Causal Relationship Between Lung Function and Atrial Fibrillation: A Two Sample Univariable and Multivariable, Bidirectional Mendelian Randomization Study

Rationale, considerations, and goals for atrial fibrillation centers of excellence: A Heart Rhythm Society perspective

Background: Hypertensive patients are at increased risk of atrial fibrillation (AF). Although low baseline HDL levels have been associated with a higher risk of AF in some analyses, this has not been born out in recent population-based studies; whether changing levels of HDL over time are more strongly related to the risk of new AF has not been examined. Methods: Incident AF was examined in relation to baseline and in-treatment HDL levels prior to development of AF in 8267 hypertensive patients with no history of AF, in sinus rhythm on their baseline ECG, randomly assigned to losartan- or atenolol-based treatment. HDL levels at baseline and each year of testing were categorized into quartiles according to baseline HDL levels. Results: During 4.7±1.1 years follow-up, new AF developed in 645 patients (7.8%). In univariate analyses, compared with HDL >1.78 mMol/L, patients with in-treatment HDL <1.21 entered as a time-varying covariate had a 53% greater risk of new AF; patients with in-treatment HDL in the 2 nd or 3 rd quartiles had intermediate increased risks of AF. Baseline HDL was only a weak predictor of new AF. In multivariate Cox analyses adjusting for multiple AF risk factors, including the previously demonstrated predictive value of in-treatment heart rate and Cornell product LVH, there was no attenuation of the risk of new AF associated with low in-treatment HDL. In-treatment non-HDL cholesterol (p=0.171) and statin use (p=0.626) were not significant predictors of new AF in the multivariate model including in-treatment HDL. Baseline HDL was not a significant predictor of AF in multivariate analysis. Conclusions: Lower in-treatment HDL is strongly associated with risk of new AF, even after adjusting for other potential AF risk factors and treatment effects. These findings suggest that serial assessment of HDL can better estimate AF risk in hypertensive patients. Further study is indicated to determine whether therapies that increase HDL can lower risk of developing AF.

CE-452780-4 NEUROTICISM AND THE OCCURRENCE OF ATRIAL FIBRILLATION: EVIDENCE FROM OBSERVATIONAL EPIDEMIOLOGIC AND MENDELIAN RANDOMIZATION

Background and ObjectivesAtrial fibrillation (AF) is a common arrhythmia that is known as an important independent risk factor for stroke. However, limited information is available on AF in Korea. This study evaluated the incidence of AF, its associated co-morbidities and risk factors for AF in Korea.Subjects and MethodsThe National Health Insurance Service database between 2002 and 2010 was used in the study. Individuals<30 years old and those diagnosed with AF between 2002 and 2004 were excluded. Hazard ratios (HRs) according to co-morbidities and risk factors for AF were determined using a Cox proportional hazard model. Population attributable fractions (PAFs) of AF risk factors were determined.ResultsDuring a 6-year follow-up period, 3517 (1.7%) developed AF. The incidence rates in men and women aged 30-39 years were 0.82 and 0.55 per 1000 person-years, respectively; the incidence rates further increased with age to 13.09 and 11.54 per 1000 person-years in men and women aged≥80 years, respectively. The risk factors for incident AF were age, sex, body mass index (BMI), hypertension, ischemic heart disease (IHD) and heart failure. After adjusting for variables related to AF, the risk of AF was significantly associated with hypertension (HR 1.667), IHD (HR 1.639), heart failure (HR 1.521), and the PAFs for age, sex, BMI, hypertension, IHD, heart failure and diabetes mellitus were 30.6%, 10.1%, 3.4%, 16.6%, 8.2%, 5.3% and 0.8%, respectively.ConclusionIncidence of AF increased with age and was higher in men than in women. A larger proportion of AF events was attributable to hypertension than to other co-morbidities.

