjusting for C-reactive protein and B-type natriuretic peptide, and interim MI and CHF, and in analyses excluding individuals who currently smoked. eCO was not significantly associated with LA size and prevalent AF. Conclusion: In our community-based sample of individuals without AF, higher mean eCO concentrations were associated with incident AF. Further investigation is needed to explore the biological mechanisms linking eCO with AF.

Abstract Most prior studies on the prognostic significance of newly-diagnosed atrial fibrillation (AF) in COVID-19 did not differentiate newly-diagnosed AF from pre-existing AF. To determine the association between newly-diagnosed AF and in-hospital and 30-day mortality among regular users of Veterans Health Administration using data linked to Medicare. We identified Veterans aged ≥ 65 years who were hospitalized for ≥ 24 h with COVID-19 from 06/01/2020 to 1/31/2022 and had ≥ 2 primary care visits within 24 months prior to the index hospitalization. We performed multivariable logistic regression analyses to estimate adjusted risks, risk differences (RD), and odds ratios (OR) for the association between newly-diagnosed AF and the mortality outcomes adjusting for patient demographics, baseline comorbidities, and presence of acute organ dysfunction on admission. Of 23,299 patients in the study cohort, 5.3% had newly-diagnosed AF, and 29.2% had pre-existing AF. In newly-diagnosed AF adjusted in-hospital and 30-day mortality were 16.5% and 22.7%, respectively. Newly-diagnosed AF was associated with increased mortality compared to pre-existing AF (in-hospital: OR 2.02, 95% confidence interval [CI] 1.72–2.37; RD 7.58%, 95% CI 5.54–9.62) (30-day: OR 1.86; 95% CI 1.60–2.16; RD 9.04%, 95% CI 6.61–11.5) or no AF (in-hospital: OR 2.24, 95% CI 1.93–2.60; RD 8.40%, 95% CI 6.44–10.4) (30-day: 2.07, 95% CI 1.80–2.37; RD 10.2%, 95% CI 7.89–12.6). There was a smaller association between pre-existing AF and the mortality outcomes. Newly-diagnosed AF is an important prognostic marker for patients hospitalized with COVID-19. Whether prevention or treatment of AF improves clinical outcomes in these patients remains unknown.

ABSTRACTSystemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p

Background Individuals with both atrial fibrillation (AF) and myocardial infarction (MI) have higher mortality compared with individuals with only 1 condition. Whether mortality differs according to the temporal order of AF and MI is unclear. Methods and Results We included participants from the FHS (Framingham Heart Study) from 1960 and onwards. We assessed the hazard ratio (HR) of new‐onset AF and MI, and mortality according to MI and AF status (prevalent and interim) using multivariable‐adjusted Cox proportional hazards models. Interim diseases were modeled as time‐varying variables. For the analysis of new‐onset AF, 10 923 participants (55% women; mean±SD age, 54±8 years) were included. For new‐onset MI, 10 804 participants (55% women; mean±SD age, 54±8 years) were included. Compared with no MI, the hazard of new‐onset AF was higher in participants with prevalent (HR, 1.60 [95% CI, 1.32–1.94]) and interim MI (HR, 3.96 [95% CI, 3.18–4.91]). Both ST‐segment–elevation MI and non–ST‐segment–elevation MI were associated with new‐onset AF. Interim AF, not prevalent AF, was associated with higher hazard rate of new‐onset MI (HR, 2.21 [95% CI, 1.67–2.92]). Interim AF was associated with both ST‐segment–elevation MI and non–ST‐segment–elevation MI. Mortality was significantly greater among participants with AF and MI compared with participants with 1 of the 2, regardless of temporal order. Conclusions We report a bidirectional association between AF and MI, which was observed for both non–ST‐segment–elevation MI and ST‐segment–elevation MI. Participants with both AF and MI had considerably higher mortality compared with participants with only 1 of the 2 conditions, regardless of order.

While the impact of combustible cigarette smoking on cardiovascular disease (CVD) is well-established, the longitudinal association of non-traditional tobacco products with subclinical and clinical CVD has not been fully explored due to: 1) limited data availability; and 2) the lack of well-phenotyped prospective cohorts. Therefore, there is the need for sufficiently powered well-phenotyped datasets to fully elucidate the CVD risks associated with non-cigarette tobacco products. The Cross-Cohort Collaboration (CCC)-Tobacco is a harmonized dataset of 23 prospective cohort studies predominantly in the US. A priori defined variables collected from each cohort included baseline characteristics, details of traditional and non-traditional tobacco product use, inflammatory markers, and outcomes including subclinical and clinical CVD. The definitions of the variables in each cohort were systematically evaluated by a team of two physician-scientists and a biostatistician. Herein, we describe the method of data acquisition and harmonization and the baseline sociodemographic and risk profile of participants in the combined CCC-Tobacco dataset. The total number of participants in the pooled cohort is 322782 (mean age: 59.7 ± 11.8 years) of which 76% are women. White individuals make up the majority (73.1%), although there is good representation of other race and ethnicity groups including African American (15.6%) and Hispanic/Latino individuals (6.4%). The prevalence of participants who never smoked, formerly smoked, and currently smoke combustible cigarettes is 50%, 36%, and 14%, respectively. The prevalence of current and former cigar, pipe, and smokeless tobacco is 7.3%, 6.4%, and 8.6%, respectively. E-cigarette use was measured only in follow-up visits of select studies, totaling 1704 former and current users. CCC-Tobacco is a large, pooled cohort dataset that is uniquely designed with increased power to expand knowledge regarding the association of traditional and non-traditional tobacco use with subclinical and clinical CVD, with extension to understudied groups including women and individuals from underrepresented racial-ethnic groups.

Abstract Background This study explores the association between psychosocial stressors and current e-cigarette use among adolescents in the United States. Methods We used data from 12,767 participants in the 2019 National Youth Risk Behavioral Survey to examine the association between psychosocial stressors (bullying, sexual assault, safety-related absence from school, depressive symptoms, suicidal ideation, physical altercation, and weapon threats) and past-30-day e-cigarette use using multivariable-adjusted logistic regression models. We examined the association for each stressor and then as a burden score (0–7). To compare the strength of the association between stressors and current e-cigarette use to current combustible cigarette use, we additionally examined the association between each stressor and current combustible cigarette use. Results Approximately 32.7% reported current e-cigarette use. The weighted prevalence of current e-cigarette use was higher among individuals who experienced stressors than those who did not. For example, bullying (43.9% vs. 29.0%). Similar prevalence patterns were seen among other stressors. Individuals who experienced stressors had significantly higher adjusted odds of current e-cigarette use than those who did not (OR [Odds Ratio] range: 1.47–1.75). Similarly, individuals with higher burden scores had a higher prevalence (zero [20.5%], one [32.8%], two [41.4%], three [49.6%], four to seven [60.9%]) and higher odds of current e-cigarette use (OR range: 1.43–2.73) than those with a score of zero. The strength of the association between the stressors and e-cigarette use was similar to that between the stressors and combustible cigarette use. Conclusion The study demonstrates a significant association between psychosocial stressors and adolescent e-cigarette use, highlighting the potential importance of interventions, such as targeted school-based programs that address stressors and promote stress management, as possible means of reducing adolescent e-cigarette use. Future research directions include exploring underlying mechanisms linking stressors to e-cigarette use and evaluating the effectiveness of interventions addressing stressors in reducing adolescent e-cigarette use.

