Background and aims: Evaluating associations of circulating electrolytes with atrial fibrillation (AF) and burden of supraventricular arrhythmias can give insights into arrhythmia pathogenesis. Methods and results: We conducted a cross-sectional analysis of 6398 participants of the Atherosclerosis Risk in Communities (ARIC) study, ages 71–90, with data on serum electrolytes (magnesium, calcium, potassium, phosphorus, chloride, sodium). Prevalence of AF was determined from electrocardiograms and history of AF hospitalizations. A subset of 317 participants also underwent electrocardiographic recordings for up to 14 days using the Zio® patch. Burden of other supraventricular arrhythmias [premature atrial contractions (PACs), supraventricular tachycardia] was determined with the Zio® patch. We used logistic and linear regression adjusting for potential confounders to determine associations of electrolytes with arrhythmia prevalence and burden. Among 6394 eligible participants, 614 (10%) had AF. Participants in the top quintiles of magnesium [odds ratio (OR) 0.82, 95% confidence interval (CI) 0.62, 1.08], potassium (OR 0.82, 95%CI 0.68, 1.00), and phosphorus (OR 0.73, 95%CI 0.59, 0.89) had lower AF prevalence compared to those in the bottom quintiles. No clear association was found for circulating chloride, calcium or sodium. Higher concentrations of circulating calcium were associated with lower prevalence of PACs in the 12-lead electrocardiogram, while higher concentrations of potassium, chloride and sodium were associated with higher PAC prevalence. Circulating electrolytes were not significantly associated with burden of PACs or supraventricular tachycardia among 317 participants with extended electrocardiographic monitoring. Conclusion: Concentrations of circulating electrolytes present complex associations with selected supraventricular arrhythmias. Future studies should evaluate underlying mechanisms.

AIMS: Heart failure (HF) is a leading cause of death. Early intervention is the key to reduce HF-related morbidity and mortality. This study assesses the utility of electrocardiograms (ECGs) in HF risk prediction. METHODS AND RESULTS: Data from the baseline visits (1987-89) of the Atherosclerosis Risk in Communities (ARIC) study was used. Incident hospitalized HF events were ascertained by ICD codes. Participants with good quality baseline ECGs were included. Participants with prevalent HF were excluded. ECG-artificial intelligence (AI) model to predict HF was created as a deep residual convolutional neural network (CNN) utilizing standard 12-lead ECG. The area under the receiver operating characteristic curve (AUC) was used to evaluate prediction models including (CNN), light gradient boosting machines (LGBM), and Cox proportional hazards regression. A total of 14 613 (45% male, 73% of white, mean age ± standard deviation of 54 ± 5) participants were eligible. A total of 803 (5.5%) participants developed HF within 10 years from baseline. Convolutional neural network utilizing solely ECG achieved an AUC of 0.756 (0.717-0.795) on the hold-out test data. ARIC and Framingham Heart Study (FHS) HF risk calculators yielded AUC of 0.802 (0.750-0.850) and 0.780 (0.740-0.830). The highest AUC of 0.818 (0.778-0.859) was obtained when ECG-AI model output, age, gender, race, body mass index, smoking status, prevalent coronary heart disease, diabetes mellitus, systolic blood pressure, and heart rate were used as predictors of HF within LGBM. The ECG-AI model output was the most important predictor of HF. CONCLUSIONS: ECG-AI model based solely on information extracted from ECG independently predicts HF with accuracy comparable to existing FHS and ARIC risk calculators.

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1–4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.

