Lower Risk Of Atrial Fibrillation Research Articles

Long-term weight change in midlife, cardiac magnetic resonance parameters, risk of atrial fibrillation: a large prospective cohort study

Abstract Background Although obesity is a well-established risk factor for atrial fibrillation (AF), the relationship between weight change and the risk of AF remains controversial. Furthermore, the extent to which obesity-associated AF risk is mediated by cardiac remodeling is unclear. Purpose We aimed to evaluate the impacts of obesity and weight change on the risk of atrial fibrillation, and the role of cardiac remodeling in obesity-AF association. Methods This is a population-based prospective cohort of UK Biobank participants recruited from 2006 to 2010. A total of 490,969 participants and 19,634 participants were included for BMI and BMI change analysis, respectively. Body mass index (BMI) was assessed at baseline and follow-up assessment (2012-2013). Cardiovascular measurements were derived from cardiovascular magnetic resonance. Cox proportional hazard models were used to assess the associations of obesity and change in BMI with AF. The nonlinear associations of BMI and BMI change with AF were tested using a restricted cubic spine (RCS). Mediation analysis was conducted to quantify the role of cardiac remodeling in the association between obesity and AF. Results Among the 490,969 participants included (mean age: 56.4 ± 8.1 years, 54.9% women), 33,297 incident AF cases were observed during a median follow-up of 14.0 years. Overweight (hazard ratio [HR], 1.12, 95% confidence interval [CI] 1.09-1.15, P < 0.001) and obesity (1.73, 1.68-1.78, P < 0.001) significantly increased the risk of AF, particularly in men, those with age < 60 years and low genetic risk. During a median follow-up of 4.43 years, 1,217 (6.2%) participants experienced > 2% BMI loss per year and 1,318 (6.7%) participants experienced > 2% BMI gain per year. Compared to stable BMI, BMI loss was associated with a lower risk of AF (0.75, 0.57-0.99, P = 0.039). In addition, we found that BMI loss from obesity to overweight was associated with a reduced risk of AF (0.74, 0.54-1.02, P = 0.069) compared with maintaining baseline BMI category. Participants with stable obesity had a higher risk of AF (1.81, 1.52-2.16, P < 0.001) than those with stable normal weight. In addition, RCS indicated BMI had a J-shaped association with AF while BMI change had a linear association with AF. Mediation analyses revealed that left ventricular myocardial mass, left atrial maximum volume, and left atrial minimum volume were the three strongest mediating factors between obesity and AF, with a mediated proportion of 85.28%, 64.43%, and 55.89% of the total effect, respectively. Conclusion BMI decrease over 2% per year was associated with a lower risk of AF, especially in those changing from obesity to overweight. Left ventricular myocardial mass plays a central role in mediating obesity-related AF. Our findings support weight management at the population level to mitigate the growing epidemic of AF and ways targeting left ventricular myocardial mass are waiting to be further explored.Associations of BMI, BMI change with AFThe mediating role of cardiac remodeling

The Comparison of the Effectiveness of Dapagliflozin and Empagliflozin in the Prevention of Cardiovascular Outcomes in Patients With Type 2 Diabetes: A Network Meta-Analysis.

Type 2 diabetes mellitus (T2DM) is a significant risk factor for cardiovascular diseases, prompting research into treatments that can mitigate this risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, particularly dapagliflozin and empagliflozin, have shown promising cardiovascular benefits in T2DM patients. This meta-analysis aimed to directly compare the cardiovascular outcomes of these two drugs. To achieve this, we conducted a comprehensive literature search across multiple databases up to August 5, 2024, including both randomized controlled trials (RCTs) and observational studies. The primary outcomes of interest were major adverse cardiovascular events (MACE), atrial fibrillation (AF), cardiovascular mortality, myocardial infarction (MI), and hospitalization for heart failure (HF). Twelve studies met the inclusion criteria for this meta-analysis. The pooled analysis revealed several key findings. Notably, dapagliflozin demonstrated superior efficacy in preventing atrial fibrillation compared to empagliflozin. However, no significant differences were observed between the two drugs in terms of MACE, cardiovascular mortality, hospitalization for heart failure (HHF), or myocardial infarction. When compared to placebo, both dapagliflozin and empagliflozin showed greater effectiveness in preventing adverse cardiovascular outcomes in T2DM patients.These results reinforce the cardiovascular benefits of both dapagliflozin and empagliflozin in patients with T2DM. The comparable efficacy in most outcomes suggests that clinicians have flexibility in prescribing either of these SGLT2 inhibitors. However, the lower risk of atrial fibrillation associated with dapagliflozin may be a crucial factor in treatment decisions, especially for patients with a history of or at high risk for atrial fibrillation.