Arterial tonometry and vascular calcification measures are useful in cardiovascular disease (CVD) risk assessment. Prior studies found associations between tonometry measures, arterial calcium, and CVD risk. Activated platelets release angiopoietin-1 and other factors, which may connect vascular structure and platelet function. We analyzed arterial tonometry, platelet function, aortic, thoracic and coronary calcium, and thoracic and abdominal aorta diameters measured in the Framingham Heart Study Gen3/NOS/OMNI-2 cohorts (n = 3,429, 53.7% women, mean age 54.4 years ±9.3). Platelet reactivity in whole blood or platelet-rich plasma was assessed using 5 assays and 7 agonists. We analyzed linear mixed effects models with platelet reactivity phenotypes as outcomes, adjusting for CVD risk factors and family structure. Higher arterial calcium trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity. Characteristic impedance (Zc) and central pulse pressure positively trended with various platelet traits, while pulse wave velocity and Zc negatively trended with collagen, ADP, and epinephrine traits. All results did not pass a stringent multiple test correction threshold (p

Introduction E-cigarette use among youth and young adults remains of public health concern. Pod-based e-cigarettes, including JUUL, significantly changed the e-cigarette landscape in the US. Using an online survey, we explored the socio-behavioral correlates, predisposing factors, and addictive behaviors, among young adult pod-mod users within a University in Maryland, USA. Methods In total, 112 eligible college students aged 18–24 years, recruited from a University in Maryland, who reported using pod-mods were included in this study. Participants were categorized into current/non-current users based on past- 30-day use. Descriptive statistics were used to analyze participants’ responses. Results The mean age of the survey participants was 20.5 ± 1.2 years, 56.3% were female, 48.2% White, and 40.2% reported past-30-day (current) use of pod-mods. The mean age of first experimentation with pod-mods was 17.8 ± 1.4 years, while the mean age of regular use was 18.5 ± 1.4 years, with the majority (67.9%) citing social influence as the reason for initiation. Of the current users, 62.2% owned their own devices, and 82.2% predominantly used JUUL and menthol flavor (37.8%). A significant proportion of current users (73.3%) reported buying pods in person, 45.5% of whom were aged

Summary: Surveillance of e-cigarette use among different population groups is important for the timely implementation and evaluation of tobacco regulatory policies. In this review, we identified 13 nationally representative, repeatedly conducted epidemiologic surveys that assess e-cigarette use among U.S. youth and/or adults and have been instrumental in e-cigarette surveillance. These surveys included National Youth Tobacco Survey, Youth Risk Behavior Surveillance System, Monitoring the Future Survey, International Tobacco Control Policy Evaluation Project (ITC) Youth Tobacco and Vaping Survey, Behavioral Risk Factor Surveillance System, National Health Interview Survey, Tobacco Use Supplement of the Current Population Survey, Health Information National Trends Survey, Tobacco Products and Risk Perception Surveys, ITC Four Country Smoking and Vaping Survey, National Health and Nutrition Examination Survey, National Survey on Drug Use and Health, and Population Assessment of Tobacco and Health. These surveys vary in scope and detail, with their unique strengths and the regulatory questions that can be answered using each survey data. We also highlighted the gaps in these surveys and made recommendations for improvement.

Abstract Long-term use of digital devices is critical for successful clinical or research use, but digital health studies are challenged by a rapid drop-off in participation. A nested e-cohort (eFHS) is embedded in the Framingham Heart Study and uses three system components: a new smartphone app, a digital blood pressure (BP) cuff, and a smartwatch. This study aims to identify factors associated with the use of individual eFHS system components over 1-year. Among 1948 eFHS enrollees, we examine participants who returned surveys within 90 days (n = 1918), and those who chose to use the smartwatch (n = 1243) and BP cuff (n = 1115). For each component, we investigate the same set of candidate predictors for usage and use generalized linear mixed models to select predictors (P

Abstract Chronic inflammation is a continuous low-grade activation of the systemic immune response. Whereas downstream inflammatory markers are associated with atrial fibrillation (AF), upstream inflammatory effectors including eicosanoids are less studied. To examine the association between eicosanoids and incident AF. We used a liquid chromatography-mass spectrometry for the non-targeted measurement of 161 eicosanoids and eicosanoid-related metabolites in the Framingham Heart Study. The association of each eicosanoid and incident AF was assessed using Cox proportional hazards models and adjusted for AF risk factors, including age, sex, height, weight, systolic/diastolic blood pressure, current smoking, antihypertensive medication, diabetes, history of myocardial infarction and heart failure. False discovery rate (FDR) was used to adjust for multiple testing. Eicosanoids with FDR

Abstract Physical activity is regarded as favorable to health but effects across the spectrum of human disease are poorly quantified. In contrast to self-reported measures, wearable accelerometers can provide more precise and reproducible activity quantification. Using wrist-worn accelerometry data from the UK Biobank prospective cohort study, we test associations between moderate-to-vigorous physical activity (MVPA) – both total MVPA minutes and whether MVPA is above a guideline-based threshold of ≥150 min/week—and incidence of 697 diseases using Cox proportional hazards models adjusted for age, sex, body mass index, smoking, Townsend Deprivation Index, educational attainment, diet quality, alcohol use, blood pressure, anti-hypertensive use. We correct for multiplicity at a false discovery rate of 1%. We perform analogous testing using self-reported MVPA. Among 96,244 adults wearing accelerometers for one week (age 62 ± 8 years), MVPA is associated with 373 (54%) tested diseases over a median 6.3 years of follow-up. Greater MVPA is overwhelmingly associated with lower disease risk (98% of associations) with hazard ratios (HRs) ranging 0.70–0.98 per 150 min increase in weekly MVPA, and associations spanning all 16 disease categories tested. Overall, associations with lower disease risk are enriched for cardiac (16%), digestive (14%), endocrine/metabolic (10%), and respiratory conditions (8%) (chi-square p

Accurate classification of genetic variants is critical for research and patient care. Here, the authors report that population-based associations between rare variants and quantitative endophenotypes for monogenic diseases can provide support for variant pathogenicity.