Background Electronic medical records are increasingly used to identify disease cohorts; however, computable phenotypes using electronic medical record data are often unable to distinguish between prevalent and incident cases. Methods and Results We identified all Olmsted County, Minnesota residents aged ≥18 with a first-ever International Classification of Diseases, Ninth Revision (ICD-9) diagnostic code for atrial fibrillation or atrial flutter from 2000 to 2014 (N=6177), and a random sample with an International Classification of Diseases, Tenth Revision (ICD-10) code from 2016 to 2018 (N=200). Trained nurse abstractors reviewed all medical records to validate the events and ascertain the date of onset (incidence date). Various algorithms based on number and types of codes (inpatient/outpatient), medications, and procedures were evaluated. Positive predictive value (PPV) and sensitivity of the algorithms were calculated. The lowest PPV was observed for 1 code (64.4%), and the highest PPV was observed for 2 codes (any type) >7 days apart but within 1 year (71.6%). Requiring either 1 inpatient or 2 outpatient codes separated by >7 days but within 1 year had the best balance between PPV (69.9%) and sensitivity (95.5%). PPVs were slightly higher using ICD-10 codes. Requiring an anticoagulant or antiarrhythmic prescription or electrical cardioversion in addition to diagnostic code(s) modestly improved the PPVs at the expense of large reductions in sensitivity. Conclusions We developed simple, exportable, computable phenotypes for atrial fibrillation using structured electronic medical record data. However, use of diagnostic codes to identify incident atrial fibrillation is prone to some misclassification. Further study is warranted to determine whether more complex phenotypes, including unstructured data sources or using machine learning techniques, may improve the accuracy of identifying incident atrial fibrillation.

BACKGROUND: Increased carotid intima-media thickness, interadventitial diameter, presence of carotid plaque, and lower dis-tensibility are predictors for cardiovascular disease. These indices likely relate to cerebrovascular disease, and thus may constitute a form of vascular contributions to dementia and Alzheimer disease– related dementia. Therefore, we assessed the relationship of carotid measurements and arterial stiffness with incident dementia in the ARIC (Atherosclerosis Risk in Communities) study. METHODS AND RESULTS: A total of 12 459 ARIC participants with carotid arterial ultrasounds in 1990 to 1992 were followed through 2017 for dementia. Dementia cases were identified using in-person and phone cognitive status assessments, hospitalization discharge codes, and death certificate codes. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for incident dementia. Participants were aged 57±6 at baseline, 57% were women, and 23% were Black individu-als. Over a median follow-up time of 24 years, 2224 dementia events were ascertained. After multivariable adjustments, the highest quintile of carotid intima-media thickness and interadventitial diameter in midlife was associated with increased risk of dementia (HR [95% CIs], 1.25 [1.08–1.45]; and 1.22 [1.04–1.43], respectively) compared with its respective lowest quintile. Presence of carotid plaque did not have a significant association with dementia (HR [95% CI], 1.06 [0.97–1.15]). Higher distensibility was associated with lower risk of dementia (HR [95% CI] highest versus lowest quintile, 0.76 [0.63– 0.91]). CONCLUSIONS: Greater carotid intima-media thickness, interadventitial diameter, and lower carotid distensibility are associated with an increased risk of incident dementia. These findings suggest that both atherosclerosis and carotid stiffness may be implicated in dementia risk.

BACKGROUND: Psychosocial factors predict heart disease risk, but our understanding of underlying mechanisms is limited. We sought to evaluate the physiologic correlates of psychosocial factors by measuring their relationships with heart rate variability (HRV), a measure of autonomic health, in the ARIC (Atherosclerosis Risk in Communities) study. We hypothesize that increased psychosocial stress associates with lower HRV. METHODS AND RESULTS: We studied 9331 participants in ARIC with short-term HRV data at visits 2 and 4. The mean (SD) age was 54.4 (5.7) years, 55% were women, and 25% were Black. Psychosocial factors included: (1) vital exhaustion (VE), (2) anger proneness, a personality trait, and (3) perceived social support. Linear models adjusted for sociodemographic and cardiovascular risk factors. Low frequency HRV (ln ms2) was significantly lower in the highest versus lowest quartiles of VE (B=−0.14, 95% CI, −0.24 to −0.05). When comparing this effect to age (B=−0.04, 95% CI, −0.05 to −0.04), the difference was equivalent to 3.8 years of accelerated aging. Perceived social support associated with lower time-domain HRV. High VE (versus low VE) also associated with greater decreases in low frequency over time, and both anger and VE associated with greater increases in resting heart rate over time. Survival analyses were performed with Cox models, and no evidence was found that HRV ex-plains the excess risk found with high VE and low perceived social support. CONCLUSIONS: Vital exhaustion, and to a lesser extent anger and social support, were associated with worse autonomic function and greater adverse changes over time.

