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Purpose: Among patients with atrial fibrillation (AF), a nonpharmacologic option (e.g., percutaneous left atrial appendage occlusion [LAAO]) is needed for patients with oral anticoagulant (OAC) contraindications. Among beneficiaries in the Medicare fee-for-service coverage 20% sample databases (2015-18) who had AF and an elevated CHA 2 DS 2 -VASc score, we assessed the association between percutaneous LAAO versus OAC use and risk of stroke, hospitalized bleeding, and death., Methods: Patients undergoing percutaneous LAAO were matched to up to five OAC users by sex, age, date of enrollment, index date, CHA 2 DS 2 -VASc score, and HAS-BLED score. Overall, 17 156 patients with AF (2905 with percutaneous LAAO) were matched (average ± SD 78 ± 6 years, 44% female). Cox proportional hazards model were used., Results: Median follow-up was 10.3 months. After multivariable adjustments, no significant difference for risk of stroke or death was noted when patients with percutaneous LAAO were compared with OAC users (HRs [95% CIs]: 1.14 [0.86-1.52], 0.98 [0.86-1.10]). There was a 2.94-fold (95% CI: 2.50-3.45) increased risk for hospitalized bleeding for percutaneous LAAO compared with OAC use. Among patients 65 to <78 years old, those undergoing percutaneous LAAO had higher risk of stroke compared with OAC users. No association was present in those ≥78 years., Conclusion: In this analysis of real-world AF patients, percutaneous LAAO versus OAC use was associated with similar risk of death, nonsignificantly elevated risk of stroke, and an elevated risk of bleeding in the post-procedural period. Overall, these results support results of randomized trials that percutaneous LAAO may be an alternative to OAC use for patients with contraindications., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Contemporary use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNi) in patients with atrial fibrillation (AF) and heart failure (HF) has not been described., Methods and Results: We analyzed the MarketScan databases for the period January 1, 2021 to July 30, 2022. Validated algorithms were used to identify patients with AF and HF, and to classify patients into HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF). We assessed the prevalence of SGLT2i and ARNi use overall and by HF type. Additionally, we explored correlates of lower use, including demographics and comorbidities. The study population included 60 927 patients (mean age, 75 years; 43% women) diagnosed with AF and HF (85% with HFpEF, 15% with HFrEF). Prevalence of ARNi use was 11% overall (30% in HFrEF, 8% in HFpEF), whereas the corresponding figure was 6% for SGLT2i (13% in HFrEF, 5% in HFpEF). Use of both medications increased over the study period: ARNi from 9% to 12% (22%-29% in HFrEF, 6%-8% in HFpEF), and SGLT2i from 3% to 9% (6%-16% in HFrEF, 2%-7% in HFpEF). Female sex, older age, and specific comorbidities were associated with lower use of these 2 medication types overall and by HF type., Conclusions: Use of ARNi and SGLT2i in patients with AF and HF is suboptimal, particularly among women and older individuals, though use is increasing. These results underscore the need for understanding reasons for these disparities and developing interventions to improve adoption of evidence-based therapies among patients with comorbid AF and HF.

Background: Recent evidence indicates that abnormal P-wave parameters (PWPs)-ECG markers of atrial myopathy-are associated with incident dementia, independent of atrial fibrillation (AF) and clinical ischemic stroke. However, the mechanisms remain unclear and may include subclinical vascular brain injury. Hence, we evaluated the association of abnormal PWPs with brain MRI correlates of vascular brain injury in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)., Methods: ARIC-NCS participants who underwent 3T brain MRI scans in 2011-2013 were included. PWPs were measured from standard 12-lead ECGs. Brain MRI outcomes included cortical infarcts, lacunar infarcts, cerebral microhemorrhages, brain volumes, and white matter disease (WMD) volume. We used weighted multivariable logistic and linear regression to evaluate the associations of abnormal PWPs with brain MRI outcomes., Results: Among 1715 participants (mean age, 76.1 years; 61% women; 29% Black), 797 (46%) had ≥1 abnormal PWP. After multivariable adjustment, including adjusting for prevalent AF, abnormal P-wave terminal force in lead V1 (aPTFV1) and prolonged P-wave duration (PPWD) were associated with increased odds of both cortical (OR 1.41; 95% CI, 1.14 to 1.74 and OR 1.30; 95% CI, 1.04 to 1.63, respectively) and lacunar infarcts (OR 1.36; 95% CI, 1.15 to 1.63 and OR 1.37; 95% CI, 1.15 to 1.65, respectively). Advanced interatrial block (aIAB) was associated with higher odds of subcortical microhemorrhage (OR 2.04; 95% CI, 1.36 to 3.06). Other than a significant association between aPTFV1 with lower parietal lobe volume, there were no other significant associations with brain or WMD volume., Conclusion: In this exploratory analysis of a US community-based cohort, ECG surrogates of atrial myopathy are associated with a higher prevalence of brain infarcts and microhemorrhage, suggesting subclinical vascular brain injury as a possible mechanism underlying the association of atrial myopathy with dementia., (© 2023 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Background: Serum magnesium (Mg) has been reported to be inversely associated with the risk of atrial fibrillation (AF), coronary artery disease (CAD), and major adverse cardiovascular events (MACE). The association between serum Mg and the risk of MACE, heart failure (HF), stroke, and all-cause mortality among patients with AF has not been evaluated. Objective: We aim to examine whether higher serum Mg is associated with a lower risk of MACE, heart failure (HF), stroke, and all-cause mortality among patients with AF. Methods: We evaluated prospectively 413 participants of the Atherosclerosis Risk in Communities (ARIC) Study with a diagnosis of AF at the time of Mg measurement participating in visit 5 (2011-2013). Serum Mg was modeled in tertiles and as a continuous variable in standard deviation units. Endpoints (HF, MI, stroke, cardiovascular (CV) death, all-cause mortality, and MACE) were identified and modeled separately using Cox proportional hazard regression adjusting for potential confounders. Results: During a mean follow-up of 5.8 years, there were 79 HFs, 34 MIs, 24 strokes, 80 CV deaths, 110 MACEs, and 198 total deaths. After adjustment for demographic and clinical variables, participants in the second and third tertiles of serum Mg had lower rates of most endpoints, with the strongest inverse association for the incidence of MI (HR 0.20, 95% CI 0.07, 0.61) comparing top to bottom tertile. Serum Mg modeled linearly as a continuous variable did not show clear associations with endpoints except MI (HR 0.50, 95% CI 0.31, 0.80). Due to the limited number of events, the precision of most estimates of association was relatively low. Conclusions: Among patients with AF, higher serum Mg was associated with a lower risk of developing incident MI and, to a lesser extent, other CV endpoints. Further studies in larger patients with AF cohorts are needed to evaluate the role of serum Mg in preventing adverse CV outcomes in these patients.

Background: Atrial fibrillation (AF) is widely perceived to originate from the left atrium (LA). Whether increases in right ventricular (RV) afterload in older adults play an etiological role in AF genesis independent of LA and left ventricular (LV) remodeling is unknown., Research Question: Is higher RV afterload associated with greater AF risk independent of LA and LV remodeling?, Study Design and Methods: In this observational prospective study, we included 2,246 community-dwelling older adults (mean age, 75 years) without known cardiovascular disease, with LV ejection fraction > 50%, LA volume index < 34 mL/m 2 , and E/e' ratio < 14 and a measurable functional tricuspid regurgitation jet velocity. From 2D-echocardiograms, we estimated pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR). We ascertained incident AF (through 2018) from hospital discharge codes and death certificates. We estimated hazard ratios (HR) by Cox regression., Results: During follow-up (median, 6.3 years; interquartile interval, 5.5-6.9 years), 215 participants developed AF. AF risk was significantly higher in the third (vs first) tertile of PASP (HR, 1.65; 95% CI, 1.08-2.54) and PVR (HR, 1.38; 95% CI, 1.00-2.08) independent of LA and LV structure and function, heart rate, BMI, prevalent sleep apnea, systemic BP, antihypertensive medications, and lung, kidney, and thyroid function. These associations persisted after further exclusion of participants with tricuspid regurgitation jet velocity > 2.8 m/s and lateral and septal mitral annular velocity above age- and sex-specific reference limits., Interpretation: In older adults, higher RV afterload is associated with greater AF risk independent of LA and LV remodeling. Future research should focus on confirming this novel association and elucidate underlying mechanisms., (Published by Elsevier Inc.)

