Patients with atrial fibrillation (AF) have many comorbidities and excess risks of hospitalization and death. Whether the impact of comorbidities on outcomes is greater in AF than the general population is unknown. Methods One thousand four hundred thirty patients with AF and community controls matched 1:1 on age and sex were obtained from Olmsted County, Minnesota. Andersen-Gill and Cox regression estimated associations of 19 comorbidities with hospitalization and death, respectively. Results AF cases had a higher prevalence of most comorbidities. Hypertension (25.4%), coronary artery disease (17.7%), and heart failure (13.3%) had the largest attributable risk of AF; these along with obesity and smoking explained 51.4% of AF. Over a mean follow-up of 6.3 years, patients with AF experienced higher rates of hospitalization and death than did population controls. However, the impact of comorbidities on hospitalization and death was generally not greater in patients with AF compared with controls, with the exception of smoking. Ever smokers with AF experienced higher-than-expected risks of hospitalization and death, with observed vs expected (assuming additivity of effects) hazard ratios compared with never smokers without AF of 1.78 (1.56-2.02) vs 1.52 for hospitalization and 2.41 (2.02-2.87) vs 1.84 for death. Conclusions Patients with AF have a higher prevalence of most comorbidities; however, the impact of comorbidities on hospitalization and death is generally similar in AF and controls. Smoking is a notable exception; ever smokers with AF experienced higher-than-expected risks of hospitalization and death. Thus, interventions targeting modifiable behaviors may benefit patients with AF by reducing their risk of adverse outcomes.

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.

Background: Observational studies have identified an association between body mass index (BMI) and incident atrial fibrillation (AF). Inferring causality from observational studies, however, is subject to residual confounding, reverse causation, and bias. The primary objective of this study was to evaluate the causal association between BMI and AF by using genetic predictors of BMI. Methods: We identified 51 646 individuals of European ancestry without AF at baseline from 7 prospective population-based cohorts initiated between 1987 and 2002 in the United States, Iceland, and the Netherlands with incident AF ascertained between 1987 and 2012. Cohort-specific mean follow-up ranged from 7.4 to 19.2 years, over which period there was a total of 4178 cases of incident AF. We performed a Mendelian randomization with instrumental variable analysis to estimate a cohort-specific causal hazard ratio for the association between BMI and AF. Two genetic instruments for BMI were used: FTO genotype (rs1558902) and a BMI gene score comprising 39 single-nucleotide polymorphisms identified by genome-wide association studies to be associated with BMI. Cohort-specific estimates were combined by random-effects, inverse variance-weighted meta-analysis. Results: In age- and sex-adjusted meta-analysis, both genetic instruments were significantly associated with BMI (FTO: 0.43 [95% confidence interval, 0.32-0.54] kg/m 2 per A-allele, P < 0.001; BMI gene score: 1.05 [95% confidence interval, 0.90-1.20] kg/m 2 per 1-U increase, P < 0.001) and incident AF (FTO, hazard ratio, 1.07 [1.02-1.11] per A-allele, P=0.004; BMI gene score, hazard ratio, 1.11 [1.05-1.18] per 1-U increase, P < 0.001). Age- and sex-adjusted instrumental variable estimates for the causal association between BMI and incident AF were hazard ratio, 1.15 (1.04-1.26) per kg/m 2 , P=0.005 (FTO) and 1.11 (1.05-1.17) per kg/m 2 , P < 0.001 (BMI gene score). Both of these estimates were consistent with the meta-analyzed estimate between observed BMI and AF (age- and sex-adjusted hazard ratio 1.05 [1.04-1.06] per kg/m 2 , P < 0.001). Multivariable adjustment did not significantly change findings. Conclusions: Our data are consistent with a causal relationship between BMI and incident AF. These data support the possibility that public health initiatives targeting primordial prevention of obesity may reduce the incidence of AF.

