Bidirectional Association Between Atrial Fibrillation and Myocardial Infarction, and Relation to Mortality in the Framingham Heart Study.

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.

Incidence and prognostic significance of newly-diagnosed atrial fibrillation among older U.S. veterans hospitalized with COVID-19.

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.

Association Between Electrocardiographic Age and Cardiovascular Events in Community Settings: The Framingham Heart Study.

BACKGROUND: Deep neural networks have been used to estimate age from ECGs, the electrocardiographic age (ECG-age), which predicts adverse outcomes. However, this prediction ability has been restricted to clinical settings or relatively short periods. We hypothesized that ECG-age is associated with death and cardiovascular outcomes in the long-standing community-based FHS (Framingham Heart Study). METHODS: We tested the association of ECG-age with chronological age in the FHS cohorts in ECGs from 1986 to 2021. We calculated the gap between chronological and ECG-age (Δage) and classified individuals as having normal, accelerated, or decelerated aging, if Δage was within, higher, or lower than the mean absolute error of the model, respectively. We assessed the associations of Δage, accelerated and decelerated aging with death or cardiovascular outcomes (atrial fibrillation, myocardial infarction, and heart failure) using Cox proportional hazards models adjusted for age, sex, and clinical factors. RESULTS: The study population included 9877 FHS participants (mean age, 55±13 years; 54.9% women) with 34 948 ECGs. ECG-age was correlated to chronological age (r=0.81; mean absolute error, 9±7 years). After 17±8 years of follow-up, every 10-year increase of Δage was associated with 18% increase in all-cause mortality (hazard ratio [HR], 1.18 [95% CI, 1.12-1.23]), 23% increase in atrial fibrillation risk (HR, 1.23 [95% CI, 1.17-1.29]), 14% increase in myocardial infarction risk (HR, 1.14 [95% CI, 1.05-1.23]), and 40% increase in heart failure risk (HR, 1.40 [95% CI, 1.30-1.52]), in multivariable models. In addition, accelerated aging was associated with a 28% increase in all-cause mortality (HR, 1.28 [95% CI, 1.14-1.45]), whereas decelerated aging was associated with a 16% decrease (HR, 0.84 [95% CI, 0.74-0.95]). CONCLUSIONS: ECG-age was highly correlated with chronological age in FHS. The difference between ECG-age and chronological age was associated with death, myocardial infarction, atrial fibrillation, and heart failure. Given the wide availability and low cost of ECG, ECG-age could be a scalable biomarker of cardiovascular risk.

The bidirectional association between atrial fibrillation and myocardial infarction.

Atrial fibrillation (AF) is associated with an increased risk of myocardial infarction (MI) and vice versa. This bidirectional association relies on shared risk factors as well as on several direct and indirect mechanisms, including inflammation, atrial ischaemia, left ventricular remodelling, myocardial oxygen supply-demand mismatch and coronary artery embolism, through which one condition can predispose to the other. Patients with both AF and MI are at greater risk of stroke, heart failure and death than patients with only one of the conditions. In this Review, we describe the bidirectional association between AF and MI. We discuss the pathogenic basis of this bidirectional relationship, describe the risk of adverse outcomes when the two conditions coexist, and review current data and guidelines on the prevention and management of both conditions. We also identify important gaps in the literature and propose directions for future research on the bidirectional association between AF and MI. The Review also features a summary of methodological approaches for the study of bidirectional associations in population-based studies.

The association between eicosanoids and incident atrial fibrillation in the Framingham Heart Study.

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 < 0.05 were considered significant. In total, 2676 AF-free individuals (mean age 66 ± 9 years, 56% females) were followed for mean 10.8 ± 3.4 years; 351 participants developed incident AF. Six eicosanoids were associated with incident AF after adjusting for multiple testing (FDR < 0.05). A joint score was built from the top eicosanoids weighted by their effect sizes, which was associated with incident AF (HR = 2.72, CI = 1.71-4.31, P = 2.1 × 10-5). In conclusion, six eicosanoids were associated with incident AF after adjusting for clinical risk factors for AF.

The association between social network index, atrial fibrillation, and mortality in the Framingham Heart Study.