Whether statins, as upstream therapy for atrial fibrillation (AF), can reduce the incidence of AF in elderly individuals remains unclear. This study aimed to examine whether statin use is linked to a lower risk of incident AF in older adults from Shanghai, China. To provide important implications for optimizing the prevention and management strategies of AF in the elderly. Data for this retrospective cohort study were collected from a community health service center in Shanghai. Individuals had no history of AF in 2018 and before were included, and new cases of AF were documented in 2019, 2020, and 2021. A Poisson generalized linear model was used to evaluate the relationship between statin treatment and AF incidence. Both standard covariate adjustment and propensity score matching (PSM) to control for confounding factors. To evaluate the risk factors for new-onset AF among the elderly, univariate logistic analysis was conducted. Variables with statistical significance in univariate analysis (p < 0.05), such as sex, age, SBP, BMI, WHR, Scr and HbA1c were selected as covariates for inclusion in the multivariable logistic regression model. Out of the 5675 individuals in the study group (43.5% male; median age of 68years), 456 participants (8.0%) received statin treatment. The propensity score unmatched and matched cohorts of 453 participants (stain users and nou-users) were evaluated, in each group. There was no reduction in AF incidence with statin use (95%CI, 0.948 to 1.018) in the unmatched cohort and in the matched cohort (95%CI, 0.459 to 1.512). The multivariate regression analysis results showed that age, SBP, BMI, HbA1c and Scr were factors independently linked to the occurrence of new-onset AF. Despite extensive analysis, our study did not find evidence that statin use reduces the risk of new-onset AF in this population. For older people, taking statins did not reduce risk of new on-set AF. Independent predictors of AF onset including age, SBP, BMI, HbA1c and Scr. This is a retrospective cohort study, making it difficult to completely control for all confounding factors, and the short follow-up period may have resulted in insufficient statistical power to detect a meaningful effect of statins on atrial fibrillation. Future studies may use randomized controlled studies to explore the effects of different types and doses of statins on new-onset atrial fibrillation in older adults.

Risk of New-Onset Atrial Fibrillation Associated With Targeted Treatment of Lymphoma

Introduction: The prevalence of atrial fibrillation (AF) increases with age and inflammation plays a key pathophysiologic role. Somatic mosaicism increases with age and promotes inflammation. Therefore, we investigated whether Clonal Hematopoiesis of Indeterminate Potential (CHIP) is a risk factor for incident AF. Methods: We assessed exome sequence (ES) data from 200,628 participants in the UK biobank. Using the Genome Analysis Toolkit pipeline, we ascertained a predefined list of CHIP mutations in DNMT3A , TET2 , and ASXL1 . CHIP was defined as variant allele frequency (VAF) &gt;10% and those with VAF &lt;2% served as controls. AF was ascertained based on self-report and ICD codes. Lone AF was defined as AF in the absence of heart failure, mitral stenosis, mitral valve repair/valvotomy/replacement, and congenital heart disease. Those with AF prior to or at the time of enrollment were excluded from analyses to ascertain incident events. Cox proportional hazard models adjusted for age, sex, self-reported race/ethnicity, diabetes, hypertension, smoking, and obesity were used to identify associations between CHIP and incident AF. Results: Of 200,628 participants, 3885 (1.9%) had CHIP. The number of participants with mutations in DNMT3A , TET2 , and ASXL1 was 2512, 1065, and 439, respectively. During a median follow-up of 9 years, 4,676 incident AF and 3,584 incident lone AF occurred. CHIP was an independent risk factor for developing incident AF and also for developing lone AF. CHIP in TET2 and ASXL1 but not DNMT3A was associated with AF ( Table 1 ). Conclusions: The presence of CHIP involving TET2 and ASXL1 is associated with an increased risk of incident AF including the subset with lone AF. Our findings reveal somatic mosaicism in blood cells to be a novel risk factor for AF.

Introduction: Higher body mass index (BMI) is associated with an increased risk of incident atrial fibrillation (AF), but it is not known if this relationship varies based on race/ethnicity. Hypothesis: The relationship between BMI and incident AF will vary by race/ethnicity. Methods: Eligible MESA participants had no AF at baseline. The risk of incident AF as a function of baseline BMI was modelled using Cox proportional hazards. Formal tests of interaction by race/ethnicity were performed. Restricted cubic splines models were used to explore non-linear relationships. Results: Among 6,739 participants, 0.8% were underweight, 27.8% had normal BMI, 39.0% were overweight, 21.1% had grade I obesity, 7.6% had grade II obesity, and 3.7% had grade III obesity. Over 79,860 person-years of follow-up (median 13.8), 991 participants (14.7%) had new-onset AF. With BMI modeled as a categorical variable, only those with grade II and grade III obesity had an increased risk of AF (HR 1.48, 95% CI 1.13 - 1.94, p = 0.005 for grade II obesity and HR 2.21, 95% CI 1.11 - 4.40, p = 0.02 for grade III obesity ). The relationship between BMI and AF risk was non-linear, best characterized as J-shaped. However, the risk of AF as a function of BMI varied substantially by race/ethnicity (p-value for interaction = 0.02), with Chinese-American participants having a much higher risk of AF with higher BMI and African-American participants having minimal increased risk of AF with higher BMI (Figure 1). Conclusions: Obesity is associated with an increased risk of incident AF. The relationship between BMI and the risk of AF is J-shaped and this relationship differs by race/ethnicity, such that Chinese-Americans have a more pronounced increased risk of AF with higher BMI, while African-Americans have minimal increased risk. Further exploration of the differential effects of BMI by race/ethnicity on cardiovascular outcomes is needed.