Although dementia and atrial fibrillation (AF) are common in older adults, risk factors for dementia have not been sufficiently characterized in patients with AF. We studied 621,773 patients with AF without dementia at the time of AF diagnosis who were enrolled in the MarketScan Commercial and Medicare Supplemental databases from 2007 to 2015. Dementia incidence and presence of predictors at the time of AF diagnosis (cardiometabolic conditions, mental and neurologic disorders, and other chronic conditions) were based on International Classification of Diseases, Ninth Revision, Clinical Modification codes in outpatient and inpatient claims, whereas medication usage was based on outpatient pharmacy claims. A frailty score was calculated using a previously established algorithm. The associations between the predictors of interest and dementia were assessed with multivariable Cox models. Patients had a mean age of 68 years (SD 14 years) and 41% were women. During a mean follow-up of 2.0 years, there were 16,073 cases of dementia. The strongest predictors of dementia were frailty (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.40 to 1.45, per 1-SD increase in the score), cognitive impairment (HR 1.50, 95% CI 1.36 to 1.65), mood disorders (HR 1.49, 95% CI 1.32 to 1.70), schizophrenia (HR 1.86, 95% CI 1.75 to 1.98), and substance abuse (HR 1.58, 95% CI 1.39 to 1.80). Among cardiometabolic conditions, only stroke (HR 1.17, 95% CI 1.13 to 1.22) and diabetes mellitus (HR 1.14, 95% CI 1.11 to 1.18) were associated with small increases in dementia risk after adjusting for demographics, frailty, co-morbidities, and medications. We have identified several risk factors for dementia in patients with AF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Data are needed on the use of oral anticoagulation in patients with atrial fibrillation (AF) in rural versus urban areas, including the initiation of direct oral anticoagulants (DOACs)., Objective: We used Medicare data to examine rural/urban differences in anticoagulation use in patients with AF., Methods: We identified incident AF in a 20% sample of fee-for-service Medicare beneficiaries (aged ≥ 65 years) from 2011 to 2016 and collected ZIP code and covariates at the time of AF. We identified the first anticoagulant prescription filled, if any, following AF diagnosis. We categorized beneficiaries into four rural/urban areas using rural-urban commuting area codes and used Poisson regression models to compare anticoagulant use., Results: We included 447,252 patients with AF (mean age 79 ± 8 years), of which 82% were urban, 9% large rural, 5% small rural, and 4% isolated. The percentage who initiated an anticoagulant rose from 34% in 2011 to 53% in 2016, paralleling the uptake of DOACs. In a multivariable-adjusted analysis, those in rural areas (vs. urban) were more likely to initiate an anticoagulant. However, rural beneficiaries (vs. urban) were less likely to initiate a DOAC; those in isolated areas were 17% less likely (95% confidence interval [CI] 13-20), those in small rural areas were 12% less likely (95% CI 9-15), and those in large rural areas were 10% less likely (95% CI 8-12)., Conclusion: Among Medicare beneficiaries with AF, anticoagulation use was low but increased over time with the introduction of DOACs. Rural beneficiaries were less likely to receive a DOAC., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Women with atrial fibrillation (AF) experience greater symptomatology, worse quality of life, and have a higher risk of stroke as compared to men, but are less likely to receive rhythm control treatment. Whether these differences exist in elderly patients with AF, and whether sex modifies the effectiveness of rhythm versus rate control therapy has not been assessed., Methods: We studied 135,850 men and 139,767 women aged ≥ 75 years diagnosed with AF in the MarketScan Medicare database between 2007 and 2015. Anticoagulant use was defined as use of warfarin or a direct oral anticoagulant. Rate control was defined as use of rate control medication or atrioventricular node ablation. Rhythm control was defined by use of anti-arrhythmic medication, catheter ablation or cardioversion. We used multivariable Poisson and Cox regression models to estimate the association of sex with treatment strategy and to determine whether the association of treatment strategy with adverse outcomes (bleeding, heart failure and stroke) differed by sex., Results: At the time of AF, women were on average (SD) 83.8 (5.6) years old and men 82.5 (5.2) years, respectively. Compared to men, women were less likely to receive an anticoagulant or rhythm control treatment. Rhythm control (vs. rate) was associated with a greater risk for heart failure with a significantly stronger association in women (HR women = 1.41, 95% CI 1.34-1.49; HR men = 1.21, 95% CI 1.15-1.28, p < 0.0001 for interaction). No sex differences were observed for the association of treatment strategy with the risk of bleeding or stroke., Conclusion: Sex differences exist in the treatment of AF among patients aged 75 years and older. Women are less likely to receive an anticoagulant and rhythm control treatment. Women were also at a greater risk of experiencing heart failure as compared to men, when treated with rhythm control strategies for AF. Efforts are needed to enhance use AF therapies among women. Future studies will need to delve into the mechanisms underlying these differences., (© 2021. The Author(s).)

Plasma proteomic profiling may aid in the discovery of novel biomarkers upstream of the development of atrial fibrillation (AF). We used data from the Atherosclerosis Risk in Communities study to examine the relation between large-scale proteomics and incident AF in a cohort of older-aged adults in the United States. We quantified 4,877 plasma proteins in Atherosclerosis Risk in Communities participants at visit 5 (2011-2013) using an aptamer-based proteomic profiling platform. We used Cox proportional hazards models to assess the association between protein levels and incident AF, and explored relation of selected protein biomarkers using annotated pathway analysis. Our study included 4,668 AF-free participants (mean age 75 ± 5 years; 59% female; 20% Black race) with proteomic measures. A total of 585 participants developed AF over a mean follow-up of 5.7 ± 1.7 years. After adjustment for clinical factors associated with AF, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with the risk of incident AF (hazard ratio, 1.82; 95% CI, 1.68 to 1.98; p, 2.91 × 10 -45 per doubling of NT-proBNP). In addition, 36 other proteins were also significantly associated with incident AF after Bonferroni correction. We further adjusted for medication use and estimated glomerular filtration rate and found 17 proteins, including angiopoietin-2 and transgelin, that remained significantly associated with incident AF. Pathway analyses implicated the inhibition of matrix metalloproteases as the top canonical pathway in AF pathogenesis. In conclusion, using a large-scale proteomic platform, we identified both novel and established proteins associated with incident AF and explored mechanistic pathways of AF development., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Black Americans have more atrial fibrillation risk factors but lower atrial fibrillation risk than White Americans. Left atrial (LA) enlargement and/or dysfunction, frequent atrial tachycardia (AT), and premature atrial contractions (PAC) are associated with increased atrial fibrillation risk. Racial differences in these factors may exist that could explain the difference in atrial fibrillation risk. Methods and Results We included 2133 ARIC (Atherosclerosis Risk in Communities) study participants (aged 74±4.5 years[mean±SD], 59% women, 27% Black participants) who had echocardiograms in 2011 to 2013 and wore the Zio XT Patch (a 2-week continuous heart monitor) in 2016 to 2017. Linear regression was used to analyze (1) differences in AT/day or PAC/hour between Black and White participants, (2) differences in LA measures between Black and White participants, and (3) racial differences in the association of LA measures with AT or PAC frequency. Compared with White participants, Black participants had a higher prevalence of cardiovascular risk factors and disease, lower AT frequency, greater LA size, and lower LA function. After multivariable adjustments, Black participants had 37% (95% CI, 24%-47%) fewer AT runs/day than White participants. No difference in PAC between races was noted. Greater LA size and reduced LA function are associated with more AT and PAC runs; however, no race interaction was present. Conclusions Differences in LA measures are unlikely to explain the difference in atrial fibrillation risk between Black and White individuals. Despite more cardiovascular risk factors and greater atrial remodeling, Black participants have lower AT frequency than White participants. Future research is needed to elucidate the protective mechanisms that confer resilience to atrial arrhythmias in Black individuals.

Background: Stiff arteries increase left ventricular (LV) end-systolic workload, leading over time to left atrial and ventricular remodeling, and providing the substrate for atrial fibrillation (AF) development. We investigated if carotid femoral pulse wave velocity (cfPWV), a measure of central arterial stiffness, is associated with incident AF., Methods: In 2011-2013, cfPWV was measured in 3882 participants of the Atherosclerosis Risk in Communities Cohort Study (ARIC) without prevalent AF. Participants were followed through 2017 for the incidence of AF. Individuals were categorized in cfPWV quartiles based on visit measurements. Multivariable Cox regression models were used to evaluate the association of cfPWV with incident AF., Results: Mean age was 75 years (SD 5), 60% were female and 20% were African American. Over a median follow-up of 5.5 years we identified 331 incident cases of AF. cfPWV demonstrated U-shaped associations with AF risk. In models adjusted for age, race, center, sex, education levels, and hemodynamic and clinical factors, hazard ratios (HR) of AF for participants in the first, third and fourth quartiles were 1.49 (95% CI 1.06, 2.10), 1.59 (1.14, 2.10), and 1.56(1.10, 2.19), respectively, compared to those in the second quartile., Conclusion: Among community-dwelling older adults, low and high central arterial stiffness is associated with AF risk.