Background: Limited information exists on the lifetime risk of atrial fibrillation (AF) in African Americans and by socioeconomic status. Methods: We studied 15 343 participants without AF at baseline from the ARIC (Atherosclerosis Risk in Communities) cohort recruited in 1987 to 1989 from 4 communities in the United States when they were 45 to 64 years of age. Participants have been followed through 2014. Incidence rates of AF were calculated dividing the number of new cases by person-years of follow-up. Lifetime risk of AF was estimated by a modified Kaplan-Meier method considering death as a competing risk. Participants' family income and education were obtained at baseline. Results: We identified 2760 AF cases during a mean follow-up of 21 years. Lifetime risk of AF was 36% (95% confidence interval, 32%-38%) in white men, 30% (95% confidence interval, 26%-32%) in white women, 21% (95% confidence interval, 13%-24%) in African American men, and 22% (95% confidence interval, 16%-25%) in African American women. Regardless of race and sex, incidence rates of AF decreased from the lowest to the highest categories of income and education. In contrast, lifetime risk of AF increased in individuals with higher income and education in most sex-race groups. Cumulative incidence of AF was lower in those with higher income and education compared with their low socioeconomic status counterparts through earlier life but was reversed after age 80. Conclusions: Lifetime risk of AF in the ARIC cohort was ≈1 in 3 among whites and 1 in 5 among African Americans. Socioeconomic status was inversely associated with cumulative incidence of AF before the last decades of life.

Low heart rate variability (HRV) has been linked to increased total mortality in the general population; however, the relationship between low HRV and sudden cardiac death (SCD) is less well-characterized. The goal of this study was to evaluate the relationship between low HRV and SCD in a community-based cohort. Our cohort consisted of 12,543 participants from the Atherosclerosis Risk in Communities (ARIC) study. HRV measures were derived from 2-minute electrocardiogram recordings obtained during the baseline exam (1987-89). Time domain measurements included the standard deviation of all normal RR intervals (SDNN) and the root mean squared successive difference (r-MSSD). Frequency domain measurements included low frequency power (LF) and high frequency (HF) power. During a median follow-up of 13 years, 215 SCDs were identified from physician adjudication of all coronary heart disease deaths through 2001. In multivariable adjusted Cox proportional hazards models, each standard deviation decrement in SDNN, LF, and HF were associated with 24%, 27% and 16% increase in SCD risk, respectively. Low HRV is independently associated with increased risk of SCD in the general population.

Objective: The incidence and prevalence of cognitive decline and dementia are significantly higher among African Americans compared with non-Hispanic Whites. The aim of this study was to determine whether inheritance of the sickle cell trait (SCT) i.e. heterozygosity for the sickle cell mutation increases the risk of cognitive decline or dementia Among African Americans. Methods: We studied African American participants enrolled in the Atherosclerosis Risk in Communities study. SCT genotype at baseline and outcome data from cognitive assessments at visits 2, 4 and 5, and an MRI performed at visit 5 were analyzed for the association between SCT and risk of cognitive impairment and/or dementia. Results: There was no significant difference in risk factors profile between participants with SCT (N = 176) and those without SCT (N = 2532). SCT was not independently associated with a higher prevalence of global or domain-specific cognitive impairment at baseline or with more rapid cognitive decline. Participants with SCT had slightly lower incidence of dementia (HR = 0.63 [0.38, 1.05]). On the other hand, SCT seems to interact with the apolipoprotein E ε4 risk allele resulting in poor performance on digit symbol substitution test at baseline (z-score = −0.08, Pinteraction = 0.05) and over time (z-score = −0.12, Pinteraction = 0.04); and with diabetes mellitus leading to a moderately increased risk of dementia (HR = 2.06 [0.89, 4.78], Pinteraction = 0.01). Conclusions: SCT was not an independent risk factor for prevalence or incidence of cognitive decline or dementia, although it may interact with and modify other putative risk factors for cognitive decline and dementia.