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 < 0.0001) were associated with lower risk of death. Social isolation was associated with a higher rate of mortality without diagnosed AF. In contrast to our hypothesis, we observed that poor social connectedness was associated with a lower rate of incident AF. This finding should be interpreted cautiously since there were very few participants in the lowest social connectedness group. Additionally, the seemingly protective effect of social isolation on AF incidence may be simply an artifact of the strong association between social isolation and increased mortality rate in combination with the large number of deaths as compared to AF events in our study. Further study is warranted.

Neck Circumference and Risk of Incident Atrial Fibrillation in the Framingham Heart Study.

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<0.0001). The association remained significant after adjustment for BMI (sHR, 1.51; 95% CI, 1.21-1.89; P=0.0003), waist circumference (sHR, 1.47; 95% CI, 1.18-1.83; P<0.0001), and height/weight (sHR, 1.37; 95% CI, 1.09-1.72; P=0.007). Conclusions High neck circumference was associated with incident AF adjusting for traditional adiposity measures such as BMI and waist circumference.

Temporal trends in cause-specific mortality among individuals with newly diagnosed atrial fibrillation in the Framingham Heart Study.

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 (< 70, 70 to < 80, and ≥ 80 years) and epoch of AF diagnosis (< 1990, 1990-2002, and ≥ 2003). We followed participants until death or the last follow-up. We categorized death causes into CVD, non-CVD, and unknown causes. For each age group, we tested for trends in the cumulative incidence of cause-specific death across epochs. We fit multivariable Fine-Gray models to assess subdistribution hazard ratios (HR) between clinical risk factors at AF diagnosis and cause-specific mortality. RESULTS: We included 2125 newly diagnosed AF cases (mean age 75.5 years, 47.8% women). During a median follow-up of 4.8 years, 1657 individuals with AF died. There was evidence of decreasing CVD mortality among AF cases diagnosed < 70 years and 70 to < 80 years (ptrend < 0.001) but not ≥ 80 years (p = 0.76). Among the cases diagnosed < 70 years, the cumulative incidence of CVD death at 75 years was 67.7% in epoch 1 and 13.9% in epoch 3; among those 70 to < 80 years, the incidence at 85 years was 58.9% in epoch 1 and 18.9% in epoch 3. Advancing age (HR per 1 SD increase 6.33, 95% CI 5.44 to 7.37), prior heart failure (HR 1.49, 95% CI 1.14-1.94), and prior myocardial infarction (HR 1.44, 95% CI 1.15-1.80) were associated with increased rate of CVD death. CONCLUSIONS: In this community-based cohort, CVD mortality among AF cases decreased over time. Most deaths in individuals with AF are no longer CVD-related, regardless of age at AF diagnosis.

Relations of arterial stiffness and endothelial dysfunction with incident venous thromboembolism.

INTRODUCTION: Association between arterial vascular dysfunction and risk of venous thromboembolism (VTE) is uncertain. We determined the associations between comprehensive measures of arterial vascular function and risk of incident VTE in a community-based cohort study with robust longitudinal follow-up. MATERIALS AND METHODS: In the Framingham Heart Study Original, Offspring, Third Generation, and Omni cohorts, we measured carotid-femoral pulse wave velocity and central pulse pressure (n = 8261, age 51.5 ± 15.5 years, 54% women), flow-mediated dilation and hyperemic velocity (n = 6540, age 47.9 ± 14.1 years, 54% women), and peripheral arterial tonometry ratio (n = 4998, age 54.3 ± 16.0 years, 52% women). Deep venous thrombosis and pulmonary embolism were diagnosed with imaging studies and adjudicated by three Framingham Heart Study physicians. RESULTS AND CONCLUSIONS: The rate of incident VTE was 1.6-2.1 per 1000 person-years during mean follow-up of 8.5-11.2 years. In age- and sex-adjusted Cox proportional hazards regression models, carotid-femoral pulse wave velocity was associated with increased risk of VTE (HR 1.32, 95% CI 1.05-1.66, p = 0.02), however the association was no longer statistically significant after multivariable adjustment (HR 1.24, 95% CI 0.96-1.61, p = 0.10). None of the other vascular variables were associated with the risk of VTE in any of the models. In our comprehensive examination of arterial vascular function and risk of VTE, we did not observe any association between select arterial function measures and risk of VTE after multivariable adjustment.