Introduction The goal of academic mentoring relationships is to enable the mentee to identify/achieve professional advancement. Although mentors of clinician educators (CEs) must understand the criteria for successful career advancement, few have received formal CE mentor training. Methods The National Research Mentoring Network convened an expert panel to develop a 90-minute module for training CE mentors. This module included individual development plans, case studies involving challenges for CE faculty, and examples of the broadened scope of scholarly activity. The workshop was delivered to 26 participants across four institutions and evaluated by a retrospective pre/post survey. Results Using a 7-point scale (1 = very low, 4 = average, 7 = very high), participants rated the overall quality of their CE mentoring as slightly below average preworkshop (M = 3.9) and as above average postworkshop (M = 5.2, p < .001). Areas of greatest self-perceived change in skills on a 7-point scale (1 = not at all skilled, 4 = moderately skilled, 7 = extremely skilled ) included setting clear expectations of the mentoring relationship (pre M = 3.6, post M = 5.1, p < .001), aligning mentor expectations with those of mentees (pre M = 3.6, post M = 5.0, p < .001), and helping mentees set career goals (pre M = 3.9, post M = 5.4, p < .001). Discussion This module trains CE mentors using an interactive and collective problem-solving approach. Workshop participants better defined demonstrable markers for CE progression with potential to impact tailored guidance for mentees.

Background The American Heart Association's framework “ideal cardiovascular health” (CVH) focuses on modifiable risk factors to reduce cardiovascular disease (CVD). Metabolomics provides important pathobiological insights into risk factors and CVD development. We hypothesized that metabolomic signatures associate with CVH status, and that metabolites, at least partially, mediate the association of CVH score with atrial fibrillation (AF) and heart failure (HF). Methods and Results We studied 3056 adults in the FHS (Framingham Heart Study) cohort to evaluate CVH score and incident outcomes of AF and HF. Metabolomics data were available in 2059 participants; mediation analysis was performed to evaluate the mediation of metabolites in the association of CVH score and incident AF and HF. In the smaller cohort (mean age, 54 years; 53% women), CVH score was associated with 144 metabolites, with 64 metabolites shared across key cardiometabolic components (body mass index, blood pressure, and fasting blood glucose) of the CVH score. In mediation analyses, 3 metabolites (glycerol, cholesterol ester 16:1, and phosphatidylcholine 32:1) mediated the association of CVH score with incident AF. Seven metabolites (glycerol, isocitrate, asparagine, glutamine, indole‐3‐proprionate, phosphatidylcholine C36:4, and lysophosphatidylcholine 18:2), partly mediated the association between CVH score and incident HF in multivariable‐adjusted models. Conclusions Most metabolites that associated with CVH score were shared the most among 3 cardiometabolic components. Three main pathways: (1) alanine, glutamine, and glutamate metabolism; (2) citric acid cycle metabolism; and (3) glycerolipid metabolism mediated CVH score with HF. Metabolomics provides insights into how ideal CVH status contributes to the development of AF and HF.

Background Systolic blood pressure increases with age after midlife, particularly in women, and contributes to development of wide pulse pressure hypertension in middle‐aged and older adults. Relative contributions of aortic stiffness and premature wave reflection to increases in pulse pressure remain controversial. Methods and Results We evaluated visit‐specific values and change in key correlates of pulse pressure, aortic characteristic impedance, forward and backward wave amplitude, and global reflection coefficient, at 3 sequential examinations of the Framingham Generation 3 (N=4082), Omni‐2 (N=410), and New Offspring Spouse (N=103) cohorts (53% women). Data were analyzed using repeated‐measures linear mixed models adjusted for age, sex, and risk factor exposures. Pulse pressure increased markedly with age after midlife (age and age‐squared terms, P

Summary: Background: Arterial stiffening is central to the vascular ageing process and a powerful predictor and cause of diverse vascular pathologies and mortality. We investigated age and sex trajectories, regional differences, and global reference values of arterial stiffness as assessed by pulse wave velocity (PWV). Methods: Measurements of brachial-ankle or carotid-femoral PWV (baPWV or cfPWV) in generally healthy participants published in three electronic databases between database inception and August 24th, 2020 were included, either as individual participant-level or summary data received from collaborators (n = 248,196) or by extraction from published reports (n = 274,629). Quality was appraised using the Joanna Briggs Instrument. Variation in PWV was estimated using mixed-effects meta-regression and Generalized Additive Models for Location, Scale, and Shape. Findings: The search yielded 8920 studies, and 167 studies with 509,743 participants from 34 countries were included. PWV depended on age, sex, and country. Global age-standardised means were 12.5 m/s (95% confidence interval: 12.1–12.8 m/s) for baPWV and 7.45 m/s (95% CI: 7.11–7.79 m/s) for cfPWV. Males had higher global levels than females of 0.77 m/s for baPWV (95% CI: 0.75–0.78 m/s) and 0.35 m/s for cfPWV (95% CI: 0.33–0.37 m/s), but sex differences in baPWV diminished with advancing age. Compared to Europe, baPWV was substantially higher in the Asian region (+1.83 m/s, P = 0.0014), whereas cfPWV was higher in the African region (+0.41 m/s, P

Among adolescents, sole use is the most common pattern of e-cigarette use. However, concurrent use of e-cigarettes with other tobacco products is not uncommon and may be associated with high-risk behaviors. We used data from 12,767 participants in the 2019 Youth Risk Behavior Survey to examine the patterns of tobacco product use among youth in the US. First, we examined the prevalence of e-cigarette-specific patterns of tobacco use (nonuse[no tobacco product use], sole use[sole e-cigarette use], dual-use[e-cigarette and one other tobacco product], and poly use[e-cigarette and two or more other tobacco products]). Then, using multivariable Poisson regression, we assessed how the tobacco use patterns were associated with the misuse of nine substances of abuse (alcohol, marijuana, cocaine, ecstasy, hallucinogens, heroin, inhalants, injectables, and methamphetamines).62.9% of youth reported nonuse of any tobacco product. The weighted prevalence of sole e-cigarette use, dual use, and poly use was 23.2%, 4.2%, and 3.3%, respectively. Across all the substances explored, the prevalence was highest among poly users, followed by dual users, sole users, and non-users. Compared to non-users, sole, dual, and poly users had 7.8(95 %CI:6.1–10.0), 14.3(95 %CI:10.8–18.8), and 19.7(95 %CI:15.0–25.9) times higher adjusted prevalence of reporting past-30-day binge drinking, after adjusting for age, sex, race/ethnicity, sexual orientation, and depressive symptoms. This pattern was seen across all the different substances explored. These findings highlight the high prevalence of substance misuse among youth who use tobacco products and the need to educate and counsel on substances of abuse among this population, particularly among poly-tobacco users.