The American Heart Association's Life's Simple 7 (LS7) metric consists of 7 modifiable risk factors. Although a more favorable LS7 risk factor profile is associated with lower AF incidence, this relation is unknown in regard to AF burden. We assessed the prospective association of overall LS7 score and individual LS7 risk factors in midlife with AF burden in late-life in the Atherosclerosis Risk in Communities Study. LS7 components were assessed at Visit 3 (1993 to 1995) and a composite score ranging from 0 to 14 was calculated. A higher score indicates better cardiovascular health. AF burden was measured at Visit 6 (2016 to 2017) with a 2-week Zio XT Patch. AF burden, defined as the percent of time a participant was in AF, was categorized as none, intermittent (>0 to <100%), or continuous (100%). Weighted multinomial logistic regression was used. Of the 2,363 participants, 58% were female and 24% were black. Participants were aged 57 ± 5 years at Visit 3 and 79 ± 5 years at Visit 6. From the Zio XT Patch, 5% had continuous AF, 4% had intermittent AF, and 91% had none. After multivariable adjustment, each 1-point increase in LS7 score had 0.87 (95% CI: 0.79 to 0.95) higher odds of continuous AF than no AF. Individually, poor levels of physical activity, BMI, and fasting blood glucose were associated with greater AF burden. In conclusion, this population-based prospective cohort study reports that unfavorable cardiovascular health profile in midlife is associated with higher AF burden in late-life and future research to evaluate the effectiveness of optimizing physical activity, BMI, and fasting blood glucose in lowering AF burden is warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this report., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Social determinants of health are relevant to cardiovascular outcomes but have had limited examination in atrial fibrillation (AF)., Objectives: The purpose of this study was to examine the association of annual household income and cardiovascular outcomes in individuals with AF., Methods: We analysed administrative claims for individuals with AF from 2009 to 2015 captured by a health claims database. We categorised estimates of annual household income as <$40 000; $40-$59 999; $60-$74 999; $75-$99 999; and ≥$100 000. Covariates included demographics, education, cardiovascular disease risk factors, comorbid conditions and anticoagulation. We examined event rates by income category and in multivariable-adjusted models in reference to the highest income category (≥$100 000)., Results: Our analysis included 336 736 individuals (age 72.7±11.9 years; 44.5% women; 82.6% white, 8.4% black, 7.0% Hispanic and 2.1% Asian) with AF followed for median (25th and 75th percentile) of 1.5 (95% CI 0.6 to 3.0) years. We observed an inverse association between income and heart failure and myocardial infarction (MI) with evidence of progressive risk across decreased income categories. Individuals with household income <$40 000 had the greatest risk for heart failure (HR 1.17; 95% CI 1.05 to 1.30) and MI (HR 1.18; 95% CI 0.98 to 1.41) compared with those with income ≥$100 000., Conclusions: We identified an association between lower household income and adverse outcomes in a large cohort of individuals with AF. Our findings support consideration of income in the evaluation of cardiovascular risk in individuals with AF., Competing Interests: Competing interests: Disclosures: LB is an employee of Optum. There are no other author disclosures., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Paroxysmal atrial fibrillation (AF) is challenging to diagnose due to its intermittent nature. Circadian rhythmicity has been reported for cardiovascular events such as myocardial infarction; whether diurnal variation exists for paroxysmal AF is less known. We characterized the temporal pattern of AF initiation in the Atherosclerosis Risk in Communities (ARIC) study, a prospective community-based cohort study., Methods: We included 74 ARIC study participants with paroxysmal AF detected by the Zio XT Patch at ARIC Visit 6 in 2016-17. We divided each participant's 2-week continuous monitoring data into 3-h intervals and summed the number of AF episodes in each interval. We performed Poisson regression using generalized estimating equations to estimate the effect of time of day on the number of AF episodes., Results: Compared to the reference interval of time 00:00-02:59, the time intervals 12:00-14:59, 15:00-17:59, and 18:00-20:59 had significantly higher frequency of AF initiation. Rate ratios (95% CI) for mean number of episodes in these three intervals were 1.91 (1.11, 2.92), 2.54 (1.42, 4.53), and 1.99 (1.19, 3.25) respectively. Furthermore, we found no significant association between duration of episode and time of day., Conclusion: There is diurnal variation in the initiation of AF episodes, with a peak in frequency in the late afternoon. Our finding is consistent with sympathetically driven AF. Pulse palpation or obtaining an electrocardiogram in the late afternoon may produce the highest diagnostic yield for AF., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The burden imposed by multimorbidity on outcomes and on the effectiveness of atrial fibrillation therapies in elderly adults with atrial fibrillation is unknown., Methods: Patients with nonvalvular atrial fibrillation ages ≥75 years in the MarketScan Medicare Supplemental database from 2007-2015. Prevalence of 14 chronic conditions at the time of atrial fibrillation diagnosis were obtained and classified as cardiometabolic or noncardiometabolic. Cox regression estimated the associations of the number and type of conditions with stroke, severe bleeding, and heart failure hospitalizations. Tests for interaction were assessed between atrial fibrillation treatments and multimorbidity., Results: Among 275,617 patients with atrial fibrillation (mean age 83 years, 51% women), the mean (SD) number of conditions per participant was 3.0 (2.1). Over a mean follow-up of 23 months, 7814 strokes, 13,622 severe bleeds, and 19,252 heart failure events occurred. After adjustment, an increase in the number of cardiometabolic conditions was associated with greater risk of stroke (hazard ratio [HR] 1.07; 95% confidence interval [CI], 1.05-1.10), severe bleeding (HR 1.09; 95% CI, 1.07-1.11), and heart failure (HR 1.19, 95% CI, 1.18-1.20). In contrast, number of noncardiometabolic conditions had weak or null associations with risk of cardiovascular endpoints. Overall, the effectiveness of atrial fibrillation treatment on stroke and heart failure were similar across multimorbidity status, but bleeding risk associated with atrial fibrillation treatments was higher in patients with overall and subgroup multimorbidity., Conclusion: Cardiometabolic multimorbidity was associated with worse outcomes and modified bleeding risk in atrial fibrillation patients. These findings underscore the impact of cardiometabolic conditions on atrial fibrillation outcomes and highlights the need to incorporate multimorbidity management in atrial fibrillation treatment guidelines., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Low serum magnesium (Mg) is associated with an increased incidence of atrial and ventricular arrhythmias. A richer phenotyping of arrhythmia indices, such as burden or frequency, may provide etiologic insights., Objectives: To evaluate cross-sectional associations of serum Mg with burden of atrial arrhythmias [atrial fibrillation (AF), premature atrial contractions (PAC), supraventricular tachycardia (SVT)], and ventricular arrhythmias [premature ventricular contractions (PVC), non-sustained ventricular tachycardia (NSVT)] over 2-weeks of ECG monitoring., Methods: We included 2513 ARIC Study visit 6 (2016-2017) participants who wore the Zio XT Patch-a leadless, ambulatory ECG-monitor-for up to 2-weeks. Serum Mg was modeled categorically and continuously. AF burden was categorized as intermittent or continuous based on the percent of analyzable time spent in AF. Other arrhythmia burdens were defined by the average number of abnormal beats per day. Linear regression was used for continuous outcomes; logistic and multinomial regression were used for categorical outcomes., Results: Participants were mean ± SD age 79 ± 5 years, 58% were women and 25% black. Mean serum Mg was 0.82 ± 0.08 mmol/L and 19% had hypomagnesemia (<0.75 mmol/L). Serum Mg was inversely associated with PVC burden and continuous AF. The AF association was no longer statistically significant with further adjustment for traditional lifestyle risk factors, only the association with PVC burden remained significant. There were no associations between serum Mg and other arrhythmias examined., Conclusions: In this community-based cohort of older adults, we found little evidence of independent cross-sectional associations between serum Mg and arrhythmia burden., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background Polypharmacy is highly prevalent in elderly people with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly patients with AF remains unaddressed. Methods and Results We studied 338 810 AF patients ≥75 years of age enrolled in the MarketScan Medicare Supplemental database in 2007-2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis (defined by the presence of International Classification of Diseases, Ninth Revision, Clinical Modification [ ICD-9-CM ] codes) based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular end points (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient, and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular end points and the interaction between polypharmacy and AF treatments in relation to cardiovascular end points. Prevalence of polypharmacy was 52%. Patients with polypharmacy had increased risk of major bleeding (hazard ratio [HR], 1.16; 95% CI, 1.12-1.20) and heart failure (HR, 1.33; 95% CI, 1.29-1.36) but not ischemic stroke (HR, 0.96; 95% CI, 0.92-1.00), compared with those not receiving polypharmacy. Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. Rhythm control (versus rate control) was more effective in preventing heart failure hospitalization in patients not receiving polypharmacy (HR, 0.87; 95% CI, 0.76-0.99) than among those with polypharmacy (HR, 0.98; 95% CI, 0.91-1.07; P =0.02 for interaction). Conclusion Polypharmacy is common among patients ≥75 with AF, is associated with adverse outcomes, and may modify the effectiveness of AF treatments. Optimizing management of polypharmacy in AF patients ≥75 may lead to improved outcomes.