P-wave signal-averaged electrocardiography: Reference values, clinical correlates, and heritability in the Framingham Heart Study.

BACKGROUND: P-wave signal-averaged electrocardiography (P-SAECG) quantifies atrial electrical activity. P-SAECG measures and their clinical correlates and heritability have had limited characterization in community-based cohorts. OBJECTIVE: The purpose of this study was to (1) establish reference values; (2) identify clinical risk factors associated with P-SAECG; and (3) estimate genetic heritability for P-SAECG traits. METHODS: We performed P-SAECG in 2 generations of Framingham Heart Study participants. We performed backward elimination regression models to assess associations of clinical factors with each SAECG trait (P-wave [PW] duration, root mean square voltage in terminal 40 ms [RMS40], terminal 30 ms RMS30, terminal 20 ms RMS20, RMS PW, and PW integral). We estimated the adjusted genetic heritability of P-SAECG measures using the Sequential Oligogenic Linkage Analysis Routines (SOLAR) program. RESULTS: We included 4307 participants (age 55 ± 14 years; 56% female). The reference values were derived from 1752 participants without cardiovascular risk factors. Median (2.5th percentile; 97.5th percentile) total PW duration was 118 ms (93; 146) in women and 128 ms (104; 158) in men in the reference sample, and 121 ms (94; 151) in women and 129 ms (103; 159) in the entire study cohort (broad sample). In the broad sample, after adjusting for age and sex, total PW duration was positively associated with height, weight, prevalent heart failure, history of atrial fibrillation (AF), and atrioventricular node blockers, and negatively associated with smoking, waist circumference, heart rate, and diabetes. The estimated heritability of P-SAECG traits was moderate, ranging from 11.9% for RMS30 to 24.9% for PW integral. CONCLUSION: P-SAECG traits are associated with multiple AF-related risk factors and are moderately heritable.

New biomarkers from multiomics approaches: improving risk prediction of atrial fibrillation.

Atrial fibrillation (AF) is a common cardiac arrhythmia leading to many adverse outcomes and increased mortality. Yet the molecular mechanisms underlying AF remain largely unknown. Recent advances in high-throughput technologies make large-scale molecular profiling possible. In the past decade, multiomics studies of AF have identified a number of potential biomarkers of AF. In this review, we focus on the studies of multiomics profiles with AF risk. We summarize recent advances in the discovery of novel biomarkers for AF through multiomics studies. We also discuss limitations and future directions in risk assessment and discovery of therapeutic targets for AF.

Association Between Frailty and Atrial Fibrillation in Older Adults: The Framingham Heart Study Offspring Cohort.

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.

Evaluation of a Multi-Session Group Designed to Prevent Commercial Sexual Exploitation of Minors: The "My Life My Choice" Curriculum.

The commercial sexual exploitation (CSE) of children is a consequential public health and criminal justice problem, but no CSE prevention programs have been evaluated. The Boston-based My Life My Choice (MLMC) program offers a multisession psychoeducation group to girls who are identified as "at-disproportionate-risk" for CSE victimization and trains other agencies throughout the U.S. to offer this curriculum. The curriculum was designed to improve knowledge about the commercial sex industry and shift-related attitudes and behaviors. The current project was a multi-year, multi-site evaluation to assess the effectiveness of the MLMC prevention group. Using a one-group longitudinal design, changes in participant behavior and CSE knowledge were measured at baseline (n = 354), upon group completion (n = 296), and 3 months after group completion (n = 241). The sample was 95% female-identified, 28% Black/African American, 26% White/non-Hispanic, 25% Hispanic/Latina, and 22% other race. The mean age of participants was 15.6 years old. Approximately 28% identified as bisexual, and 10% identified as lesbian, asexual, pansexual, or other. In multivariable-adjusted models, participants reported fewer episodes of sexually explicit behavior at follow up as compared to baseline (relative risk [RR]: 0.52, 95% confidence interval [CI]: 0.37-0.72 at Follow-up 1, and 0.53, 95% CI: 0.35-0.82 at Follow-up 2). Participants were 24% less likely to report dating abuse at Follow-up 2 as compared to baseline (p = .06). In addition, as compared to baseline, participants were 40% more likely to have given help or information about CSE to a friend at Follow-up 2, and participants demonstrated increased knowledge and awareness about CSE and its harms over the follow-up period. Although additional evaluation using a comparison group and long-term follow up would increase confidence that observed changes are attributable to the group instead of other factors, results suggest that the MLMC curriculum may be effective in reducing the risk of CSE and improving other conditions for youth who are at-disproportionate-risk of CSE.