Integrative multi-omics summary-based mendelian randomization identifies key oxidative stress-related genes as therapeutic targets for atrial fibrillation and flutter.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with substantial morbidity and mortality. Oxidative stress (OS) has been implicated in the pathogenesis of AF, suggesting that targeting OS-related genes could offer novel therapeutic opportunities. This study aimed to identify causal OS-related genes contributing to AF through a comprehensive multi-omics Summary-based Mendelian Randomization (SMR) approach. This study integrated data from genome-wide association studies (GWAS) with methylation quantitative trait loci (mQTL), expression QTL (eQTL), and protein QTL (pQTL) to explore the relationships between oxidative stress-related (OS-related) genes and AF risk. Genes associated with oxidative stress and AF were obtained from the Nielsen et al. study (discovery) and the FinnGen study (replication). The SMR analysis and HEIDI test were utilized to assess causal associations, followed by Bayesian co-localization analysis (PPH4 > 0.5) to confirm shared causal variants. Multi-omics data were employed to analyze the associations within mQTL-eQTL pathways. A two-sample MR analysis was conducted for sensitivity verification. The significance of findings was determined using a false discovery rate (FDR) < 0.05 and p_HEIDI > 0.01. At the DNA methylation level, 19 CpG sites near 7 unique genes were found to have causal effects on AF and strong co-localization evidence support (PPH4 > 0.70). At the gene expression level, six oxidative stress-related genes from eQTLGen and three from GTEx (v8), including TNFSF10, CDKN1A, ALOX15, TTN, PTK2, ALB, KCNJ5, and CASQ2, were found to have causal effects on AF in the sensitivity and co-localization analyses (PPH4 > 0.50). At the circulating protein level, both ALAD (OR 0.898, 95% CI 0.845-0.954, PPH4 = 0.67) and APOH (OR 0.896, 95% CI 0.844-0.952, PPH4 = 0.93) were associated with a lower risk of AF, and APOH was validated in the replication group. After integrating the multi-omics data between mQTL and eQTL, we identified two oxidative stress-related genes, TTN and CASQ2. The methylation of cg09915519 and cg10087519 in TTN was associated with higher expression of TTN and a lower risk of AF, which aligns with the negative effect of TTN gene expression on AF risk. TTN may play a protective role in AF. This study identified several OS-related genes, particularly TTN, as having causal roles in AF, which were verified across three-omics pathways. The findings underscore the importance of these genes in AF pathogenesis and highlight their potential as therapeutic targets. The integration of multi-omics data provides a comprehensive understanding of the molecular mechanisms underlying AF, paving the way for targeted therapeutic strategies.

Smoking Cessation and Incident Atrial Fibrillation in a Longitudinal Cohort

BackgroundAlthough smoking heightens the risk of AF, it remains unknown if that risk is amenable to modification after smoking cessation. ObjectivesThis study sought to evaluate the association between smoking cessation and atrial fibrillation (AF) risk in a large longitudinal cohort. MethodsAfter excluding those with prevalent AF and no history of smoking at baseline, we evaluated 146,772 UK Biobank participants with serial smoking assessments. We compared AF risk between former smokers at baseline and those who quit smoking during the study to current smokers. Incident AF was ascertained from outpatient and inpatient encounters and identified using International Classification of Diseases codes. Cox models were used to compare the risk of incident AF among current and former smokers as well as those who quit smoking during the study while controlling for age, sex, race, body mass index, education, cardiovascular comorbidities, alcohol use, and pack-years. ResultsAmong the 146,772 participants (48.3% female; age: 57.3 ± 7.9 years), 37,377 (25.5%) currently smoked; 105,429 (72.0%) were former smokers; and 3,966 (2.7%) quit smoking during the study. Over a mean 12.7 ± 2.0 years of follow-up, 11,214 (7.6%) participants developed AF. Compared to current smokers, the adjusted risk of AF was 13% lower in former smokers (HR: 0.87; 95% CI: 0.83-0.91) and 18% lower in those who quit smoking during the study (HR: 0.82; 95% CI: 0.70-0.95). ConclusionsCompared to those who continue to smoke, smoking cessation was associated with a lower risk of AF.