Hyperthyroidism is an established risk factor for atrial fibrillation (AF), but information concerning the association with variations within the normal range of thyroid function and subgroups at risk is lacking. This study aimed to investigate the association between normal thyroid function and AF prospectively and explore potential differential risk patterns. From the Rotterdam Study we included 9166 participants ≥ 45 y with TSH and/or free T4 (FT4) measurements and AF assessment (1997-2012 median followup, 6.8 y), with 399 prevalent and 403 incident AF cases. Outcome measures were 3-fold: 1) hazard ratios (HRs) for the risk of incident AF by Cox proportional-hazards models, 2) 10-year absolute risks taking competing risk of death into account, and 3) discrimination ability of adding FT4 to the CHARGE-AF simple model, an established prediction model for AF. Higher FT4 levels were associated with higher risks of AF (HR 1.63, 95% confidence interval, 1.19-2.22), when comparing those in the highest quartile to those in lowest quartile. Absolute 10-year risks increased with higher FT4 in participants ≤ 65 y from 1-9% and from 6-12% in subjects ≥ 65 y. Discrimination of the prediction model improved when adding FT4 to the simple model (c-statistic, 0.722 vs 0.729; P = .039). TSH levels were not associated with AF. There is an increased risk of AF with higher FT4 levels within the normal range, especially in younger subjects. Adding FT4 to the simple model slightly improved discrimination of risk prediction.

Hypertension is the most common risk factor for atrial fibrillation (AF). The ability to screen for potential AF during blood pressure (BP) measurement may be a valuable tool for early AF detection. This study evaluated the frequency of irregular pulse rates suggestive of AF in subjects undergoing ambulatory BP monitoring (ABPM) and compared the characteristics of patients at low risk of presumed AF vs. those at high risk. ABPM recordings were obtained in 4419 subjects aged ≥65 years visiting 304 community pharmacies, with clinically validated automated monitors equipped with an algorithm for detecting possible AF episodes during BP measurement. Subjects with <30% of the readings suggestive of AF were categorized as having a low risk of AF, and those with ≥30% of readings were classified as high risk. A total of 531 subjects (12.0%) were categorized as having a high risk of AF, with the risk increasing with advancing age. Subjects at high risk of AF had lower average systolic BP, higher average diastolic BP and pulse rate (PR), increased BP and PR variabilities, and blunted sleep-associated reductions in BP and PR. In repeated recordings, the reliability of the AF detection algorithm per se was good (kappa 0.476, p = 0.0001; intraclass correlation coefficient 0.56, p = 0.0001). Simultaneous BP measurement and screening for potential AF by ABPM in elderly people in clinical practice may help improve BP control and the detection of subjects at high risk of AF. However, a finding of presumed AF must always be confirmed by an electrocardiogram (ECG).

Background Second-hand tobacco smoke (SHS) is related to coronary artery disease and increases susceptibility to arrhythmia inducibility including atrial fibrillation (AF). However, epidemiologic evidence on the relationship between SHS and the risk of incident AF remains controversial. Purpose To evaluate the effect of SHS exposure on the long-term risk of AF and assess whether gene-environment interaction (synergism) exists by utilising the population-based data from the UK biobank. Methods We performed a nationwide population-based cohort study using the UK Biobank database. Participants with previous AF or current smokers were excluded. Participants were categorised into SHS-exposure and non-exposure groups. The risk of incident AF was assessed using the multivariable Cox proportional hazards model. We also evaluated the synergistic effect of SHS exposure and the polygenic risk score (PRS) of AF. Results Out of 400,493 participants, AF occurred in 23,471 (5.9%) during a median follow-up of 12.5 years. The SHS-exposure group (mean exposure 2.2 ± 5.2 hours/week) had a higher proportion of male participants with a younger age. The risk of incident AF was significantly increased in the SHS-exposure group (multivariable-adjusted hazard ratio [aHR] 1.06, 95% confidence interval 1.03-1.10, P &amp;lt;0.001) compared to the non-exposure group, suggesting a dose-dependent manner (aHR of severe SHS-exposure group, 1.11 [1.03-1.20], P = 0.005). The risk of AF increases regardless of the exposure location (home, outside, or workplace). When SHS-exposure was combined with the high genetic risk of AF, significant additive interaction was observed on the risk AF (Synergy Index of SHS-exposure with 3rdtertile of AF PRS, 1.13 [1.02-1.25], P = 0.024). Conclusion Exposure to SHS is a significant predictor for an increased risk of AF, with a synergistic effect when combined with genetic predisposition. Minimising SHS exposure, especially in individuals with a heightened genetic susceptibility to AF, may hold potential benefits for reducing the future risk of AF.