Association Between Leptin, Cognition, and Structural Brain Measures Among "Early" Middle-Aged Adults: Results from the Framingham Heart Study Third Generation Cohort.

BACKGROUND: There is growing interest in the pathophysiological processes of preclinical Alzheimer's disease (AD), including the potential role of leptin. Human studies have shown that both low and high levels of leptin can be associated with worse neurocognitive outcomes, suggesting this relationship may be moderated by another risk factor. OBJECTIVE: We examined the association between plasma leptin levels and both neuropsychological test performance and structural neuroimaging and assessed whether body mass index (BMI) is an effect modifier of these associations. METHODS: Our study sample consisted of 2,223 adults from the Framingham Heart Study Third Generation Cohort (average age = 40 years, 53% women). RESULTS: Among the entire sample, there was no association between leptin and any of the neuropsychological domain measures or any of the MRI brain volume measures, after adjustment for BMI, APOE4, and other clinical factors. However, we did observe that BMI category was an effect modifier for the association between leptin and verbal memory (p for interaction = 0.03), where higher levels of leptin were associated with better performance among normal weight participants (BMI 18.5-24.9) kg/m2 (beta = 0.12, p = 0.02). No association was observed between leptin level and verbal memory test performance among participants who were overweight or obese. CONCLUSION: These findings suggest that the association between leptin and cognitive function is moderated by BMI category. Prospective examination of individuals transitioning from middle age to older adulthood will help to clarify the contribution of leptin to AD and other neurodegenerative conditions.

Novel Risk Modeling Approach of Atrial Fibrillation With Restricted Mean Survival Times: Application in the Framingham Heart Study Community-Based Cohort.

BACKGROUND: Risk prediction models for atrial fibrillation (AF) do not give information about when AF might develop. Restricted mean survival time (RMST) quantifies risk into the time domain. Our objective was to use RMST to re-express individualized AF risk predictions. METHODS AND RESULTS: We included AF-free participants from the Framingham Heart Study community-based cohorts. We predicted new-onset AF over 10-year follow-up according to baseline covariates: age, height, weight, systolic blood pressure, diastolic blood pressure, current smoking, antihypertensive treatment, diabetes mellitus, prevalent heart failure, and prevalent myocardial infarction. First, we fitted a Cox regression model and estimated the 10-year predicted risk of AF. Second, we fitted an RMST model and estimated the predicted mean time free of AF and alive over a time horizon of 10 years. We included 7586 AF-free participants contributing to 11 088 examinations (mean age 61±11 years, 44% were men). During 10-year follow-up, 822 participants developed AF. The Cox and RMST models were in agreement regarding the direction, strength, and statistical significance of associations for all covariates. Low (<5%), intermediate (5%-15%), and high (>15%) 10-year predicted risk of AF corresponded to predicted mean time alive and free of AF of 9.9, 9.6, and 8.8 years, respectively. A 60-year-old woman with a body mass index of 25 kg/m2, no use of hypertension treatment and no history of heart failure had a predicted mean time alive and free of AF of 9.9 years, whereas a 70-year-old man with a body mass index of 30 kg/m2, use of hypertension treatment, and with prevalent heart failure had a predicted mean time alive and free of AF of 7.9 years. CONCLUSIONS: The RMST can be used to develop risk prediction models to express results in a time scale. RMST may offer a complementary risk communication tool for AF in clinical practice.

Protein Biomarkers and Risk of Atrial Fibrillation: The FHS.