Adulthood weight changes, body mass index in youth, genetic susceptibility and risk of atrial fibrillation: a population-based cohort study

BackgroundEpidemiological evidence on weight change and atrial fibrillation (AF) remains limited and inconsistent. Previous studies on body mass index (BMI) in youth and AF rarely considered subsequent BMI. This study aimed to assess the associations of AF with weight change and BMI in youth, as well as modified effect by genetic susceptibility of AF.MethodsThe study included 21,761 individuals (mean age 57.8 years) from the Malmö Diet and Cancer cohort. Weight information was obtained at three time points, including recalled weight at age 20 years, measured weight at baseline (middle adulthood), and reported weight at 5-year follow-up examination (late middle adulthood). A weighted genetic risk score of AF was created using 134 variants.ResultsDuring a median follow-up of 23.2 years, a total of 4038 participants developed AF. The association between weight change from early to middle adulthood and AF risk was modified by sex (Pinteraction = 0.004); weight loss was associated with a lower AF risk in females, but not in males. Conversely, weight gain was positively associated with AF risk in a linear manner in females, whereas increased AF risk appeared only when weight gain exceeded a threshold in males. Participants with weight gain of > 5 kg from middle to late middle adulthood had a 19% higher risk of AF relative to those with stable weight, whereas weight loss showed a null association. Compared to individuals with a lower BMI at age 20 years, those with a BMI above 25 kg/m2 had an increased risk of AF (HR = 1.14; 95% CI: 1.02–1.28), after controlling for baseline BMI; this association was more pronounced in males or those with a lower genetic risk of AF.ConclusionsWeight gain in middle adulthood was associated with higher AF risk. Weight loss from early to middle adulthood, but not from middle to late middle adulthood, was associated with a lower risk of AF only in females. Higher BMI in youth was associated with an increased risk of AF, particularly among males or those with a lower genetic risk of AF.

Sweetened beverages and atrial fibrillation in people with prediabetes or diabetes.

To assess the association of intake of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with new-onset atrial fibrillation (AF) in people with prediabetes or diabetes. A total of 31 433 participants with prediabetes and diabetes from the UK Biobank were included. Information on the intake of SSBs, ASBs and NJs was accessed by 24-hour dietary recalls from 2009 to 2012. The study outcome was new-onset AF. During a median follow-up of 12.0 years, 2470 (7.9%) AF cases were documented. Both the intake of SSBs (per 1 unit/day increment; adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.04-1.18) and ASBs (per 1 unit/day increment; adjusted HR = 1.08; 95% CI: 1.02-1.14) were linearly and positively associated with new-onset AF, while NJ intake was not significantly associated with new-onset AF (per 1 unit/day increment; adjusted HR = 1.00; 95% CI: 0.93-1.08). Accordingly, compared with non-consumers, participants who consumed more than one unit per day of SSBs (adjusted HR = 1.30; 95% CI: 1.11-1.53) or ASBs (adjusted HR = 1.21; 95% CI:1.05-1.40) had an increased risk of AF. Substituting 1 unit/day of NJs for SSBs was associated with a 9% (adjusted HR = 0.91; 95% CI: 0.83-0.99) lower risk of new-onset AF, while replacing SSBs with ASBs was not significantly associated with new-onset AF (adjusted HR = 0.97; 95% CI: 0.89-1.06). Both the intake of SSBs and ASBs were linearly and positively associated with new-onset AF, while NJ intake did not show a significant association with AF in people with prediabetes or diabetes. Replacing an equivalent amount of SSB intake with NJs, but not ASBs, was associated with a lower risk of AF.

Plant Omega-3 Fatty Acids May Lower Risk of Atrial Fibrillation in Individuals with a Low Intake of Marine Omega-3 Fatty Acids

BackgroundOmega-3 fatty acids derived from seafood acids may influence cardiac arrhythmogenesis, whereas the role of the major plant-derived omega-3 fatty acid, alpha-linolenic acid (ALA), on atrial fibrillation (AF) is largely unknown. ObjectivesWe aimed to investigate the association between ALA intake and risk of incident AF overall and in subjects with a low intake of marine omega-3 fatty acids. MethodsWe followed a total of 54,260 middle-aged men and women enrolled into the Danish Diet, Cancer, and Health cohort for development of AF using nationwide registries. Intake of ALA was assessed using a validated food frequency questionnaire and modeled as a restricted cubic spline. Statistical analyses were conducted using Cox proportional hazards regression. ResultsWe identified a total of 4902 incident AF events during a median of 16.9 y of follow-up. In multivariable analyses, we observed indications of a statistically nonsignificant inverse association between ALA intake and risk of AF up to an ALA intake of 2.5 g/d, whereas no appreciable association was found for higher intakes of ALA. A statistically significant dose-dependent negative association was found between ALA intake and risk of AF in individuals consuming < 250 mg marine omega-3 fatty acids daily, whereas no association was found in those with a higher intake of marine omega-3 fatty acids. ConclusionsIntake of ALA was associated with a lower risk of AF in individuals consuming a low intake of marine omega-3 fatty acids. This finding is novel and warrants further investigation.