Background A parental history of cardiovascular disease (CVD) confers greater risk of future CVD among offspring. Whether the presence of parental modifiable risk factors contribute to or modify CVD risk in offspring is unclear. Methods and Results We studied 6278 parent–child trios in the multigenerational longitudinal Framingham Heart Study. We assessed parental history of CVD and modifiable risk factors (smoking, hypertension, diabetes, obesity, and hyperlipidemia). Multivariable Cox models were used to evaluate the association of parental history and future CVD among offspring. Among 6278 individuals (mean age 45±11 years), 44% had at least 1 parent with history of CVD. Over a median follow‐up of 15 years, 353 major CVD events occurred among offspring. Parental history of CVD conferred 1.7‐fold increased hazard of future CVD (hazard ratio [HR], 1.71 [95% CI, 1.33–2.21]). Parental obesity and smoking status were associated with higher hazard of future CVD (obesity: HR, 1.32 [95% CI, 1.06–1.64]; smoking: HR, 1.34 [95% CI, 1.07–1.68], attenuated after adjusting for offspring smoking status). By contrast, parental history of hypertension, diabetes, and hypercholesterolemia were not associated with future CVD in offspring (P>0.05 for all). Furthermore, parental risk factors did not modify the association of parental CVD history on future offspring CVD risk. Conclusions Parental history of obesity and smoking were associated with a higher hazard of future CVD in offspring. By contrast, other parental modifiable risk factors did not alter offspring CVD risk. In addition to parental CVD, the presence of parental obesity should prompt a focus on disease prevention.

Abstract Social isolation might be considered as a marker of poor health and higher mortality. The aim of our analysis was to assess the association of social network index (SNI) with incident AF and death. We selected participants aged ≥ 55 years without prevalent AF from the Framingham Heart Study. We evaluated the association between social isolation measured by the Berkman-Syme Social Network Index (SNI), incident AF, and mortality without diagnosed AF. We assessed the risk factor-adjusted associations between SNI (the sum of 4 components: marriage status, close friends/relatives, religious service attendance, social group participation), incident AF, and mortality without AF by using Fine-Gray competing risk regression models. We secondarily examined the outcome of all-cause mortality. We included 3454 participants (mean age 67 ± 10 years, 58% female). During 11.8 ± 5.2 mean years of follow-up, there were 686 incident AF cases and 965 mortality without AF events. Individuals with fewer connections had lower rates of incident AF (P = 0.04) but higher rates of mortality without AF (P = 0.03). Among SNI components, only social group participation was associated with higher incident AF (subdistribution hazards ratio [sHR] 1.35, 95% CI 1.16–1.57, P = 0.0001). For mortality without AF, social group participation (sHR = 0.81, 95% CI 0.71–0.93, P = 0.002) and regular religious service attendance sHR = 0.76, 95% CI 0.67–0.87, P

Abstract Aims Atrial fibrillation (AF) constitutes a major burden to health services, but the importance of incident AF in patients with heart failure (HF) is unclear. We examined the associations between incident AF and hospital utilization in patients with HF. Methods and results In a nationwide matched‐cohort study of HF patients, we identified patients diagnosed with incident AF between 2008 and 2018 in the Danish Heart Failure Registry (N = 4463), and we compared them to matched referents without AF (N = 17 802). Incident AF was associated with a multivariable‐adjusted 4.8‐fold increase (95% CI 4.1–5.6) and 4.3‐fold increase (95% CI 3.9–4.8) in the cumulative incidence of inpatient and outpatient contacts within 30 days, respectively. At 1 year, the cumulative incidence ratios were 1.8 (95% CI 1.7–1.9) and 1.4 (95% CI 1.4–1.5). Incident AF was also associated with increases in the total numbers of inpatient and outpatient hospital contacts within 30 days (multivariable‐adjusted rate ratio 1.4, 95% CI 1.4–1.5, and 1.6, 95% CI 1.6–1.7, respectively). At 1 year, the ratios were 2.2 (95% CI 2.1–2.3) and 2.0 (95% CI 1.9–2.1). The multivariable‐adjusted proportion of bed‐day use among HF patients with incident AF was 10.9‐fold (95% CI 9.3–12.9) higher at 30 days and 5.3‐fold (95% CI 4.3–6.4) higher at 1 year compared with AF‐free referents. Conclusions Incident AF in HF is associated with earlier hospital contact, more hospital contacts, and more hospital bed‐days. More evidence on interventions that may prevent the risk and subsequent burden of AF in HF is urgently needed.

Background Stiffness of the proximal aorta may play a critical role in adverse left ventricular (LV)–vascular interactions and associated LV diastolic dysfunction. In a community‐based sample, we sought to determine the association between proximal aortic stiffness measured by cardiovascular magnetic resonance (CMR) and several clinical measures of LV diastolic mechanics. Methods and Results Framingham Heart Study Offspring adults (n=1502 participants, mean 67±9 years, 54% women) with available 1.5T CMR and transthoracic echocardiographic measures were included. Measures included proximal descending aortic strain and aortic arch pulse wave velocity by CMR (2002–2006) and diastolic function (mitral Doppler E and A wave velocity, E wave area, and LV tissue Doppler e' velocity) by echocardiography (2005–2008). Multivariable linear regression analysis was used to relate CMR aortic stiffness measures to measures of echocardiographic LV diastolic function. All continuous variables were standardized. In multivariable‐adjusted regression analyses, aortic strain was inversely associated with E wave deceleration time (estimated β=−0.10±0.032, P=0.001), whereas aortic arch pulse wave velocity was inversely associated with E/A ratio (estimated β=−0.094±0.027, P=0.0006), E wave area (estimated β=−0.070±0.027, P=0.010), and e' (estimated β=−0.061±0.027, P=0.022), all indicating associations of higher aortic stiffness by CMR with less favorable LV diastolic function. Compared with men, women had a larger inverse relationship between pulse wave velocity and E/A ratio (interaction β=−0.085±0.031, P=0.0064). There was no significant effect modification by age or a U‐shaped (quadratic) relation between aortic stiffness and LV diastolic function measures. Conclusions Higher proximal aortic stiffness is associated with less favorable LV diastolic function. Future studies may clarify temporal relations of aortic stiffness with varying patterns and progression of LV diastolic dysfunction.