BACKGROUND: Identification of protein biomarkers associated with incident atrial fibrillation (AF) may improve the understanding of the pathophysiology, risk prediction, and development of new therapeutics for AF. We examined the associations between 85 protein biomarkers and incident AF. METHODS: We included participants ≥50 years of age from the FHS (Framingham Heart Study) Offspring and Third Generation cohorts, who had 85 fasting plasma proteins measured using Luminex xMAP platform. Hazard ratios (per 1 SD increment of rank-normalized biomarker [hazard ratio]) and 95% CIs for incident AF were calculated using Cox regression models adjusted for age, sex, height, weight, current smoking, systolic blood pressure, diastolic blood pressure, hypertension treatment, diabetes mellitus, valvular heart disease, prevalent myocardial infarction, and prevalent heart failure. We used the false discovery rate to account for multiple testing. RESULTS: The study sample comprised 3378 participants (54% women) with mean (SD) age of 61.5 (8.4) years. In total, 401 developed AF over a mean follow-up of 12.3±3.8 years. We observed lower hazard of incident AF associated with higher mean levels of IGF1 (insulin-like growth factor 1; hazard ratio per 1 SD increment in protein level, 0.84 [95% CI, 0.76-0.93]), and higher hazard of incident AF associated with higher mean levels of both IGFBP1 (insulin-like growth factor-binding protein 1; hazard ratio, 1.24 [95% CI, 1.1-1.39]) and NT-proBNP (N-terminal pro-B-type natriuretic peptide; hazard ratio, 1.73 [95% CI, 1.52-1.96]). CONCLUSIONS: Decreased levels of IGF1 and increased levels of IGFBP1 and NT-proBNP were associated with higher risk of incident AF.

A longitudinal evaluation of a survivor-mentor program for child survivors of sex trafficking in the United States.

BACKGROUND: Commercial sexual exploitation (CSE) of children is a significant public health and criminal justice problem, but there are few evaluated models of CSE mentorship service. OBJECTIVES: To assess whether youth who participated in a CSE survivor-mentor program evidenced changes in CSE victimization, dating abuse victimization, health, delinquency, social support, and coping during the year following their enrollment in the program. PARTICIPANTS: 41 youth who were CSE-experienced at baseline (72%) or determined very high risk, 11-18 years old, 95% female, 58% heterosexual, 29% White, 29% Hispanic, and 42% other races/ethnicities. SETTING: An urban city in the Northeast United States. METHODS: We used a one-group repeated measures design and a GEE analysis. Data were collected at baseline, six months after baseline (71% follow-up) and 12 months after baseline (68% follow-up). RESULTS: At baseline 72% could be characterized as CSE-experienced, while at 6 months the percentage decreased to 24% (p < 0.001) and at 12 months to 14% (p < 0.001). After 6 months of receiving survivor-mentor services, youth were less likely to have experienced CSE, engaged in sexually explicit behavior (SEB), used illicit drugs, engaged in delinquent behavior, been arrested or detained by police, and they had better social support and coping skills. After 12 months, youth were less likely to have experienced CSE, to have engaged in delinquent behavior, be arrested or detained by police, and had improved coping skills. CONCLUSION: Findings demonstrate that youth who received survivor-mentor services from MLMC experienced improved well-being and less drug use, delinquent behavior, and exploitation.

Relationship of Cancer to Brain Aging Markers of Alzheimer's Disease: The Framingham Heart Study.

BACKGROUND: Previous studies have demonstrated a strong inverse association between cancer and risk of Alzheimer's disease (AD). This study aimed to further investigate this association by examining measures of cognitive performance and neuroimaging. METHODS: Neuropsychological (NP) test batteries consisting of quantitative measures of memory and executive function and volumetric brain magnetic resonance imaging (MRI) scans measuring brain and white-matter hyperintensity volumes were administered to 2,043 dementia-free participants (54% women) in the Framingham Heart Study (FHS) Offspring cohort from 1999-2005. History of cancer was assessed at examination visits and through hospital records. Linear regression was used to examine the association between cancer history and NP/MRI variables. RESULTS: There were 252 and 1,791 participants with and without a previous history of cancer, respectively. Cancer survivors had an average time between diagnosis and NP/MRI exam of 9.8 years. History of any invasive cancer was associated with better executive function (Beta=0.16, p=0.04) but not memory function. Non-invasive cancer was not associated with any change in cognitive performance. Patients with prostate cancer had larger frontal brain volumes (Beta=4.13, p=0.03). Cancer history was not associated with any other MRI measure. CONCLUSIONS: We did not find any strong evidence linking cancer to cognitive or neuroimaging biomarkers that would explain a lower risk of subsequent AD, although a previous FHS study demonstrated a strong inverse association between cancer and risk of AD. Future work should examine the association between cancer and other biomarkers of AD as well as more sensitive metrics of AD-related brain aging markers.