Metformin and Atrial Fibrillation: A Systematic Review of Their Association.

Atrial fibrillation (AF) is a common cardiac arrhythmia with a significant impact on patient outcomes and healthcare systems. Given the rising incidence of AF with age and its association with conditions, such as diabetes, there is growing interest in exploring pharmacological interventions that might mitigate AF risk. Metformin, a widely prescribed antihyperglycemic agent for type 2 diabetes mellitus (T2DM), has demonstrated various cardiovascular benefits, including anti-inflammatory and antioxidative properties, leading to speculations about its potential role in AF prevention. This systematic review synthesizes findings from five studies examining the association between metformin use and AF risk in patients with T2DM. The review included a dynamic cohort study, three retrospective cohort studies, and a case report, all sourced from databases, such as PubMed, Embase, and the Cochrane Library. The results are mixed; while some studies suggest that metformin use is linked to a reduced incidence of AF, others report no significant association, particularly in postoperative settings. The largest cohort study highlighted a dose-response relationship, suggesting prolonged metformin use correlates with lower AF risk. Conversely, a case report raised concerns about metformin-induced lactic acidosis potentially triggering AF episodes. The review underscores the heterogeneity in study designs and outcomes, pointing to the need for more robust research to establish causality and clarify underlying mechanisms. Future studies should prioritize prospective designs and explore the pleiotropic effects of metformin on atrial remodeling and electrophysiology to better understand its potential role in AF prevention.

Leisure-time physical activity and the incidence of atrial fibrillation in senior adults: a prospective cohort study.

Whether physical activity could reduce the risk of atrial fibrillation (AF) remains unclear. This study was to investigate the relationship of leisure-time physical activity (LTPA) with AF incidence among Chinese older adults. A total of 3253 participants aged ≥60years from the Guangzhou Heart Study were successfully followed between March 2018 and September 2019. LTPA was assessed using a modified Global Physical Activity Questionnaire. AF was ascertained by 12-lead electrocardiograms, 24-hour single-lead Holter and clinical examination. The Cox proportional hazards model was used to the estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for confounders, and the population-attributable fraction (PAF) was estimated. A total of 76 (2.34%) new-onset cases of AF were identified during a median of 31.13months of follow-up. After adjustment for confounders, subjects who had LTPA at least 10.0 metabolic equivalent (MET)-hours/week had a 55% lower risk of developing AF (HR: 0.45, 95%CI: 0.25-0.81), and at least 20 MET-hours/week reduced the risk by 45% (HR: 0.55, 95%CI: 0.34-0.92). At least 11% (PAF: 11%, 95%CI: 0%-20%) or 14% (PAF: 14%, 95%CI: 0%-26%) of AF cases could be avoided, respectively, if the subjects do LTPA at least 10 MET-hours/week or 20 MET-hours/week. A significant exposure-response trend was also observed between LTPA and AF risk (Plinear-trend = 0.002). For a specific LTPA, doing housework was associated with a 43% reduced risk, while engaging in ball games was associated with an increased risk. This prospective cohort study indicated that a higher LTPA volume was associated with a lower AF risk in Chinese older adults.

Life’s Essential 8, Genetic Susceptibility, and Incident Cardiac Arrhythmias: A Population-Based Prospective Cohort Study

BackgroundIdeal cardiovascular health (CVH) has been associated with reduced cardiovascular disease risk and mortality, but its association with cardiac arrhythmias was still unsettled. In this prospective cohort study, we investigated the relationship between CVH and subsequent arrhythmias risk, including atrial fibrillation (AF)/flutter, ventricular arrhythmias, and bradyarrhythmias. MethodsData from 287,264 participants initially free of arrhythmias in the UK Biobank were included in the analysis. Cox regression models were used to examine the relationship between CVH levels calculated by the American Heart Association’s Life’s Essential 8 (LE8) metrics, with cardiac arrhythmias risk. ResultsDuring a median follow-up period of 12.8 years, 16,802 incident AF, 2186 incident ventricular arrhythmias, and 4128 incident bradyarrhythmias were identified. After adjustment for confounding factors, participants with high initial CVH levels had significantly lower risks for AF (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.59-0.68), ventricular arrhythmias (HR, 0.48; 95% CI, 0.40-0.59), and bradyarrhythmias (HR, 0.64; 95% CI, 0.55-0.74) compared with those with low CVH levels. Furthermore, each standard deviation (SD) increase in LE8 scores was associated with a 15% lower risk of AF, 21% for ventricular arrhythmias, and 13% for bradyarrhythmias, respectively. In addition, a significant interaction was observed between CVH levels and the genetic risk of AF (P for interaction, 0.021). The reverse correlation seemed to be more noticeable in individuals with a lower genetic susceptibility to AF. ConclusionsWe concluded that higher levels of CVH, estimated by the LE8 metrics, were associated with significantly reduced risks of AF, ventricular arrhythmias, and bradyarrhythmias.