Importance: Warfarin is prescribed to patients with atrial fibrillation (AF) for the prevention of cardioembolic complications. Whether warfarin adversely affects bone health is controversial. The availability of alternate direct oral anticoagulant (DOAC) options now make it possible to evaluate the comparative safety of warfarin in association with fracture risk., Objective: To test the hypothesis that, among patients with nonvalvular AF, use of DOACs vs warfarin is associated with lower risk of incident fracture., Design, Setting, and Participants: This comparative effectiveness cohort study used the MarketScan administrative claims databases to identify patients with nonvalvular AF and who were prescribed oral anticoagulants from January 1, 2010, through September 30, 2015. To reduce confounding, patients were matched on age, sex, CHA2DS2-VASc (congestive heart failure, hypertension, age [>65 years = 1 point; >75 years = 2 points], diabetes, and previous stroke/transient ischemic attack [2 points], vascular disease) score, and high-dimensional propensity scores. The final analysis included 167 275 patients with AF. Data were analyzed from February 27, 2019 to September 18, 2019., Exposures: Warfarin and DOACs (dabigatran etexilate, rivaroxaban, and apixaban)., Main Outcomes and Measures: Incident hip fracture, fracture requiring hospitalization, and all clinical fractures (identified using inpatient or outpatient claims) defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes., Results: In the study population of 167 275 patients with AF (38.0% women and 62.0% men; mean [SD] age, 68.9 [12.5] years), a total of 817 hip fractures, 2013 hospitalized fractures, and 7294 total fractures occurred during a mean (SD) follow-up of 16.9 (13.7) months. In multivariable-adjusted, propensity score-matched Cox proportional hazards regression models, relative to new users of warfarin, new users of DOACs tended to be at lower risk of fractures requiring hospitalization (hazard ratio [HR], 0.87; 95% CI, 0.79-0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88-0.98), whereas the association with hip fractures (HR, 0.91; 95% CI, 0.78-1.07) was not statistically significant. When comparing individual DOACs with warfarin, the strongest findings were for apixaban (HR for hip fracture, 0.67 [95% CI, 0.45-0.98]; HR for fractures requiring hospitalization, 0.60 [95% CI, 0.47-0.78]; and HR for all clinical fractures, 0.86 [95% CI, 0.75-0.98]). In subgroup analyses, DOACs appeared more beneficial among patients with AF who also had a diagnosis of osteoporosis than among those without a diagnosis of osteoporosis., Conclusions and Relevance: In this real-world population of 167 275 patients with AF, use of DOACs-particularly apixaban-compared with warfarin use was associated with lower fracture risk. These associations were more pronounced among patients with a diagnosis of osteoporosis. Given the potential adverse effects of warfarin on bone health, these findings suggest that caution should be used when prescribing warfarin to patients with AF at high risk of fracture.

The aim of the present study was to investigate the association between atrial fibrillation (AF) and total and regional brain volumes among participants in the community-based Atherosclerosis Risk in Communities Neurocognitive study (ARIC-NCS). A total of 1,930 participants (130 with AF) with a mean age of 76.3 ± 5.2, who underwent 3T brain MRI scans in 2011 to 2013 were included. Prevalent AF was ascertained from study ECGs and hospital discharge codes. Brain volumes were measured using FreeSurfer image analysis software. Markers of subclinical cerebrovascular disease included lobar microhemorrhages, subcortical microhemorrhages, cortical infarcts, subcortical infarcts, lacunar infarcts, and volume of white matter hyperintensities. Linear regression models were used to assess the associations between AF status and brain volumes. In adjusted analyses, AF was not associated with markers of subclinical cerebrovascular disease. However, AF was associated with smaller regional brain volumes (including temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus [all p <0.05]) after controlling for demographics, cardiovascular risk factors, prevalent cardiovascular disease, and markers of subclinical cerebrovascular disease. Subgroup analysis revealed a significant interaction between AF and total brain volume with respect to age (p = 0.02), with associations between AF and smaller brain volumes being stronger for older individuals. In conclusion, AF was associated with smaller brain volumes, and the association was stronger among older individuals. This finding may be related to the longer exposure period of the older population to AF or the possibility that older people are more susceptible to the effects of AF on brain volume., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Atrial fibrillation (AF) is associated with cognitive decline. Whether left atrial enlargement (LAE), a critical substrate for AF, is also associated is less well established. Therefore, we assessed the association of LAE and AF with cognitive decline in the ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). Methods and Results Participants (n=3391; mean age, 75±5 years; 59% women) underwent cognitive tests and 2-dimensional echocardiograms at visit 5 (2011-2013) and follow-up cognitive tests at visit 6 (2016-2017). LAE was defined as left atrium volume index ≥34 mL/m 2 . AF was ascertained using study ECGs and hospitalization discharge codes. We assessed the association of AF and LAE with (a) cognitive domain scores at visit 5 and (b) cognitive domain score changes between visit 5 and visit 6. At visit 5, compared with the reference group (without AF, normal left atrium), participants with LAE and AF had significantly lower global cognition ( Z score, -0.24; 95% CI, -0.38 to -0.10), whereas participants with AF and without LAE and participants with LAE and without AF did not have lower global cognition. In longitudinal analysis, compared with the reference group, participants with AF but without LAE had significantly greater decline in global cognition ( Z score, -0.13; 95% CI, -0.21 to -0.06). However, LAE, with or without AF, was not associated with greater cognitive decline. Conclusion Although LAE with AF was significantly associated with lower cognitive function in cross-sectional analysis, LAE, with or without AF, was not associated with greater cognitive decline over 5 years, highlighting the importance of evaluating longitudinal cognitive function. Future studies should have longer follow-up and evaluate left atrium function.

Background: Atrial fibrillation and obstructive sleep apnea are common conditions, but little is known about obstructive sleep apnea and cardiovascular risk among atrial fibrillation patients., Methods: Using the Truven Health MarketScan databases, we constructed a prospective cohort of atrial fibrillation patients from 2007 to 2014. Atrial fibrillation, obstructive sleep apnea, stroke, myocardial infarction, and confounders were defined using the International Classification of Disease-9-CM codes. We matched individuals with an obstructive sleep apnea diagnosis with up to five individuals without a diagnosis by age, sex, and enrollment date. Cox proportional hazards models adjusted for confounders and high-dimensional propensity scores. We included migraines as a control outcome. Bias analysis used published sensitivities and specificities to generate rate ratios adjusted for obstructive sleep apnea misclassification., Results: We matched 56,969 individuals with an obstructive sleep apnea diagnosis to 323,246 without. During a mean follow-up of 16 months, 3234 incident strokes and 4639 incident myocardial infarctions occurred. After adjustment, obstructive sleep apnea diagnosis was strongly associated with reduced risk of incident stroke (hazard ratio = 0.48, 95% confidence interval = 0.43, 0.53) and myocardial infarction (0.40, [0.37, 0.44]) and a smaller reduced risk of migraines (0.82, [0.68, 0.99]). Bias analysis produced wide-ranging or inestimable rate ratios adjusted for misclassification of obstructive sleep apnea., Conclusions: Obstructive sleep apnea diagnosis in atrial fibrillation patients was strongly associated with reduced risk of incident cardiovascular disease. We discuss misclassification, selection bias, and residual confounding as potential explanations.

Background and Purpose- Metabolic syndrome (MetS), a prothrombotic state, is associated with an increased risk of atrial fibrillation (AF) and stroke. The CHA 2 DS 2 -VASc score does not account for the MetS components of prehypertension, prediabetes mellitus, abdominal obesity, elevated triglycerides, and low HDL (high-density lipoprotein). Data are limited on the association of MetS with stroke in AF, independent of CHA 2 DS 2 -VASc variables. Our aim was to identify MetS components associated with ischemic stroke in participants with AF in the ARIC study (Atherosclerosis Risk in Communities). Methods- We included 1172 participants with incident AF within 5 years of measurement of MetS components. MetS was defined by ATP criteria and International Diabetes Federation criteria. Incident ischemic stroke was physician adjudicated. Multivariable Cox proportional hazards regression was used to assess the association of MetS components with stroke. Results- After a median follow-up of 14.8 years, there were 113 ischemic stroke cases. Of the individual MetS components, low HDL was borderline associated with increased stroke risk (hazard ratio, 1.48 [95% CI, 0.99-2.21]) after adjustment for CHA 2 DS 2 -VASc variables while the remaining MetS variables were not associated with stroke risk. The presence of ≥3 components of MetS was not significantly associated with ischemic stroke after adjustment for CHA 2 DS 2 -VASc variables (hazard ratio, 1.38 [95% CI, 0.91-2.11]). The risk of stroke increased by 13% for each additional component of MetS; however, this association was borderline significant (hazard ratio, 1.13 [95% CI, 0.99-1.28]). Conclusions- The presence of MetS was not significantly associated with ischemic stroke after adjustment for CHA 2 DS 2 -VASc variables. Consideration of MetS is unlikely to improve stroke prediction in AF.

Background Circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, a well-known indicator of atrial wall stress and remodeling, inversely correlate with body mass index. Both are strongly predictive of atrial fibrillation (AF). Their potential interaction in relation to incident AF, however, has not been explored. Methods and Results In total, 9556 participants of the ARIC (Atherosclerosis Risk in Communities) study who had 2 measurements of NT-proBNP and no baseline AF or heart failure were followed from 1996 to 1998 through 2016 for the occurrence of incident AF. Participants were categorized as obese (body mass index ≥30) and nonobese (body mass index <30) and by NT-proBNP levels (using the median of 68.2 pg/mL as the cutoff). Over a median follow-up of 18.3 years, we identified 1806 incident cases of AF. Analysis using multivariable Cox regression models showed that obese participants with high NT-proBNP levels at visit 4 had a higher adjusted risk of incident AF (hazard ratio: 3.64; 95% CI, 3.15-4.22) compared with nonobese individuals with low NT-proBNP levels. The association of obesity with AF risk was not modified by NT-proBNP levels ( P =0.46 for interaction). Increasing BNP among participants from 1990-1992 to 1996-1998 was associated with increased AF risk. After further adjustment for clinical risk factors and medications, results were similar. Conclusions Individuals who had both elevated body mass index and NT-proBNP and were free of clinically recognized heart failure were at higher risk of AF development. Those who experienced an increase in NT-proBNP levels between visits 2 and 4 were at higher risk of AF.