Alcohol Abstinence Around Atrial Fibrillation Ablation: Breaking Common Habits.

BackgroundBodyweight variability is a risk factor for atrial fibrillation (AF). We aimed to examine the relationship between bodyweight variability and the risk of AF in patients with type 2 diabetes mellitus (DM), and whether this relationship was affected by baseline body mass index (BMI), weight change, or advanced diabetic stage.MethodsA nationwide population-based cohort of 670,797 patients with type 2 DM from the Korean National Health Insurance Service database without a history of AF and with ≥ 3 measurements of bodyweight over a 5-year period were followed up for AF development. Intra-individual bodyweight variability was calculated using variability independent of mean, and high bodyweight variability was defined as the quintile with the highest variability with the lower four quintiles as reference.ResultsDuring a median of 7.0 years of follow-up, 22,019 patients (3.3%) newly developed AF. After multivariate adjustment, those in the highest quintile of bodyweight variability showed a higher risk of incident AF (HR 1.16, 95% CI 1.12–1.20) compared to those in the lower 4 quintiles with reference bodyweight variability, irrespective of baseline BMI group and direction of overall weight change. This association was greater in magnitude in subjects with lower BMI, those on insulin, and those with a DM duration of greater than 5 years. In sensitivity analyses, high bodyweight variability was consistently associated with AF development using other indices of variability and adjusting for glycemic variability.ConclusionsHigh variability in bodyweight was associated with AF development, independently of traditional cardiovascular risk factors and baseline BMI. This association was stronger in underweight patients and with advanced diabetic stage. Weight fluctuation may interfere with the beneficial effects of weight loss and should be avoided when possible in weight control regimens for DM patients.

Decreased lung function is related to higher cardiovascular disease (CVD) incidence and mortality. However, little is known about the relationship between the risk factors of CVD and pulmonary function. The aim of the study was to assess the relationship between the prevalence of cardiovascular risk factors, the total CVD risk, and pulmonary function. The analysis included 4104 men and women aged 45 to 69 years, participants of the Polish part of the Health, Alcohol, and Psychosocial factors In Eastern Europe (HAPIEE) Project, who provided valid measurements of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) using a Micro-Medical Microplus spirometer. The prevalence of CVD risk factors was defined as follows: hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or taking hypertension medication), diabetes (glucose ≥ 7.1 mmol/L or self-reported diabetes), and hypercholesterolaemia (total cholesterol ≥ 5 mmol/L or low-density lipoprotein-cholesterol ≥ 3 mmol/L or taking lipid lowering medication). Categories of total CVD risk were defined according to the 2016 European Guidelines on CVD prevention in clinical practice. The analysis of covariance was used to compare the lung function in the CVD risk factors and the total CVD risk categories. Mean values of FEV1 and FVC, adjusted for age and height, were significantly higher in men than in women (3.02 L; 95% confidence interval [CI] 2.96-3.08 L vs. 2.52 L; 95% CI 2.45-2.63 L for FEV1 and 3.62 L; 95% CI 3.56-3.69 L vs. 3.05 L; 95% CI 2.98-3.12 L for FVC). Obesity was significantly associated with FVC in men and women; it was associated with FEV1 only in men. Compared with participants with normal body mass index, obese men and women had 280 mL and 112 mL lower mean FVC, respectively. Men without hypertension had almost 100 mL higher mean FVC than those with hypertension. The difference in FVC in women was approximately 80 mL. Diabetes was associated with lower values of FVC in both sexes and with FEV1 in women. A significant negative trend was observed in the mean FVC and FEV1 by the considered CVD risk categories. Impaired lung function was associated with higher CVD risk, which could be explained partly by an adverse association between lung function and prevalence of obesity, hypertension, and diabetes.

C-Reactive Protein Levels and Atrial Fibrillation After Cardiac Surgery in Women