Sodium-glucose cotransporter-2 inhibitors and incidence of atrial fibrillation in older adults with type 2 diabetes: a retrospective cohort analysis

ObjectivesTo investigate the risk of atrial fibrillation (AF) with sodium-glucose cotransporter-2 inhibitors (SGLT2is) compared to dipeptidyl peptidase-4 inhibitor (DPP4i) use in older US adults and across diverse subgroups.MethodsWe conducted a retrospective cohort analysis using claims data from 15% random samples of Medicare fee-for-service beneficiaries. Patients were adults with type 2 diabetes (T2D), no preexisting AF, and were newly initiated on SGLT2i or DPP4i. The outcome was the first incident AF. Inverse probability treatment weighting (IPTW) was used to balance the baseline covariates between the treatment groups including sociodemographics, comorbidities, and co-medications. Cox regression models were used to assess the effect of SGLT2i compared to DPP4i on incident AF.ResultsOf the 97,436 eligible individuals (mean age 71.2 ± 9.8 years, 54.6% women), 1.01% (n = 983) had incident AF over a median follow-up of 361 days. The adjusted incidence rate was 8.39 (95% CI: 6.67–9.99) and 11.70 (95% CI: 10.9–12.55) per 1,000 person-years in the SGLT2i and DPP4i groups, respectively. SGLT2is were associated with a significantly lower risk of incident AF (HR 0.73; 95% CI, 0.57 to 0.91; p = 0.01) than DPP4is. The risk reduction of incident AF was significant in non-Hispanic White individuals and subgroups with existing atherosclerotic cardiovascular diseases and chronic kidney disease.ConclusionCompared to the use of DPP4i, that of SGLT2i was associated with a lower risk of AF in patients with T2D. Our findings contribute to the real-world evidence regarding the effectiveness of SGLT2i in preventing AF and support a tailored therapeutic approach to optimize treatment selection based on individual characteristics.

Migraine and risk of atrial fibrillation: A 9-year follow-up based on the Trøndelag Health Study.

Data from some population-based studies have indicated an increased risk of atrial fibrillation (AF) among patients with migraine, particularly among individuals with migraine with aura. The present study aimed to assess the association between primary headache disorders and AF. In a population-based 9-year follow-up design, we evaluated the questionnaire-based headache diagnosis, migraine and tension-type headache (TTH) included, collected in the Trøndelag Health Study (HUNT3) conducted in 2006-2008, and the subsequent risk of AF in the period until December 2015. The population at risk consisted of 39,340 individuals ≥20 years without AF at HUNT3 baseline who answered headache questionnaire during HUNT3. The prospective association was evaluated by multivariable Cox proportional hazard models with 95% confidence intervals (CIs). Among the 39,340 participants, 1524 (3.8%) developed AF during the 9-year follow up, whereof 91% of these were ≥55 years. In the multivariable analyses, adjusting for known confounders, we did not find any association between migraine or TTH and risk of AF. The adjusted hazard ratios (HRs) were respectively 0.84 (95% CI = 0.64-1.11) for migraine, 1.16 (95% CI = 0.86-1.27) for TTH and 1.04 (95% CI = 0.86-1.27) for unclassified headache. However, in sensitivity analyses of individuals aged ≥55 years, a lower risk of AF was found for migraine (HR = 0.53; 95% CI = 0.39-0.73). In this large population-based study, no increased risk of AF was found among individuals with migraine or TTH at baseline. Indeed, among individuals aged ≥55 years, migraine was associated with a lower risk for AF.

Rate of atrial fibrillation by Holter-Stroke Risk Analysis in undetermined TIA/rapidly improving stroke symptoms patients.

