Background: Atrial fibrillation (AF) significantly increases the ischemic stroke risk. However, the relationship between age at diagnosis of AF and subsequent stroke risk remains poorly understood. Methods and Results: We analyzed data from 5 prospective cohorts: ARIC (Atherosclerosis Risk in Communities) study, CHS (Cardiovascular Health Study), CARDIA (Coronary Artery Risk Development in Young Adults), MESA (Multi‐Ethnic Study of Atherosclerosis), and Framingham Heart Study (including Offspring cohort and the Third‐Generation cohorts). Cox regression models and competing risk survival analyses were used to assess incidence rates and hazard ratios (HRs) for ischemic stroke stratified by age groups. Among 47 239 participants (median follow‐up: 21.1 years), 6689 (14.2%) developed AF, and 536 (8.0%) subsequently experienced ischemic stroke. Younger age at AF diagnosis was significantly associated with a higher ischemic stroke risk. Fully adjusted HRs for ischemic stroke were 5.35 (95% CI, 3.56–8.03), 2.99 (95% CI, 2.32–3.86), 2.13 (95% CI, 1.75–2.58), and 1.93 (95% CI, 1.59–2.34) for AF diagnosed at ages 55, 65, 75, and 85, respectively. Compared with participants without AF at age 55, HRs for ischemic stroke were 7.30 (95% CI, 3.27–16.31) for AF diagnosed >10 years earlier, 4.98 (95% CI, 2.99–8.29) for 6 to 10 years earlier, and 4.60 (95% CI, 1.48–14.34) for ≤5 years earlier ( P ‐trend <0.001). The presence of AF yielded a 13.9 years earlier occurrence of ischemic stroke among those with AF diagnosis at 55 years compared with 1.5 years earlier at age 85. Conclusions: Younger age at AF diagnosis was associated with a higher risk of subsequent ischemic stroke.

Aims: Both genetic and environmental factors contribute to the development of ventricular arrhythmias (VAs). However, the extent to which genetic susceptibility modifies the effects of air pollutants on the risk of VAs remains poorly understood. Methods and results: This study included 491 305 participants without VAs at baseline from UK Biobank. Exposure to ambient air pollutants, including particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX), was estimated through land use regression modelling. The associations between air pollutants and the incidence of VAs were then investigated using a Cox proportional hazards model adjusted for covariates. Additionally, we established a polygenic risk score for VAs and assessed the joint effect of genetic susceptibility and air pollution on incident VAs. During a median follow-up of 14.3 years, 4333 participants were diagnosed with VAs. Increased long-term exposure to PM2.5, PM10, NO2, and NOx was significantly associated with higher risks of VAs, with hazard ratios (HRs) per quintile increase of 1.07 (95% confidence interval, 95% CI: 1.03–1.11), 1.07 (1.03–1.11), 1.10 (1.06–1.14), and 1.08 (1.05–1.12) for each pollutant, respectively. Notably, there were significant additive interactions between air pollutants and genetic risk. Participants with both high genetic risk and high exposure to air pollution exhibited the greatest risk of VAs, with the highest HRs observed for PM2.5 (HR, 4.51; 95% CI, 3.66–5.56), PM10 (HR, 4.28; 95% CI, 3.52–5.22), NO2 (HR, 4.90; 95% CI, 3.97–6.03), and NOx (HR, 4.56; 95% CI, 3.72–5.60), respectively. Conclusion: Long-term exposure to air pollution is associated with an increased risk of VAs, especially in individuals with a high genetic risk.

Background: Patient prevalence of atrial fibrillation (AF) and heart failure (HF) is increasing, and anticoagulation for patients from heterogeneous backgrounds with both conditions remains controversial. In this meta-analysis, we are aiming to compare the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in AF patients with HF and preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) ejection fraction.Methods and results: We systematically searched the PubMed, Cochrane, and Embase databases until January 2022. The primary effectiveness and safety outcomes were stroke or systemic embolism (SSE) and major bleeding, respectively. We abstracted risk ratios (RR) and 95% confidence intervals (CIs) and compiled them using a random-effects model. We analyzed data of 266,291 patients from 10 studies. By comparing NOACs with warfarin, patients with AF and HF have reduced the risk of SSE (RR: 0.83, 95% CI 0.76–0.91), all-cause mortality (RR: 0.85, 95% CI 0.80–0.91), major bleeding (RR: 0.79, 95% CI 0.69–0.90), and intracranial hemorrhage (RR: 0.54, 95% CI 0.46–0.63). Further analyses based on the HF subtypes showed that NOACs reduced the chances of SSE (RR: 0.71, 95% CI 0.53–0.94) in the HFrEF group and major bleeding (RR: 0.74, 95% CI 0.57–0.95) in HFmrEF and HFpEF groups. There were no differences regarding SSE (RR: 0.91, 95% CI 0.76–1.09) in HFmrEF and HFpEF groups and major bleeding (RR: 0.99, 95% CI 0.79–1.23) in the HFrEF group.Conclusion: For patients with AF and HF, NOACs have better or similar effectiveness and safety than warfarin, but the stroke prevention superiority of NOACs over warfarin varies in different HF subtypes.

Lower socioeconomic status, intelligence, and cognition are linked to a higher likelihood of atrial fibrillation (AF). However, whether these factors directly cause AF or whether others mediate this relationship is unclear. Our study aimed to determine the causal link between lower socioeconomic status, intelligence, cognition, and AF, and identify mediators. We conducted a 2-sample Mendelian randomization analysis with data from European ancestry genome-wide association studies. Genetic instruments for education, intelligence, cognition, income, and occupation (n = 248,847-1,131,881) evaluated their relationship with AF (FinnGen study: 50,743 cases and 210,652 control subjects; 6 European studies: 60,620 and 970,216). The pooled results from meta-analysis combining data from 2 studies indicated that education, intelligence, and cognition were causally associated with AF (P < 0.05). Genetically predicted, each 1-SD increase in educational attainment was associated with a 19% decreased risk of AF (OR: 0.81; 95% CI: 0.71-0.92), independent of intelligence and cognition. Among 44 candidate mediators, 8 factors were identified to mediate the education-AF association, including heart failure (mediation proportion: 95.35%), body fat mass (44.05%), waist circumference (42.93%), coronary heart disease (30.1%), body mass index (29.0%), myocardial infarction (28.8%), diastolic blood pressure (21.7%), and waist-to-hip ratio (14.3%). Our study suggests that education exerts a causal and protective effect against AF, independent of intelligence and cognition. Heart failure, obesity, and ischemic heart disease serve as mediating factors in the pathway from education to AF, underscoring the importance of considering these conditions in preventing AF associated with education inequality.