Background: The prevalence of subclinical atrial fibrillation (AF) in the elderly general population is unclear. We sought to define the prevalence of subclinical AF in a community-based elderly population and to characterize subclinical AF and the incremental diagnostic yield of 4 versus 2 weeks of continuous ECG monitoring., Methods: We conducted a cross-sectional analysis within the community-based multicenter observational ARIC study (Atherosclerosis Risk in Communities) using visit 6 (2016-2017) data. The 2616 ARIC study participants who wore a leadless, ambulatory ECG monitor (Zio XT Patch) for up to 2 weeks were aged 79±5 years, 42% men, and 26% black. In a subset, 386 participants without clinically recognized AF wore the monitor twice, each time for up to 2 weeks. We characterized the prevalence of subclinical AF (ie, AF detected on the Zio XT Patch without clinically recognized AF) over 2 weeks of monitoring and the diagnostic yield of 4 versus 2 weeks of monitoring., Results: The prevalence of subclinical AF was 2.5%; the prevalence of subclinical AF was 3.3% among white men, 2.5% among white women, 2.1% among black men, and 1.6% among black women. Subclinical AF was mostly intermittent (75%). Among those with intermittent subclinical AF, 91% had AF burden ≤10% during the monitoring period. In a subset of 386 participants without clinical AF, 78% more subclinical AF was detected by 4 weeks versus 2 weeks of ECG monitoring., Conclusions: In our study, the prevalence of subclinical AF was lower than previously reported and monitoring beyond 2 weeks provided substantial incremental diagnostic yield. Future studies should focus on individuals with higher risk to increase diagnostic yield and consider continuous monitoring duration longer than 2 weeks.

Background: Outcomes among atrial fibrillation (AF) patients may differ according to race/ethnicity and sex due to differences in biology, the prevalence of cardiovascular risk factors, and the use and effectiveness of AF treatments. We aimed to characterize patterns of cardiovascular risk across subgroups of AF patients by sex and race/ethnicity, since doing so may provide opportunities to identify interventions. We also evaluated whether these patterns changed over time., Methods: We utilized administrative claims data from the Optum Clinformatics® Datamart database from 2009 to 2015. Patients with AF with ≥6 months of enrollment prior to the first non-valvular AF diagnosis were included in the analysis. Final analysis utilized Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for cardiovascular outcomes stratified by sex and race/ethnicity. An additional analysis stratified outcomes by calendar year of AF diagnosis to evaluate changes in outcomes over time., Results: In a cohort of 380,636 AF patients, women had a higher risk of ischemic stroke [HR (95% CI): 1.25 (1.19, 1.31)] and lower risk of heart failure and myocardial infarction [HR (95% CI): 0.91 (0.88, 0.94) and 0.81 (0.77, 0.86), respectively)] compared to men. Black patients had elevated risk across all endpoints compared to whites, while Hispanics and Asian Americans showed no significant differences in any outcome compared to white patients. These sex and race/ethnic differences did not change over time., Conclusions: We found sex and race/ethnic differences in risk of cardiovascular outcomes among AF patients, without evidence of improvement over time., Competing Interests: LGSB is employed by Optum, but neither they nor the rest of the authors have had special access or privileges to the Optum data that others would not have. This does not alter our adherence to PLOS ONE policies on sharing data and materials, with the restrictions stated above. Authors do not have any other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products.

Background: Stroke risk stratification scores (eg, CHA 2 DS 2 -VASc) are used to tailor therapeutic recommendations for patients with atrial fibrillation (AF) in different risk groups., Objective: The purpose of this study was to develop a tool to estimate stroke risk in patients receiving oral anticoagulants (OACs) and to identify patients who remain at high risk for stroke despite anticoagulation therapy., Methods: Patients with nonvalvular AF initiating OACs were identified in the MarketScan data from 2007 to 2015. Using bootstrapping methods and backward selection of 44 candidate variables, we developed a model that selected variables predicting stroke. The final model was validated in patients with nonvalvular AF in the Optum database in the period 2009-2015. In both databases, the discrimination of existing stroke scores were individually evaluated and compared with our new model termed the AntiCoagulaTion-specific Stroke (ACTS) score., Results: Among 135,523 patients with AF initiating OACs in the MarketScan dataset, 2028 experienced an ischemic stroke after anticoagulant initiation. The stepwise model identified 11 variables (including type of OAC) associated with ischemic stroke. The discrimination (C statistic) of the model was adequate (0.68; 95% confidence interval [CI] 0.66-0.70), showing excellent calibration (χ 2 = 6.1; P = .73). ACTS was then applied to 84,549 AF patients in the Optum dataset (1408 stroke events) and showed similar discrimination (C statistic 0.67; 95% CI 65-0.69). However, previously developed predictive models had similar discriminative ability (CHA 2 DS 2 -VASc 0.67; 95% CI 0.65-0.68)., Conclusion: A novel model to identify AF patients at higher risk of ischemic stroke, using extensive administrative health care data including type of anticoagulant, did not perform better than established simpler models., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: Oral anticoagulation (OAC) prescribed to AF patients for the prevention of cardioembolic complications likely has the added benefit of preventing venous thromboembolism (VTE). This study evaluated, among AF patients who are anticoagulated, whether type of OAC was associated with subsequent VTE risk., Methods: Non-valvular AF patients prescribed OACs between 2010 and September 2015 were identified via the MarketScan administrative claims databases. OACs included warfarin and direct OACs (DOACs: dabigatran, rivaroxaban, and apixaban). Incident VTE was defined by ICD-9-CM codes. Patients were matched on age, sex, CHA 2 DS 2 -VASc, and high-dimensional propensity scores. The final analysis included 117,912 AF patients., Results: In total, 1357 VTE events accrued over a mean follow-up of 484 days. In multivariable-adjusted, propensity score-matched Cox models, relative to new users of warfarin, risk of incident VTE was lower among new users of dabigatran [hazard ratio (95% confidence interval) = 0.55 (0.47-0.66)] and apixaban [0.51 (0.39-0.68)], but similar among new users of rivaroxaban [1.01 (0.87-1.19)]. In head-to-head DOAC comparisons, VTE risk was lower among users of dabigatran [0.48 (0.36-0.64)] and apixaban [0.61 (0.47-0.78)] vs rivaroxaban. Findings were mostly similar across patient sub-groups., Conclusions: In this large practice-based population of AF patients prescribed OACs for primary prevention of stroke and systemic embolization, subsequent risk of VTE was lowest among those prescribed apixaban and dabigatran, while risk was similar with prescriptions for warfarin and rivaroxaban. Among AF patients prescribed OACs, lowering the risk of VTE may be an additional benefit of apixaban and dabigatran, beyond the reduced bleeding risk observed in randomized clinical trials.

Aim: To determine whether regional variation in stroke incidence exists among individuals with AF., Methods: Using healthcare utilization claims from 2 large US databases, MarketScan (2007-2014) and Optum Clinformatics (2009-2015), and the 2010 US population as the standard, we estimated age-, sex-, race- (only in Optum) standardized stroke incidence rates by the 9 US census divisions. We also used Poisson regression to examine incidence rate ratios (IRR) of stroke and the probability of anticoagulation prescription fills across divisions., Results: Both databases combined included 970,683 patients with AF who experienced 15,543 strokes, with a mean follow-up of 23 months. In MarketScan, the age- and sex-standardized stroke incidence rate was highest in the Middle Atlantic and East South Central divisions at 3.8/1000 person-years (PY) and lowest in the West North Central at 3.2/1000 PY. The IRR of stroke and the probability of anticoagulation fills were similar across divisions. In Optum Clinformatics, the age-, sex-, and race-standardized stroke incidence rate was highest in the East North Central division at 5.0/1000 PY and lowest in the New England division at 3.3/1000 PY. IRR of stroke and the probability of anticoagulation fills differed across divisions when compared to New England., Conclusions: These findings suggest regional differences in stroke incidence among AF patients follow a pattern that differs from the hypothesized trend found in the general population and that other factors may be responsible for this new pattern. Cross-database differences provide a cautionary tale for the identification of regional variation using health claims data., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose- Atrial fibrillation (AF) is associated with dementia independent of clinical stroke. The mechanisms underlying this association remain unclear. In a community-based cohort, the ARIC study (Atherosclerosis Risk in Communities), we evaluated (1) the longitudinal association of incident AF and (2) the cross-sectional association of prevalent AF with brain magnetic resonance imaging (MRI) abnormalities. Methods- The longitudinal analysis included 963 participants (mean age, 73±4.4 years; 62% women; 51% black) without prevalent stroke or AF who underwent a brain MRI in 1993 to 1995 and a second MRI in 2004 to 2006 (mean, 10.6±0.8 years). Outcomes included subclinical cerebral infarctions, sulcal size, ventricular size, and, for the cross-sectional analysis, white matter hyperintensity volume and total brain volume. Results- In the longitudinal analysis, 29 (3.0%) participants developed AF after the first brain MRI. Those who developed AF had higher odds of increase in subclinical cerebral infarctions (odds ratio [OR], 3.08; 95% CI, 1.39-6.83), worsening sulcal grade (OR, 3.56; 95% CI, 1.04-12.2), and worsening ventricular grade (OR, 9.34; 95% CI, 1.24-70.2). In cross-sectional analysis, of 969 participants, 35 (3.6%) had prevalent AF at the time of the 2004 to 2006 MRI scan. Those with AF had greater odds of higher sulcal (OR, 3.9; 95% CI, 1.7-9.1) and ventricular grade (OR, 2.4; 95% CI, 1.0-5.7) after multivariable adjustment and no difference in white matter hyperintensity or total brain volume. Conclusions- AF is independently associated with increase in subclinical cerebral infarction and worsening sulcal and ventricular grade-morphological changes associated with aging and dementia. More research is needed to define the mechanisms underlying AF-related neurodegeneration.