Holter-SRA (Stroke Risk Analysis) is an automated analysis of ECG monitoring for Atrial Fibrillation (AF) detection. The aim of this study was to evaluate the rate of AF in undetermined TIA/Rapidly improving stroke symptoms (RISS) patients. Prospective study of undetermined TIA/RISS patients who presented to the emergency department. Early vascular studies (angio CT, transthoracic echocardiography and ECG) were performed in emergency department. The Holter-SRA device was placed for 2 h and the patients were classified into: confirmed AF, high risk of AF or low risk of AF. Prolonged ambulatory monitoring (7 days) was carried out every month for patients with a high-risk pattern. The results were evaluated until definitive detection of AF or low-risk pattern. The endpoints were rate of AF and vascular recurrence at 90 days. Over a period of 24 months, 83 undetermined TIA/RISS patients were enrolled. The mean age was 70 ± 10 years and 61% were men. The median ABCD2 score was 4 points (1-7). After 2 h of monitoring in the emergency department, AF was detected in one patient (1.2%), 51 patients with a low-risk pattern and 31 patients (37.3%) showed a high-risk pattern of AF. During the ambulatory monitoring, of the 31 patients high risk pattern patients, AF was diagnosed to 17 cases and of the 51 patients with a low-risk pattern, one case experienced a recurrent vascular due to undetected AF (1.9% false negative). Three patients (3.6%) suffered a vascular recurrence within the first 90 days, before AF diagnosis. In our study, AF was detected in 22.9% of the 83 patients with indeterminate TIA/RISS. Holter-SRA has allowed us to increase the detection of AF, especially those patients with a high-risk pattern in the first 3 months.

Genetically predicted dietary macronutrient intakes and atrial fibrillation risk: a Mendelian randomization study

Background and aimPrevious observational investigations have indicated a potential association between relative dietary macronutrient intakes and atrial fibrillation and flutter (AF) risk. In this study, we employed Mendelian Randomization (MR) to evaluate the presence of causality and to elucidate the specific causal relationship.MethodsWe employed six, five, and three single nucleotide polymorphisms (SNPs) as instrumental variables for relative carbohydrate, protein, and fat intake, identified from a genome-wide association study that included 268,922 individuals of European descent. Furthermore, we acquired summary statistics for genome-wide association studies on AF from the FinnGen consortium, which involved 22,068 cases and 116,926 controls. To evaluate the causal estimates, we utilized the random effect inverse variance weighted method (IVW) and several other MR methods, including MR-Egger, weighted median, and MR-PRESSO, to confirm the robustness of our findings.ResultsOur analysis indicates a convincing causal relationship between genetically predicted relative carbohydrate and protein intake and reduced AF risk. Inverse variance weighted analysis results for carbohydrates (OR = 0.29; 95% CI (0.14, 0.59); P < 0.001) and protein (OR = 0.47; 95% CI (0.26, 0.85); P = 0.01) support this association. Our MR analysis did not identify a significant causal relationship between relative fat intake and AF risk.ConclusionOur study provides evidence supporting a causal relationship between higher relative protein and carbohydrate intake and a lower risk of atrial fibrillation (AF).

Effect of physical activity on incident atrial fibrillation in individuals with varying duration of diabetes: a nationwide population study

BackgroundDiabetes mellitus (DM) duration affects incident atrial fibrillation (AF) risk; the effect of physical activity on mitigating AF risk related to varying DM duration remains unknown. We assessed the effect of physical activity on incident AF in patients with DM with respect to known DM duration.MethodsPatients with type 2 DM who underwent the Korean National Health Insurance Service health examination in 2015–2016 were grouped by DM duration: new onset and < 5, 5–9, and ≥ 10 years. Physical activity was classified into four levels: 0, < 500, 500–999, 1,000–1,499, and ≥ 1,500 metabolic equivalent task (MET)-min/week, with the primary outcome being new-onset AF.ResultsThe study enrolled 2,392,486 patients (aged 59.3 ± 12.0 years, 39.8% female) with an average follow-up of 3.9 ± 0.8 years and mean DM duration of 5.3 ± 5.1 years. Greater physical activity was associated with a lower AF risk. Lowering of incident AF risk varied with different amounts of physical activity in relation to known DM duration. Among patients with new-onset DM, DM duration < 5 years and 5–9 years and 1,000–1,499 MET-min/week exhibited the lowest AF risk. Physical activity ≥ 1,500 MET-min/week was associated with the lowest incident AF risk in patients with DM duration ≥ 10 years (by 15%), followed DM duration of 5–9 years (12%) and < 5 years (9%) (p-for-interaction = 0.002).ConclusionsLonger DM duration was associated with a high risk of incident AF, while increased physical activity generally reduced AF risk. Engaging in > 1,500 MET-min/week was associated with the greatest AF risk reduction in patients with longer DM duration, highlighting the potential benefits of higher activity levels for AF prevention.