BACKGROUND: We examined the relationships of anger, vital exhaustion, anti-depressant use, and poor social ties with incident atrial fibrillation in a biracial cohort of middle and older-aged adults. METHODS: This analysis included 11,445 Atherosclerosis Risk in Communities Study participants who were free of atrial fibrillation at baseline in 1990-1992. Vital exhaustion was assessed at baseline and defined as a score in the highest quartile on the 21-item Vital Exhaustion Questionnaire. Baseline anti-depressant use was self-reported. The Spielberger Trait Anger Scale to assess anger and both the Interpersonal Support Evaluation List and the Lubben Social Network Scale to assess social ties were also administered at baseline. The primary outcome was incident atrial fibrillation throughout 2016, identified by electrocardiogram, hospital discharge coding of atrial fibrillation, and death certificates. RESULTS: A total of 2220 incident atrial fibrillation cases were detected over a median follow-up of 23.4 years. After adjusting for age, race-center, sex, education, and height, participants in the 4th Vital Exhaustion Questionnaire quartile (referent = 1st Vital Exhaustion Questionnaire quartile) and those reporting anti-depressant use were at increased risk for atrial fibrillation (hazard ratio = 1.45, 95% confidence interval 1.29-1.64 for Vital Exhaustion Questionnaire; hazard ratio = 1.37, 95% confidence interval 1.11-1.69 for anti-depressant use). The increased atrial fibrillation risk observed for 4th Vital Exhaustion Questionnaire quartile participants remained significant after additional adjustment for relevant comorbidities (hazard ratio = 1.20; confidence interval 1.06-1.35). No significant associations were observed for anger or poor social ties with development of atrial fibrillation. CONCLUSIONS: Vital exhaustion is associated with an increased risk of incident atrial fibrillation.

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF.

Background Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance. Methods and Results We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor. Participants were randomly assigned to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin versus usual care. The primary outcome was the development of either AF or AFL as diagnosed by serial study ECGs or by Medicare claims data. Among 14 837 participants without prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5±3.2 years of follow-up. Compared with chlorthalidone, randomization to either lisinopril (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; P=0.46) or amlodipine (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; P=0.16) was not associated with a significant reduction in incident AF/AFL. Conclusions Compared with chlorthalidone, treatment with lisinopril is not associated with a meaningful reduction in incident AF or AFL among older adults with a history of hypertension. Clinical Trial Registration URL: Http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Background: Electrocardiographic left ventricular hypertrophy (ECG-LVH) represents preclinical cardiovascular disease and predicts cardiovascular disease morbidity and mortality. While the newly developed Peguero-Lo Presti ECG-LVH criteria have greater sensitivity for LVH than the Cornell voltage and Sokolow–Lyon criteria, its short-term repeatability is unknown. Therefore, we characterized the short-term repeatability of Peguero-Lo Presti ECG-LVH criteria and evaluate its agreement with Cornell voltage and Sokolow–Lyon ECG-LVH criteria. Methods: Participants underwent two resting, standard, 12-lead ECGs at each of two visits one week apart (n = 63). We defined a Peguero-Lo Presti index as a sum of the deepest S wave amplitude in any single lead and lead V4 (i.e., SD + SV4) and defined Peguero-Lo Presti LVH index as ≥ 2,300 µV among women and ≥ 2,800 µV among men. We estimated repeatability as an intraclass correlation coefficient (ICC), agreement as a prevalence-adjusted bias-adjusted kappa coefficient (κ), and precision using 95% confidence intervals (CIs). Results: The Peguero-Lo Presti index was repeatable: ICC (95% CI) = 0.94 (0.91–0.97). Within-visit agreement of Peguero-Lo Presti LVH was high at the first and second visits: κ (95% CI) = 0.97 (0.91–1.00) and 1.00 (1.00–1.00). Between-visit agreement of the first and second measurements at each visit was comparable: κ (95% CI) = 0.90 (0.80–1.00) and 0.93 (0.85–1.00). Agreement of Peguero-Lo Presti and Cornell or Sokolow–Lyon LVH on any one of the four ECGs was slightly lower: κ (95% CI) = 0.71 (0.54–0.89). Conclusion: The Peguero-Lo Presti index and LVH have excellent repeatability and agreement, which support their use in clinical and epidemiological studies.