Detailed description of the prevalence and sources of e-cigarettes among youth is needed to inform effective regulatory policies. We used the Youth Risk Behavior Surveillance System data (2015–2019) to assess trends in current (past-30-day-use) and frequent (≥10 days in past-30-days) e-cigarette use among United States high schoolers before the COVID-19 pandemic. First, we assessed trends overall and then stratified by participants’ sociodemographic characteristics, use of other tobacco products, and experiences of psychosocial stress. We also evaluated past year quit attempts and the changing sources of e-cigarettes.Our sample size was 41,021 (15,356–2015; 12,873–2017; 12,792–2019). The prevalence of current e-cigarette use increased from 24.0% (95%CI:21.9%–26.3%) in 2015 to 32.7% (30.4%–35.1%) in 2019. The proportion of current users who reported frequent use also increased significantly from 22.6% (20.4%–24.8%) to 45.4% (42.7%–48.2%). Thus, an increasing proportion of US high school students who use e-cigarettes reported frequent use, indicating greater nicotine dependence. The increase in current and frequent e-cigarette use was more pronounced in youth who reported other substance use and psychosocial stressors such as bullying. Between 2017 and 2019, there was a decline in the proportion of youth who bought e-cigarettes online (6.9% to 3.2%) or from convenience stores (22.0% to 16.6%). Conversely, there was an increase in the proportion who borrowed (34.5% to 40.1%) or purchased e-cigarettes through other people (10.7% to 18.0%), indicating that most youth are evading age-related restrictions by obtaining e-cigarettes from other people. Finally, a considerable proportion of youth tobacco users are making quit attempts; 47.6% (45.1%–50.1%) in 2019.

Abstract Background All-cause mortality following atrial fibrillation (AF) has decreased over time. Data regarding temporal trends in causes of death among individuals with AF are scarce. The aim of our study was to analyze temporal trends in cause-specific mortality and predictors for cardiovascular (CVD) and non-CVD deaths among participants with incident AF in the Framingham Heart Study. Methods We categorized all newly diagnosed AF cases according to age at AF diagnosis (

Background: The electronic Framingham Heart Study (eFHS) is an ongoing nested study, which includes FHS study participants, examining associations between health data from mobile devices with cardiovascular risk factors and disease. Objective: To describe application (app) design, report user characteristics, and describe usability and survey response rates. Methods: Eligible FHS participants were consented and offered a smartwatch (Apple Watch), a digital blood pressure (BP) cuff, and the eFHS smartphone app for administering surveys remotely. We assessed usability of the new app using 2 domains (functionality, aesthetics) of the Mobile App Rating Scale (MARS) and assessed survey completion rates at baseline and 3 months. Results: A total of 196 participants were recruited using the enhanced eFHS app. Of these, 97 (49.5%) completed the MARS instrument. Average age of participants was 53 ± 9 years, 51.5% were women, and 93.8% were white. Eighty-six percent of participants completed at least 1 measure on the baseline survey, and 50% completed the 3-month assessment. Overall subjective score of the app was 4.2 ± 0.7 on a scale from 1 to 5 stars. Of those who shared their health data with others, 46% shared their BP and 7.7% shared their physical activity with a health care provider. Conclusion: Participants rated the new, enhanced eFHS app positively overall. Mobile app survey completion rates were high, consistent with positive in-app ratings from participants. These mobile data collection modalities offer clinicians new opportunities to engage in conversations about health behaviors.

OBJECTIVES:. In critically ill patients with neurologic disease, pupil examination abnormalities can signify evolving intracranial pathology. Analgesic and sedative medications (analgosedatives) target pupillary pathways, but it remains unknown how analgosedatives alter pupil findings in the clinical care setting. We assessed dexmedetomidine and other analgosedative associations with pupil reactivity and size in a heterogeneous cohort of critically ill patients with acute intracranial pathology. DESIGN:. Retrospective cohort study. SETTING:. Two neurologic ICUs between 2016 and 2018. PATIENTS:. Critically ill adult patients with pupil measurements within 60 minutes of analgosedative administration. Patients with a history of intrinsic retinal pathology, extracranial injury, inaccessible brain imaging, or no Glasgow Coma Scale (GCS) data were excluded. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We used mixed-effects linear regression accounting for intrapatient correlations and adjusting for sex, age, GCS score, radiographic mass effect, medication confounders, and ambient light. We tested the association between an initiation or increased IV infusion of dexmedetomidine and pupil reactivity (Neurologic Pupil Index [NPi]) and resting pupil size (mm) obtained using NeurOptics NPi—200 (NeurOptics, Irvine, CA) pupillometer. Of our 221 patients with 9,897 pupil observations (median age, 60 [interquartile range, 50–68]; 59% male), 37 patients (166 pupil observations) were exposed to dexmedetomidine. Dexmedetomidine was associated with higher average NPi (β = 0.18 per 1 unit increase in rank-normalized NPi ± 0.04; p < 0.001) and smaller pupil size (β = –0.25 ± 0.05; p < 0.001). Exploratory analyses revealed that acetaminophen was associated with higher average NPi (β = 0.04 ± 0.02; p = 0.02) and that most IV infusion analgosedatives including propofol, fentanyl, and midazolam were associated with smaller pupil size. CONCLUSIONS:. Dexmedetomidine is associated with higher pupil reactivity (high NPi) and smaller pupil size in a cohort of critically ill patients with neurologic injury. Familiarity with expected pupil changes following analgosedative administration is important for accurate interpretation of pupil examination findings, facilitating optimal management of patients with acute intracranial pathology.

Background To support diversity in biomedical science, the American Heart Association launched the Supporting Undergraduate Research Experiences for undergraduate students from underrepresented backgrounds to provide mentorship and high‐level exposure at 5 leading medical institutions. Here we describe the initial formation of the partnership and the alteration made in response to the program to accommodate COVID‐19 safety precautions. Methods and Results We outline how programming shifted from local, in‐person programming in the summer of 2019 to a collaborative, mainly virtual curriculum in 2020 using students’ self‐reported before and after surveys from both 2019 (n=33) and 2020 (n=42). Students from both in‐person (2019) and virtual programs (2020) self‐reported significant gains in scientific proficiency. A qualitative‐directed content analysis of student open‐response questions was performed. Students reported extensive benefits from the 2020 virtual training, including Personal Gains, Research Skills, Thinking and Working Like a Scientist, and Attitudes and Behaviors. Notedly, we observed increases in the Attitudes and Behaviors category. We outline the pros and cons of in‐person and virtual programming and make recommendations moving forward in a postpandemic world with hybrid work and learning systems. Conclusions Our effort informs the development of future undergraduate research training programs, significantly maximizing a hybrid training modality. The American Heart Association Supporting Undergraduate Research Experiences serves as a model for building multi‐institutional partnerships and providing research experiences that overcome institutional barriers and support students' interests, commitment, and ability to persist in science, technology, engineering, and math fields.

