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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We previously reported that incident atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. We now aimed to identify predictors of SCD in persons with AF from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort study. We included all participants who attended visit 1 (1987–89) and had no prior AF (n = 14,836). Incident AF was identified from study electrocardiograms and hospitalization discharge codes through 2012. SCD was physician-adjudicated. We used cause-specific Cox proportional hazards models, followed by stepwise selection (backwards elimination, removing all variables with p>0.10) to identify predictors of SCD in participants with AF. AF occurred in 2321 (15.6%) participants (age 45–64 years, 58% male, 18% black). Over a median of 3.3 years, SCD occurred in 110 of those with AF (4.7%). Predictors of SCD in AF included higher age, body mass index (BMI), coronary heart disease, hypertension, diabetes, current smoker, left ventricular hypertrophy, increased heart rate, and decreased albumin. Predictors associated only with SCD and not other cardiovascular (CV) death included increased BMI (HR per 5-unit increase, 1.15, 95% CI, 0.97–1.36, p = 0.10), increased heart rate (HR per SD increase, 1.18, 95% CI 0.99–1.41, p = 0.07), and low albumin (HR per SD decrease 1.23, 95% CI 1.02–1.48, p = 0.03). In the ARIC study, predictors of SCD in AF that are not associated with non-sudden CV death included increased BMI, increased heart rate, and low albumin. Further research to confirm these findings in larger community-based cohorts and to elucidate the underlying mechanisms to facilitate prevention is warranted. [ABSTRACT FROM AUTHOR]

Background: Although current alcohol consumption is a risk factor for incident atrial fibrillation (AF), the more clinically relevant question may be whether alcohol cessation is associated with a reduced risk. Methods and results: We studied participants enrolled in the Atherosclerosis Risk in Communities Study (ARIC) between 1987 and 1989 without prevalent AF. Past and current alcohol consumption were ascertained at baseline and at 3 subsequent visits. Incident AF was ascertained via study ECGs, hospital discharge ICD-9 codes, and death certificates. Of 15,222 participants, 2,886 (19.0%) were former drinkers. During a median follow-up of 19.7 years, there were 1,631 cases of incident AF, 370 occurring in former consumers. Former drinkers had a higher rate of AF compared to lifetime abstainers and current drinkers. After adjustment for potential confounders, every decade abstinent from alcohol was associated with an approximate 20% (95% CI 11–28%) lower rate of incident AF; every additional decade of past alcohol consumption was associated with a 13% (95% CI 3–25%) higher rate of AF; and every additional drink per day during former drinking was associated with a 4% (95% CI 0–8%) higher rate of AF. Conclusions: Among former drinkers, the number of years of drinking and the amount of alcohol consumed may each confer an increased risk of AF. Given that a longer duration of abstinence was associated with a decreased risk of AF, earlier modification of alcohol use may have a greater influence on AF prevention. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population. Methods: We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes. Results: During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14–1.70), coronary heart disease (HR 1.72, 95%CI 1.11–2.66), heart failure (HR 2.87, 95%CI 2.17–3.80), stroke (HR 1.56, 95%CI 0.99–2.46), AF (HR 5.75, 95%CI 4.43–7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9–67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51–2.66), AF (HR 4.25, 95%CI 3.28–5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8–32.1). Conclusion: Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation. [ABSTRACT FROM AUTHOR]