Background: It is unknown whether early cardiology involvement shortly after atrial fibrillation (AF) diagnosis is associated with favorable outcomes in AF patients who have cancer., Objectives: The purpose of this study was to examine the relationship between early cardiology involvement after AF diagnosis in patients with history of cancer., Methods: This study examined associations of early cardiology involvement with oral anticoagulation use, stroke, and bleeding among nonvalvular AF patients (n = 388,045; mean age 68 ± 15 years; 59% male) with a history of cancer (past or active) from the MarketScan database (2009 to 2014). International Classification of Disease-9th Revision-Clinical Modification codes in any position were used to identify cancer diagnosis prior to AF diagnosis. Provider specialty and filled anticoagulant prescriptions 3 months prior to and 6 months after AF diagnosis were obtained. Poisson regression models were used to compute the probability of an oral anticoagulant prescription fill, and Cox regression was used to estimate the risks of stroke and major bleeding., Results: A total of 64,016 (17%) AF patients had a history of cancer. Cardiology involvement was less likely to occur among patients with a history of cancer than those without (relative risk [RR]: 0.92 [95% confidence interval (CI): 0.91 to 0.93]). Patients with history of cancer were less likely to fill prescriptions for anticoagulants (RR: 0.89 [95% CI: 0.88 to 0.90]) than those without cancer, and similar results were observed across cancer types. Patients with cancer were more likely to fill prescriptions for anticoagulants (RR: 1.48 [95% CI: 1.45 to 1.52]) if seen by a cardiologist. A reduced risk of stroke (hazard ratio: 0.89 [95% CI: 0.81 to 0.99]) was observed among all cancer patients who were seen by a cardiology provider, without an increased risk of bleeding (hazard ratio: 1.04 [95% CI: 0.95 to 1.13]). Similar results were observed when the analysis was stratified by active versus remote history of cancer., Conclusions: Although AF patients with cancer were less likely to see a cardiologist, or fill anticoagulant prescriptions, cardiology involvement was associated with increased anticoagulant prescription fills and favorable AF-related outcomes in AF patients with cancer., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) predicts incidence of atrial fibrillation (AF), but the association of longitudinal changes in NT-proBNP concentrations with incident AF has not been explored., Methods: We studied 9705 individuals without prevalent AF in 1996-1998 and with available NT-proBNP measurements obtained in samples collected during two visits in 1990-1992 (visit 2) and 1996-1998 (visit 4) in the Atherosclerosis Risk in Communities (ARIC) Study. Participants were followed through the end of 2013. AF was ascertained from electrocardiograms, hospital discharge codes, and death certificates. Multivariable Cox regression was used to evaluate the association of absolute change in log-transformed NT-proBNP [ln(NT-proBNP)] with incident AF. We also assessed the impact of adding ln(NT-proBNP) change as a predictor of AF by difference in the C-statistic and net reclassification improvement (NRI)., Results: Over a median follow up of 16 years, there were 1503 incident cases of AF. The means (SD) ln(NT-proBNP) at visit 2 and visit 4 were 3.83 (1.01) and 4.35 (0.94), respectively. There was a 0.52 (0.79) increase in ln(NT-proBNP) over the 6-year period. Greater increases in ln(NT-proBNP) were associated with higher risk of AF [hazard ratio, 2.82 (95% confidence interval 2.34, 3.39), comparing top to bottom quintiles, and 1.74 (1.61, 1.87) per 1-unit increase in ln(NT-proBNP)]. Adding ln(NT-proBNP) change to a model with multiple predictors including baseline NT-proBNP had relatively limited impact in the C-statistic (increase from 0.748, 95%CI 0.736-0.761, to 0.762, 95%CI 0.750, 0.774). Adding ln(NT-proBNP) change to initial predictive models resulted in a categorical NRI of 0.062 (95% CI 0.033, 0.092) and a continuous NRI of 0.092 (95%CI, 0.017, 0.182)., Conclusion: Positive NT-proBNP change is associated with an increased incidence rate of AF. Adding NT-proBNP change into the prediction model modestly improved incident AF prediction. Future studies should assess the value of monitoring NT-proBNP concentration among individuals at high risk of developing AF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: No scores presently exist to predict bleeding in atrial fibrillation (AF) populations using direct oral anticoagulants (DOACs). We used data from two independent healthcare claims databases to develop and validate a predictive model of major bleeding in a contemporary AF population., Methods: Patients with non-valvular AF initiating oral anticoagulation were identified in the MarketScan databases from 2007-2014. Using Cox regression models in 1000 bootstrapped samples, we developed a model that selected variables predicting major bleeding in the first year after anticoagulant initiation. The final model was validated in patients with non-valvular AF in the Optum Clinformatics database in the period 2009-2015. The discriminative ability of existing bleeding scores were individually evaluated and compared with the new bleeding model termed Anticoagulation-specific Bleeding Score (ABS) in both MarketScan and Optum., Results: Among 119,083 patients with AF initiating oral anticoagulation in the derivation cohort, 4,030 experienced a bleeding event. The variable selection model identified 15 variables (including individual type of oral anticoagulant) associated with major bleeding. Discrimination of the model was modest [c-statistic 0.68, 95% confidence interval (CI) 0.67-0.69]. The model was subsequently applied to 81,285 AF patients in the validation data set (3,238 bleeding events), showing similar discrimination (c-statistic 0.68, 95% CI 0.67-0.69). In both cohorts, the predictive performance of the ABS was better than the existing models for bleeding prediction in AF., Conclusions: We developed a model that uses administrative healthcare data for the identification of AF patients at higher risk of bleeding after initiation of oral anticoagulation, taking into account the lower bleeding risk in DOAC compared to warfarin users., Competing Interests: We have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Lindsay Bengtson is an employee of Optum. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors have declared that no competing interests exist.

Early cardiology involvement after atrial fibrillation (AF) diagnosis is associated with increased oral anticoagulant prescription fills and reduced stroke risk. It is unknown if this association varies by race, sex, or education. We examined anticoagulant fills in 223,891 patients with incident nonvalvular AF (mean age = 71 years; 44% women; 84% white; 9% black; 5% Hispanic; 2% Asian) from the Optum Clinformatics database (2009 to 2014). Provider specialty and filled anticoagulant prescriptions 3 months before and 6 months after AF diagnosis were obtained. Poisson regression was used to compute the probability of oral anticoagulant prescription fill and Cox regression was used to estimate the risk of stroke and major bleeding. Cardiology involvement was less likely among nonwhites (white = Referent; black = relative risk = 0.96, 95% confidence interval (0.95 to 0.97); Hispanic = 0.99 (0.98 to 1.00); Asian = 0.95 (0.93 to 0.97)) and women (0.92 (0.91 to 0.93)), but more likely with higher education level (high school or less = Referent; some college = 1.03 (1.02 to 1.04); college or more = 1.08 (1.07 to 1.09)). Patients seen by cardiology providers were more likely to fill anticoagulant prescriptions (Any = 1.67 (1.64 to 1.69); direct oral anticoagulants = 2.59 (2.49 to 2.68); warfarin = 1.38 (1.35 to 1.41)) compared with patients not seen by a cardiology provider. Patients seen by a cardiologist had a reduced stroke risk (hazard ratio = 0.84 (0.79 to 0.88)) and similar bleeding risk (1.01 (0.96 to 1.06)). Outcomes did not vary by race, sex, or education level. In conclusion, although race, sex, and education differences exist in early cardiology involvement after AF diagnosis, the influence of cardiology involvement on anticoagulant prescription fills and AF-related outcomes does not vary by these factors. Initiatives to improve early cardiology referral in nonwhites, women, and those with lower educational attainment may improve AF outcomes., (Copyright © 2018. Published by Elsevier Inc.)