Abstract 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.

Abstract Background Adherence to regular outpatient visits is vital to managing noncommunicable diseases (NCDs), a growing burden in low and middle-income countries. We characterized visit adherence among patients with NCDs in rural Haiti, hypothesizing higher poverty and distance from the clinic were associated with lower adherence. Methods We analyzed electronic medical records from a cohort of adults in an NCD clinic in Mirebalais, Haiti (April 2013 to June 2016). Visit adherence was: 1) visit constancy (≥1 visit every 3 months), 2) no gaps in care (> 60 days between visits), 3) ≥1 visit in the last quarter, and 4) ≥6 visits per year. We incorporated an adapted measure of intensity of multidimensional poverty. We calculated distance from clinic as Euclidean distance or self-reported transit time. We used multivariable logistic regressions to assess the association between poverty, distance, and visit adherence. Results We included 463 adult patients, mean age 57.8 years (SE 2.2), and 72.4% women. Over half of patients had at least one visit per quarter (58.1%), but a minority (19.6%) had no gaps between visits. Seventy percent of patients had a visit in the last quarter, and 73.9% made at least 6 visits per year. Only 9.9% of patients met all adherence criteria. In regression models, poverty was not associated with any adherence measures, and distance was only associated with visit in the last quarter (OR 0.87, 95% CI [0.78 to 0.98], p = 0.03) after adjusting for age, sex, and hardship financing. Conclusions Visit adherence was low in this sample of adult patients presenting to a NCD Clinic in Haiti. Multidimensional poverty and distance from clinic were not associated with visit adherence measures among patients seen in the clinic, except for visit in the last quarter. Future research should focus on identifying and addressing barriers to visit adherence.

Background Increased neck circumference, a proxy for upper‐body subcutaneous fat, is associated with cardiovascular risk and metabolic risk factors, accounting for body mass index (BMI) and waist circumference. The association between neck circumference and incident atrial fibrillation (AF) is unclear. The aim of current study was to evaluate the association between neck circumference and incident AF. Methods and Results We selected participants from the Framingham Heart Study aged ≥55 years without diagnosed AF and with available neck circumference, BMI, and waist circumference measurements. We defined high neck circumference as ≥14 inches in women and ≥17 inches in men on the basis of the Contal and O’Quigley changepoint method. We used Fine‐Gray models to estimate subdistribution hazards ratios (sHRs) for the association between neck circumference and incident AF accounting for the competing risk of death. We adjusted models for clinical risk factors. We then additionally adjusted separately for BMI, waist circumference, and height/weight. The study sample included 4093 participants (mean age 64±7 years, 55% female). During 11.2±5.7 mean years of follow‐up, incident AF occurred in 571 participants. High neck circumference was associated with incident AF (sHR for high versus low: 1.58; 95% CI, 1.32–1.90, P

Abstract Introduction: In an era of complex, multi-institutional, team-based science, there is little guidance for the successful creation of effective, collaborative, multisite training programs. Objective: We designed, implemented, and evaluated a multi-institutional Tobacco Regulatory Science (TRS) fellowship representing a scalable program that may be customized for other research areas. Methods: Using a mixed-methods approach, we analyzed program evaluations from trainees enrolled in the first 7 years of the American Heart Association (AHA) Tobacco Regulation and Addiction Center (A-TRAC) fellowship (2014–2021). We also reported the program outcomes, including published TRS manuscripts, independent grant funding, Food and Drug Administration (FDA) Docket comments submitted on TRS topics, TRS oral and poster presentations, research awards, and promotions in the TRS field. Results: Thirty-five unique trainees (49% [n = 17] female, 29% [n = 10] Black) from eight institutions within the A-TRAC network participated in the fellowship since its inception. The trainees reported 74 TRS publications, 78 TRS oral or poster presentations, 25 FDA Docket comment submissions, and 13 funded grant awards. Participant evaluations indicated six areas of programmatic strength: 1) blended instruction medium with webinars and in-person meetings, 2) curricular emphasis on theories of experiential learning, 3) focus on career and professional development, 4) integrated mentorship model, 5) culture of feedback and feedforward to foster successful learning, and 6) focus on recruiting diverse participants. The A-TRAC model stresses experiential education, feedback and feedforward, and peer learning. Conclusions: Our resource-effective, needs-driven program is a reproducible model for institutions interested in developing multisite, virtual research education programs in the era of team science.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

Objective: Atrial fibrillation (AF) may remain undiagnosed until the development of complications. We aimed to examine the epidemiology and racial/ethnic and rural/urban differences in the frequency of newly diagnosed AF manifesting as ischemic stroke in a nationally representative sample of Medicare beneficiaries.Methods: We used a 5% random sample of Medicare claims to identify patients newly diagnosed with AF in 2016. The primary dependent variable was stroke or transient ischemic attack (TIA) in the 7 days prior to the first AF diagnosis, i.e., stroke or TIA as the initial manifestation of AF. We constructed a multivariable logistic regression to quantify the association between race/ethnicity, urban/rural residence, and the primary dependent variable.Results: Among 39,409 patients newly diagnosed with AF (mean age 77 ± 10 years; 58% women; 7.2% Black, 87.8% White, 5.1% others), 2,819 (7.2%) had ischemic stroke or TIA in the 7 days prior to AF diagnosis. Black patients (adjusted OR [95% CI]: 1.21 [1.05, 1.40], vs. White) and urban residents (1.21 [1.08, 1.35], vs. rural) were at increased risk of stroke as the initial manifestation of AF. Racial differences were larger among patients aged ≥75 years, with adjusted ORs of 1.43 (1.19, 1.73) for Black vs. White patients, but non-significant for those aged

Background Atrial fibrillation (AF) commonly occurs in the setting of acute conditions. We aimed to identify the acute conditions associated with secondary AF (AF precipitants) including pneumonia/sepsis, pneumothorax, respiratory failure, myocarditis, pericarditis, alcohol intoxication, thyrotoxicosis, cardiothoracic surgery, other surgery in patients with newly diagnosed AF and determine their association with subsequent oral anticoagulant use. Methods and Results We assembled a cohort of patients in the UMass Memorial Healthcare system with a new diagnosis of AF with and without AF precipitants. We used combinations of International Classification of Diseases, Tenth Revision (ICD‐10) codes, Current Procedural Terminology codes, laboratory values, imaging reports, and physician notes including discharge summary texts to identify AF precipitants. We then manually reviewed the individual charts to validate presence of AF precipitants. The study sample consisted of 185 patients with and 172 patients without AF precipitants. Pneumonia/sepsis, myocardial infarction, respiratory failure, and cardiothoracic surgery were the most common precipitants identified. In multivariable analyses adjusting for age, sex, patient comorbidities, left atrial enlargement, left ventricular ejection fraction, and antiplatelet use, patients with AF precipitants were less likely to receive subsequent anticoagulation therapy at 30 days after the initial AF diagnosis (odds ratio, 0.31; 95% CI, 0.19–0.52). The association was persistent after excluding men with CHA2DS2‐VASc score