Introduction: The objective of this study was to investigate whether 10 phospholipids/metabolites previously identified as prospectively predictive of mild cognitive impairment (MCI) or dementia in whites would also be predictive in a mostly African-American cohort. Methods: We repeatedly measured 188 phospholipids/metabolites in plasma samples of 221 participants of the Atherosclerosis Risk in Communities study, 97% African American, who were followed between 2004–2006 and 2011–2013. Results: After a mean follow-up of 7.3 years, 77 were classified as having MCI and 18 as having dementia. Our study failed to replicate previous findings in this mostly African American cohort, in that the 10 phospholipids/metabolites only achieved a C statistic/AUC of 0.609 in predicting development of MCI or dementia (compared to 0.96) and 0.607 in distinguishing normal from MCI or dementia at the follow-up visit. Conclusion: A panel of 10 phospholipids/metabolites previously associated with incident dementia was not predictive of MCI or dementia in an independent cohort.

Intimate partner violence has adverse health consequences, but little is known about its association with hypertension. This study investigates sex differences in the relationship between intimate partner violence and blood pressure outcomes. Data included 9,699 participants from waves 3 (2001-02) and 4 (2008-09) of the National Longitudinal Study of Adolescent Health (51% female). Systolic (SBP) and diastolic (DBP) blood pressure and incident hypertension (SBP≥140 mmHg, DBP≥90 mmHg, or taking antihypertensive medication) were ascertained at wave 4. Intimate partner violence was measured at wave 3 with 8 items from the revised Conflict Tactics Scales. Separate victimization and perpetration scores were calculated. Sex-specific indicators of severe victimization and perpetration were created using the 66th percentile among those exposed as a cut point. Sex-specific, linear and logistic regression models were developed adjusting for age, race, financial stress, and education. Thirty-three percent of men and 47% of women reported any intimate partner violence exposure; participants were categorized as having: no exposure, moderate victimization and / or perpetration only, severe victimization, severe perpetration, and severe victimization and perpetration. Men experiencing severe perpetration and victimization had a 2.66 mmHg (95% CI: 0.05, 5.28) higher SBP and a 59% increased odds (OR: 1.59, 95% CI: 1.07, 2.37) of incident hypertension compared to men not exposed to intimate partner violence. No other category of violence was associated with blood pressure outcomes in men. Intimate partner violence was not associated with blood pressure outcomes in women. Intimate partner violence may have long-term consequences for men's hemodynamic health. Screening men for victimization and perpetration may assist clinicians to identify individuals at increased risk of hypertension.

Resting heart rate (RHR) is independently associated with cardiovascular disease (CVD) risk. We determined whether RHR, measured in mid-life, is also associated with cognitive decline. We studied 13,720 middle-aged white and black ARIC participants without a history of stroke or atrial fibrillation. RHR was obtained from a 12-lead resting electrocardiogram at the baseline visit (1990 to 1992) and categorized into groups as <60 (reference), 60 to 69, 70 to 79 and ≥80 beats/min. Cognitive scores were obtained at baseline and at up to 2 additional visits (1996 to 1998 and 2011 to 2013). The primary outcome was a global composite cognitive score (Z-score) derived from 3 tests: delayed word recall, digit symbol substitution, and word fluency. The associations of RHR with cognitive decline and incident dementia were examined using linear mixed-effects and Cox hazard models, respectively, adjusting for sociodemographics, CVD risk factors, and AV-nodal blockade use. Multiple imputation methods were used to account for attrition over follow-up. Participants had mean ± SD age of 58 ± 6 years; 56% were women, 24% black. Average RHR was 66 ± 10 beats/min. Over a mean follow-up of 20 years, those with RHR ≥80 beats/min had greater global cognitive decline (average adjusted Z-score difference −0.12 [95% confidence interval −0.21, −0.03]) and increased risk for incident dementia (hazard ratio 1.28 (1.04, 1.57), compared with those with RHR <60 beats/min. In conclusion, elevated RHR is independently associated with greater cognitive decline and incident dementia over 20 years. Further studies are needed to determine whether the associations are causal or secondary to another underlying process, and whether modification of RHR can affect cognitive decline.