Low magnesium may increase the risk of atrial fibrillation. We conducted a double-blind pilot randomized trial to assess adherence to oral magnesium supplementation (400 mg of magnesium oxide daily) and a matching placebo, estimate the effect on circulating magnesium concentrations, and evaluate the feasibility of using an ambulatory heart rhythm monitoring device (ZioPatch) for assessing premature atrial contractions. A total of 59 participants were randomized; 73% were women, and the mean age was 62 years. A total of 98% of the participants completed the follow-up. In the magnesium supplement group, 75% of pills were taken, and in the placebo group, 83% were taken. The change in magnesium concentrations was significantly greater for those given the magnesium supplements than for those given the placebo (0.07; 95% confidence interval: 0.03, 0.12 mEq/L; p = 0.002). The ZioPatch wear time was approximately 13 of the requested 14 days at baseline and follow-up. There was no difference by intervention assignment in the change in log premature atrial contractions burden, glucose, or blood pressure. Gastrointestinal changes were more common among the participants assigned magnesium (50%) than among those assigned the placebo (7%), but only one person discontinued participation. In sum, compliance with the oral magnesium supplementation was very good, and acceptance of the ZioPatch monitoring was excellent. These findings support the feasibility of a larger trial for atrial fibrillation (AF) prevention with oral magnesium supplementation.

Background: Differences in anticoagulation rates and direct oral anticoagulant use by provider specialty may identify an area of practice improvement to reduce future stroke events in patients with atrial fibrillation (AF)., Methods and Results: We examined anticoagulant prescription fills in 388 045 (mean age, 68±15 years; 59% male) patients with incident AF from the MarketScan databases between 2009 and 2014. Provider specialty and filled anticoagulant prescriptions around the time of AF diagnosis (3 months before through 6 months after) were obtained from outpatient services and pharmacy claims. We estimated the association of provider specialty (cardiology versus primary care) with filling oral anticoagulant prescriptions, adjusting for patient characteristics. The risk of stroke and bleeding events also was explored. A total of 235 739 patients (61%) had a cardiology provider claim, whereas 152 306 (39%) were exclusively managed by primary care. Patients seen by cardiology providers were more likely to fill anticoagulant prescriptions than those seen by primary care (39% versus 27%; relative risk, 1.39; 95% confidence interval [CI], 1.37-1.40). Differences were observed for direct oral anticoagulants (relative risk, 1.74; 95% CI, 1.71-1.78) and warfarin (relative risk, 1.24; 95% CI, 1.22-1.26). A reduced risk of stroke events was observed among those seen by cardiology providers (hazard ratio, 0.90; 95% CI, 0.86-0.94) compared with primary care, without an increased bleeding risk (hazard ratio, 1.03; 95% CI, 0.98-1.07)., Conclusions: Patients seen by an outpatient cardiology provider shortly after AF diagnosis were more likely to initiate oral anticoagulation and were at lower risk of future stroke events without a higher rate of bleeding. Early referral to cardiology specialists may increase initiation of anticoagulant therapies and improve outcomes in AF., (© 2018 The Authors and Mayo Clinic. Published on behalf of the American Heart Association, Inc., by Wiley.)

Randomized clinical trials comparing direct oral anticoagulants (DOACs) to warfarin in cancer patients have not been performed. We evaluated the effectiveness and associated risk of DOACs vs warfarin, as well as comparisons of DOACs, in a large population of cancer patients with nonvalvular atrial fibrillation (AF). Using the MarketScan databases, we identified 16 096 AF patients (mean age, 74 years) initiating oral anticoagulant and being actively treated for cancer between 2010 and 2014. Anticoagulant users were matched by age, sex, enrollment date, and drug initiation date. Study end points were identified with diagnostic codes and included ischemic stroke, severe bleeding, other bleeding, and venous thromboembolism (VTE). Cox regression was used to estimate associations of anticoagulants with study end points. Compared with warfarin, rates of bleeding (hazard ratio [95% confidence interval]) were similar in rivaroxaban (1.09 [0.79, 1.39]) and dabigatran (0.96 [0.72, 1.27]) users, whereas apixaban users experienced lower rates (0.37 [0.17, 0.79]). Rates of ischemic stroke did not differ among anticoagulant users. Compared with warfarin, rate of VTE (hazard ratio [95% confidence interval]) was lower among rivaroxaban (0.51 [0.41, 0.63]), dabigatran (0.28 [0.21, 0.38]), and apixaban (0.14 [0.07, 0.32]) users. In head-to-head comparisons among DOACs, dabigatran users had lower rates of VTE than rivaroxaban users; apixaban users had lower rates of VTE and severe bleeding than rivaroxaban users. In this population of patients with AF and cancer, DOAC users experienced lower or similar rates of bleeding and stroke compared with warfarin users, and a lower rate of incident VTE., (© 2018 by The American Society of Hematology.)

Background: Rivaroxaban is an oral anticoagulant approved in the US for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). We determined the effectiveness and associated risks of rivaroxaban versus other oral anticoagulants in a large real-world population., Methods: We selected NVAF patients initiating oral anticoagulant use in 2010-2014 enrolled in MarketScan databases. Rivaroxaban users were matched with warfarin and dabigatran users by age, sex, enrolment date, anticoagulant initiation date, and high-dimensional propensity score. Study endpoints, including ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding, were identified from inpatient diagnostic codes. Multivariable Cox models were used to assess associations between type of anticoagulant and outcomes., Results: The analysis included 44,340 rivaroxaban users matched to 89,400 warfarin and 16,957 dabigatran users (38% female, mean age 70) with 12 months of mean follow-up. Anticoagulant-naïve rivaroxaban initiators, but not those switching from warfarin, had lower risk of ischemic stroke [hazard ratio (HR) (95% confidence interval (CI)): 0.75 (0.62, 0.91)] and ICB [HR (95%CI): 0.55, (0.39, 0.78)] than warfarin users. In contrast, anticoagulant-experienced rivaroxaban initiators had higher risk of GI bleeding than warfarin users [HR (95%CI): 1.55 (1.32, 1.83)]. Endpoint rates were similar when comparing anticoagulant-naïve rivaroxaban and dabigatran initiators, with the exception of higher GI bleeding risk in rivaroxaban users [HR (95%CI) 1.28 (1.06, 1.54)]. There were no significant differences in the risk of MI among the comparison groups., Conclusion: In this large real-world sample of NVAF patients, effectiveness and risks of rivaroxaban versus warfarin differed by prior anticoagulant status, while effectiveness of rivaroxaban versus dabigatran differed in GI bleeding risk.

Objective: To assess the risk of liver injury hospitalisation in patients with atrial fibrillation (AF) after initiation of direct oral anticoagulants (DOACs) or warfarin and to determine predictors of liver injury hospitalisation in this population., Methods: We studied 113 717 patients (mean age 70, 39% women) with AF included in the MarketScan Commercial and Medicare Supplemental databases with a first prescription for oral anticoagulation after 4 November 2011, followed through 31 December 2014. Of these, 56 879 initiated warfarin, 17 286 initiated dabigatran, 30 347 initiated rivaroxaban and 9205 initiated apixaban. Liver injury hospitalisation and comorbidities were identified from healthcare claims., Results: During a median follow-up of 12 months, 960 hospitalisations with liver injury were identified. Rates of liver injury hospitalisation (per 1000 person-years) by oral anticoagulant were 9.0 (warfarin), 4.0 (dabigatran), 6.6 (rivaroxaban) and 5.6 (apixaban). After multivariable adjustment, liver injury hospitalisation rates were lower in initiators of DOACs compared with warfarin: HR (95% CI) of 0.57 (0.46 to 0.71), 0.88 (0.75 to 1.03) and 0.70 (0.50 to 0.97) for initiators of dabigatran, rivaroxaban, and apixaban, respectively (vs. warfarin). Compared with dabigatran initiators, rivaroxaban initiators had a 56% increased risk of liver injury hospitalisation (HR 1.56, 95% CI 1.22 to 1.99). In addition to type of anticoagulant, prior liver, gallbladder and kidney disease, cancer, anaemia, heart failure and alcoholism significantly predicted liver injury hospitalisation. A predictive model including these variables had adequate discriminative ability (C-statistic 0.67, 95% CI 0.64 to 0.70)., Conclusions: Among patients with non-valvular AF, DOACs were associated with lower risk of liver injury hospitalisation compared with warfarin, with dabigatran showing the lowest risk., Competing Interests: Competing interests: AA had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. LGSB is an employee of Optum., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Effectiveness data on novel oral anticoagulants (NOACs) versus warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) by prior warfarin use are limited., Methods: We used data from the US MarketScan databases from 2009 to 2012. NVAF patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users. Propensity score-adjusted Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for relevant endpoints in NOACs versus warfarin users. Separate analyses were conducted to compare anticoagulant-naïve users of NOACs and those switching from warfarin., Results: Among 32,918 dabigatran, 3301 rivaroxaban, and 109,447 warfarin users with NVAF, 225 intracranial bleeds, 1035 ischemic strokes, 958 myocardial infarctions, and 1842 gastrointestinal bleeds were identified. Compared to warfarin users, patients initiating NOACs had similar ischemic stroke rates and lower intracranial bleeding rates, while the gastrointestinal bleeding rate was higher in dabigatran users than warfarin users. Associations of dabigatran with ischemic stroke risk differed between anticoagulant-naïve initiators and patients switching from warfarin; dabigatran was associated with lower ischemic stroke rates in naïve users (HR 0.65, 95% CI 0.52-0.82) but not in switchers (HR 1.20, 95% CI 0.95-1.51), compared to warfarin. Risk of stroke and bleeding was not different between rivaroxaban and warfarin users., Conclusions: Real-world effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in published clinical trials. However, harms and benefits of switching from warfarin to dabigatran need to be evaluated., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Aims: To assess the prospective association between circulating 25-hydroxyvitamin D [25(OH)D] and atrial fibrillation (AF) risk., Methods and Results: We studied 12 303 participants from the Atherosclerosis Risk in Communities study without baseline AF (1990-92). Baseline serum total 25(OH)D was measured using mass spectrometry. Incident AF cases were identified from electrocardiograms, hospital discharge codes, and death certificates through 2012. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) of AF across clinical categories of serum 25(OH)D concentrations with multivariable Cox models, and tested interactions by age, race, and sex. We meta-analysed our results with those from published prospective studies that reported associations between 25(OH)D and AF risk. During a median follow-up of 21 years, we identified 1866 AF events. In multivariable models, deficient 25(OH)D status (<20 ng/mL), compared with optimal levels (≥30 ng/mL), was not associated with AF risk (HR, 95% CI: 1.10, 0.96-1.26). A significant interaction of 25(OH)D concentrations with age (P = 0.01), but not with race or sex (P > 0.40), was identified, with higher risk of AF among those with deficient 25(OH)D status in younger (HR, 95% CI: 1.35, 1.05-1.73) but not older individuals (HR, 95% CI: 1.02, 0.86-1.21). A meta-analysis of these results and four prospective studies did not support a clinically relevant association of circulating 25(OH)D with AF risk [pooled HR, 95%CI: 1.04, 1.00-1.08, per 1 SD lower 25(OH)D]., Conclusion: Low serum 25(OH)D was not associated with incident AF in a community-based cohort and in a meta-analysis of prospective studies. A possible association in younger individuals warrants further investigation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts., Methods: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score., Results: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04)., Conclusions: In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.