Background Performance of existing atrial fibrillation (AF) risk prediction models in poststroke populations is unclear. We evaluated predictive utility of an AF risk model in patients with acute stroke and assessed performance of a fully refitted model. Methods and Results Within an academic hospital, we included patients aged 46 to 94 years discharged for acute ischemic stroke between 2003 and 2018. We estimated 5‐year predicted probabilities of AF using the Cohorts for Heart and Aging Research in Genomic Epidemiology for Atrial Fibrillation (CHARGE‐AF) model, by recalibrating CHARGE‐AF to the baseline risk of the sample, and by fully refitting a Cox proportional hazards model to the stroke sample (Re‐CHARGE‐AF) model. We compared discrimination and calibration between models and used 200 bootstrap samples for optimism‐adjusted measures. Among 551 patients with acute stroke, there were 70 incident AF events over 5 years (cumulative incidence, 15.2%; 95% CI, 10.6%–19.5%). Median predicted 5‐year risk from CHARGE‐AF was 4.8% (quartile 1–quartile 3, 2.0–12.6) and from Re‐CHARGE‐AF was 16.1% (quartile 1–quartile 3, 8.0–26.2). For CHARGE‐AF, discrimination was moderate (C statistic, 0.64; 95% CI, 0.57–0.70) and calibration was poor, underestimating AF risk (Greenwood‐Nam D’Agostino chi‐square, P

Rationale & Objective: The relation of vascular stiffness, endothelial function, and kidney function is incompletely elucidated in African Americans. Our hypothesis was that increased vascular stiffness and endothelial dysfunction are associated with low estimated glomerular filtration rate (eGFR) and albuminuria in African Americans. Study Design: Cross-sectional cohort analysis of data from the Jackson Heart Study. Settings & Patients: 2,244 Jackson Heart Study participants (2012-2017 after Exam 3) who had undergone noninvasive hemodynamic assessment using arterial tonometry. Predictors: Baseline carotid-femoral pulse wave velocity, pulsatile hemodynamics forward wave amplitude, and hyperemic brachial artery flow were measured. Reduced eGFR was defined as eGFR between 15 and 60 mL/min/1.73 m2. Outcomes: Prevalent albuminuria, urinary albumin-creatinine ratio. Analytical Approach: 2-sample t test for continuous variables and χ2 test for categorical variables in addition to logistic and linear regression models to assess the risk for chronic kidney disease with each proposed hemodynamic variable. Results: Among 2,244 participants, mean age was 66 ± 11 years and 64% were women. Reduced eGFR was present in 233 (10.4%), and elevated urinary albumin-creatinine ratio, in 232 (10.4%). In multivariable-adjusted analyses, higher carotid-femoral pulse wave velocity was associated with the presence of reduced eGFR (OR, 1.37 [95% CI, 1.08-1.75] per SD; P = 0.01) and with prevalent albuminuria (OR, 1.66 [95% CI, 1.32-2.11]; P < 0.001). Higher forward wave amplitude was significantly associated with prevalent albuminuria (OR, 1.37 [95% CI, 1.14-1.65]; P = 0.001). Limitations: Cross-sectional analyses cannot inform causality. Conclusions: Higher arterial stiffness and pulsatility are associated with higher odds of reduced eGFR in African Americans. Future studies should focus on whether improving arterial stiffness contributes to kidney protection in African Americans.

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.

Background Although tobacco product use and transitions have been characterized in the general population, few studies have focused on individuals with established cardiovascular disease (CVD) in a population‐based sample. Methods and Results We examined tobacco use prevalence and longitudinal patterns of tobacco product transitions in adults (≥18 years) of the nationally representative PATH (Population Assessment of Tobacco and Health) study, from 2013 to 2014 (Wave 1) through 2016 to 2018 (Wave 4). Prevalent CVD was classified through self‐report of having had a heart attack, heart failure, stroke, or other heart condition. Factors associated with tobacco product use and transitions were investigated using survey logistic regression. We examined 2615 participants with self‐reported CVD at Wave 1. Overall, 28.9% reported current tobacco use, equating to ≈6.2 million adults in the United States with prevalent CVD and current tobacco use. Among adults with CVD who are current tobacco users, the most commonly used product was cigarettes (82.8%), followed by any type of cigar (23.7%), and e‐cigarette use (23.3%). E‐cigarette use without concurrent cigarette use among participants with prevalent CVD was uncommon (1.1%). Factors associated with tobacco use were younger age, male sex, had lower education level, and lack of knowledge about the association between smoking and CVD. Men with prevalent CVD were less likely to use e‐cigarettes compared with women (odds ratio [OR], 0.7; 95% CI, 0.5–0.9). Among cigarette users with CVD, transition rates between Waves 1 and 4 demonstrated

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.

Blood biomarkers for dementia have the potential to identify preclinical disease and improve participant selection for clinical trials. Machine learning is an efficient analytical strategy to simultaneously identify multiple candidate biomarkers for dementia. We aimed to identify important candidate blood biomarkers for dementia using three machine learning models. We included 1642 (mean 69 ± 6 yr, 53% women) dementia-free Framingham Offspring Cohort participants attending examination, 7 who had available blood biomarker data. We developed three machine learning models, support vector machine (SVM), eXtreme gradient boosting of decision trees (XGB), and artificial neural network (ANN), to identify candidate biomarkers for incident dementia. Over a mean 12 ± 5 yr follow-up, 243 (14.8%) participants developed dementia. In multivariable models including all 38 available biomarkers, the XGB model demonstrated the strongest predictive accuracy for incident dementia (AUC 0.74 ± 0.01), followed by ANN (AUC 0.72 ± 0.01), and SVM (AUC 0.69 ± 0.01). Stepwise feature elimination by random sampling identified a subset of the nine most highly informative biomarkers. Machine learning models confined to these nine biomarkers showed improved model predictive accuracy for dementia (XGB, AUC 0.76 ± 0.01; ANN, AUC 0.75 ± 0.004; SVM, AUC 0.73 ± 0.01). A parsimonious panel of nine candidate biomarkers were identified which showed moderately good predictive accuracy for incident dementia, although our results require external validation.