Drug Target Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia with significant clinical implications. The potential influence of lipid-lowering therapies, specifically PCSK9 inhibitors (PCSK9i) and HMG-CoA reductase inhibitors (statins), on AF risk remains a topic of interest. This mendelian randomization (MR) study aimed to elucidate the causal relationship between genetically predicted inhibition of PCSK9 and HMG-CoA reductase and the risk of AF. Methods: Utilizing publicly available, summary-level genome-wide association study data, we employed single-nucleotide polymorphisms associated with lower LDL-C levels as instruments for gene-simulated inhibition of PCSK9 and HMG-CoA reductase. Multiple MR techniques were applied to estimate the causal effects, and sensitivity analyses were conducted to validate the results. Results: Genetically predicted inhibition of PCSK9 demonstrated a reduced risk of AF, with an odds ratio (OR) of 0.92 (95% CI: 0.85–0.99, p = 0.01) using the inverse variance-weighted (IVW) method. In contrast, the inhibition of HMG-CoA reductase did not exhibit a statistically significant association with AF risk (IVW: OR = 1.11, 95% CI: 1.00–1.22, p = 0.05). Conclusion: Our MR study suggests that genetically predicted inhibition of PCSK9, but not HMG-CoA reductase, is associated with a lower risk of AF. These findings provide evidence for a causal protective effect of PCSK9i on AF and support the use of PCSK9i for AF prevention in patients with dyslipidemia. Further studies are needed to elucidate the mechanisms underlying the differential effects of PCSK9i and statins on AF and to confirm the clinical implications of our findings.

Aldehyde Dehydrogenase 2 (ALDH2) Deficiency, Obesity, and Atrial Fibrillation Susceptibility: Unraveling the Connection.

Atrial fibrillation (AF), characterized by structural remodeling involving atrial myocardial degradation and fibrosis, is linked with obesity and transforming growth factor beta 1 (TGF-β1). Aldehyde dehydrogenase 2 (ALDH2) deficiency, highly prevalent in East Asian people, is paradoxically associated with a lower AF risk. This study investigated the impact of ALDH2 deficiency on diet-induced obesity and AF vulnerability in mice, exploring potential compensatory upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1 (HO-1). Wild-type (WT) and ALDH2*2 knock-in (KI) mice were administered a high-fat diet (HFD) for 16 weeks. Despite heightened levels of reactive oxygen species (ROS) post HFD, the ALDH2*2 KI mice did not exhibit a greater propensity for AF compared to the WT controls. The ALDH2*2 KI mice showed equivalent myofibril degradation in cardiomyocytes compared to WT after chronic HFD consumption, indicating suppressed ALDH2 production in the WT mice. Atrial fibrosis did not proportionally increase with TGF-β1 expression in ALDH2*2 KI mice, suggesting compensatory upregulation of the Nrf2 and HO-1 pathway, attenuating fibrosis. In summary, ALDH2 deficiency did not heighten AF susceptibility in obesity, highlighting Nrf2/HO-1 pathway activation as an adaptive mechanism. Despite limitations, these findings reveal a complex molecular interplay, providing insights into the paradoxical AF-ALDH2 relationship in the setting of obesity.

Trends and Outcomes Associated With Bariatric Surgery and Pharmacotherapies With Weight Loss Effects Among Patients With Heart Failure and Obesity.

Utilization patterns of bariatric surgery among older patients with heart failure (HF), and the associations with cardiovascular outcomes, are not well known. Medicare beneficiaries with HF and at least class II obesity from 2013 to 2020 were identified with Medicare Provider Analysis and Review 100% inpatient files and Medicare 5% outpatient files. Patients who underwent bariatric surgery were matched to controls in a 1:2 ratio (matched on exact age, sex, race, body mass index, HF encounter year, and HF hospitalization rate pre-surgery/matched period). In an exploratory analysis, patients prescribed pharmacotherapies with weight loss effects (semaglutide, liraglutide, naltrexone-bupropion, or orlistat) were identified and matched to controls with a similar strategy in addition to HF medical therapy data. Cox models evaluated associations between weight loss therapies (as a time-varying covariate) and mortality risk and HF hospitalization rate (calculated as the rate of HF hospitalizations following index HF encounter per 100 person-months) during follow-up. Of 298 101 patients with HF and body mass index ≥35 kg/m2, 2594 (0.9%) underwent bariatric surgery (45% men; mean age, 56.2 years; mean body mass index, 51.5 kg/m2). In propensity-matched analyses over a median follow-up of 4.7 years, bariatric surgery was associated with lower risk of all-cause mortality (HR, 0.55 [95% CI, 0.49-0.63]; P<0.001), greater reduction in HF hospitalization rate (rate ratio, 0.72 [95% CI, 0.67-0.77]; P<0.001), and lower atrial fibrillation risk (HR, 0.78 [95% CI, 0.65-0.93]; P=0.006). Use of pharmacotherapies with weight loss effects was low (4.8%), with 96.3% prescribed GLP-1 (glucagon-like peptide-1) agonists (semaglutide, 23.6%; liraglutide, 72.7%). In propensity-matched analysis over a median follow-up of 2.8 years, patients receiving pharmacotherapies with weight loss effects (versus matched controls) had a lower risk of all-cause mortality (HR, 0.82 [95% CI, 0.71-0.95]; P=0.007) and HF hospitalization rate (rate ratio, 0.87 [95% CI, 0.77-0.99]; P=0.04). Bariatric surgery and pharmacotherapies with weight loss effects are associated with a lower risk of adverse outcomes among older patients with HF and obesity; however, overall utilization remains low.