Background: Atrial fibrillation (AF) is associated with increased risk of hospitalization. Little is known about the impact of AF on utilization of noninpatient health care or about sex or race differences in AF-related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities study., Methods and Results: Participants with incident AF enrolled in fee-for-service Medicare for at least 12 continuous months between 1991 and 2009 (n=932) were matched on age, sex, race and field center with up to 3 participants without AF (n=2729). Healthcare utilization was ascertained from Medicare claims and classified by primary International Classification of Diseases, ninth revision code. The average annual numbers of days hospitalized were 13.2 (95% CI 11.6 to 15.0) and 2.8 (95% CI 2.5 to 3.1) for those with and without AF, respectively. The corresponding numbers of annual outpatient claims were 53.3 (95% CI 50.5 to 56.3) and 22.9 (95% CI 22.1 to 23.8) for those with and without AF, respectively. Most utilization among AF patients was attributable to non-AF conditions. The adjusted rate ratio for annual days hospitalized for other cardiovascular disease-related reasons was 4.58 (95% CI: 3.41 to 6.16) for those with AF versus those without AF. The association between AF and healthcare utilization was similar among men and women and among white and black participants., Conclusions: Participants with AF had considerably greater healthcare utilization, and the difference in utilization for other cardiovascular disease-related reasons was substantial. In addition to rate or rhythm treatment, AF management should focus on the accompanying cardiovascular comorbidities., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Increased concentrations of circulating fibroblast growth factor 23 (FGF-23) have been associated with higher risk of cardiovascular disease. The association between FGF-23 and the risk of atrial fibrillation (AF), a common arrhythmia, is less defined. Thus, we explored whether FGF-23 concentration was associated with AF incidence in a large community-based cohort., Methods and Results: We studied 12 349 men and women enrolled in the Atherosclerosis Risk in Communities (ARIC) study, without prevalent AF at baseline in 1990-1992. Serum intact FGF-23 concentration was measured with the Kainos 2-site ELISA. Incident AF through 2010 was ascertained from study ECGs and hospital discharge codes. Cox proportional hazards models adjusted for potential confounding factors, including kidney function, were used to estimate the association between FGF-23 and AF risk. We identified 1572 AF events during a mean follow-up of 17 years. In multivariable analysis, a difference of 1 SD (16 pg/mL) in baseline FGF-23 was not associated with the risk of AF (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.99, 1.09). Results were similar when FGF-23 was modeled in quartiles (HR, 1.09; 95% CI, 0.94, 1.26, comparing extreme quartiles). Reduced kidney function was associated with increased AF risk across quartiles of FGF-23 levels., Conclusion: In this large community-based cohort, baseline FGF-23 levels were not associated with AF risk independently of kidney function. Our results do not support a major role for FGF-23 as a risk factor for AF or as a mediator of the association between chronic kidney disease and AF., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Atrial fibrillation (AF) frequently coexists in the setting of myocardial infarction (MI), being associated with increased mortality. Nonetheless, temporal trends in the occurrence of AF complicating MI and in the prognosis of these patients are not well described. We examined temporal trends in prevalence of AF in the setting of MI and the effect of AF on prognosis in the community. We studied a population-based sample of 20,049 validated first-incident nonfatal hospitalized MIs among 35- to 74-year old residents of 4 communities in the Atherosclerosis Risk in Communities (ARIC) Study from 1987 through 2009. Prevalence of AF in the setting of MI increased from 11% to 15% during the 23-year study period. The multivariable adjusted odds ratio for prevalent AF, per 5-year increment, was 1.11 (95% confidence interval 1.04 to 1.19). Overall, in patients with MI, AF was associated with increased 1-year case fatality (odds ratio 1.47, 95% confidence interval 1.07 to 2.01) compared with those without AF. However, there was no evidence that the impact of AF on MI survival changed over time or differed over time by sex, race, or MI classification (all p values >0.10). In conclusion, co-occurrence of AF in MI slightly increased between 1987 and 2009. The adverse impact of AF on survival in the setting of MI was consistent throughout. In the setting of MI, co-occurrence of AF should be viewed as a critical clinical event, and treatment needs unique to this population should be explored further., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Purpose: In randomized trials, patients with atrial fibrillation (AF) receiving dabigatran, a direct oral anticoagulant, had lower risk of intracranial bleeding (ICB) than those on warfarin. However, concerns exist about potential worse outcomes in dabigatran users if bleeding occurs, given the lack of approved reversal agents. Thus, we examined in-hospital mortality in AF patients with ICB being treated with dabigatran versus warfarin in a real-world population in the United States., Methods: We analyzed healthcare utilization claims in the Truven Health Marketscan Research Databases. The study sample included patients with AF admitted to a hospital with a primary diagnosis of ICB. Information on medications, inpatient, and outpatient diagnoses was obtained from available claims. Propensity score-adjusted risk ratios and 95% confidence intervals of in-hospital mortality comparing current users of dabigatran versus warfarin were estimated using relative risk regression., Results: Among 2391 AF patients admitted with ICB (2290 on warfarin, 101 on dabigatran), 531 died during their admission. In-hospital mortality was similar in those treated with warfarin (22%) or dabigatran (20%). Compared with warfarin users, the propensity score-adjusted risk ratio (95% confidence interval) of mortality in dabigatran users was 0.93 (0.62-1.37). Associations were similar across different ICB subtypes (intracerebral hemorrhage, subarachnoid hemorrhage, and subdural hematoma)., Conclusions: In this sample of AF patients with ICB on oral anticoagulants, dabigatran was not associated with higher in-hospital mortality compared with warfarin. Hence, reluctance to use dabigatran because of a lack of approved reversal agents is not supported by our results., (© 2014 American Heart Association, Inc.)

Objective: Increasingly, epidemiologic studies use administrative data to identify atrial fibrillation (AF). Capture of incident AF is not well documented. We examined incidence rates and concordance of AF diagnosis based on active cohort follow-up versus surveillance of Centers for Medicare and Medicaid Services data in the Atherosclerosis Risk in Communities study., Methods: Atherosclerosis Risk in Communities cohort participants without prevalent AF enrolled in fee-for-service Medicare, with inpatient and outpatient coverage, for at least 12 continuous months between 1991 and 2009 were included. In active Atherosclerosis Risk in Communities study follow-up, annual telephone calls captured hospitalizations and deaths with incident AF diagnosis codes. For Centers for Medicare and Medicaid Services data, incident AF was defined by billed inpatient and outpatient diagnoses., Results: Of 10,134 eligible cohort participants, 738 developed AF according to both Atherosclerosis Risk in Communities and Centers for Medicare and Medicaid Services data; an additional 93 and 288 incident cases were identified using only Atherosclerosis Risk in Communities and Centers for Medicare and Medicaid Services data, respectively. Incidence rates per 1,000 person-years were 10.8 (95% confidence interval: 10.1-11.6) and 13.6 (95% confidence interval: 12.8-14.4) in Atherosclerosis Risk in Communities and Centers for Medicare and Medicaid Services, respectively; agreement was 96%; kappa was 0.77 (95% confidence interval: 0.75-0.80). Earlier AF ascertainment by one system versus the other was not associated with any cardiovascular disease risk factors, after accounting for sociodemographic factors. Additional Centers for Medicare and Medicaid Services events did not alter observed associations between risk factors and AF., Conclusion: Among fee-for-service enrollees, AF incidence rates were slightly lower for active cohort follow-up than for Centers for Medicare and Medicaid Services surveillance, because the latter included outpatient atrial fibrillation. Concordance was high and combining the two approaches could provide a more complete picture of newly-diagnosed AF.