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

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 Frailty is associated bidirectionally with cardiovascular disease. However, the relations between frailty and atrial fibrillation (AF) have not been fully elucidated. Methods and Results Using the FHS (Framingham Heart Study) Offspring cohort, we sought to examine both the association between frailty (2005–2008) and incident AF through 2016 and the association between prevalent AF and frailty status (2011–2014). Frailty was defined using the Fried phenotype. Models adjusted for age, sex, and smoking. Cox proportional hazards models, adjusted for competing risk of death, assessed the association between prevalent frailty and incident AF. Logistic regression models assessed the association between prevalent AF and new‐onset frailty. For the incident AF analysis, we included 2053 participants (56% women; mean age, 69.7±6.9 years). By Fried criteria, 1018 (50%) were robust, 903 (44%) were prefrail, and 132 (6%) were frail. In total, 306 incident cases of AF occurred during an average 9.2 (SD, 3.1) follow‐up years. After adjustment, there was no statistically significant association between prevalent frailty status and incident AF (prefrail versus robust: hazard ratio [HR], 1.22 [95% CI, 0.95–1.55]; frail versus robust: HR, 0.92 [95% CI, 0.57–1.47]). At follow‐up, there were 111 new cases of frailty. After adjustment, there was no statistically significant association between prevalent AF and new‐onset frailty (odds ratio, 0.48 [95% CI, 0.17–1.36]). Conclusions Although a bidirectional association between frailty and cardiovascular disease has been suggested, we did not find evidence of an association between frailty and AF. Our findings may be limited by sample size and should be further explored in other populations.

Background Measures of vascular dysfunction are related to adverse cardiovascular disease (CVD) outcomes in non‐Hispanic, White populations; however, data from Black individuals are limited. We aimed to investigate the associations between novel hemodynamic measures and prevalent CVD in a sample of Black individuals. Methods and Results Among older Black participants of the Jackson Heart Study, we assessed noninvasive vascular hemodynamic measures using arterial tonometry and Doppler ultrasound. We assessed 5 measures of aortic stiffness and wave reflection (carotid‐femoral pulse wave velocity, pulse wave velocity ratio, forward pressure wave amplitude, central pulse pressure, and augmentation index), and 2 measures of microvascular function (baseline and hyperemic brachial flow velocity). Using multivariable logistic regression models, we examined the relations between vascular hemodynamic measures and prevalent CVD. In models adjusted for traditional CVD risk factors, higher carotid‐femoral pulse wave velocity (odds ratio [OR],1.25; 95% CI, 1.01–1.55; P=0.04), lower augmentation index (OR, 0.84; 95% CI, 0.70–0.99; P=0.05), and lower hyperemic brachial flow velocity (OR, 0.77; 95% CI, 0.65–0.90; P=0.001) were associated with higher odds of CVD. After further adjustment for hypertension treatment, lower augmentation index (OR, 0.84; 95% CI, 0.70–0.99; P=0.04) and hyperemic brachial flow velocity (OR, 0.79; 95% CI, 0.67–0.94; P=0.006), but not carotid‐femoral pulse wave velocity (OR, 1.23; 95% CI, 0.99–1.051; P=0.06), were associated with higher odds of CVD. Conclusions In a sample of older Black individuals, more severe microvascular damage and aortic stiffness were associated with prevalent CVD. Further research on hemodynamic mechanisms that contribute to cardiovascular risk among older Black individuals is merited.

Aims: Atrial fibrillation (AF) is a public health problem and its prevalence is increasing worldwide. Electronic cohorts, with large electrocardiogram (ECG) databases linked to mortality data, can be useful in determining prognostic value of ECG abnormalities. Our aim is to evaluate the risk of mortality in patients with AF from Brazil. Methods: This observational retrospective study of primary care patients was developed with the digital ECG database from the Telehealth Network of Minas Gerais, Brazil. ECGs performed from 2010 to 2017 were interpreted by cardiologists and the University of Glasgow automated analysis software. An electronic cohort was obtained linking data from ECG exams and those from a national mortality information system, using standard probabilistic linkage methods. We considered only the first ECG of each patient. Patients under 16 years were excluded. Hazard ratios (HR) for mortality were adjusted for demographic and self-reported clinical factors and estimated with Cox regression. Results: From a dataset of 1,773,689 patients, 1,558,421 were included, mean age 51.6 years; 40.2% male. There were 3.34% deaths from all causes in 3.68 years of median follow up. The prevalence of AF was 1.33%. AF was an independent risk factor for all-cause mortality (HR 2.10, 95%CI 2.03–2.17) and cardiovascular mortality (HR 2.06, 95%CI 1.86–2.29). Females with AF had a higher risk of overall and cardiovascular mortality compared with males (p < 0.001). Conclusions: AF was a strong predictor of cardiovascular and all-cause mortality in a primary care population, with increased risk in women. Condensed abstract To assess risk of mortality in AF patients, an electronic cohort was obtained linking data from ECG exams of Brazilian primary care patients and a national mortality information system. From 1,558,421 patients, AF (prevalence 1.33%) carried a higher risk of overall and cardiovascular mortality, with increased risk in women. What’s New This is the first study with a large Brazilian electronic cohort to evaluate the risk of mortality linked to AF in primary care patients. AF patients from a Brazilian primary care population had a higher risk of death for all causes (HR 2.10, 95%CI 2.03–2.17) and cardiovascular mortality (HR 2.06, 95%CI 1.86–2.29). Female patients with AF had an increased risk of overall and cardiovascular mortality compared with male patients (p < 0.001).

Background Myocardial infarction is an important cause of morbidity and mortality in both men and women. Atypical or the absence of symptoms, more prevalent among women, may contribute to unrecognized myocardial infarctions and missed opportunities for preventive therapies. The aim of this research is to investigate sex‐based differences of undiagnosed myocardial infarction in the general population. Methods and Results In the Lifelines Cohort Study, all individuals ≥18 years with a normal baseline ECG were followed from baseline visit till first follow‐up visit (≈5 years, n=97 203). Individuals with infarct‐related changes between baseline and follow‐up ECGs were identified. The age‐ and sex‐specific incidence rates were calculated and sex‐specific cardiac symptoms and predictors of unrecognized myocardial infarction were determined. Follow‐up ECG was available after a median of 3.8 (25th and 75th percentile: 3.0–4.6) years. During follow‐up, 198 women experienced myocardial infarction (incidence rate 1.92 per 1000 persons‐years) compared with 365 men (incidence rate 3.30; P