Distribution of cerebral microbleeds in the East and West: Individual participant meta-analysis.

OBJECTIVE: We investigated differences in the anatomical distribution of cerebral microbleeds (CMBs) on MRI, hypothesized to indicate the type of underlying cerebral small vessel disease (SVD), between Eastern and Western general populations. METHODS: We analyzed data from 11 studies identified by a PubMed search between 1996 and April 2014 according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data. Study quality measures indicated low or medium risk of bias. We included stroke-free participants from populations aged between 55 and 75 years, categorized by geographic location (Eastern or Western). We categorized CMB distribution (strictly lobar, deep and/or infratentorial [D/I], or mixed [i.e., CMBs located in both lobar and D/I regions]). We tested the hypothesis that Eastern and Western populations have different anatomical distributions of CMBs using multivariable mixed effects logistic regression analyses adjusted for age, sex, and hypertension and clustering by institution. RESULTS: Among 8,595 stroke-free individuals (mean age [SD] 66.7 [5.6] years; 48% male; 42% from a Western population), 624 (7.3%) had CMBs (strictly lobar in 3.1%; D/I or mixed in 4.2%). In multivariable mixed effects models, Eastern populations had higher odds of D/I or mixed CMBs (adjusted odds ratio 2.78, 95% confidence interval [CI] 1.77-4.35) compared to Western populations. Eastern populations had a higher number of D/I or mixed CMBs (adjusted prevalence ratio 2.83, 95% CI 1.27-6.31). CONCLUSIONS: Eastern and Western general populations have different anatomical distributions of CMBs, suggesting differences in the spectrum of predominant underlying SVDs, with potential implications for SVD diagnosis and treatment.

Lifetime risk of atrial fibrillation according to optimal, borderline, or elevated levels of risk factors: cohort study based on longitudinal data from the Framingham Heart Study.

OBJECTIVE: To examine the association between risk factor burdens-categorized as optimal, borderline, or elevated-and the lifetime risk of atrial fibrillation. DESIGN: Community based cohort study. SETTING: Longitudinal data from the Framingham Heart Study. PARTICIPANTS: Individuals free of atrial fibrillation at index ages 55, 65, and 75 years were assessed. Smoking, alcohol consumption, body mass index, blood pressure, diabetes, and history of heart failure or myocardial infarction were assessed as being optimal (that is, all risk factors were optimal), borderline (presence of borderline risk factors and absence of any elevated risk factor), or elevated (presence of at least one elevated risk factor) at index age. MAIN OUTCOME MEASURE: Lifetime risk of atrial fibrillation at index age up to 95 years, accounting for the competing risk of death. RESULTS: At index age 55 years, the study sample comprised 5338 participants (2531 (47.4%) men). In this group, 247 (4.6%) had an optimal risk profile, 1415 (26.5%) had a borderline risk profile, and 3676 (68.9%) an elevated risk profile. The prevalence of elevated risk factors increased gradually when the index ages rose. For index age of 55 years, the lifetime risk of atrial fibrillation was 37.0% (95% confidence interval 34.3% to 39.6%). The lifetime risk of atrial fibrillation was 23.4% (12.8% to 34.5%) with an optimal risk profile, 33.4% (27.9% to 38.9%) with a borderline risk profile, and 38.4% (35.5% to 41.4%) with an elevated risk profile. Overall, participants with at least one elevated risk factor were associated with at least 37.8% lifetime risk of atrial fibrillation. The gradient in lifetime risk across risk factor burden was similar at index ages 65 and 75 years. CONCLUSIONS: Regardless of index ages at 55, 65, or 75 years, an optimal risk factor profile was associated with a lifetime risk of atrial fibrillation of about one in five; this risk rose to more than one in three a third in individuals with at least one elevated risk factor.