Difference Between Estimated GFR Based on Cystatin C Versus Creatinine and Incident Atrial Fibrillation: A Cohort Study of the UK Biobank

The difference between cystatin C-based and creatinine-based estimated glomerular filtration rate (eGFRdiff) has been suggested to reflect factors distinct from kidney function that are associated with cardiovascular risk. However, the association between eGFRdiff and atrial fibrillation (AF) risk has not been extensively evaluated. Prospective cohort study. Using data from the UK Biobank, this study included 363,494 participants with measured serum creatinine and cystatin C levels and without a prior diagnosis of AF or a history of related procedures. Estimated GFRdiff, calculated as cystatin C-based eGFR minus creatinine-based eGFR. Estimated GFRdiff was also categorized as negative (<-15mL/min/1.73m2), midrange (-15 to 15mL/min/1.73m2), or positive (≥15mL/min/1.73m2). Incident AF. Subdistribution hazard models were fit, treating death that occurred before development of AF as a competing event. During the median follow-up period of 11.7 years, incident AF occurred in 18,994 (5.2%) participants. In the multivariable-adjusted model, participants with a negative eGFRdiff had a higher risk of incident AF (subdistribution HR [SHR], 1.25 [95% CI, 1.20-1.30]), whereas participants with a positive eGFRdiff had a lower risk of AF (SHR, 0.81 [95% CI, 0.77-0.87]) compared with those with a midrange eGFRdiff. When eGFRdiff was treated as a continuous variable in the adjusted model, every 10mL/min/1.73m2 higher eGFRdiff was associated with a 0.90-fold decrease in the risk of incident AF. A single measurement of baseline serum creatinine and cystatin C levels. The difference between cystatin C- and creatinine-based eGFRs was associated with the risk of AF development. A higher eGFRdiff was associated with a lower risk of AF. These findings may have implications for the management of patients at risk of incidentAF. The difference between cystatin C-based estimated glomerular filtration rate (eGFR) and creatinine-based eGFR has recently gained attention as a potential indicator of cardiovascular outcomes influenced by factors other than kidney function. This study investigated the association between the differences in 2 eGFRs (cystatin C-based eGFR minus creatinine-based eGFR) and incident atrial fibrillation (AF) among>340,000 participants from the UK Biobank Study. Compared with those with a near zero eGFR difference, participants with a negative eGFR difference had a higher risk of AF, while those with a positive eGFR difference had a lower risk. These findings suggest that measuring eGFR differences may help identify individuals at a higher risk of developing AF.

Ideal cardiovascular health and cardiovascular-related events: a systematic review and meta-analysis.

The aim of this study was to systematically review and quantitatively summarize the evidence on the association between Life Simple's 7 (LS7) and multiple cardiovascular diseases (CVDs) and cardiometabolic diseases (CMDs). EMBASE and PubMed were searched from January 2010 to March 2022 for observational studies that investigated the association between ideal cardiovascular health (CVH) with CVD or CMD outcomes in an adult population. Two reviewers independently selected studies according to the eligibility criteria, extracted data, and evaluated risk of bias. Data were analysed with a random-effects meta-analysis. This meta-analysis included 59 studies (1 881 382 participants). Participants with ideal CVH had a considerably lower risk of a variety of CVDs and CMDs as compared with those with poor CVH, varying from 40% lower risk for atrial fibrillation (AF) {hazard ratio [HR] = 0.60 [95% confidence interval (CI) 0.44-0.83]} to 82% lower risk for myocardial infarction [HR = 0.18 (95% CI 0.12-0.28)]. Intermediate CVH was associated with 27-57% lower risk in CVDs and CMDs compared with poor CVH, with the highest hazard for AF [HR = 0.73 (95% CI 0.59-0.91)] and the lowest hazard for peripheral arterial disease [HR = 0.43 (95% CI 0.30-0.60)]. Ideal and moderate CVH were associated with a lower incidence of CVDs and CMDs than poor CVH. Life Simple's 7 holds significant potential for promoting overall CVH and thereby contributing to the prevention of CVDs.